P1 P2 PS2 PS3 PS1 PS5 PS4 PS6 P3 S1 S3 S2 DMSO6 DMSO5 DMSO4 DMSO3 DMSO2 DMSO1 Only.identified.by.site Reverse Potential.contaminant ANOVA Significant Cluster Peptides Razor...unique.peptides Unique.peptides Sequence.coverage.... Unique...razor.sequence.coverage.... Unique.sequence.coverage.... Mol..weight..kDa. Q.value Score Intensity MS.MS.count -Log ANOVA p value ANOVA q-value Protein.IDs Majority.protein.IDs Protein.names Gene.names id Uniprot function Uniprot subcellular location GOBP name GOMF name GOCC name KEGG pathway name KEGG disease name KEGG drug targets name Reactome name Corum name #!{Type}E E E E E E E E E E E E E E E E E E C C C C C N N N N N N N N N N N N N T T T T T T T T T T T T T T T #!{C:Group1}P P PS PS PS PS PS PS P S S S DMSO DMSO DMSO DMSO DMSO DMSO #!{C:Batch}1 1 1 1 1 2 2 2 1 2 2 2 2 2 2 1 1 1 -0.170483082532883 0.0670348927378654 -0.0245458669960499 -0.38418647646904 0.711957216262817 0.46470707654953 -0.0364083126187325 0.0503512285649776 -0.200643748044968 -2.03788757324219 -1.39027428627014 -1.63952016830444 1.19224047660828 1.67808485031128 1.71874010562897 0.119956195354462 0.119956195354462 -0.23907895386219 + Cluster -674 4 4 4 20.3 20.3 20.3 6.6478 0 13.711 26691000000 30 3.41165130964345 0.00051031894934334 P62861 P62861 40S ribosomal protein S30 FAU 1375 antibacterial humoral response;antimicrobial humoral immune response mediated by antimicrobial peptide;defense response to Gram-positive bacterium;innate immune response in mucosa;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;extracellular space;nucleoplasm;small ribosomal subunit Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic -0.955061197280884 0.388970136642456 0.0968773365020752 0.257296472787857 -0.0328554175794125 1.71776044368744 1.22487807273865 0.0995537117123604 -0.270501315593719 -2.0614058971405 -1.89248764514923 -1.28484797477722 0.559727013111115 0.707928836345673 0.928883135318756 0.124356165528297 0.00195790897123516 0.388970136642456 + Cluster -674 17 17 17 45.5 45.5 45.5 55.023 0 133.49 22314000000 64 3.59585728472026 0.000363834422657952 O60701;O60701-3;O60701-2 O60701;O60701-3;O60701-2 UDP-glucose 6-dehydrogenase UGDH 282 hyaluronan, chondroitin sulfate, and heparan sulfate.;Involved in the biosynthesis of glycosaminoglycans gastrulation with mouth forming second;glycosaminoglycan biosynthetic process;UDP-glucose metabolic process;UDP-glucuronate biosynthetic process electron transfer activity;NAD binding;UDP-glucose 6-dehydrogenase activity cytosol;extracellular exosome;nucleoplasm;nucleus Amino sugar and nucleotide sugar metabolism;Ascorbate and aldarate metabolism;Metabolic pathways;Pentose and glucuronate interconversions Formation of the active cofactor, UDP-glucuronate -1.05930626392365 0.620020866394043 1.09841156005859 0.298705220222473 0.939740717411041 1.14953923225403 1.34250390529633 0.953070163726807 -0.43063023686409 -2.18161106109619 -1.5777792930603 -0.728666245937347 0.724184811115265 0.0607457980513573 0.258122265338898 -0.518210589885712 -0.518210589885712 -0.43063023686409 + Cluster -674 28 28 22 19.8 19.8 15.2 218 0 323.31 51278000000 115 3.64622191248668 0.000330337078651685 Q14839;Q14839-2;Q8TDI0 Q14839;Q14839-2 Chromodomain-helicase-DNA-binding protein 4 CHD4 1735 Chromatin-remodeling protein that binds DNA throughhistones and regulates gene transcription. May specificallyrecognize and bind trimethylated 'Lys-27' (H3K27me3) and non-methylated 'Lys-4' of histone H3. Plays a role in the developmentof the nervous system by activating the expression of genespromoting neuron terminal differentiation. In parallel, it mayalso positively regulate the trimethylation of histone H3 at 'Lys-27' thereby specifically repressing genes that promote thedifferentiation into non-neuronal cell lineages. Tumor suppressor,it regulates the expression of genes involved in cellproliferation and differentiation. Downstream activated genes mayinclude CDKN2A that positively regulates the p53/TP53 pathway,which in turn, prevents cell proliferation. In spermatogenesis, itprobably regulates histone hyperacetylation and the replacement ofhistones by transition proteins in chromatin, a crucial step inthe condensation of spermatid chromatin and the production offunctional spermatozoa.;Component of the histone deacetylase NuRD complex whichparticipates in the remodeling of chromatin by deacetylatinghistones. Nucleus {ECO:0000269|PubMed:17626165,ECO:0000269|PubMed:27616479}. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:17626165}.Note=Associates with centrosomes in interphase.{ECO:0000250|UniProtKB:Q6PDQ2}.;Nucleus {ECO:0000269|PubMed:21931736,ECO:0000269|PubMed:23948251}. Note=Associates withheterochromatin. {ECO:0000250}. ATP-dependent chromatin remodeling;cerebral cortex neuron differentiation;histone H3-K27 trimethylation;histone H4 acetylation;negative regulation of cell proliferation;positive regulation of signal transduction by p53 class mediator;regulation of transcription by RNA polymerase II;regulation of transcription involved in cell fate commitment;spermatogenesis, exchange of chromosomal proteins ATP binding;ATP-dependent DNA helicase activity;DNA binding;H3K27me3 modified histone binding;helicase activity;histone deacetylase activity;histone deacetylase binding;metal ion binding;RNA polymerase II repressing transcription factor binding;zinc ion binding centrosome;cytoplasm;cytosol;heterochromatin;membrane;nuclear chromatin;nuclear speck;nucleoplasm;nucleus;NuRD complex;protein-containing complex Human papillomavirus infection;Viral carcinogenesis ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;HDACs deacetylate histones;Regulation of PTEN gene transcription;Regulation of TP53 Activity through Acetylation;RNA Polymerase I Transcription Initiation Anti-HDAC2 complex;ATR-HDAC2-CHD4 complex;CDH4-HDAC2-MTA2-RBBP7-TWIST1 complex;Emerin complex 32;LARC complex (LCR-associated remodeling complex);MeCP1 complex;Mi2/NuRD complex;Mi2/NuRD-BCL6-MTA3 complex;MTA2 complex;NRD complex (Nucleosome remodeling and deacetylation complex);NuRD.1 complex;PID complex -2.07525944709778 -0.492597818374634 1.23331439495087 0.973067760467529 1.11560368537903 1.38425326347351 0.88623172044754 0.741690933704376 -0.0282228291034698 -1.92432045936584 -0.644164323806763 -0.582746207714081 0.692162454128265 -0.100362472236156 -0.45274493098259 -0.52694171667099 -0.234634965658188 0.0356707908213139 + Cluster -674 8 8 8 14.5 14.5 14.5 115.93 0 105.22 4633700000 24 3.47207311714012 0.000456521739130435 Q02218;Q02218-2;Q02218-3 Q02218;Q02218-2;Q02218-3 2-oxoglutarate dehydrogenase, mitochondrial OGDH 1492 2-oxoglutarate dehydrogenase (E1) component of the 2-oxoglutarate dehydrogenase complex, which mediates thedecarboxylation of alpha-ketoglutarate (PubMed:24495017). The 2-oxoglutarate dehydrogenase complex catalyzes the overallconversion of 2-oxoglutarate to succinyl-CoA and CO(2)(PubMed:24495017). The 2-oxoglutarate dehydrogenase complex ismainly active in the mitochondrion (PubMed:29211711). A fractionof the 2-oxoglutarate dehydrogenase complex also localizes in thenucleus and is required for lysine succinylation of histones:associates with KAT2A on chromatin and provides succinyl-CoA tohistone succinyltransferase KAT2A (PubMed:29211711) Mitochondrion matrix{ECO:0000305|PubMed:29211711}. Nucleus{ECO:0000269|PubMed:29211711}. Note=Mainly localizes in themitochondrion. A small fraction localizes to the nucleus, wherethe 2-oxoglutarate dehydrogenase complex is required for histonesuccinylation. {ECO:0000269|PubMed:29211711}. 2-oxoglutarate metabolic process;cerebellar cortex development;generation of precursor metabolites and energy;glycolytic process;hippocampus development;histone succinylation;NADH metabolic process;olfactory bulb mitral cell layer development;pyramidal neuron development;striatum development;succinyl-CoA metabolic process;tangential migration from the subventricular zone to the olfactory bulb;thalamus development;tricarboxylic acid cycle chaperone binding;heat shock protein binding;metal ion binding;oxoglutarate dehydrogenase (NAD+) activity;oxoglutarate dehydrogenase (succinyl-transferring) activity;thiamine pyrophosphate binding mitochondrial matrix;mitochondrial membrane;mitochondrion;nucleus;oxoglutarate dehydrogenase complex Carbon metabolism;Citrate cycle (TCA cycle);Metabolic pathways Alpha-ketoglutarate dehydrogenase complex deficiency;Diseases of the tricarboxylic acid cycle Citric acid cycle (TCA cycle);Glyoxylate metabolism and glycine degradation;Lysine catabolism KAT2A-Oxoglutarate dehydrogenase complex -1.7441338300705 0.0533390566706657 0.917735993862152 1.38282310962677 1.32438158988953 1.39427745342255 0.96357661485672 0.927797973155975 0.036327239125967 -1.04546761512756 -1.0226526260376 -1.32432568073273 0.519572854042053 -0.256921857595444 -0.155822068452835 -0.973746538162231 -0.413959443569183 -0.582802295684814 + Cluster -674 8 8 8 16.2 16.2 16.2 66.898 0 34.936 3274700000 11 4.1738843319525 0.000104761904761905 Q4G0J3;Q4G0J3-3;Q4G0J3-2 Q4G0J3;Q4G0J3-3;Q4G0J3-2 La-related protein 7 LARP7 1893 Negative transcriptional regulator of polymerase IIgenes, acting by means of the 7SK RNP system. Within the 7SK RNPcomplex, the positive transcription elongation factor b (P-TEFb)is sequestered in an inactive form, preventing RNA polymerase IIphosphorylation and subsequent transcriptional elongation Nucleus, nucleoplasm{ECO:0000269|PubMed:18483487}. RNA processing RNA binding cytosol;nucleoplasm;ribonucleoprotein complex Alazami syndrome 7SK RNP complex -1.0787467956543 0.00284737162292004 1.62012994289398 0.985185980796814 0.770040333271027 1.44029116630554 0.81270045042038 1.55116879940033 -0.228684782981873 -0.202548950910568 -0.778997123241425 0.450406432151794 -1.39992296695709 -1.27155721187592 -0.601526737213135 -1.0787467956543 -0.565338671207428 -0.426700294017792 + Cluster -674 5 5 5 54.9 54.9 54.9 16.46 0 55.708 34353000000 40 4.82416114242386 2.33644859813084E-05 P47813;O14602 P47813;O14602 Eukaryotic translation initiation factor 1A, X-chromosomal;Eukaryotic translation initiation factor 1A, Y-chromosomal EIF1AX;EIF1AY 1065 Seems to be required for maximal rate of proteinbiosynthesis. Enhances ribosome dissociation into subunits andstabilizes the binding of the initiator Met-tRNA(I) to 40 Sribosomal subunits (By similarity).;Seems to be required for maximal rate of proteinbiosynthesis. Enhances ribosome dissociation into subunits andstabilizes the binding of the initiator Met-tRNA(I) to 40 Sribosomal subunits. translational initiation RNA binding;translation factor activity, RNA binding;translation initiation factor activity cytosol RNA transport Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Ribosomal scanning and start codon recognition;Translation initiation complex formation IPO13-RAN-EIF1AX complex -1.50268006324768 0.00599540630355477 1.71424448490143 1.21267783641815 0.822126805782318 1.12327802181244 1.12327802181244 1.01219093799591 -0.810494184494019 -0.539590537548065 -0.626823425292969 0.804665923118591 -1.27445268630981 -0.626823425292969 -0.99574089050293 -0.998176455497742 -0.12993098795414 -0.313744992017746 + Cluster -674 6 6 6 49.4 49.4 49.4 16.648 0 166.11 43544000000 69 4.05833033224461 0.00013353115727003 Q9UHV9 Q9UHV9 Prefoldin subunit 2 PFDN2 3115 Binds specifically to cytosolic chaperonin (c-CPN) andtransfers target proteins to it. Binds to nascent polypeptidechain and promotes folding in an environment in which there aremany competing pathways for nonnative proteins Nucleus {ECO:0000269|PubMed:17936702}.Cytoplasm {ECO:0000269|PubMed:17936702}. Mitochondrion{ECO:0000269|PubMed:17936702}. positive regulation of cytoskeleton organization;protein folding protein binding involved in protein folding;unfolded protein binding cytoplasm;cytosol;mitochondrion;nucleus;prefoldin complex Prefoldin mediated transfer of substrate to CCT/TriC CCT-Prefoldin complex;CCT-Prefoldin complex, testis specific;Kinase maturation complex 1;Prefoldin complex;URI complex (Unconventional prefoldin RPB5 Interactor) -2.24015474319458 0.102930881083012 1.37198984622955 1.22488832473755 1.69266557693481 0.707500457763672 1.13625586032867 0.707500457763672 -0.506551384925842 0.319726765155792 -0.284384608268738 -0.34404993057251 -0.898525059223175 -0.64955472946167 -0.694456458091736 -0.946761310100555 -0.247475609183311 -0.451544255018234 + Cluster -674 20 20 20 29.7 29.7 29.7 87.301 0 318.49 53089000000 110 3.72281965217613 0.000278846153846154 P54886;P54886-2 P54886;P54886-2 Delta-1-pyrroline-5-carboxylate synthase;Glutamate 5-kinase;Gamma-glutamyl phosphate reductase ALDH18A1 1229 Bifunctional enzyme that converts glutamate to glutamate5-semialdehyde, an intermediate in the biosynthesis of proline,ornithine and arginine. Mitochondrion inner membrane{ECO:0000269|PubMed:26297558, ECO:0000269|PubMed:26320891}. cellular amino acid biosynthetic process;citrulline biosynthetic process;glutamate metabolic process;L-proline biosynthetic process;ornithine biosynthetic process;proline biosynthetic process ATP binding;delta1-pyrroline-5-carboxylate synthetase activity;glutamate 5-kinase activity;glutamate-5-semialdehyde dehydrogenase activity;identical protein binding;RNA binding cytosol;mitochondrial inner membrane;mitochondrion Arginine and proline metabolism;Biosynthesis of amino acids;Metabolic pathways Cutis laxa;Hereditary spastic paraplegia;Secondary hyperammonemia Amino acid synthesis and interconversion (transamination) -2.66410708427429 -0.111329130828381 1.37410819530487 1.21731305122375 1.32438349723816 0.875120580196381 1.03544390201569 0.792112767696381 -0.311051219701767 -0.147387772798538 -0.0994977578520775 -0.219340413808823 -1.06172013282776 -0.587359666824341 -0.587359666824341 -0.421979159116745 -0.052101694047451 -0.355248332023621 + Cluster -674 14 14 14 9.2 9.2 9.2 629.09 0 83.353 9737000000 27 3.35693072435838 0.000551537070524412 Q09666 Q09666 Neuroblast differentiation-associated protein AHNAK AHNAK 1556 May be required for neuronal cell differentiation. Nucleus. protein complex oligomerization;regulation of RNA splicing;regulation of voltage-gated calcium channel activity cadherin binding;RNA binding;S100 protein binding;structural molecule activity conferring elasticity actin cytoskeleton;cell-cell contact zone;costamere;cytoplasm;cytosol;extracellular exosome;focal adhesion;lysosomal membrane;membrane;nucleus;plasma membrane;sarcolemma;T-tubule;vesicle DNA ligase IV-XRCC4-AHNK complex;S100A10-annexin A2-AHNAK -2.12128520011902 0.330086946487427 1.89943253993988 1.45021736621857 0.844186186790466 0.855361998081207 0.761602461338043 0.867966651916504 -0.776320159435272 0.1013313382864 -0.0879045873880386 -0.0518849678337574 -0.917496681213379 -0.681286871433258 -0.847716987133026 -1.03726303577423 -0.24356871843338 -0.345458179712296 + Cluster -674 6 6 6 24.8 24.8 24.8 34.577 0 42.233 9093900000 30 3.53330515366782 0.000394683026584867 O00487 O00487 26S proteasome non-ATPase regulatory subunit 14 PSMD14 95 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. The PSMD14 subunitis a metalloprotease that specifically cleaves 'Lys-63'-linkedpolyubiquitin chains within the complex. Plays a role in responseto double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linkedpolyubiquitin, thereby promoting retention of JMJD2A/KDM4A onchromatin and restricting TP53BP1 accumulation. Also involved inhomologous recombination repair by promoting RAD51 loading double-strand break repair via homologous recombination;double-strand break repair via nonhomologous end joining;neutrophil degranulation;post-translational protein modification;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination;protein K63-linked deubiquitination;regulation of proteasomal protein catabolic process;response to ethanol;ubiquitin-dependent protein catabolic process endopeptidase activator activity;Lys63-specific deubiquitinase activity;metal ion binding;metallopeptidase activity;proteasome binding;thiol-dependent ubiquitin-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity cytosol;cytosolic proteasome complex;extracellular region;ficolin-1-rich granule lumen;nucleoplasm;nucleus;proteasome accessory complex;proteasome complex;proteasome regulatory particle, lid subcomplex;secretory granule lumen Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Metalloprotease DUBs;Neddylation;Negative regulation of NOTCH4 signaling;Neutrophil degranulation;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 PA700 complex;PA700-20S-PA28 complex -1.64989852905273 0.343530863523483 1.44180631637573 1.26537358760834 1.13036870956421 1.52357947826385 1.22109365463257 0.681095063686371 -0.450530856847763 -1.40181028842926 -0.114257387816906 -0.0539267659187317 -0.588783323764801 -0.401379495859146 -0.865683794021606 -0.85666960477829 -0.642014980316162 -0.581892549991608 + Cluster -674 9 9 9 11.3 11.3 11.3 100.45 0 98.031 8066700000 26 4.12504212090977 0.000116207951070336 Q9BZJ0;Q9BZJ0-2;Q9BZJ0-3 Q9BZJ0;Q9BZJ0-2;Q9BZJ0-3 Crooked neck-like protein 1 CRNKL1 2730 Involved in pre-mRNA splicing process Nucleus {ECO:0000269|PubMed:11991638,ECO:0000269|PubMed:12801913, ECO:0000269|PubMed:28076346,ECO:0000269|PubMed:28502770}. Nucleus speckle{ECO:0000269|PubMed:12084575}. Note=Colocalizes with corespliceosomal snRNP proteins (PubMed:12084575).{ECO:0000269|PubMed:12084575}. mRNA splicing, via spliceosome;spliceosomal complex assembly RNA binding catalytic step 2 spliceosome;nuclear speck;nucleoplasm;nucleus;post-mRNA release spliceosomal complex;Prp19 complex;spliceosomal complex;U2-type catalytic step 2 spliceosome Spliceosome mRNA Splicing - Major Pathway C complex spliceosome;Spliceosome -2.19406676292419 -0.249960333108902 0.914005815982819 1.64374852180481 0.732420921325684 1.34692716598511 1.15430390834808 1.15430390834808 -0.763641953468323 -1.30241870880127 -0.766394138336182 -0.224480450153351 -0.380289494991302 -0.601736664772034 -0.380289494991302 -0.0274774376302958 -0.0274774376302958 -0.0274774376302958 + Cluster -674 35 35 35 39.9 39.9 39.9 120.84 0 323.31 185380000000 361 4.41208110726106 6.13718411552347E-05 P53396;P53396-2;P53396-3 P53396;P53396-2;P53396-3 ATP-citrate synthase ACLY 1200 ATP-citrate synthase is the primary enzyme responsiblefor the synthesis of cytosolic acetyl-CoA in many tissues. Has acentral role in de novo lipid synthesis. In nervous tissue it maybe involved in the biosynthesis of acetylcholine Cytoplasm. acetyl-CoA biosynthetic process;cholesterol biosynthetic process;citrate metabolic process;coenzyme A metabolic process;fatty acid biosynthetic process;fatty-acyl-CoA biosynthetic process;lipid biosynthetic process;neutrophil degranulation;oxaloacetate metabolic process;positive regulation of cellular metabolic process ATP binding;ATP citrate synthase activity;cofactor binding;metal ion binding azurophil granule lumen;citrate lyase complex;cytosol;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;membrane;nucleoplasm;plasma membrane Citrate cycle (TCA cycle);Metabolic pathways Bempedoic acid ChREBP activates metabolic gene expression;Fatty acyl-CoA biosynthesis;Neutrophil degranulation -2.26001930236816 -0.270151346921921 1.30851888656616 1.6772540807724 1.02849614620209 1.14968121051788 0.909661710262299 0.971364200115204 -0.35720956325531 -0.622497737407684 0.0365330167114735 -0.108658336102962 -0.684483170509338 -0.498330950737 -1.15335702896118 -0.685310244560242 -0.241835653781891 -0.199655935168266 + Cluster -674 10 3 3 28.7 12.7 12.7 49.263 0 92.013 26445000000 48 4.11298924300441 0.000117824773413897 P55795 P55795 Heterogeneous nuclear ribonucleoprotein H2 HNRNPH2 1247 This protein is a component of the heterogeneous nuclearribonucleoprotein (hnRNP) complexes which provide the substratefor the processing events that pre-mRNAs undergo before becomingfunctional, translatable mRNAs in the cytoplasm. Binds poly(RG). Nucleus, nucleoplasm. mRNA splicing, via spliceosome;RNA metabolic process RNA binding cytosol;membrane;nucleoplasm;nucleus;postsynaptic density;ribonucleoprotein complex Syndromic X-linked mental retardation mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA -1.7213739156723 0.502229452133179 1.39180850982666 1.29096293449402 1.62046217918396 0.857452392578125 1.09234583377838 0.924407482147217 -0.384627282619476 -0.54655522108078 -0.484417617321014 0.255483597517014 -0.657448649406433 -0.827451586723328 -0.61375504732132 -0.794249296188354 -1.15997886657715 -0.745294690132141 + Cluster -674 5 5 5 12.7 12.7 12.7 46.649 0 54.786 8311800000 27 4.33429164981341 7.43243243243243E-05 Q969G3;Q969G3-6;Q969G3-5;Q969G3-3;Q969G3-2;Q969G3-4 Q969G3;Q969G3-6;Q969G3-5;Q969G3-3;Q969G3-2;Q969G3-4 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 SMARCE1 2382 Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and theneuron-specific chromatin remodeling complex (nBAF complex).During neural development a switch from a stem/progenitor to apostmitotic chromatin remodeling mechanism occurs as neurons exitthe cell cycle and become committed to their adult state. Thetransition from proliferating neural stem/progenitor cells topostmitotic neurons requires a switch in subunit composition ofthe npBAF and nBAF complexes. As neural progenitors exit mitosisand differentiate into neurons, npBAF complexes which containACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologousalternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunitsin neuron-specific complexes (nBAF). The npBAF complex isessential for the self-renewal/proliferative capacity of themultipotent neural stem cells. The nBAF complex along with CRESTplays a role regulating the activity of genes essential fordendrite growth (By similarity). Required for the coactivation ofestrogen responsive promoters by SWI/SNF complexes and theSRC/p160 family of histone acetyltransferases (HATs). Alsospecifically interacts with the CoREST corepressor resulting inrepression of neuronal specific gene promoters in non-neuronalcells. Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267, ECO:0000269|PubMed:12192000}. ATP-dependent chromatin remodeling;chromatin remodeling;negative regulation of transcription, DNA-templated;neurogenesis;nucleosome disassembly;regulation of transcription by RNA polymerase II chromatin binding;DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;N-acetyltransferase activity;nuclear receptor binding;protein N-terminus binding;RNA binding;transcription coactivator activity nBAF complex;npBAF complex;nuclear chromatin;nuclear chromosome;nucleoplasm;nucleus;protein-containing complex;SWI/SNF complex Hepatocellular carcinoma;Thermogenesis Coffin-Siris syndrome;Meningioma RMTs methylate histone arginines;RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known BAF complex;BRD7-CBP-SWI\u2013SNF complex;BRD7-SWI\u2013SNF complex;BRG1-associated complex;Brg1-associated complex I;BRG1-SIN3A complex;BRG1-SIN3A-HDAC containing SWI/SNF remodeling complex I;Brm-associated complex;BRM-associated complex;BRM-SIN3A complex;BRM-SIN3A-HDAC complex;EBAFa complex;EBAFb complex;LARC complex (LCR-associated remodeling complex);NUMAC complex (nucleosomal methylation activator complex);PBAF complex (Polybromo- and BAF containing complex);RNA polymerase II complex, chromatin structure modifying;SWI/SNF-related chromatin-remodeling complex;SWI-SNF chromatin remodeling-related-BRCA1 complex;WINAC complex -1.63480818271637 0.414390087127686 1.04776477813721 1.68577194213867 0.97624659538269 1.21630609035492 0.640569269657135 1.33617973327637 -0.0492981411516666 -0.989270925521851 -0.385600060224533 0.575436055660248 -0.845939636230469 -0.879911661148071 -0.667820930480957 -1.18041980266571 -0.676999270915985 -0.582596004009247 + Cluster -674 36 36 36 22.2 22.2 22.2 267.29 0 323.31 26395000000 115 3.65816379085272 0.000331050228310502 P12270;P12270-2 P12270 Nucleoprotein TPR TPR 641 associates both with chromatin in the HSP70promoter and with mRNAs transcribed from this promoter understress-induced conditions. Modulates the nucleocytoplasmictransport of activated MAPK1/ERK2 and huntingtin/HTT and may serveas a docking site for the XPO1/CRM1-mediated nuclear exportcomplex. According to some authors, plays a limited role in theregulation of nuclear protein export (PubMed:22253824 andPubMed:11952838). Plays also a role as a structural and functionalelement of the perinuclear chromatin distribution; involved in theformation and/or maintenance of NPC-associated perinuclearheterochromatin exclusion zones (HEZs). Finally, acts as a spatialregulator of the spindle-assembly checkpoint (SAC) responseensuring a timely and effective recruitment of spindle checkpointproteins like MAD1L1 and MAD2L1 to unattached kinetochore duringthe metaphase-anaphase transition before chromosome congression.Its N-terminus is involved in activation of oncogenic kinases;Component of the nuclear pore complex (NPC), a complexrequired for the trafficking across the nuclear envelope.Functions as a scaffolding element in the nuclear phase of the NPCessential for normal nucleocytoplasmic transport of proteins andmRNAs, plays a role in the establishment of nuclear-peripheralchromatin compartmentalization in interphase, and in the mitoticspindle checkpoint signaling during mitosis. Involved in thequality control and retention of unspliced mRNAs in the nucleus;in association with NUP153, regulates the nuclear export ofunspliced mRNA species bearing constitutive transport element(CTE) in a NXF1- and KHDRBS1-independent manner. Negativelyregulates both the association of CTE-containing mRNA with largepolyribosomes and translation initiation. Does not play any rolein Rev response element (RRE)-mediated export of unspliced mRNAs.Implicated in nuclear export of mRNAs transcribed from heat shockgene promoters Peripheral membrane protein{ECO:0000269|PubMed:11514627, ECO:0000269|PubMed:9024684,ECO:0000269|PubMed:9828100, ECO:0000269|PubMed:9864356};Cytoplasmic side {ECO:0000269|PubMed:12802065,ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:7798308}.Note=Detected as discrete intranuclear foci with IFI204 (Bysimilarity). In interphase, localizes to the nucleoplasmic side ofthe nuclear pore complex (NPC) core structure, forming a fibrousstructure called the nuclear basket. Detected exclusively to thecytoplasmic margin of NPC (PubMed:7798308). Docking to the innernucleoplasmic side of the NPC is mediated through binding tonucleoporins. Anchored by NUP153 to the NPC. The assembly of theNPC is a stepwise process in which Trp-containing peripheralstructures assemble after other components, including p62.Detected as filaments that emanate from the nuclear basket of theNPC and extend to the nucleolus to delineate a chromatin-freenetwork extending from the nuclear envelope to the perinucleolarregion. Detected in diffuse and discrete spheroidal intranuclearfoci. Nucleocytoplasmic shuttling protein imported into thenucleus in a XPO1/CRM1- and Importin alpha/Importin beta receptor-dependent manner. Remains localized to the nuclear membrane afterpoliovirus (PV) infection. During mitosis, remains associated withthe nuclear envelope until prometaphase. Associated with themitotic spindle from late prometaphase until anaphase. Reorganizedduring mitosis in a viscous and dynamic nuclear-derived spindlematrix that embeds the microtubule spindle apparatus from pole topole in a microtubule-independent manner. Recruited to thereforming nuclear envelope during telophase and cytokinesis.Detected at kinetochores during prometaphase (PubMed:18981471).Colocalizes with MAD2L1 in the spindle matrix but not atkinetochore (PubMed:19273613). Colocalizes with dynein, dynactin,tubulin at kinetochore during the metaphase-anaphase transition.Colocalizes with DYNLL1 at the mitotic spindle. {ECO:0000250,ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613,ECO:0000269|PubMed:7798308}.;Nucleoplasmic side {ECO:0000269|PubMed:11514627,ECO:0000269|PubMed:9024684, ECO:0000269|PubMed:9828100,ECO:0000269|PubMed:9864356}. Nucleus envelope{ECO:0000269|PubMed:12424524, ECO:0000269|PubMed:7798308}.Nucleus, nuclear pore complex {ECO:0000269|PubMed:11514627,ECO:0000269|PubMed:11839768, ECO:0000269|PubMed:12802065,ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:18981471,ECO:0000269|PubMed:7798308, ECO:0000269|PubMed:9024684,ECO:0000269|PubMed:9828100, ECO:0000269|PubMed:9864356}. Cytoplasm{ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:12802065}.Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:19273613}.Chromosome, centromere, kinetochore {ECO:0000269|PubMed:18981471}.Nucleus membrane {ECO:0000269|PubMed:12802065,ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:7798308};Nucleus {ECO:0000269|PubMed:12802065}.Nucleus membrane {ECO:0000269|PubMed:11514627,ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:18794356,ECO:0000269|PubMed:9024684, ECO:0000269|PubMed:9828100,ECO:0000269|PubMed:9864356};Peripheral membrane protein {ECO:0000269|PubMed:12802065,ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:7798308} cell division;cellular response to heat;cellular response to interferon-alpha;mitotic spindle assembly checkpoint;mRNA export from nucleus;mRNA export from nucleus in response to heat stress;negative regulation of RNA export from nucleus;negative regulation of transcription by RNA polymerase II;negative regulation of translational initiation;nuclear pore organization;positive regulation of heterochromatin assembly;positive regulation of intracellular protein transport;positive regulation of mitotic cell cycle spindle assembly checkpoint;positive regulation of protein export from nucleus;positive regulation of protein import into nucleus;protein import into nucleus;regulation of mitotic sister chromatid separation;regulation of mitotic spindle assembly;regulation of protein localization;response to epidermal growth factor;RNA export from nucleus;RNA import into nucleus;viral process chromatin binding;dynein complex binding;heat shock protein binding;mitogen-activated protein kinase binding;mRNA binding;protein homodimerization activity;RNA binding;structural constituent of nuclear pore;tubulin binding cytoplasm;cytoplasmic dynein complex;extrinsic component of membrane;kinetochore;mitotic spindle;nuclear envelope;nuclear inclusion body;nuclear membrane;nuclear periphery;nuclear pore;nuclear pore nuclear basket;nucleoplasm;nucleus Pathways in cancer;RNA transport;Thyroid cancer Thyroid cancer Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC);ISG15 antiviral mechanism;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Rev-mediated nuclear export of HIV RNA;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs -1.65400230884552 0.766291737556458 0.94873708486557 1.70431685447693 1.56070423126221 0.952939033508301 0.922145664691925 0.624439179897308 -0.152990907430649 -0.531074166297913 -0.567924737930298 0.272424101829529 -0.360568821430206 -0.499250084161758 -0.813066780567169 -1.36441445350647 -0.749053955078125 -1.05965173244476 + Cluster -674 4 4 4 23.2 23.2 23.2 34.193 0 60.513 3974800000 16 3.29620552211522 0.000598615916955017 P50897;P50897-2 P50897 Palmitoyl-protein thioesterase 1 PPT1 1144 Removes thioester-linked fatty acyl groups such aspalmitate from modified cysteine residues in proteins or peptidesduring lysosomal degradation. Prefers acyl chain lengths of 14 to18 carbons (PubMed:8816748). Lysosome {ECO:0000269|PubMed:19941651}.Secreted {ECO:0000250|UniProtKB:P45478}. adult locomotory behavior;associative learning;brain development;cellular protein catabolic process;cofactor metabolic process;cofactor transport;fatty-acyl-CoA biosynthetic process;grooming behavior;lipid catabolic process;lysosomal lumen acidification;membrane raft organization;negative regulation of apoptotic process;negative regulation of cell growth;negative regulation of neuron apoptotic process;nervous system development;neuron development;neurotransmitter secretion;pinocytosis;positive regulation of pinocytosis;positive regulation of receptor-mediated endocytosis;protein catabolic process;protein depalmitoylation;protein transport;receptor-mediated endocytosis;regulation of phospholipase A2 activity;regulation of synapse structure or activity;response to stimulus;sphingolipid catabolic process;visual perception palmitoyl-(protein) hydrolase activity;palmitoyl-CoA hydrolase activity axon;cytosol;dendrite;extracellular exosome;extracellular region;Golgi apparatus;lysosomal lumen;lysosome;membrane;membrane raft;neuronal cell body;nucleus;synaptic vesicle Fatty acid elongation;Fatty acid metabolism;Lysosome;Metabolic pathways Neuronal ceroid lipofuscinosis;Santavuori-Haltia disease Fatty acyl-CoA biosynthesis -1.13772094249725 0.284670829772949 1.68126833438873 1.56417262554169 1.25043535232544 0.985182523727417 0.819852650165558 1.04955816268921 -0.763983905315399 -0.114119559526443 -0.14247727394104 0.106303609907627 -0.94608610868454 -0.657522320747375 -1.10068166255951 -1.22906243801117 -0.873079001903534 -0.77671080827713 + Cluster -674 7 7 7 19.2 19.2 19.2 71.689 0 159.71 3370700000 16 6.15428322886298 1.26582278481013E-05 O60216 O60216 Double-strand-break repair protein rad21 homolog RAD21 255 Cleavable component of the cohesin complex, involved inchromosome cohesion during cell cycle, in DNA repair, and inapoptosis. The cohesin complex is required for the cohesion ofsister chromatids after DNA replication. The cohesin complexapparently forms a large proteinaceous ring within which sisterchromatids can be trapped. At metaphase-anaphase transition, thisprotein is cleaved by separase/ESPL1 and dissociates fromchromatin, allowing sister chromatids to segregate. The cohesincomplex may also play a role in spindle pole assembly duringmitosis. Also plays a role in apoptosis, via its cleavage bycaspase-3/CASP3 or caspase-7/CASP7 during early steps ofapoptosis: the C-terminal 64 kDa cleavage product may act as anuclear signal to initiate cytoplasmic events involved in theapoptotic pathway. Nucleus {ECO:0000269|PubMed:10623634}.Chromosome {ECO:0000269|PubMed:11073952}. Chromosome, centromere{ECO:0000269|PubMed:11073952}. Note=Associates with chromatin.Before prophase it is scattered along chromosome arms. Duringprophase, most of cohesin complexes dissociate from chromatinprobably because of phosphorylation by PLK, except at centromeres,where cohesin complexes remain. At anaphase, it is cleaved byseparase/ESPL1, leading to the dissociation of the complex fromchromosomes, allowing chromosome separation. Once cleaved bycaspase-3, the C-terminal 64 kDa cleavage product translocates tothe cytoplasm, where it may trigger apoptosis.{ECO:0000269|PubMed:11073952}. apoptotic process;cell division;DNA recombination;double-strand break repair;meiotic cell cycle;negative regulation of G2/M transition of mitotic cell cycle;negative regulation of mitotic metaphase/anaphase transition;positive regulation of sister chromatid cohesion;protein localization to chromatin;reciprocal meiotic recombination;regulation of transcription by RNA polymerase II;sister chromatid cohesion chromatin binding chromatin;chromosome;chromosome, centromeric region;cohesin complex;condensed nuclear chromosome;cytosol;meiotic cohesin complex;membrane;nuclear matrix;nucleoplasm Cell cycle Cornelia de Lange syndrome Cohesin Loading onto Chromatin;Establishment of Sister Chromatid Cohesion;Estrogen-dependent gene expression;Meiotic synapsis;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids;SUMOylation of DNA damage response and repair proteins Cohesin-SA1 complex;Cohesin-SA2 complex;DDX11-RAD21-SMC1A-SMC3 complex;SNF2h-cohesin-NuRD complex;Sororin-cohesin complex -1.47589874267578 0.0638985186815262 0.932899653911591 1.54896223545074 1.54896223545074 1.00828838348389 1.00828838348389 1.00828838348389 -0.802873611450195 -0.438362717628479 0.507562637329102 0.22272501885891 -1.36786794662476 -0.852431058883667 -1.09652805328369 -0.701554536819458 -0.701554536819458 -0.412803888320923 + Cluster -674 20 20 10 55.1 55.1 31.1 48.991 0 290.7 189100000000 180 5.18687127735704 1.84049079754601E-05 Q13838;Q13838-2 Q13838;Q13838-2 Spliceosome RNA helicase DDX39B DDX39B 1665 itsATPase activity is cooperatively stimulated by RNA andALYREF/THOC4 and ATP hydrolysis is thought to trigger thedissociation from RNA to allow the association of ALYREF/THOC4 andthe NXF1-NXT1 heterodimer. Involved in transcription elongationand genome stability.Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction ofU2 snRNP with the branchpoint. Has both RNA-stimulated ATPbinding/hydrolysis activity and ATP-dependent RNA unwindingactivity. Even with the stimulation of RNA, the ATPase activity isweak. Can only hydrolyze ATP but not other NTPs. The RNAstimulation of ATPase activity does not have a strong preferencefor the sequence and length of the RNA. However, ssRNA stimulatesthe ATPase activity much more strongly than dsRNA. Can unwind 5'or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase andhelicase activities are not influenced by U2AF2; the ATP-bound form is proposedto recruit export adapter ALYREF/THOC4 to intronless mRNA; the effect ofALYREF/THOC4 is reported conflictingly with [PubMed:23299939]reporting a stimulatory effect.;Involved in nuclear export of spliced and unsplicedmRNA. Assembling component of the TREX complex which is thought tocouple mRNA transcription, processing and nuclear export, andspecifically associates with spliced mRNA and not with unsplicedpre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junctioncomplex (EJC) and is recruited in a splicing- and cap-dependentmanner to a region near the 5' end of the mRNA where it functionsin mRNA export to the cytoplasm via the TAP/NFX1 pathway. Mayundergo several rounds of ATP hydrolysis during assembly of TREXto drive subsequent loading of components such as ALYREF/THOC andCHTOP onto mRNA. The TREX complex is essential for the export ofKaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAsand infectious virus production. Also associates with pre-mRNAindependent of ALYREF/THOC4 and the THO complex. Involved in thenuclear export of intronless mRNA Nucleus. Nucleus speckle. Cytoplasm.Note=Can translocate to the cytoplasm in the presence of MX1. TREXcomplex assembly seems to occur in regions surrounding nuclearspeckles known as perispeckles. liver development;mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;negative regulation of DNA damage checkpoint;positive regulation of cell growth involved in cardiac muscle cell development;positive regulation of DNA biosynthetic process;positive regulation of DNA-templated transcription, elongation;positive regulation of translation;positive regulation of vascular smooth muscle cell proliferation;RNA export from nucleus;RNA secondary structure unwinding;RNA splicing;spliceosomal complex assembly;viral mRNA export from host cell nucleus ATP binding;ATPase activity;ATP-dependent protein binding;ATP-dependent RNA helicase activity;identical protein binding;protein-containing complex binding;RNA binding;RNA-dependent ATPase activity;U4 snRNA binding;U6 snRNA binding cytoplasm;nuclear matrix;nuclear speck;nucleoplasm;nucleus;spliceosomal complex;transcription export complex mRNA surveillance pathway;RNA transport;Spliceosome Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;Transport of Mature mRNA derived from an Intron-Containing Transcript Exon junction complex;Spliceosome;TREX complex -1.86469125747681 -0.150017768144608 1.23169183731079 1.97294294834137 1.23169183731079 0.858255088329315 0.880892097949982 0.69980663061142 -0.035895723849535 -0.435107052326202 0.228957131505013 0.0189910940825939 -0.761111378669739 -0.729545950889587 -0.761111378669739 -1.47174465656281 -0.293378382921219 -0.620625138282776 + Cluster -674 7 7 7 17.4 17.4 17.4 73.747 0 70.114 3625300000 15 3.86057165052208 0.000221354166666667 Q9BW19 Q9BW19 Kinesin-like protein KIFC1 KIFC1 2690 Minus end-directed microtubule-dependent motor requiredfor bipolar spindle formation (PubMed:15843429). May contribute tomovement of early endocytic vesicles (By similarity). Regulatescilium formation and structure (By similarity) Nucleus {ECO:0000250|UniProtKB:Q9QWT9}.Cytoplasm, cytoskeleton, microtubule organizing center, centrosome{ECO:0000250|UniProtKB:Q9QWT9}. Cytoplasm, cytoskeleton, spindle{ECO:0000250|UniProtKB:Q9QWT9}. Early endosome{ECO:0000250|UniProtKB:Q9QWT9}. Note=Associated with nucleusduring interphase, centrosomes in early and spindle in latermitosis. {ECO:0000250|UniProtKB:Q9QWT9}. cell division;microtubule-based movement;mitotic metaphase plate congression;mitotic sister chromatid segregation;mitotic spindle assembly;spermatogenesis ATP binding;ATPase activity;microtubule binding;microtubule motor activity early endosome;kinesin complex;membrane;microtubule;microtubule organizing center;mitotic spindle;nucleus COPI-dependent Golgi-to-ER retrograde traffic;Kinesins -1.78920936584473 -0.256176322698593 1.25006103515625 1.84893906116486 1.0798956155777 1.18176698684692 0.606486737728119 1.08531713485718 -0.131607621908188 -0.19253197312355 -0.0965784192085266 0.42318069934845 -1.04291820526123 -0.962163627147675 -1.00259602069855 -0.813188433647156 -0.678603529930115 -0.510073721408844 + Cluster -674 9 9 9 37 37 37 24.327 0 102.42 18358000000 40 4.87099892787293 1.95121951219512E-05 Q9UKK9 Q9UKK9 ADP-sugar pyrophosphatase NUDT5 3149 Enzyme that can either act as an ADP-sugarpyrophosphatase in absence of diphosphate or catalyze thesynthesis of ATP in presence of diphosphate (PubMed:27257257). Inabsence of diphosphate, hydrolyzes with similar activities variousmodified nucleoside diphosphates such as ADP-ribose, ADP-mannose,ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP (PubMed:10567213,PubMed:10722730, PubMed:19699693, PubMed:21389046,PubMed:17052728). Can also hydrolyze other nucleotide sugars withlow activity (PubMed:19699693, PubMed:21389046). In presence ofdiphosphate, mediates the synthesis of ATP in the nucleus bycatalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate. Nuclear ATP synthesis takes place when dephosphorylatedat Thr-45 (PubMed:27257257). Nuclear ATP generation is requiredfor extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Does not play a role in U8 snoRNAdecapping activity (By similarity). Binds U8 snoRNA (Bysimilarity). Nucleus {ECO:0000305|PubMed:27257257}. ATP generation from poly-ADP-D-ribose;chromatin remodeling;D-ribose catabolic process;nucleobase-containing small molecule catabolic process;nucleoside phosphate metabolic process;nucleotide metabolic process;ribonucleoside diphosphate catabolic process;ribose phosphate metabolic process 8-oxo-dGDP phosphatase activity;ADP-ribose diphosphatase activity;ADP-sugar diphosphatase activity;magnesium ion binding;nucleotidyltransferase activity;protein homodimerization activity;snoRNA binding cytosol;extracellular exosome;intracellular;nucleus Metabolic pathways;Purine metabolism Phosphate bond hydrolysis by NUDT proteins -0.6090207695961 0.241931438446045 1.48991537094116 1.1922048330307 0.892139852046967 -0.238446041941643 1.22939658164978 1.54323434829712 -0.477571427822113 0.216537818312645 0.328062146902084 0.419864028692245 -1.50349402427673 -0.60899543762207 -1.38604533672333 -1.53298914432526 -0.653630495071411 -0.54309356212616 + Cluster -674 17 17 17 25.1 25.1 25.1 96.022 0 230.46 17477000000 69 4.12994168545111 0.000113846153846154 Q8WUM4;Q8WUM4-2;Q8WUM4-3 Q8WUM4;Q8WUM4-2 Programmed cell death 6-interacting protein PDCD6IP 2291 Multifunctional protein involved in endocytosis,multivesicular body biogenesis, membrane repair, cytokinesis,apoptosis and maintenance of tight junction integrity. Class E VPSprotein involved in concentration and sorting of cargo proteins ofthe multivesicular body (MVB) for incorporation into intralumenalvesicles (ILVs) that are generated by invagination and scissionfrom the limiting membrane of the endosome. Binds to thephospholipid lysobisphosphatidic acid (LBPA) which is abundant inMVBs internal membranes. The MVB pathway requires the sequentialfunction of ESCRT-O, -I,-II and -III complexes (PubMed:14739459).The ESCRT machinery also functions in topologically equivalentmembrane fission events, such as the terminal stages ofcytokinesis (PubMed:17853893, PubMed:17556548). Adapter for asubset of ESCRT-III proteins, such as CHMP4, to function atdistinct membranes. Required for completion of cytokinesis(PubMed:17853893, PubMed:17556548, PubMed:18641129). May play arole in the regulation of both apoptosis and cell proliferation.Regulates exosome biogenesis in concert with SDC1/4 and SDCBP(PubMed:22660413). By interacting with F-actin, PARD3 and TJP1secures the proper assembly and positioning of actomyosin-tightjunction complex at the apical sides of adjacent epithelial cellsthat defines a spatial membrane domain essential for themaintenance of epithelial cell polarity and barrier (Bysimilarity). Cytoplasm, cytosol{ECO:0000250|UniProtKB:Q9QZA2}. Melanosome{ECO:0000269|PubMed:17081065}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome{ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}.Secreted, exosome {ECO:0000269|PubMed:22660413}. Cell junction,tight junction {ECO:0000250|UniProtKB:Q9WU78}. Midbody, Midbodyring {ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129}.Note=Identified by mass spectrometry in melanosome fractions fromstage I to stage IV. Colocalized with CEP55 at centrosomes of non-dividing cells. Component of the actomyosin-tight junction complex(By similarity). PDCD6IP targeting to the midbody requires theinteraction with CEP55 (PubMed:18641129).{ECO:0000250|UniProtKB:Q9QZA2, ECO:0000250|UniProtKB:Q9WU78,ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:17556548,ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129}. actomyosin contractile ring assembly;apoptotic process;bicellular tight junction assembly;maintenance of epithelial cell apical/basal polarity;midbody abscission;mitotic cytokinesis;multivesicular body assembly;positive regulation of exosomal secretion;positive regulation of extracellular exosome assembly;protein homooligomerization;protein transport;regulation of centrosome duplication;regulation of extracellular exosome assembly;regulation of membrane permeability;ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway;viral budding;viral budding via host ESCRT complex;viral life cycle calcium-dependent protein binding;protein homodimerization activity;proteinase activated receptor binding actomyosin;bicellular tight junction;cytosol;endoplasmic reticulum exit site;extracellular exosome;extracellular vesicle;Flemming body;focal adhesion;immunological synapse;melanosome;membrane;microtubule organizing center Endocytosis Budding and maturation of HIV virion;Uptake and function of anthrax toxins -2.001460313797 0.0422051288187504 0.483615934848785 1.47710788249969 1.66845786571503 0.779577553272247 0.731875121593475 0.888351500034332 -0.872588753700256 0.464775800704956 0.0861717462539673 0.330126255750656 -1.74883949756622 -0.766033470630646 -0.766033470630646 -0.631592512130737 0.163931116461754 -0.329647958278656 + Cluster -674 3 3 3 5.5 5.5 5.5 71.289 0 11.52 473750000 5 3.15007884293431 0.000811501597444089 Q9UG63;Q9UG63-2 Q9UG63;Q9UG63-2 ATP-binding cassette sub-family F member 2 ABCF2 3097 ATP binding;ATPase activity;transporter activity membrane;mitochondrial envelope SNW1 complex -1.72665631771088 0.487875670194626 0.487875670194626 1.19982254505157 1.64286351203918 1.13370966911316 1.73046314716339 0.495719581842422 -1.00512862205505 0.153276860713959 -0.368959486484528 -0.0794071406126022 -1.1500449180603 -1.05818712711334 -0.85645854473114 -0.648678958415985 -0.149554118514061 -0.288531392812729 + Cluster -674 17 17 17 44.1 44.1 44.1 48.633 0 134.41 33649000000 78 3.3117747976157 0.000586690017513135 P35998;P35998-2 P35998;P35998-2 26S protease regulatory subunit 7 PSMC2 945 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. PSMC2 belongs to theheterohexameric ring of AAA (ATPases associated with diversecellular activities) proteins that unfolds ubiquitinated targetproteins that are concurrently translocated into a proteolyticchamber and degraded into peptides. Cytoplasm {ECO:0000269|PubMed:22078707}.Note=Colocalizes with TRIM5 in cytoplasmic bodies.{ECO:0000269|PubMed:22078707}. neutrophil degranulation;osteoblast differentiation;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;post-translational protein modification;protein deubiquitination;ubiquitin-dependent protein catabolic process ATP binding;ATPase activity;proteasome-activating ATPase activity;TBP-class protein binding cytoplasm;cytoplasmic ribonucleoprotein granule;cytosol;dendritic spine;extracellular region;ficolin-1-rich granule lumen;membrane;nucleoplasm;nucleus;P-body;proteasome accessory complex;proteasome complex;proteasome regulatory particle, base subcomplex;secretory granule lumen Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;Neutrophil degranulation;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 26S proteasome;PA700 complex;PA700-20S-PA28 complex -2.0345344543457 -0.094757966697216 0.649809777736664 1.41472578048706 1.14750063419342 0.711970567703247 1.25179290771484 1.09699201583862 -0.555849075317383 0.398983478546143 -0.393872916698456 0.60957944393158 -1.42917847633362 -0.899585366249084 -1.34665715694427 -0.34651643037796 0.0466124005615711 -0.227015182375908 + Cluster -674 3 3 3 31.3 31.3 31.3 17.162 0 59.85 9017100000 16 3.30600785249725 0.000587108013937282 Q9BX68 Q9BX68 Histidine triad nucleotide-binding protein 2, mitochondrial HINT2 2703 Hydrolase probably involved in steroid biosynthesis. Mayplay a role in apoptosis. Has adenosine phosphoramidase activity Mitochondrion {ECO:0000269|PubMed:16762638,ECO:0000269|PubMed:18653718}. apoptotic process;lipid catabolic process;negative regulation of peptidyl-lysine acetylation;steroid biosynthetic process hydrolase activity;nucleotide binding mitochondrion;nucleolus -1.18846476078033 -0.506694912910461 1.20455479621887 0.957454264163971 0.957454264163971 0.888774693012238 0.980442523956299 0.888774693012238 -0.478823572397232 0.375691503286362 0.504188239574432 0.925127923488617 -2.02319407463074 -1.36610889434814 -1.17370462417603 -0.808142960071564 -0.180815815925598 0.0434866584837437 + Cluster -674 12 12 10 49.7 49.7 42.7 40.058 0 207.15 82920000000 93 4.33022138706969 7.38255033557047E-05 Q9P0M6 Q9P0M6 Core histone macro-H2A.2 H2AFY2 3042 Variant histone H2A which replaces conventional H2A in asubset of nucleosomes where it represses transcription.Nucleosomes wrap and compact DNA into chromatin, limiting DNAaccessibility to the cellular machineries which require DNA as atemplate. Histones thereby play a central role in transcriptionregulation, DNA repair, DNA replication and chromosomal stability.DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code,and nucleosome remodeling. May be involved in stable X chromosomeinactivation. Nucleus {ECO:0000269|PubMed:11262398,ECO:0000269|PubMed:11331621, ECO:0000269|PubMed:15621527}.Chromosome {ECO:0000269|PubMed:11262398,ECO:0000269|PubMed:11331621, ECO:0000269|PubMed:15621527}.Note=Enriched in inactive X chromosome chromatin (PubMed:11331621,PubMed:11262398) and in senescence-associated heterochromatin(PubMed:15621527). {ECO:0000269|PubMed:11262398,ECO:0000269|PubMed:11331621, ECO:0000269|PubMed:15621527}. brain development;chromatin organization;dosage compensation;establishment of protein localization to chromatin;negative regulation of gene expression, epigenetic;negative regulation of transcription by RNA polymerase II;negative regulation of transcription of nucleolar large rRNA by RNA polymerase I;nucleosome assembly;positive regulation of keratinocyte differentiation chromatin DNA binding;DNA binding;protein heterodimerization activity;RNA polymerase II regulatory region sequence-specific DNA binding;transcription regulatory region DNA binding Barr body;extracellular exosome;nuclear chromatin;nuclear chromosome, telomeric region;nucleoplasm;nucleosome Alcoholism;Necroptosis;Systemic lupus erythematosus -1.31676924228668 -0.043853797018528 1.01474618911743 1.35012674331665 0.697284638881683 1.53441166877747 0.0343940369784832 0.970566213130951 0.183770477771759 0.642865180969238 0.642865180969238 0.466119825839996 -1.76014816761017 -1.25034010410309 -1.28077828884125 -0.702019453048706 -0.758234620094299 -0.425006330013275 + Cluster -674 3 3 3 8.9 8.9 8.9 43.973 0 16.033 1138300000 8 4.00614585368676 0.000139130434782609 Q9NR46;Q9NR46-2 Q9NR46;Q9NR46-2 Endophilin-B2 SH3GLB2 2913 Cytoplasm {ECO:0000269|PubMed:11161816}. cadherin binding;identical protein binding cytoplasm;cytosol;nucleoplasm Endocytosis -1.23137259483337 0.162768125534058 0.287213027477264 1.53025412559509 0.872661113739014 1.05506455898285 1.03017210960388 1.07869076728821 -0.338571399450302 0.576191246509552 0.311600804328918 0.420841008424759 -1.93495178222656 -1.26878666877747 -1.26878666877747 -1.11093032360077 -0.0807021930813789 -0.0913552418351173 + Cluster -674 12 11 11 37.2 35 35 46.659 0 127.73 29184000000 55 3.57672327291708 0.000379310344827586 O75874 O75874 Isocitrate dehydrogenase [NADP] cytoplasmic IDH1 362 Cytoplasm, cytosol{ECO:0000269|PubMed:10521434}. Peroxisome{ECO:0000269|PubMed:10521434}. 2-oxoglutarate metabolic process;female gonad development;glutathione metabolic process;glyoxylate cycle;isocitrate metabolic process;NADP metabolic process;NADPH regeneration;neutrophil degranulation;protein targeting to peroxisome;regulation of phospholipid biosynthetic process;regulation of phospholipid catabolic process;response to oxidative stress;response to steroid hormone;tricarboxylic acid cycle (R)-2-hydroxyglutarate dehydrogenase activity;cadherin binding;identical protein binding;isocitrate dehydrogenase (NADP+) activity;magnesium ion binding;NAD binding;NADP binding;protein homodimerization activity;signaling receptor binding cytoplasm;cytosol;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;mitochondrion;peroxisomal matrix;peroxisome;secretory granule lumen;tertiary granule lumen 2-Oxocarboxylic acid metabolism;Biosynthesis of amino acids;Carbon metabolism;Central carbon metabolism in cancer;Citrate cycle (TCA cycle);Glutathione metabolism;Metabolic pathways;Peroxisome Myelodysplastic syndrome;Peripheral T cell lymphoma Ivosidenib Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate;NADPH regeneration;Neutrophil degranulation;Peroxisomal protein import Isocitrate dehydrogenase [NADP], cytoplasmic -1.9047384262085 -0.400721192359924 0.956753075122833 1.3143059015274 0.762303709983826 0.92808997631073 1.1423271894455 0.877278983592987 -0.77705329656601 0.475027024745941 0.583386123180389 0.075235940515995 -1.73082327842712 -1.2088760137558 -1.14168620109558 -0.260229527950287 0.154710054397583 0.154710054397583 + Cluster -674 11 10 10 44.5 42.2 42.2 36.926 0 297.69 166470000000 167 3.45107507172367 0.000469465648854962 P31942;P31942-2;P31942-3;P31942-4;P31942-5;P31942-6 P31942;P31942-2;P31942-3 Heterogeneous nuclear ribonucleoprotein H3 HNRNPH3 893 Involved in the splicing process and participates inearly heat shock-induced splicing arrest. Due to their greatstructural variations the different isoforms may possess differentfunctions in the splicing reaction. Nucleus {ECO:0000269|PubMed:8999868}. epithelial cell differentiation;mRNA splicing, via spliceosome;RNA processing;RNA splicing RNA binding nucleoplasm;nucleus;spliceosomal complex -0.857232570648193 0.354510456323624 0.63720577955246 1.20502912998199 1.40809297561646 0.40043979883194 1.61839330196381 1.12792468070984 -0.816408455371857 -0.429221481084824 -0.351757019758224 1.23563253879547 -1.35687279701233 -1.0180938243866 -1.22644150257111 -0.89393162727356 -0.40302899479866 -0.634240508079529 + + Cluster -674 1 1 1 2.3 2.3 2.3 42.636 1 -2 37414000 2 3.64804988411411 0.000328828828828829 Q86UD0 Q86UD0 Suppressor APC domain-containing protein 2 SAPCD2 2104 Plays a role in planar mitotic spindle orientation inretinal progenitor cells (RPCs) and promotes the production ofsymmetric terminal divisions (By similarity). Negatively regulatesthe mitotic apical cortex localization of GPSM2 (PubMed:26766442).Involved also in positive regulation of cell proliferation andtumor cell growth (PubMed:23576022, PubMed:23704824) Cytoplasm {ECO:0000269|PubMed:17525738}.Nucleus {ECO:0000269|PubMed:17525738}. Cytoplasm, cell cortex{ECO:0000269|PubMed:26766442}. Apical cell membrane{ECO:0000250|UniProtKB:Q9D818}. Cell junction, tight junction{ECO:0000269|PubMed:26766442}. Note=Localized at the apicalcortical region during the M phase. In horizontally retinalprogenitor dividing cells, localized at the pole cortical regionfrom prophase to telophase cells. In vertically retinal progenitordividing cells, not detected at the pole cortical region at anystage of mitosis. {ECO:0000250|UniProtKB:Q9D818}. establishment of mitotic spindle orientation;negative regulation of protein localization to cell cortex;positive regulation of cell proliferation;regulation of establishment of planar polarity;symmetric cell division apical cortex;apical junction complex;apical plasma membrane;bicellular tight junction;cytosol;nucleolus;nucleus SAPCD2-Galphai-LGN complex -1.52090513706207 -0.220971152186394 0.854966044425964 0.555293440818787 1.21549272537231 1.24888062477112 1.79564476013184 1.24888062477112 -0.220971152186394 0.112698957324028 -0.547500371932983 0.112698957324028 -1.32376492023468 -1.32376492023468 -1.32376492023468 -0.220971152186394 -0.220971152186394 -0.220971152186394 + Cluster -674 14 14 14 75.8 75.8 75.8 18.012 0 323.31 1415900000000 724 3.86148980669217 0.000222513089005236 P62937;P62937-2;F5H284;Q9Y536;P0DN26;A0A0B4J2A2;A0A075B767;A0A075B759;P0DN37 P62937;P62937-2 Peptidyl-prolyl cis-trans isomerase A;Peptidyl-prolyl cis-trans isomerase A, N-terminally processed PPIA 1385 PPIases accelerate the folding of proteins. It catalyzesthe cis-trans isomerization of proline imidic peptide bonds inoligopeptides (By similarity).;PPIases accelerate the folding of proteins. It catalyzesthe cis-trans isomerization of proline imidic peptide bonds inoligopeptides. Cytoplasm {ECO:0000250|UniProtKB:P62937}.;Cytoplasm {ECO:0000269|PubMed:16527992}.Secreted {ECO:0000269|PubMed:16527992}. Note=Secretion occurs inresponse to oxidative stress in vascular smooth muscle through avesicular secretory pathway that involves actin remodeling andmyosin II activation, and mediates ERK1/2 activation. entry into host cell;establishment of integrated proviral latency;fusion of virus membrane with host plasma membrane;interleukin-12-mediated signaling pathway;leukocyte migration;lipid droplet organization;neutrophil degranulation;positive regulation of protein secretion;positive regulation of viral genome replication;protein folding;protein peptidyl-prolyl isomerization;protein refolding;regulation of viral genome replication;RNA-dependent DNA biosynthetic process;uncoating of virus;viral life cycle;viral release from host cell;virion assembly cyclosporin A binding;peptidyl-prolyl cis-trans isomerase activity;RNA binding;unfolded protein binding;virion binding cytoplasm;cytosol;extracellular exosome;extracellular region;extracellular space;ficolin-1-rich granule lumen;focal adhesion;membrane;nucleus;protein-containing complex;secretory granule lumen;vesicle Necroptosis APOBEC3G mediated resistance to HIV-1 infection;Assembly Of The HIV Virion;Basigin interactions;Binding and entry of HIV virion;Budding and maturation of HIV virion;Calcineurin activates NFAT;Early Phase of HIV Life Cycle;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Integration of provirus;Minus-strand DNA synthesis;Neutrophil degranulation;Platelet degranulation;Plus-strand DNA synthesis;Uncoating of the HIV Virion AIF-CYPA-DNA complex -1.00625848770142 0.286780834197998 0.862150490283966 0.986537218093872 0.76268082857132 1.31063771247864 1.93918454647064 0.711946427822113 -0.368894010782242 -0.0502614714205265 -0.243487849831581 0.613198339939117 -1.68986904621124 -1.23628449440002 -1.35503768920898 -0.686341643333435 -0.360420644283295 -0.476261138916016 + Cluster -674 2 2 1 3.7 3.7 3.7 39.171 0 30.768 1882600000 8 4.14010597312856 0.000105919003115265 O75477 O75477 Erlin-1 ERLIN1 335 Component of the ERLIN1/ERLIN2 complex which mediatesthe endoplasmic reticulum-associated degradation (ERAD) ofinositol 1,4,5-trisphosphate receptors (IP3Rs). Involved inregulation of cellular cholesterol homeostasis by regulation theSREBP signaling pathway. Binds cholesterol and may promote ERretention of the SCAP-SREBF complex (PubMed:24217618) Single-pass type II membrane protein{ECO:0000269|PubMed:11118313, ECO:0000269|PubMed:16835267,ECO:0000269|PubMed:19240031}. Note=Associated with lipid raft-likedomains of the endoplasmic reticulum membrane.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:11118313, ECO:0000269|PubMed:16835267,ECO:0000269|PubMed:19240031} cholesterol metabolic process;negative regulation of cholesterol biosynthetic process;negative regulation of fatty acid biosynthetic process;SREBP signaling pathway;transmembrane transport;ubiquitin-dependent ERAD pathway cholesterol binding;ubiquitin protein ligase binding endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;protein-containing complex Hereditary spastic paraplegia ABC-family proteins mediated transport;Defective CFTR causes cystic fibrosis erlin1/2-RNF170 complex -1.52211689949036 0.258566707372665 1.50960922241211 0.258566707372665 0.935816884040833 1.52704203128815 1.19551265239716 1.01610398292542 -0.4554762840271 -0.340279787778854 0.760437905788422 -0.340279787778854 -1.21669292449951 -1.01752996444702 -1.58448946475983 -0.588718771934509 -0.4554762840271 0.0594038143754005 + Cluster -674 66 56 54 38.5 34.7 33.4 226.53 0 323.31 118250000000 275 3.14372898095951 0.000820063694267516 P35579;P35579-2;REV__Q9UKV3-5;REV__Q9UKV3 P35579;P35579-2 Myosin-9 MYH9 934 this function is mechanicallyantagonized by MYH10.;Cellular myosin that appears to play a role incytokinesis, cell shape, and specialized functions such assecretion and capping. During cell spreading, plays an importantrole in cytoskeleton reorganization, focal contacts formation (inthe margins but not the central part of spreading cells), andlamellipodial retraction Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:Q8VDD5}. Cytoplasm, cell cortex{ECO:0000250|UniProtKB:Q8VDD5}. Note=Colocalizes with actinfilaments at lamellipodia margins and at the leading edge ofmigrating cells (PubMed:20052411). In retinal pigment epithelialcells, predominantly localized to stress fiber-like structureswith some localization to cytoplasmic puncta (PubMed:27331610).{ECO:0000269|PubMed:20052411, ECO:0000269|PubMed:27331610}. actin cytoskeleton reorganization;actin filament-based movement;actomyosin structure organization;angiogenesis;blood vessel endothelial cell migration;cytokinetic process;establishment of meiotic spindle localization;establishment of T cell polarity;in utero embryonic development;integrin-mediated signaling pathway;leukocyte migration;meiotic spindle organization;membrane protein ectodomain proteolysis;monocyte differentiation;myoblast fusion;negative regulation of actin filament severing;phagocytosis, engulfment;platelet aggregation;platelet formation;positive regulation of protein processing in phagocytic vesicle;protein transport;regulation of cell shape;uropod organization actin binding;actin filament binding;actin-dependent ATPase activity;ADP binding;ATP binding;ATPase activity;cadherin binding;calmodulin binding;integrin binding;microfilament motor activity;motor activity;protein domain specific binding;protein homodimerization activity;protein membrane anchor;RNA binding actin cytoskeleton;actomyosin;actomyosin contractile ring;brush border;cell leading edge;cell-cell adherens junction;cleavage furrow;cytoplasm;cytosol;extracellular exosome;focal adhesion;immunological synapse;membrane;myosin II complex;myosin II filament;neuromuscular junction;nucleus;plasma membrane;protein-containing complex;ruffle;spindle;stress fiber;uropod Regulation of actin cytoskeleton;Tight junction Deafness, autosomal dominant;Epstein syndrome;Fechtner syndrome;Macrothrombocytopenia;May-Hegglin anomaly;MYH9-related disease;Sebastian syndrome EPHA-mediated growth cone collapse;Regulation of actin dynamics for phagocytic cup formation;RHO GTPases activate CIT;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases Activate ROCKs;Sema4D induced cell migration and growth-cone collapse;Translocation of SLC2A4 (GLUT4) to the plasma membrane Emerin complex 1;WIP-WASp-actin-myosin-IIa complex -1.38741934299469 0.314017981290817 0.882589757442474 0.882589757442474 1.0512398481369 1.00130498409271 1.42748486995697 1.27799367904663 0.0860102474689484 0.225267380475998 -0.266945332288742 0.105796121060848 -2.14975619316101 -0.662201762199402 -0.959008276462555 -0.822609305381775 -0.0929845795035362 -0.913369834423065 + Cluster -674 37 37 37 37.1 37.1 37.1 119.91 0 323.31 128230000000 199 3.69813239521607 0.00030166270783848 Q9Y5B9 Q9Y5B9 FACT complex subunit SPT16 SUPT16H 3307 Component of the FACT complex, a general chromatinfactor that acts to reorganize nucleosomes. The FACT complex isinvolved in multiple processes that require DNA as a template suchas mRNA elongation, DNA replication and DNA repair. Duringtranscription elongation the FACT complex acts as a histonechaperone that both destabilizes and restores nucleosomalstructure. It facilitates the passage of RNA polymerase II andtranscription by promoting the dissociation of one histone H2A-H2Bdimer from the nucleosome, then subsequently promotes thereestablishment of the nucleosome following the passage of RNApolymerase II. The FACT complex is probably also involved inphosphorylation of 'Ser-392' of p53/TP53 via its association withCK2 (casein kinase II). Nucleus {ECO:0000269|PubMed:10421373}.Chromosome {ECO:0000269|PubMed:10421373}. Note=Colocalizes withRNA polymerase II on chromatin. Recruited to actively transcribedloci. DNA repair;DNA replication;DNA replication-independent nucleosome organization;nucleosome disassembly;positive regulation of DNA-templated transcription, elongation;positive regulation of transcription elongation from RNA polymerase II promoter;regulation of signal transduction by p53 class mediator;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter histone binding;nucleosome binding;RNA binding chromosome;FACT complex;nucleoplasm;nucleus Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;HIV elongation arrest and recovery;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;Regulation of TP53 Activity through Phosphorylation;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Elongation;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes CEN complex;CENP-A nucleosomal complex;FACT complex;FACT complex, UV-activated;FACT-NEK9 complex;H2AX complex, isolated from cells without IR exposure;HES1 promoter-Notch enhancer complex;WINAC complex -1.26362609863281 0.117174938321114 0.692787230014801 1.101806640625 1.44172263145447 1.08086800575256 1.50379049777985 0.977731823921204 0.117174938321114 -0.15252360701561 -0.0641298815608025 0.219883814454079 -1.64268743991852 -0.541962683200836 -1.38101637363434 -1.23110413551331 -0.133828461170197 -0.842061817646027 + Cluster -674 11 11 11 14.4 14.4 14.4 131.98 0 94.893 10307000000 38 4.44691791320537 6.2962962962963E-05 O43795;O43795-2;Q9UBC5 O43795;O43795-2 Unconventional myosin-Ib MYO1B 245 Involved in directing the movement of organelles alongactin filaments.;Motor protein that may participate in process criticalto neuronal development and function such as cell migration,neurite outgrowth and vesicular transport. actin filament bundle assembly;actin filament organization;actin filament-based movement;microvillus assembly;post-Golgi vesicle-mediated transport;sensory perception of sound;vesicle localization actin filament binding;actin-dependent ATPase activity;ATP binding;cadherin binding;calmodulin binding;microfilament motor activity;motor activity;phosphatidylinositol-3,4,5-trisphosphate binding;phosphatidylinositol-4,5-bisphosphate binding actin filament;apical part of cell;apical plasma membrane;basal plasma membrane;basolateral plasma membrane;brush border;cell periphery;cortical actin cytoskeleton;cytoplasm;early endosome;endosome membrane;extracellular exosome;filamentous actin;filopodium;lateral plasma membrane;microvillus;myosin complex;perinuclear region of cytoplasm;plasma membrane;plasma membrane raft 0.104846000671387 0.402276247739792 1.13060808181763 0.525732338428497 1.10153615474701 0.490420639514923 0.143536061048508 -0.100192546844482 0.726291358470917 0.0569347590208054 1.4460836648941 0.729527413845062 -1.46665918827057 -0.607335567474365 -0.692341327667236 -2.56641554832458 -0.583971738815308 -0.840876698493958 + Cluster -674 1 1 1 1.6 1.6 1.6 77.667 0.00032362 1.902 74904000 3 3.05191452979942 0.000977443609022556 Q8ND24;Q8ND24-2 Q8ND24;Q8ND24-2 RING finger protein 214 RNF214 2232 metal ion binding;ubiquitin-protein transferase activity -0.516007721424103 0.399123549461365 0.942584156990051 1.08076190948486 1.47899854183197 0.493072867393494 1.44983088970184 1.17767417430878 0.0452165156602859 0.207148984074593 -0.101358853280544 0.348708897829056 -1.42135381698608 -1.04783308506012 -1.10588657855988 -1.46504747867584 -0.949590981006622 -1.01604211330414 + Cluster -674 16 16 16 37 37 37 58.777 0 192.62 59433000000 95 7.02660050914774 0 P49591 P49591 Serine--tRNA ligase, cytoplasmic SARS 1106 Catalyzes the attachment of serine to tRNA(Ser) in atwo-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser)(PubMed:22353712, PubMed:24095058, PubMed:9431993,PubMed:26433229, PubMed:28236339). Is probably also able toaminoacylate tRNA(Sec) with serine, to form the misacylated tRNAL-seryl-tRNA(Sec), which will be further converted intoselenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229,PubMed:28236339). In the nucleus, binds to the VEGFA core promoterand prevents MYC binding and transcriptional activation by MYC(PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promotingdeacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibitsthe production of VEGFA and sprouting angiogenesis mediated byVEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000) Cytoplasm {ECO:0000269|PubMed:22353712,ECO:0000269|PubMed:28236339}. Nucleus{ECO:0000269|PubMed:22353712}. Note=Predominantly cytoplasmic, buta minor proportion is also found in the nucleus.{ECO:0000269|PubMed:22353712}. negative regulation of angiogenesis;negative regulation of transcription by RNA polymerase II;negative regulation of vascular endothelial growth factor production;selenocysteine metabolic process;selenocysteinyl-tRNA(Sec) biosynthetic process;seryl-tRNA aminoacylation;translation;tRNA aminoacylation for protein translation;tRNA processing ATP binding;protein homodimerization activity;RNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;selenocysteine-tRNA ligase activity;serine-tRNA ligase activity cytoplasm;cytosol;extracellular exosome;nucleus Aminoacyl-tRNA biosynthesis Cytosolic tRNA aminoacylation;Selenocysteine synthesis -0.994085788726807 0.700352489948273 1.08953416347504 0.700352489948273 1.08953416347504 0.31322705745697 1.27453827857971 0.991718053817749 0.444663316011429 -0.0597987808287144 0.700165569782257 0.700165569782257 -1.67244327068329 -0.962788879871368 -1.28478372097015 -1.32427859306335 -0.548852741718292 -1.15721952915192 + Cluster -674 82 82 82 21 21 21 532.4 0 323.31 106810000000 299 4.45901311608036 6.34328358208955E-05 Q14204 Q14204 Cytoplasmic dynein 1 heavy chain 1 DYNC1H1 1695 the force-producingpower stroke is thought to occur on release of ADP. Plays a rolein mitotic spindle assembly and metaphase plate congression(PubMed:27462074).;Cytoplasmic dynein 1 acts as a motor for theintracellular retrograde motility of vesicles and organelles alongmicrotubules. Dynein has ATPase activity Cytoplasm, cytoskeleton. antigen processing and presentation of exogenous peptide antigen via MHC class II;cell division;ciliary basal body-plasma membrane docking;cytoplasmic microtubule organization;cytoplasmic mRNA processing body assembly;endoplasmic reticulum to Golgi vesicle-mediated transport;establishment of spindle localization;G2/M transition of mitotic cell cycle;microtubule-based movement;minus-end-directed vesicle transport along microtubule;mitotic spindle organization;neutrophil degranulation;positive regulation of cold-induced thermogenesis;positive regulation of intracellular transport;positive regulation of spindle assembly;regulation of G2/M transition of mitotic cell cycle;regulation of metaphase plate congression;regulation of mitotic spindle organization;stress granule assembly ATP binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein intermediate chain binding;dynein light chain binding;dynein light intermediate chain binding;RNA binding azurophil granule lumen;centrosome;cytoplasmic dynein complex;cytosol;dynein complex;extracellular exosome;extracellular region;filopodium;membrane;microtubule Phagosome;Salmonella infection;Vasopressin-regulated water reabsorption Autosomal dominant mental retardation;Charcot-Marie-Tooth disease;Spinal muscular atrophy Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;HSP90 chaperone cycle for steroid hormone receptors (SHR);Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;MHC class II antigen presentation;Mitotic Prometaphase;Neutrophil degranulation;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Separation of Sister Chromatids CDC5L complex;Dynein complex;Dynein-dynactin complex -0.832695305347443 0.496657013893127 1.35006082057953 1.06734418869019 1.04978311061859 0.860821545124054 1.78000748157501 0.562822937965393 -0.832695305347443 0.520335674285889 -0.616204559803009 0.0069499290548265 -1.3687641620636 -0.616204559803009 -1.12973427772522 -1.36995160579681 0.0782018601894379 -1.00673472881317 + Cluster -674 4 4 4 7.2 7.2 7.2 106.1 0 37.929 1778900000 9 3.77676607029546 0.000255528255528256 Q9UNX4 Q9UNX4 WD repeat-containing protein 3 WDR3 3191 Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. rRNA processing RNA binding;snoRNA binding nuclear membrane;nucleolus;nucleoplasm;nucleus;Pwp2p-containing subcomplex of 90S preribosome;small-subunit processome Ribosome biogenesis in eukaryotes Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol -0.0310536362230778 -0.60064971446991 0.391357958316803 1.14971172809601 1.38116157054901 0.858157157897949 1.37203979492188 0.560838043689728 0.170199692249298 1.12209236621857 0.333982944488525 -0.537221848964691 -2.0815486907959 -0.86080402135849 -0.767603516578674 -1.51883625984192 -0.138835221529007 -0.802988171577454 + Cluster -674 4 4 4 26.5 26.5 26.5 24.976 0 38.704 9526300000 18 3.371308862754 0.000541970802919708 P49755 P49755 Transmembrane emp24 domain-containing protein 10 TMED10 1116 the function specifically implies SEC24C and SEC24D ofthe COPII vesicle coat and lipid raft-like microdomains of the ER.Recognizes GPI anchors structural remodeled in the ER by PGAP1 andMPPE1 (By similarity). In COPI vesicle-mediated retrogradetransport involved in the biogenesis of COPI vesicles and vesiclecoat recruitment. On Golgi membranes, acts as primary receptor forARF1-GDP which is involved in COPI-vesicle formation. Increasescoatomer-dependent GTPase-activating activity of ARFGAP2. Involvedin trafficking of G protein-coupled receptors (GPCRs). RegulatesF2LR1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to theplasma membrane thus contributing to receptor resensitization.Involved in trafficking of amyloid beta A4 protein and solubleAPP-beta release (independent of modulation of gamma-secretaseactivity). As part of the presenilin-dependent gamma-secretasecomplex regulates gamma-cleavages of the amyloid beta A4 proteinto yield amyloid-beta 40 (Abeta40). Involved in organization ofthe Golgi apparatus.;Involved in vesicular protein trafficking. Mainlyfunctions in the early secretory pathway. Thought to act as cargoreceptor at the lumenal side for incorporation of secretory cargomolecules into transport vesicles and to be involved in vesiclecoat formation at the cytoplasmic side. In COPII vesicle-mediatedanterograde transport involved in the transport of GPI-anchoredproteins and proposed to act together with TMED2 as their cargoreceptor Single-pass type I membrane protein.Endoplasmic reticulum-Golgi intermediate compartment membrane; Single-pass type Imembrane protein {ECO:0000250}. Cell membrane {ECO:0000250}. Golgiapparatus, trans-Golgi network membrane {ECO:0000250}; Single-passtype I membrane protein {ECO:0000250}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV.Cycles between compartments of the early secretatory pathway.;Golgi apparatus, cis-Golgi network membrane;Single-pass type I membrane protein. Cytoplasmic vesicle,secretory vesicle membrane {ECO:0000250};Single-pass type I membrane protein. Melanosome. Endoplasmicreticulum membrane cargo loading into vesicle;COPI coating of Golgi vesicle;COPI-coated vesicle budding;COPII vesicle coating;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi organization;intracellular protein transport;kidney development;protein complex oligomerization;regulated exocytosis;regulation of amyloid-beta formation;response to alkaloid;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;vesicle targeting, to, from or within Golgi protein-containing complex binding;syntaxin binding cis-Golgi network;COPI-coated vesicle;COPII-coated ER to Golgi transport vesicle;endoplasmic reticulum;endoplasmic reticulum membrane;endoplasmic reticulum-Golgi intermediate compartment;endoplasmic reticulum-Golgi intermediate compartment membrane;ER to Golgi transport vesicle membrane;gamma-secretase complex;Golgi apparatus;Golgi membrane;integral component of membrane;melanosome;plasma membrane;secretory granule membrane;trans-Golgi network transport vesicle;transport vesicle;zymogen granule membrane Cargo concentration in the ER;COPI-dependent Golgi-to-ER retrograde traffic;COPII-mediated vesicle transport;COPI-mediated anterograde transport Gamma-secretase complex (APH1A, PSENEN, PSEN1, NCSTN, TMP21) -0.751509964466095 0.402821213006973 0.776744723320007 0.47963672876358 1.29348516464233 0.97835373878479 1.7906790971756 0.631423115730286 -0.0222449284046888 0.948517680168152 -0.625904202461243 0.177434787154198 -1.85087382793427 -0.939698696136475 -1.10993158817291 -1.3634786605835 -0.135344311594963 -0.680109977722168 + Cluster -674 5 5 5 30.1 30.1 30.1 27.893 0 39.172 13372000000 30 3.40288798434753 0.000512059369202226 Q9P0L0;Q9P0L0-2 Q9P0L0;Q9P0L0-2 Vesicle-associated membrane protein-associated protein A VAPA 3041 Binds to OSBPL3, which mediates recruitment of VAPA toplasma membrane sites (PubMed:25447204). The ORP3-VAPA complexstimulates RRAS signaling which in turn attenuates integrin beta-1(ITGB1) activation at the cell surface (PubMed:25447204). WithOSBPL3, may regulate ER morphology (PubMed:16143324). May play arole in vesicle trafficking (PubMed:11511104, PubMed:19289470) Single-pass type IV membrane protein {ECO:0000269|PubMed:10523508,ECO:0000269|PubMed:19289470}. Cell membrane{ECO:0000269|PubMed:25447204}; Single-pass type IV membraneprotein {ECO:0000305}. Cell junction, tight junction{ECO:0000269|PubMed:10523508}. Nucleus membrane{ECO:0000250|UniProtKB:Q9Z270}. Note=Present in the plasmamembrane and in intracellular vesicles, together with SNAREproteins. May also associate with the cytoskeleton. Colocalizeswith OCLN at the tight junction in polarized epithelial cells.{ECO:0000269|PubMed:10523508}.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:10523508, ECO:0000269|PubMed:16143324,ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:25447204} cell death;COPII-coated vesicle budding;endoplasmic reticulum to Golgi vesicle-mediated transport;membrane fusion;negative regulation by host of viral genome replication;neuron projection development;neutrophil degranulation;positive regulation by host of viral genome replication;positive regulation by host of viral release from host cell;positive regulation of I-kappaB kinase/NF-kappaB signaling;protein localization to endoplasmic reticulum;sphingolipid biosynthetic process cadherin binding;FFAT motif binding;microtubule binding;protein domain specific binding;protein heterodimerization activity azurophil granule membrane;bicellular tight junction;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi membrane;integral component of membrane;microtubule cytoskeleton;nuclear membrane;plasma membrane;vesicle Cholesterol metabolism Neutrophil degranulation;Sphingolipid de novo biosynthesis SPG33-VAPA complex -0.489274084568024 0.192452266812325 1.01207482814789 0.912012457847595 1.24516808986664 1.2127343416214 1.58216738700867 1.0327342748642 0.0383763201534748 -0.375968813896179 0.135657534003258 -0.477486133575439 -1.79139149188995 -0.338304162025452 -0.980119228363037 -1.69083511829376 -0.605577111244202 -0.614421486854553 + Cluster -674 10 10 10 7.8 7.8 7.8 160.88 0 45.199 3817800000 20 5.2363116946659 1.27388535031847E-05 Q10570 Q10570 Cleavage and polyadenylation specificity factor subunit 1 CPSF1 1559 Component of the cleavage and polyadenylationspecificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence andinteracting with poly(A) polymerase and other factors to bringabout cleavage and poly(A) addition. This subunit is involved inthe RNA recognition step of the polyadenylation reaction Nucleus, nucleoplasm. mRNA 3'-end processing;mRNA export from nucleus;mRNA polyadenylation;mRNA splicing, via spliceosome;pre-mRNA cleavage required for polyadenylation;termination of RNA polymerase II transcription enzyme binding;mRNA 3'-UTR AU-rich region binding mRNA cleavage and polyadenylation specificity factor complex;nucleoplasm;nucleus mRNA surveillance pathway Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Processing of Intronless Pre-mRNAs;Transport of Mature mRNA Derived from an Intronless Transcript;tRNA processing in the nucleus Cleavage and polyadenylation factor (CPSF);Polyadenylation complex (CSTF1, CSTF2, CSTF3, SYMPK CPSF1, CPSF2, CPSF3) -0.435647696256638 0.715345323085785 1.14533424377441 1.1958259344101 1.14533424377441 1.16712963581085 1.22378754615784 0.925146639347076 -0.288352847099304 -0.630852580070496 -0.333820223808289 0.112165227532387 -1.62131464481354 -0.45522877573967 -0.387012809514999 -1.9366968870163 -0.770571231842041 -0.770571231842041 + Cluster -674 10 10 10 28.8 28.8 28.8 30.588 0 196.8 96718000000 98 4.65490091267095 4.16666666666667E-05 Q99729-3;Q99729-2;Q99729;Q99729-4 Q99729-3;Q99729-2;Q99729;Q99729-4 Heterogeneous nuclear ribonucleoprotein A/B HNRNPAB 2590 Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNAtranscripts around the RNA editing site. Nucleus {ECO:0000269|PubMed:17289661}.Cytoplasm {ECO:0000269|PubMed:17289661}. Note=Localized incytoplasmic mRNP granules containing untranslated mRNAs. epithelial to mesenchymal transition;positive regulation of transcription, DNA-templated mRNA binding;RNA binding;sequence-specific DNA binding;sequence-specific double-stranded DNA binding cytoplasm;nucleoplasm;nucleus;ribonucleoprotein complex;RNA polymerase II transcription factor complex -0.766319632530212 0.323391616344452 0.984984040260315 0.863470494747162 1.2475837469101 1.50604903697968 0.804454922676086 0.804454922676086 0.323391616344452 0.570981323719025 0.229905307292938 -0.18415330350399 -1.79681050777435 -0.837477266788483 -1.09735798835754 -1.75319600105286 -0.611676156520844 -0.611676156520844 + Cluster -674 29 21 21 43 33.3 33.3 70.942 0 323.31 249230000000 366 4.8741100493758 1.96078431372549E-05 O43390;O43390-2;O43390-3;O43390-4 O43390;O43390-2;O43390-3;O43390-4 Heterogeneous nuclear ribonucleoprotein R HNRNPR 211 Component of ribonucleosomes, which are complexes of atleast 20 other different heterogenious nuclear ribonucleoproteins(hnRNP). hnRNP play an important role in processing of precursormRNA in the nucleus. Nucleus {ECO:0000250|UniProtKB:Q7TMK9}.Microsome {ECO:0000250|UniProtKB:Q7TMK9}. Nucleus, nucleoplasm{ECO:0000269|PubMed:17289661}. Cytoplasm{ECO:0000269|PubMed:17289661}. Note=Localized in cytoplasmic mRNPgranules containing untranslated mRNAs. The tyrosinephosphorylated form bound to RNA is found in microsomes (Bysimilarity). {ECO:0000250|UniProtKB:Q7TMK9,ECO:0000269|PubMed:17289661}. circadian rhythm;mRNA destabilization;mRNA processing;mRNA splicing, via spliceosome;negative regulation of catalytic activity;RNA metabolic process mRNA 3'-UTR binding;mRNA binding;RNA binding axon terminus;catalytic step 2 spliceosome;dendrite;endoplasmic reticulum;growth cone;nucleoplasm;nucleus;ribonucleoprotein complex;spliceosomal complex mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA C complex spliceosome;DGCR8 multiprotein complex;H2AX complex, isolated from cells without IR exposure -0.783295452594757 -0.124192111194134 1.19131064414978 1.237433552742 1.78144383430481 1.18599319458008 1.06927788257599 0.660256206989288 0.001783775864169 0.0942997857928276 -0.382925987243652 -0.096072293817997 -1.24308145046234 -0.320309817790985 -0.967381119728088 -1.84486365318298 -0.581747531890869 -0.877929449081421 + Cluster -674 13 13 13 64.7 64.7 64.7 23.897 0 273.44 26553000000 52 5.31317876369071 1.35135135135135E-05 P61106 P61106 Ras-related protein Rab-14 RAB14 1295 Involved in membrane trafficking between the Golgicomplex and endosomes during early embryonic development.Regulates the Golgi to endosome transport of FGFR-containingvesicles during early development, a key process for developingbasement membrane and epiblast and primitive endoderm lineagesduring early postimplantation development. May act by modulatingthe kinesin KIF16B-cargo association to endosomes (By similarity).Regulates, together with its guanine nucleotide exchange factorDENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion. Cytoplasmic side {ECO:0000305}. Cytoplasmicvesicle, phagosome {ECO:0000269|PubMed:21255211}. Note=Recruitedto recycling endosomes by DENND6A (PubMed:22595670). Recruited tophagosomes containing S.aureus or M.tuberculosis(PubMed:21255211). {ECO:0000269|PubMed:21255211,ECO:0000269|PubMed:22595670}.; Lipid-anchor {ECO:0000305}; Lipid-anchor{ECO:0000305};Cytoplasmic side {ECO:0000305}. Golgi apparatus membrane{ECO:0000269|PubMed:16962593};Cytoplasmic side {ECO:0000305}. Golgi apparatus, trans-Golginetwork membrane {ECO:0000269|PubMed:16962593};Recycling endosome{ECO:0000269|PubMed:22595670}. Early endosome membrane{ECO:0000269|PubMed:16962593} defense response to bacterium;endocytic recycling;fibroblast growth factor receptor signaling pathway;Golgi to endosome transport;intracellular protein transport;intracellular transport;neutrophil degranulation;phagolysosome assembly involved in apoptotic cell clearance;phosphatidylinositol biosynthetic process;Rab protein signal transduction;regulation of embryonic development;regulation of protein localization;vesicle-mediated transport GDP binding;GTP binding;GTPase activity;myosin V binding cytosol;early endosome;early endosome membrane;extracellular exosome;Golgi membrane;Golgi stack;intracellular;intracellular membrane-bounded organelle;late endosome;lysosomal membrane;lysosome;nuclear outer membrane-endoplasmic reticulum membrane network;perinuclear region of cytoplasm;phagocytic vesicle;plasma membrane;recycling endosome;recycling endosome membrane;rough endoplasmic reticulum;tertiary granule membrane;trans-Golgi network;trans-Golgi network transport vesicle AMPK signaling pathway Neutrophil degranulation;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation;Synthesis of PIPs at the plasma membrane;Translocation of SLC2A4 (GLUT4) to the plasma membrane -0.700825870037079 0.371403723955154 0.724578619003296 1.12723731994629 1.12723731994629 0.796863555908203 0.938416421413422 1.11850023269653 0.0858545452356339 0.405558377504349 -0.587417006492615 0.879213452339172 -2.19857025146484 -0.239309936761856 -1.11324298381805 -1.48500764369965 -0.369729280471802 -0.880760431289673 + Cluster -674 5 5 5 22.5 22.5 22.5 33.879 0 70.461 14515000000 32 3.56077009134767 0.000384453781512605 Q9NP79;Q9NP79-2 Q9NP79;Q9NP79-2 Vacuolar protein sorting-associated protein VTA1 homolog VTA1 2873 Involved in the endosomal multivesicular bodies (MVB)pathway. MVBs contain intraluminal vesicles (ILVs) that aregenerated by invagination and scission from the limiting membraneof the endosome and mostly are delivered to lysosomes enablingdegradation of membrane proteins, such as stimulated growth factorreceptors, lysosomal enzymes and lipids. Thought to be a cofactorof VPS4A/B, which catalyzes disassembles membrane-associatedESCRT-III assemblies. Involved in the sorting and down-regulationof EGFR (By similarity). Involved in HIV-1 budding. Peripheralmembrane protein {ECO:0000305|PubMed:15644320}.;Cytoplasm {ECO:0000269|PubMed:15644320}.Endosome membrane {ECO:0000305|PubMed:15644320} ESCRT III complex disassembly;macroautophagy;multivesicular body assembly;multivesicular body sorting pathway;protein transport;viral budding;viral life cycle protein C-terminus binding cytosol;endosome membrane;extracellular exosome;intracellular membrane-bounded organelle;nucleoplasm Endocytosis Budding and maturation of HIV virion;Endosomal Sorting Complex Required For Transport (ESCRT) -0.591583490371704 0.0609960854053497 1.28041756153107 1.3368626832962 1.42959010601044 1.21159112453461 0.369804829359055 0.994703769683838 -0.253954648971558 0.536791920661926 -0.0498237758874893 0.468729794025421 -1.3119056224823 -1.13405191898346 -1.08580529689789 -1.26677167415619 -0.662466526031494 -1.33312463760376 + Cluster -674 5 5 5 10.9 10.9 10.9 73.776 0 21.097 2085100000 7 6.92826452894719 0 P23786 P23786 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 789 Matrix side.; Peripheralmembrane protein;Mitochondrion inner membrane carnitine shuttle;fatty acid beta-oxidation;positive regulation of cold-induced thermogenesis;regulation of lipid metabolic process carnitine O-palmitoyltransferase activity mitochondrial inner membrane;mitochondrion;nucleolus;nucleoplasm Fatty acid degradation;Fatty acid metabolism;PPAR signaling pathway;Thermogenesis Carnitine palmitoyltransferase II deficiency;Disorders of mitochondrial fatty-acid oxidation;Secondary hyperammonemia Perhexiline Import of palmitoyl-CoA into the mitochondrial matrix;PPARA activates gene expression -0.800333082675934 0.124852068722248 1.25383770465851 1.57753467559814 1.39324951171875 0.578164160251617 0.637411236763 0.954914689064026 0.0120839942246675 0.259141504764557 0.637411236763 0.163123100996017 -1.50253343582153 -0.863825976848602 -0.863825976848602 -1.50383830070496 -1.20399987697601 -0.853367149829865 + Cluster -674 22 22 22 23.7 23.7 23.7 144.5 0 228.29 48568000000 130 6.06934365743103 1.25E-05 P41252 P41252 Isoleucine--tRNA ligase, cytoplasmic IARS 1002 Catalyzes the specific attachment of an amino acid toits cognate tRNA in a 2 step reaction: the amino acid (AA) isfirst activated by ATP to form AA-AMP and then transferred to theacceptor end of the tRNA. Cytoplasm {ECO:0000269|PubMed:27426735,ECO:0000269|PubMed:7721108}. Cytoplasm, cytosol{ECO:0000269|PubMed:19289464}. isoleucyl-tRNA aminoacylation;osteoblast differentiation;tRNA aminoacylation for protein translation aminoacyl-tRNA editing activity;ATP binding;GTPase binding;isoleucine-tRNA ligase activity;tRNA binding aminoacyl-tRNA synthetase multienzyme complex;cytoplasm;cytosol;extracellular exosome;membrane Aminoacyl-tRNA biosynthesis Cytosolic tRNA aminoacylation;SeMet incorporation into proteins Multisynthetase complex -1.18350064754486 0.496145337820053 1.16458702087402 1.23033165931702 0.736338138580322 1.0924813747406 1.55732822418213 0.859285593032837 -0.171501219272614 0.624590456485748 -0.954961895942688 -0.104916028678417 -0.931085765361786 -0.552974581718445 -1.58980429172516 -1.29193150997162 -0.0477813519537449 -0.93263053894043 + Cluster -674 3 3 3 30.9 30.9 30.9 13.941 0 72.321 17186000000 34 3.54945280649983 0.000387163561076605 Q9BRA2 Q9BRA2 Thioredoxin domain-containing protein 17 TXNDC17 2624 Disulfide reductase. May participate in various redoxreactions through the reversible oxidation of its active centerdithiol to a disulfide and catalyze dithiol-disulfide exchangereactions. Modulates TNF-alpha signaling and NF-kappa-Bactivation. Has peroxidase activity and may contribute to theelimination of cellular hydrogen peroxide Cytoplasm {ECO:0000269|PubMed:14607844}. tumor necrosis factor-mediated signaling pathway peroxidase activity;protein-disulfide reductase activity cytosol;extracellular exosome -1.2094646692276 0.433190882205963 1.05993545055389 1.31303894519806 1.33239805698395 0.514234602451324 0.583345293998718 0.806327164173126 -0.127662196755409 0.426679283380508 0.232355773448944 0.713394284248352 -1.96334636211395 -0.437518954277039 -0.875493109226227 -1.85799014568329 -0.491257876157761 -0.452166378498077 + Cluster -674 3 3 3 4.2 4.2 4.2 141.32 0 15.346 1958800000 5 3.4719558187509 0.000455621301775148 Q8N3U4;Q8N3U4-2 Q8N3U4;Q8N3U4-2 Cohesin subunit SA-2 STAG2 2191 Component of cohesin complex, a complex required for thecohesion of sister chromatids after DNA replication. The cohesincomplex apparently forms a large proteinaceous ring within whichsister chromatids can be trapped. At anaphase, the complex iscleaved and dissociates from chromatin, allowing sister chromatidsto segregate. The cohesin complex may also play a role in spindlepole assembly during mitosis. Nucleus. Chromosome. Chromosome, centromere.Note=Associates with chromatin. Before prophase it is scatteredalong chromosome arms. During prophase, most of cohesin complexesdissociate from chromatin probably because of phosphorylation byPLK1, except at centromeres, where cohesin complexes remain. Atanaphase, the RAD21 subunit of cohesin is cleaved, leading to thedissociation of the complex from chromosomes, allowing chromosomeseparation. In germ cells, cohesin complex dissociates fromchromatin at prophase I, and may be replaced by a meiosis-specificcohesin complex. cell division;meiotic cell cycle;negative regulation of DNA endoreduplication;regulation of mitotic spindle assembly;sister chromatid cohesion chromatin binding chromatin;chromosome;chromosome, centromeric region;cohesin complex;cytosol;membrane;mitotic spindle pole;nuclear matrix;nucleoplasm;nucleus Cell cycle Cohesin Loading onto Chromatin;Establishment of Sister Chromatid Cohesion;Estrogen-dependent gene expression;Meiotic synapsis;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids;SUMOylation of DNA damage response and repair proteins Cohesin-SA2 complex;SNF2h-cohesin-NuRD complex -1.65504825115204 0.310660779476166 1.33332347869873 1.1544132232666 1.41747331619263 0.475970804691315 0.630547642707825 0.893264651298523 -0.579749047756195 0.9494788646698 -0.302084058523178 0.829159796237946 -1.55965065956116 -0.879149794578552 -1.03745138645172 -0.579749047756195 -0.757311463356018 -0.644098877906799 + Cluster -674 12 12 10 66.4 66.4 57 32.922 0 268.49 87969000000 96 3.76122812953023 0.000257281553398058 P52907 P52907 F-actin-capping protein subunit alpha-1 CAPZA1 1192 F-actin-capping proteins bind in a Ca(2+)-independentmanner to the fast growing ends of actin filaments (barbed end)thereby blocking the exchange of subunits at these ends. Unlikeother capping proteins (such as gelsolin and severin), theseproteins do not sever actin filaments. May play a role in theformation of epithelial cell junctions Cytoplasm, cytoskeleton {ECO:0000250}. actin cytoskeleton organization;antigen processing and presentation of exogenous peptide antigen via MHC class II;barbed-end actin filament capping;blood coagulation;cell junction assembly;endoplasmic reticulum to Golgi vesicle-mediated transport;innate immune response;interleukin-12-mediated signaling pathway;protein-containing complex assembly actin binding;actin filament binding;cadherin binding actin cortical patch;actin cytoskeleton;cytoskeleton;cytosol;extracellular exosome;extracellular region;F-actin capping protein complex;WASH complex Endocytosis Advanced glycosylation endproduct receptor signaling;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;Factors involved in megakaryocyte development and platelet production;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;HSP90 chaperone cycle for steroid hormone receptors (SHR);MHC class II antigen presentation CAPZalpha-CAPZbeta complex;PI4K2A-WASH complex;RICH1/AMOT polarity complex, Flag-Rich1 precipitated;WASH-CAPZalpa/beta complex -1.78573858737946 0.345123797655106 1.088458776474 1.36869752407074 1.22920274734497 0.889075100421906 0.889075100421906 0.974716603755951 -0.038471769541502 0.475271731615067 -0.145546197891235 0.212176308035851 -1.56421458721161 -0.634620726108551 -1.09595584869385 -1.36418378353119 -0.296118676662445 -0.546947360038757 + Cluster -674 25 25 25 30.2 30.2 30.2 138.34 0 303.35 39261000000 107 3.79419038332295 0.000253731343283582 P53621;P53621-2 P53621;P53621-2 Coatomer subunit alpha;Xenin;Proxenin COPA 1207 the complexalso influences the Golgi structural integrity, as well as theprocessing, activity, and endocytic recycling of LDL receptors (Bysimilarity).;The coatomer is a cytosolic protein complex that bindsto dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosyntheticprotein transport from the ER, via the Golgi up to the trans Golginetwork. Coatomer complex is required for budding from Golgimembranes, and is essential for the retrograde Golgi-to-ERtransport of dilysine-tagged proteins. In mammals, the coatomercan only be recruited by membranes associated to ADP-ribosylationfactors (ARFs), which are small GTP-binding proteins Cytoplasmic side {ECO:0000250}. Note=The coatomeris cytoplasmic or polymerized on the cytoplasmic side of theGolgi, as well as on the vesicles/buds originating from it.{ECO:0000250}.Xenin: Secreted {ECO:0000250}.; Peripheral membrane protein {ECO:0000250}; Peripheral membrane protein{ECO:0000250};Cytoplasm {ECO:0000250}. Golgi apparatusmembrane {ECO:0000250};Cytoplasmic side {ECO:0000250}. Cytoplasmic vesicle, COPI-coatedvesicle membrane {ECO:0000250} endoplasmic reticulum to Golgi vesicle-mediated transport;intracellular protein transport;intra-Golgi vesicle-mediated transport;pancreatic juice secretion;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum hormone activity;structural molecule activity COPI vesicle coat;cytoplasm;cytosol;endoplasmic reticulum membrane;extracellular exosome;extracellular space;Golgi membrane;membrane;transport vesicle COPI-dependent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport -1.15415966510773 0.0880850851535797 1.23624837398529 1.17277312278748 1.63702845573425 0.68485414981842 0.816577553749084 1.03018641471863 0.575880110263824 -0.601897656917572 0.196563184261322 0.41099339723587 -1.18778789043427 -0.601897656917572 -0.747583746910095 -1.71477448940277 -0.847228646278381 -0.993860006332397 + Cluster -674 10 10 10 44 44 44 30.692 0 319.44 91162000000 92 4.33252690143059 7.40740740740741E-05 Q9BTT0;Q9BTT0-3;Q9BTT0-2 Q9BTT0;Q9BTT0-3;Q9BTT0-2 Acidic leucine-rich nuclear phosphoprotein 32 family member E ANP32E 2656 Histone chaperone that specifically mediates the genome-wide removal of histone H2A.Z/H2AFZ from the nucleosome: removesH2A.Z/H2AFZ from its normal sites of deposition, especially fromenhancer and insulator regions. Not involved in deposition ofH2A.Z/H2AFZ in the nucleosome. May stabilize the evictedH2A.Z/H2AFZ-H2B dimer, thus shifting the equilibrium towardsdissociation and the off-chromatin state (PubMed:24463511).Inhibits activity of protein phosphatase 2A (PP2A). Does notinhibit protein phosphatase 1. May play a role in cerebellardevelopment and synaptogenesis. Cytoplasm {ECO:0000250}. Nucleus{ECO:0000250}. histone exchange histone binding;phosphatase inhibitor activity cytoplasmic vesicle;nucleus;Swr1 complex -1.45482909679413 -0.456159710884094 1.41143119335175 1.51938021183014 1.70070946216583 0.384755700826645 0.84698224067688 0.277308285236359 -0.327415108680725 0.913465440273285 0.384755700826645 0.277308285236359 -1.24348723888397 -0.597527980804443 -1.24348723888397 -0.74811315536499 -0.74811315536499 -0.896963655948639 + Cluster -674 27 27 27 45.1 45.1 45.1 88.549 0 323.31 206800000000 279 4.60297891158964 4.48979591836735E-05 Q13263;Q13263-2 Q13263;Q13263-2 Transcription intermediary factor 1-beta TRIM28 1615 the function is enhanced by MAGEC2and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclearlocalization of KOX1, ZNF268 and ZNF300 transcription factors. Inassociation with isoform 2 of ZFP90, is required for thetranscriptional repressor activity of FOXP3 and the suppressivefunction of regulatory T-cells (Treg) (PubMed:23543754). Probablyforms a corepressor complex required for activated KRAS-mediatedpromoter hypermethylation and transcriptional silencing of tumorsuppressor genes (TSGs) or other tumor-related genes in colorectalcancer (CRC) cells (PubMed:24623306). Also required to maintain atranscriptionally repressive state of genes in undifferentiatedembryonic stem cells (ESCs) (PubMed:24623306). Associates atpromoter regions of tumor suppressor genes (TSGs) leading to theirgene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complexmay play a role in recruiting ATRX to the 3'-exons of zinc-fingercoding genes with atypical chromatin signatures to establish ormaintain/protect H3K9me3 at these transcriptionally active regions(PubMed:27029610). Acts as a corepressor for ZFP568 (Bysimilarity).;Nuclear corepressor for KRAB domain-containing zincfinger proteins (KRAB-ZFPs). Mediates gene silencing by recruitingCHD3, a subunit of the nucleosome remodeling and deacetylation(NuRD) complex, and SETDB1 (which specifically methylates histoneH3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB targetgenes. Enhances transcriptional repression by coordinating theincrease in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14'acetylation (H3K9ac and H3K14ac, respectively) and the dispositionof HP1 proteins to silence gene expression. Recruitment of SETDB1induces heterochromatinization. May play a role as a coactivatorfor CEBPB and NR3C1 in the transcriptional activation of ORM1.Also corepressor for ERBB4. Inhibits E2F1 activity by stimulatingE2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. Mayserve as a partial backup to prevent E2F1-mediated apoptosis inthe absence of RB1. Important regulator of CDKN1A/p21(CIP1). HasE3 SUMO-protein ligase activity toward itself via its PHD-typezinc finger. Also specifically sumoylates IRF7, thereby inhibitingits transactivation activity. Ubiquitinates p53/TP53 leading toits proteosomal degradation Nucleus {ECO:0000269|PubMed:10330177,ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:20858735,ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24741090,ECO:0000269|PubMed:9016654}. Note=Associated with centromericheterochromatin during cell differentiation through CBX1.{ECO:0000250}. chromatin organization;convergent extension involved in axis elongation;DNA methylation involved in embryo development;DNA repair;embryo implantation;embryonic placenta morphogenesis;epithelial to mesenchymal transition;innate immune response;negative regulation of DNA demethylation;negative regulation of single stranded viral RNA replication via double stranded DNA intermediate;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;negative regulation of viral release from host cell;positive regulation of DNA binding;positive regulation of DNA repair;positive regulation of methylation-dependent chromatin silencing;positive regulation of protein import into nucleus;positive regulation of transcription, DNA-templated;protein autophosphorylation;protein complex oligomerization;protein sumoylation;Ras protein signal transduction;regulation of genetic imprinting;transcription initiation from RNA polymerase II promoter;viral process chromatin binding;chromo shadow domain binding;DNA binding;Krueppel-associated box domain binding;promoter-specific chromatin binding;protein kinase activity;RNA binding;sequence-specific DNA binding;SUMO transferase activity;transcription coactivator activity;transcription corepressor activity;ubiquitin protein ligase binding;ubiquitin-protein transferase activity;zinc ion binding chromatin;nuclear euchromatin;nuclear heterochromatin;nucleoplasm;nucleus;RNA polymerase II transcription factor complex Generic Transcription Pathway;SUMOylation of transcription cofactors Emerin complex 32;FOXP3-TRIM28-ZFP90 complex;HDAC10-PAX3-KAP1 complex;NCOR1 complex;ZNF304-corepressor complex -1.58551049232483 0.285242557525635 1.29824113845825 1.23891746997833 1.36891090869904 0.550781965255737 0.715766072273254 1.00917184352875 0.106732532382011 -0.0705614313483238 0.125638991594315 0.74547952413559 -1.63518583774567 -0.613479733467102 -0.827622950077057 -1.58551049232483 -0.51632022857666 -0.610691964626312 + Cluster -674 9 9 9 23.8 23.8 23.8 47.46 0 96.727 11989000000 37 3.69655956158325 0.000300947867298578 O96019;O96019-2;O94805 O96019;O96019-2 Actin-like protein 6A ACTL6A 458 Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner. Belongs to the neuron-specific chromatinremodeling complex (nBAF complex), as such plays a role inremodeling mononucleosomes in an ATP-dependent fashion, and isrequired for postmitotic neural development and dendriticoutgrowth. During neural development a switch from astem/progenitor to a postmitotic chromatin remodeling mechanismoccurs as neurons exit the cell cycle and become committed totheir adult state. The transition from proliferating neuralstem/progenitor cells to postmitotic neurons requires a switch insubunit composition of the npBAF and nBAF complexes. As neuralprogenitors exit mitosis and differentiate into neurons, npBAFcomplexes which contain ACTL6A/BAF53A and PHF10/BAF45A, areexchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45Bor DPF3/BAF45C subunits in neuron-specific complexes (nBAF). ThenpBAF complex is essential for the self-renewal/proliferativecapacity of the multipotent neural stem cells. The nBAF complexalong with CREST plays a role regulating the activity of genesessential for dendrite growth. ACTL6B/BAF53B is not essential forassembly of the nBAF complex but is required for targeting thecomplex and CREST to the promoter of genes essential for dendriticgrowth (By similarity).;Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner. Required for maximal ATPase activity ofSMARCA4/BRG1/BAF190A and for association of theSMARCA4/BRG1/BAF190A containing remodeling complex BAF withchromatin/nuclear matrix. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and isrequired for the proliferation of neural progenitors. Duringneural development a switch from a stem/progenitor to apostmitotic chromatin remodeling mechanism occurs as neurons exitthe cell cycle and become committed to their adult state. Thetransition from proliferating neural stem/progenitor cells topostmitotic neurons requires a switch in subunit composition ofthe npBAF and nBAF complexes. As neural progenitors exit mitosisand differentiate into neurons, npBAF complexes which containACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologousalternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunitsin neuron-specific complexes (nBAF). The npBAF complex isessential for the self-renewal/proliferative capacity of themultipotent neural stem cells. The nBAF complex along with CRESTplays a role regulating the activity of genes essential fordendrite growth (By similarity). Component of the NuA4 histoneacetyltransferase (HAT) complex which is involved intranscriptional activation of select genes principally byacetylation of nucleosomal histones H4 and H2A. This modificationmay both alter nucleosome - DNA interactions and promoteinteraction of the modified histones with other proteins whichpositively regulate transcription. This complex may be requiredfor the activation of transcriptional programs associated withoncogene and proto-oncogene mediated growth induction, tumorsuppressor mediated growth arrest and replicative senescence,apoptosis, and DNA repair. NuA4 may also play a direct role in DNArepair when recruited to sites of DNA damage. Putative corecomponent of the chromatin remodeling INO80 complex which isinvolved in transcriptional regulation, DNA replication andprobably DNA repair. Nucleus {ECO:0000269|PubMed:18026119}.;Nucleus {ECO:0000303|PubMed:26601204}. ATP-dependent chromatin remodeling;blastocyst formation;chromatin organization;chromatin remodeling;DNA recombination;DNA repair;histone H2A acetylation;histone H4 acetylation;neural retina development;protein deubiquitination;regulation of growth;regulation of transcription by RNA polymerase II;signal transduction;spinal cord development chromatin binding;structural constituent of cytoskeleton;transcription coactivator activity Ino80 complex;nBAF complex;npBAF complex;NuA4 histone acetyltransferase complex;nuclear chromatin;nucleolus;nucleoplasm;nucleus;plasma membrane;protein-containing complex;SWI/SNF complex Hepatocellular carcinoma;Thermogenesis DNA Damage Recognition in GG-NER;HATs acetylate histones;RMTs methylate histone arginines;RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;UCH proteinases BAF complex;BRD7-SWI\u2013SNF complex;BRG1-associated complex;Brg1-associated complex I;Brg1-associated complex II;Brg1-based SWI/SNF complex;BRG1-SIN3A complex;BRG1-SIN3A-HDAC containing SWI/SNF remodeling complex I;Brm-associated complex;BRM-associated complex;BRM-SIN3A complex;BRM-SIN3A-HDAC complex;c-MYC-ATPase-helicase complex;DMAP1-associated complex;EBAFa complex;EBAFb complex;INO80 chromatin remodeling complex;LARC complex (LCR-associated remodeling complex);NuA4/Tip60 HAT complex;NuA4/Tip60-HAT complex;NuA4/Tip60-HAT complex A;NuA4/Tip60-HAT complex B;p400-associated complex;PBAF complex (Polybromo- and BAF containing complex);RNA polymerase II complex, chromatin structure modifying;SIN3-ING1b complex II;SRCAP-associated chromatin remodeling complex;SWI-SNF chromatin remodeling-related-BRCA1 complex;TIP49-TIP48-BAF53 complex;TIP60 histone acetylase complex;TRRAP-BAF53-HAT complex;WINAC complex -1.63761830329895 0.324208706617355 1.57354593276978 1.26013159751892 1.57354593276978 0.848701894283295 0.595817148685455 0.435723155736923 -0.0460789613425732 0.0585271865129471 0.110214471817017 0.52878338098526 -1.24597072601318 -0.620979785919189 -0.71085524559021 -1.62364780902863 -0.619690477848053 -0.804358065128326 + Cluster -674 11 11 11 35.7 35.7 35.7 54.636 0 126.84 27334000000 64 3.69568364338574 0.000300236406619385 P07954;P07954-2 P07954;P07954-2 Fumarate hydratase, mitochondrial FH 546 Also acts as a tumor suppressor. Isoform Mitochondrial: Mitochondrion.Isoform Cytoplasmic: Cytoplasm. fumarate metabolic process;homeostasis of number of cells within a tissue;malate metabolic process;positive regulation of cold-induced thermogenesis;tricarboxylic acid cycle fumarate hydratase activity cytoplasm;extracellular exosome;mitochondrial matrix;mitochondrion;tricarboxylic acid cycle enzyme complex Carbon metabolism;Citrate cycle (TCA cycle);Cushing syndrome;Metabolic pathways;Pathways in cancer;Pyruvate metabolism;Renal cell carcinoma Bilateral macronodular adrenal hyperplasia;Cushing syndrome;Diseases of the tricarboxylic acid cycle;Fumarase deficiency;Malignant paraganglioma;Multiple cutaneous and uterine leiomyomata;Renal cell carcinoma;Uterine leiomyoma Citric acid cycle (TCA cycle) -1.32813954353333 0.633029997348785 1.03723573684692 1.79182040691376 1.63396847248077 0.273610204458237 0.899156033992767 0.78846275806427 -0.169147506356239 0.0633735582232475 -0.345422476530075 0.394119799137115 -1.05785751342773 -0.560264885425568 -0.455169826745987 -1.45322394371033 -0.992151737213135 -1.15339982509613 + Cluster -674 8 8 5 29.4 29.4 19.6 46.302 0 137.53 9503000000 28 3.59658352291779 0.000364628820960699 P31323 P31323 cAMP-dependent protein kinase type II-beta regulatory subunit PRKAR2B 886 Regulatory subunit of the cAMP-dependent protein kinasesinvolved in cAMP signaling in cells. Type II regulatory chainsmediate membrane association by binding to anchoring proteins,including the MAP2 kinase. Cytoplasm {ECO:0000269|PubMed:21423175}.Cell membrane {ECO:0000269|PubMed:21423175}. Note=Colocalizes withPJA2 in the cytoplasm and at the cell membrane. activation of protein kinase A activity;blood coagulation;cellular response to glucagon stimulus;cGMP-mediated signaling;ciliary basal body-plasma membrane docking;fatty acid metabolic process;G2/M transition of mitotic cell cycle;intracellular signal transduction;learning;modulation of chemical synaptic transmission;negative regulation of cAMP-dependent protein kinase activity;regulation of G2/M transition of mitotic cell cycle;renal water homeostasis;response to clozapine 3',5'-cyclic-GMP phosphodiesterase activity;cAMP binding;cAMP-dependent protein kinase inhibitor activity;cAMP-dependent protein kinase regulator activity;protein domain specific binding;protein kinase A catalytic subunit binding;ubiquitin protein ligase binding cAMP-dependent protein kinase complex;centrosome;ciliary base;cytoplasm;cytosol;dendritic shaft;dendritic spine;extracellular exosome;glutamatergic synapse;membrane raft;neuronal cell body;perinuclear region of cytoplasm;plasma membrane Insulin signaling pathway Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;DARPP-32 events;Factors involved in megakaryocyte development and platelet production;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Hedgehog 'off' state;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;PKA activation;PKA activation in glucagon signalling;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition;Vasopressin regulates renal water homeostasis via Aquaporins AMY-1-S-AKAP84-RII-beta complex;GSKIP-PRKAR2B complex;PKA (RII-alpha and RII-beta)-AKAP5-ADRB1 complex -0.625716388225555 -0.0170279238373041 0.848951578140259 2.04347276687622 1.48686444759369 0.0281082466244698 1.39638781547546 1.05129384994507 -1.12033903598785 -0.199206501245499 -0.779738247394562 0.481837242841721 -1.22780430316925 -0.342375993728638 -0.408483505249023 -1.19357621669769 -0.913614988327026 -0.509032607078552 + Cluster -674 4 4 4 10.7 10.7 10.7 54.812 0 4.0144 628750000 7 3.58055238552345 0.000378787878787879 O75844 O75844 CAAX prenyl protease 1 homolog ZMPSTE24 361 Proteolytically removes the C-terminal three residues offarnesylated proteins. Acts on lamin A/C. Multi-pass membrane protein{ECO:0000269|PubMed:23539603}.; Multi-pass membrane protein{ECO:0000269|PubMed:23539603}. Nucleus inner membrane{ECO:0000269|PubMed:23539603};Endoplasmic reticulum membrane{ECO:0000269|PubMed:23539603} adult walking behavior;bone mineralization;CAAX-box protein processing;calcium ion import into sarcoplasmic reticulum;CAMKK-AMPK signaling cascade;cardiac conduction;cardiac muscle fiber development;cardiac ventricle development;cellular lipid metabolic process;cellular response to gamma radiation;determination of adult lifespan;DNA repair;growth plate cartilage development;hair follicle development;heart morphogenesis;histone H2A phosphorylation;histone H2B-K5 acetylation;hypomethylation of CpG island;inflammatory cell apoptotic process;kidney morphogenesis;liver development;maintenance of rDNA;multicellular organism growth;negative regulation of production of miRNAs involved in gene silencing by miRNA;neuromuscular process;nuclear envelope organization;prenylated protein catabolic process;proteolysis;regulation of autophagy;regulation of bone mineralization;regulation of cell shape;regulation of cellular senescence;regulation of defense response to virus;regulation of DNA damage response, signal transduction by p53 class mediator;regulation of fibroblast proliferation;regulation of glucose metabolic process;regulation of histone H4-K16 acetylation;regulation of hormone metabolic process;regulation of lipid metabolic process;regulation of mitotic cell cycle DNA replication;regulation of multicellular organism growth;regulation of RNA polymerase II regulatory region sequence-specific DNA binding;regulation of stress-activated protein kinase signaling cascade;regulation of termination of RNA polymerase I transcription;regulation of TOR signaling;regulation of ventricular cardiac muscle cell membrane repolarization;response to DNA damage checkpoint signaling;thymus development;ventricular cardiac muscle tissue development double-stranded DNA binding;metal ion binding;metalloendopeptidase activity;metalloexopeptidase activity extracellular exosome;integral component of endoplasmic reticulum membrane;membrane;nuclear inner membrane;protein-containing complex Terpenoid backbone biosynthesis Mandibuloacral dysplasia;Restrictive dermopathy -0.55275171995163 0.185970067977905 1.04031670093536 1.39444148540497 1.62115740776062 0.659163177013397 1.21955072879791 1.10679829120636 -0.665504097938538 0.0226729456335306 -0.469502538442612 0.481434553861618 -1.49830734729767 -0.679727911949158 -0.842107892036438 -1.35700345039368 -0.435656070709229 -1.23094439506531 + Cluster -674 8 8 8 26.3 26.3 26.3 41.213 0 85.661 10192000000 37 5.6204270271454 8.62068965517241E-06 P19784 P19784 Casein kinase II subunit alpha CSNK2A2 736 Catalytic subunit of a constitutively activeserine/threonine-protein kinase complex that phosphorylates alarge number of substrates containing acidic residues C-terminalto the phosphorylated serine or threonine. Regulates numerouscellular processes, such as cell cycle progression, apoptosis andtranscription, as well as viral infection. May act as a regulatorynode which integrates and coordinates numerous signals leading toan appropriate cellular response. During mitosis, functions as acomponent of the p53/TP53-dependent spindle assembly checkpoint(SAC) that maintains cyclin-B-CDK1 activity and G2 arrest inresponse to spindle damage. Also required for p53/TP53-mediatedapoptosis, phosphorylating 'Ser-392' of p53/TP53 following UVirradiation. Can also negatively regulate apoptosis.Phosphorylates the caspases CASP9 and CASP2 and the apoptoticregulator NOL3. Phosphorylation protects CASP9 from cleavage andactivation by CASP8, and inhibits the dimerization of CASP2 andactivation of CASP8. Regulates transcription by directphosphorylation of RNA polymerases I, II, III and IV. Alsophosphorylates and regulates numerous transcription factorsincluding NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX,JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperonesFKBP4 and CDC37, which is essential for chaperone function.Regulates Wnt signaling by phosphorylating CTNNB1 and thetranscription factor LEF1. Acts as an ectokinase thatphosphorylates several extracellular proteins. During viralinfection, phosphorylates various proteins involved in the virallife cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV apoptotic process;cell cycle;cerebral cortex development;liver regeneration;negative regulation of apoptotic signaling pathway;negative regulation of ubiquitin-dependent protein catabolic process;peptidyl-serine phosphorylation;positive regulation of protein targeting to mitochondrion;regulation of autophagy of mitochondrion;regulation of chromosome separation;regulation of signal transduction by p53 class mediator;spermatogenesis;Wnt signaling pathway ATP binding;protein N-terminus binding;protein serine/threonine kinase activity acrosomal vesicle;chromatin;cytosol;nucleoplasm;nucleus;plasma membrane Adherens junction;Measles;Mitophagy - animal;NF-kappa B signaling pathway;PD-L1 expression and PD-1 checkpoint pathway in cancer;Ribosome biogenesis in eukaryotes;Wnt signaling pathway Condensation of Prometaphase Chromosomes;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Receptor Mediated Mitophagy;Regulation of PTEN stability and activity;Regulation of TP53 Activity through Phosphorylation;RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Signal transduction by L1;Synthesis of PC;WNT mediated activation of DVL Casein kinase II (beta-dimer, alpha, alpha');Casein kinase II (beta-dimer, alpha'-dimer);Casein kinase II-HMG1 complex;FACT complex, UV-activated -1.04813504219055 0.121391110122204 -0.397907465696335 1.51202309131622 1.7107959985733 1.41215682029724 1.21881747245789 0.959058940410614 0.187154799699783 -1.16652488708496 -1.65820896625519 -0.5062375664711 0.122407533228397 -0.0483614951372147 -0.333093702793121 -0.996145308017731 -0.557324826717377 -0.531866669654846 + Cluster -674 3 3 3 15.7 15.7 15.7 33.631 0 39.171 1268500000 10 3.09049399267753 0.000919254658385093 Q92600;Q92600-3;Q92600-2 Q92600;Q92600-3;Q92600-2 Cell differentiation protein RCD1 homolog RQCD1 2335 Component of the CCR4-NOT complex which is one of themajor cellular mRNA deadenylases and is linked to various cellularprocesses including bulk mRNA degradation, miRNA-mediatedrepression, translational repression during translationalinitiation and general transcription regulation. Additionalcomplex functions may be a consequence of its influence on mRNAexpression. Involved in down-regulation of MYB- and JUN-dependenttranscription. May play a role in cell differentiation (Bysimilarity). Can bind oligonucleotides, such as poly-G, poly-C orpoly-T (in vitro), but the physiological relevance of this is notcertain. Does not bind poly-A. Enhances ligand-dependenttranscriptional activity of nuclear hormone receptors, includingRARA, expect ESR1-mediated transcription that is not only slightlyincreased, if at all. Nucleus {ECO:0000250|UniProtKB:Q9JKY0}.Cytoplasm, P-body {ECO:0000250|UniProtKB:Q9JKY0}. Note=NANOS2promotes its localization to P-body.{ECO:0000250|UniProtKB:Q9JKY0}. cytokine-mediated signaling pathway;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;gene silencing by RNA;negative regulation of intracellular estrogen receptor signaling pathway;negative regulation of translation;nuclear-transcribed mRNA poly(A) tail shortening;positive regulation of epidermal growth factor receptor signaling pathway;positive regulation of nuclear receptor transcription coactivator activity;positive regulation of peptidyl-serine phosphorylation;sex differentiation epidermal growth factor receptor binding;kinase binding;protein domain specific binding;protein homodimerization activity CCR4-NOT complex;CCR4-NOT core complex;cytosol;membrane;nucleus;P-body;protein-containing complex RNA degradation Activation of anterior HOX genes in hindbrain development during early embryogenesis;Deadenylation of mRNA;TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain CCR4-NOT complex;CCR4-NOT-CNOT7-CNOT6 complex;CCR4-NOT-CNOT7-CNOT6L complex;CCR4-NOT-CNOT8-CNOT6 complex;CCR4-NOT-CNOT8-CNOT6L complex 0.0909915342926979 0.258280426263809 -0.104301579296589 1.36259961128235 1.52649664878845 0.794053971767426 1.04276025295258 1.56689751148224 0.258280426263809 -0.934252023696899 -1.72872638702393 -0.082393117249012 0.251557022333145 -0.082393117249012 -0.827510118484497 -1.19978499412537 -0.992771148681641 -1.19978499412537 + Cluster -674 2 2 2 4.2 4.2 4.2 82.875 0 11.284 635790000 3 3.14502402653977 0.000821371610845295 Q6PJT7;Q6PJT7-5;Q6PJT7-2;Q6PJT7-9;Q6PJT7-4;Q6PJT7-3;Q6PJT7-10;Q6PJT7-11 Q6PJT7;Q6PJT7-5;Q6PJT7-2;Q6PJT7-9;Q6PJT7-4;Q6PJT7-3;Q6PJT7-10;Q6PJT7-11 Zinc finger CCCH domain-containing protein 14 ZC3H14 2008 Involved in poly(A) tail length control in neuronalcells. Binds the polyadenosine RNA oligonucleotides Nucleus speckle{ECO:0000269|PubMed:17630287, ECO:0000269|PubMed:19303045,ECO:0000269|PubMed:24671764}. Note=Colocalizes with poly(A) RNA innuclear speckles. {ECO:0000250|UniProtKB:Q7TMD5}.Isoform 1: Nucleus speckle.Isoform 3: Nucleus speckle.Isoform 6: Cytoplasm{ECO:0000269|PubMed:21734151}. negative regulation of mRNA polyadenylation;regulation of mRNA stability metal ion binding;poly(A) binding;RNA binding axon cytoplasm;cytoplasm;dendrite cytoplasm;nuclear speck;nucleolus;nucleus;ribonucleoprotein complex Autosomal recessive mental retardation -0.634107887744904 -0.095504105091095 0.678905248641968 1.0805047750473 0.802258133888245 1.27898466587067 1.80410075187683 1.53351247310638 -0.347325444221497 -1.20466899871826 -1.73860335350037 -0.840930342674255 0.40657714009285 -0.558653712272644 -0.680355966091156 -0.240047827363014 -0.634107887744904 -0.610537767410278 + Cluster -674 7 7 7 10.4 10.4 10.4 80.529 0 34.437 4129500000 27 5.53719718027436 8.26446280991736E-06 P46977;P46977-2 P46977;P46977-2 Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A STT3A 1062 Catalytic subunit of the oligosaccharyl transferase(OST) complex that catalyzes the initial transfer of a definedglycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipidcarrier dolichol-pyrophosphate to an asparagine residue within anAsn-X-Ser/Thr consensus motif in nascent polypeptide chains, thefirst step in protein N-glycosylation. N-glycosylation occurscotranslationally and the complex associates with the Sec61complex at the channel-forming translocon complex that mediatesprotein translocation across the endoplasmic reticulum (ER). Allsubunits are required for a maximal enzyme activity. This subunitcontains the active site and the acceptor peptide and donor lipid-linked oligosaccharide (LLO) binding pockets (By similarity).STT3A is present in the majority of OST complexes and mediatescotranslational N-glycosylation of most sites on target proteins,while STT3B-containing complexes are required for efficient post-translational glycosylation and mediate glycosylation of sitesthat have been skipped by STT3A (PubMed:19167329) Multi-pass membrane protein{ECO:0000250|UniProtKB:P46978}.;Endoplasmic reticulum{ECO:0000269|PubMed:12887896}. Endoplasmic reticulum membrane{ECO:0000250|UniProtKB:P46978} co-translational protein modification;protein N-linked glycosylation via asparagine dolichyl-diphosphooligosaccharide-protein glycotransferase activity;metal ion binding endoplasmic reticulum membrane;integral component of membrane;membrane;oligosaccharyltransferase complex;oligosaccharyltransferase III complex Metabolic pathways;N-Glycan biosynthesis;Protein processing in endoplasmic reticulum Congenital disorders of glycosylation type I Asparagine N-linked glycosylation Oligosaccharyltransferase complex (Stt3A variant);SELK multiprotein complex -0.357708722352982 0.409054219722748 0.809572041034698 0.184872895479202 1.06521546840668 1.62141299247742 1.53589510917664 1.19329214096069 -0.112062349915504 -0.596285045146942 -2.20731210708618 -1.11299645900726 -0.0285540949553251 -0.163103669881821 -0.242374271154404 -0.357708722352982 -0.357708722352982 -1.28350067138672 + Cluster -674 1 1 1 2 2 2 104.4 0 57.748 223420000 2 3.91424933358504 0.000178378378378378 Q9Y5B0;Q9Y5B0-4 Q9Y5B0;Q9Y5B0-4 RNA polymerase II subunit A C-terminal domain phosphatase CTDP1 3305 Processively dephosphorylates 'Ser-2' and 'Ser-5' of theheptad repeats YSPTSPS in the C-terminal domain of the largest RNApolymerase II subunit. This promotes the activity of RNApolymerase II. Plays a role in the exit from mitosis bydephosphorylating crucial mitotic substrates (USP44, CDC20 andWEE1) that are required for M-phase-promoting factor (MPF)/CDK1inactivation. Nucleus {ECO:0000269|PubMed:22692537}.Cytoplasm, cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:22692537}. Cytoplasm, cytoskeleton, spindlepole {ECO:0000269|PubMed:22692537}. Midbody{ECO:0000269|PubMed:22692537}. Note=Found at centrosomes inprometaphase, at spindle and spindle poles in metaphase and atspindle midzone and midbody in anaphase and telophase-G1respectively. cell division;dephosphorylation of RNA polymerase II C-terminal domain;exit from mitosis;negative regulation of cell growth involved in cardiac muscle cell development;positive regulation by host of viral transcription;protein dephosphorylation;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter phosphoprotein phosphatase activity;RNA polymerase II CTD heptapeptide repeat phosphatase activity;Tat protein binding;TFIIF-class transcription factor complex binding centrosome;cytoplasm;intracellular membrane-bounded organelle;midbody;nucleoplasm;nucleus;protein-containing complex;spindle;spindle midzone;spindle pole Congenital cataracts, facial dysmorphism, and neuropathy Abortive elongation of HIV-1 transcript in the absence of Tat;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;HIV elongation arrest and recovery;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Elongation;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes FCP1-associated protein complex;RNA polymerase II (RNAPII) -0.626590728759766 0.154761120676994 0.154761120676994 0.93844872713089 1.85299217700958 0.575840592384338 1.80439734458923 1.36927759647369 -0.17773549258709 -0.123707339167595 -1.99054789543152 -0.579900026321411 -0.356069058179855 -0.254842430353165 -0.444423377513885 -0.328877240419388 -0.939715385437012 -1.02806973457336 + Cluster -674 13 13 13 85.6 85.6 85.6 14.515 0 323.31 204780000000 241 3.2319989866107 0.000699499165275459 P25398 P25398 40S ribosomal protein S12 RPS12 801 Cytoplasm. nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;Golgi apparatus;intracellular membrane-bounded organelle;membrane;nucleoplasm Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic -0.538676857948303 0.339081913232803 0.633005917072296 1.00186932086945 1.38054072856903 1.32517790794373 1.25801038742065 1.69398272037506 -0.28950509428978 -0.78641951084137 -1.65460526943207 -0.985729515552521 0.0975646451115608 -0.549483180046082 -0.398449242115021 -0.656254291534424 -0.848262190818787 -1.02184844017029 + Cluster -674 3 3 3 5.7 5.7 5.7 80.301 0 17.511 1782100000 8 5.68808734823688 9.25925925925926E-06 Q9BSC4;Q9BSC4-2;Q9BSC4-4 Q9BSC4;Q9BSC4-2;Q9BSC4-4 Nucleolar protein 10 NOL10 2638 Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) RNA binding nucleolus;small-subunit processome AATF-NGDN-NOL10 complex -1.02201759815216 0.401179194450378 2.48344826698303 0.87610250711441 1.35517883300781 0.971433281898499 0.911969542503357 0.126639232039452 -0.664102613925934 -0.19880673289299 -0.364487171173096 -0.19880673289299 -0.491154372692108 -0.26550680398941 -0.491154372692108 -0.945627212524414 -1.09114027023315 -1.39314687252045 + Cluster -674 16 16 11 44.3 44.3 34.2 58.042 0 276.77 42198000000 109 3.24541535649409 0.00068013468013468 Q13177;O75914;O75914-3;O75914-2;O75914-4 Q13177 Serine/threonine-protein kinase PAK 2;PAK-2p27;PAK-2p34 PAK2 1606 Serine/threonine protein kinase that plays a role in avariety of different signaling pathways including cytoskeletonregulation, cell migration, or cell cycle regulation. Plays a rolein dendrite spine morphogenesis as well as synapse formation andplasticity. Acts as downstream effector of the small GTPases CDC42and RAC1. Activation by the binding of active CDC42 and RAC1results in a conformational change and a subsequentautophosphorylation on several serine and/or threonine residues.Phosphorylates MAPK4 and MAPK6 and activates the downstream targetMAPKAPK5, a regulator of F-actin polymerization and cellmigration. Additionally, phosphorylates TNNI3/troponin I tomodulate calcium sensitivity and relaxation kinetics of thinmyofilaments. May also be involved in early neuronal development;Serine/threonine protein kinase that plays a role in avariety of different signaling pathways including cytoskeletonregulation, cell motility, cell cycle progression, apoptosis orproliferation. Acts as downstream effector of the small GTPasesCDC42 and RAC1. Activation by the binding of active CDC42 and RAC1results in a conformational change and a subsequentautophosphorylation on several serine and/or threonine residues.Full-length PAK2 stimulates cell survival and cell growth.Phosphorylates MAPK4 and MAPK6 and activates the downstream targetMAPKAPK5, a regulator of F-actin polymerization and cellmigration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substratesincluding histone H4 to promote assembly of H3.3 and H4 intonucleosomes, BAD, ribosomal protein S6, or MBP. Additionally,associates with ARHGEF7 and GIT1 to perform kinase-independentfunctions such as spindle orientation control during mitosis. Onthe other hand, apoptotic stimuli such as DNA damage lead tocaspase-mediated cleavage of PAK2, generating PAK-2p34, an activep34 fragment that translocates to the nucleus and promotescellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellulartranslation. Lipid-anchor. Note=Interaction with ARHGAP10probably changes PAK-2p34 location to cytoplasmic perinuclearregion. Myristoylation changes PAK-2p34 location to the membrane.;Cytoplasm {ECO:0000250}.;Serine/threonine-protein kinase PAK 2:Cytoplasm. Note=MYO18A mediates the cellular distribution of thePAK2-ARHGEF7-GIT1 complex to the inner surface of the cellmembrane.PAK-2p34: Nucleus. Cytoplasm, perinuclearregion. Membrane activation of protein kinase activity;apoptotic process;axonogenesis;cell migration;cellular response to organic cyclic compound;dendrite development;dendritic spine development;dendritic spine morphogenesis;ephrin receptor signaling pathway;Fc-epsilon receptor signaling pathway;interleukin-12-mediated signaling pathway;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis;negative regulation of protein kinase activity;peptidyl-serine phosphorylation;phosphorylation;positive regulation of dendritic spine morphogenesis;positive regulation of DNA biosynthetic process;positive regulation of extrinsic apoptotic signaling pathway;positive regulation of fibroblast migration;positive regulation of neuron apoptotic process;positive regulation of peptidyl-tyrosine phosphorylation;protein autophosphorylation;protein phosphorylation;regulation of actin filament polymerization;regulation of axonogenesis;regulation of defense response to virus by virus;regulation of growth;regulation of MAPK cascade;signal transduction;signal transduction by protein phosphorylation;stimulatory C-type lectin receptor signaling pathway;stress-activated protein kinase signaling cascade;synapse organization;T cell costimulation;T cell receptor signaling pathway;vascular endothelial growth factor receptor signaling pathway ATP binding;cadherin binding;identical protein binding;MAP kinase kinase activity;metal ion binding;protein kinase activity;protein kinase binding;protein serine/threonine kinase activity;protein tyrosine kinase activator activity;Rac GTPase binding;SH3 domain binding;small GTPase binding cytoplasm;cytosol;endosome;glutamatergic synapse;nucleus;perinuclear region of cytoplasm;plasma membrane;postsynaptic density Axon guidance;ErbB signaling pathway;Focal adhesion;Human immunodeficiency virus 1 infection;MAPK signaling pathway;Ras signaling pathway;Regulation of actin cytoskeleton;Renal cell carcinoma;T cell receptor signaling pathway X-linked mental retardation Activation of RAC1;CD209 (DC-SIGN) signaling;CD28 dependent Vav1 pathway;Ephrin signaling;FCERI mediated MAPK activation;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Generation of second messenger molecules;MAPK6/MAPK4 signaling;Nef and signal transduction;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of PAK-2p34 activity by PS-GAP/RHG10;RHO GTPases activate PAKs;Sema3A PAK dependent Axon repulsion;Smooth Muscle Contraction;Stimulation of the cell death response by PAK-2p34;VEGFA-VEGFR2 Pathway;VEGFR2 mediated vascular permeability -0.952804923057556 0.556483268737793 1.272181391716 1.272181391716 2.03862643241882 0.413642346858978 1.28011703491211 0.413642346858978 -0.341382443904877 -0.357429355382919 -0.00870183855295181 -0.68759161233902 -0.68759161233902 -0.00870183855295181 -0.357429355382919 -1.44621813297272 -0.952804923057556 -1.44621813297272 + Cluster -674 47 47 47 64.5 64.5 64.5 69.842 0 323.31 495880000000 476 3.29479457144085 0.000598275862068966 P12956;P12956-2 P12956;P12956-2 X-ray repair cross-complementing protein 6 XRCC6 647 Single-stranded DNA-dependent ATP-dependent helicase.Has a role in chromosome translocation. The DNA helicase IIcomplex binds preferentially to fork-like ends of double-strandedDNA in a cell cycle-dependent manner. It works in the 3'-5'direction. Binding to DNA may be mediated by XRCC6. Involved inDNA non-homologous end joining (NHEJ) required for double-strandbreak repair and V(D)J recombination. The XRCC5/6 dimer acts asregulatory subunit of the DNA-dependent protein kinase complexDNA-PK by increasing the affinity of the catalytic subunit PRKDCto DNA by 100-fold. The XRCC5/6 dimer is probably involved instabilizing broken DNA ends and bringing them together. Theassembly of the DNA-PK complex to DNA ends is required for theNHEJ ligation step. Required for osteocalcin gene expression.Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRPlyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. 5'-dRPlyase activity allows to 'clean' the termini of abasic sites, aclass of nucleotide damage commonly associated with strand breaks,before such broken ends can be joined. The XRCC5/6 dimer togetherwith APEX1 acts as a negative regulator of transcription. Plays arole in the regulation of DNA virus-mediated innate immuneresponse by assembling into the HDP-RNP complex, a complex thatserves as a platform for IRF3 phosphorylation and subsequentinnate immune response activation through the cGAS-STING pathway Nucleus {ECO:0000269|PubMed:22442688}.Chromosome {ECO:0000269|PubMed:22442688}. activation of innate immune response;brain development;cellular hyperosmotic salinity response;cellular response to gamma radiation;cellular response to X-ray;DNA ligation;DNA recombination;double-strand break repair via classical nonhomologous end joining;double-strand break repair via nonhomologous end joining;establishment of integrated proviral latency;innate immune response;negative regulation of transcription, DNA-templated;neutrophil degranulation;positive regulation of protein kinase activity;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;positive regulation of type I interferon production;protein heterotetramerization;regulation of smooth muscle cell proliferation;telomere maintenance 5'-deoxyribose-5-phosphate lyase activity;ATP binding;ATP-dependent DNA helicase activity;cyclin binding;damaged DNA binding;DNA binding;double-stranded DNA binding;protein C-terminus binding;protein-containing complex binding;RNA binding;telomeric DNA binding;transcription regulatory region DNA binding cytosol;extracellular region;ficolin-1-rich granule lumen;Ku70:Ku80 complex;membrane;nonhomologous end joining complex;nuclear chromosome, telomeric region;nuclear telomere cap complex;nucleolus;nucleoplasm;nucleus;protein-containing complex;protein-DNA complex;secretory granule lumen;transcription factor complex Non-homologous end-joining 2-LTR circle formation;Cytosolic sensors of pathogen-associated DNA;IRF3-mediated induction of type I IFN;Neutrophil degranulation;Nonhomologous End-Joining (NHEJ) 53BP1-containing complex;DEAF1- complex;DHX9-ADAR-vigilin-DNA-PK-Ku antigen complex;DNA double-strand break end-joining complex;DNA-PK-Ku complex;DNA-PK-Ku-eIF2-NF90-NF45 complex;Dysbindin 1-A-DNA-PK-complex;GammaH2AFX-NDHII-Ku70-DNA complex;HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex;Ku antigen complex;Ku antigen-NARG1 complex;Ku antigen-YY1-alphaMyHC promoter complex;Ku-ORC complex;MGC1-DNA-PKcs-Ku complex;NCOA6-DNA-PK-Ku-PARP1 complex;P53-BARD1-KU70 complex;PCNA-KU antigen complex;Rap1 complex;TERF2-RAP1 complex;TRF2-Ku complex;Vigilin-DNA-PK-Ku antigen complex;WRN-Ku70-Ku80-PARP1 complex;XRCC6-XRCC5-WRN complex -0.335087358951569 0.155528113245964 1.08860802650452 1.21564555168152 2.26120615005493 0.636043190956116 0.857207834720612 0.849724650382996 -0.457095116376877 0.094487376511097 -0.954567074775696 -0.174897938966751 -0.520253419876099 -0.4394910633564 -0.348263770341873 -1.72534823417664 -0.905441224575043 -1.29800570011139 + Cluster -674 1 1 1 1.9 1.9 1.9 97.207 0 9.8832 902270000 2 3.96452678041236 0.00015406162464986 Q9UKV8;Q9H9G7;Q9UL18;Q9HCK5;Q9H9G7-2;Q9UKV8-2 Q9UKV8;Q9H9G7;Q9UL18;Q9HCK5;Q9H9G7-2;Q9UKV8-2 Protein argonaute-2;Protein argonaute-3;Protein argonaute-1;Protein argonaute-4 AGO2;AGO3;AGO1;AGO4 2833 Required for RNA-mediated gene silencing (RNAi) by theRNA-induced silencing complex (RISC). The 'minimal RISC' appearsto include AGO2 bound to a short guide RNA such as a microRNA(miRNA) or short interfering RNA (siRNA). These guide RNAs directRISC to complementary mRNAs that are targets for RISC-mediatedgene silencing. The precise mechanism of gene silencing depends onthe degree of complementarity between the miRNA or siRNA and itstarget. Binding of RISC to a perfectly complementary mRNAgenerally results in silencing due to endonucleolytic cleavage ofthe mRNA specifically by AGO2. Binding of RISC to a partiallycomplementary mRNA results in silencing through inhibition oftranslation, and this is independent of endonuclease activity. Mayinhibit translation initiation by binding to the 7-methylguanosinecap, thereby preventing the recruitment of the translationinitiation factor eIF4-E. May also inhibit translation initiationvia interaction with EIF6, which itself binds to the 60S ribosomalsubunit and prevents its association with the 40S ribosomalsubunit. The inhibition of translational initiation leads to theaccumulation of the affected mRNA in cytoplasmic processing bodies(P-bodies), where mRNA degradation may subsequently occur. In somecases RISC-mediated translational repression is also observed formiRNAs that perfectly match the 3' untranslated region (3'-UTR).Can also up-regulate the translation of specific mRNAs undercertain growth conditions. Binds to the AU element of the 3'-UTRof the TNF (TNF-alpha) mRNA and up-regulates translation underconditions of serum starvation. Also required for transcriptionalgene silencing (TGS), in which short RNAs known as antigene RNAsor agRNAs direct the transcriptional repression of complementarypromoter regions.;Required for RNA-mediated gene silencing (RNAi). Bindsto short RNAs such as microRNAs (miRNAs) and represses thetranslation of mRNAs which are complementary to them. Lacksendonuclease activity and does not appear to cleave target mRNAs.Also required for RNA-directed transcription and replication ofthe human hapatitis delta virus (HDV).;Required for RNA-mediated gene silencing (RNAi). Bindsto short RNAs such as microRNAs (miRNAs) and represses thetranslation of mRNAs which are complementary to them. Proposed tobe involved in stabilization of small RNA derivates (riRNA)derived from processed RNA polymerase III-transcribed Alu repeatscontaining a DR2 retinoic acid response element (RARE) in stemcells and in the subsequent riRNA-dependent degradation of asubset of RNA polymerase II-transcribed coding mRNAs by recruitinga mRNA decapping complex involving EDC4. Possesses RNA sliceractivity but only on select RNAs bearing 5'- and 3'-flankingsequences to the region of guide-target complementarity(PubMed:29040713).;Required for RNA-mediated gene silencing (RNAi). Bindsto short RNAs such as microRNAs (miRNAs) or short interfering RNAs(siRNAs), and represses the translation of mRNAs which arecomplementary to them. Lacks endonuclease activity and does notappear to cleave target mRNAs. Also required for transcriptionalgene silencing (TGS) of promoter regions which are complementaryto bound short antigene RNAs (agRNAs) Cytoplasm, P-body {ECO:0000255|HAMAP-Rule:MF_03032, ECO:0000269|PubMed:16081698}.;Cytoplasm, P-body {ECO:0000255|HAMAP-Rule:MF_03033, ECO:0000269|PubMed:16081698,ECO:0000269|PubMed:19167051}.;Cytoplasm, P-body{ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:20616046}.;Cytoplasm, P-body{ECO:0000269|PubMed:23125361}. Nucleus{ECO:0000269|PubMed:23125361}. Note=Translational repression ofmRNAs results in their recruitment to P-bodies. Translocation tothe nucleus requires IMP8. gene silencing by RNA;male gonad development;male meiotic nuclear division;miRNA loading onto RISC involved in gene silencing by miRNA;miRNA mediated inhibition of translation;miRNA metabolic process;mRNA catabolic process;mRNA cleavage involved in gene silencing by miRNA;mRNA cleavage involved in gene silencing by siRNA;negative regulation of angiogenesis;negative regulation of apoptotic process;negative regulation of gene expression;negative regulation of translational initiation;nuclear-transcribed mRNA catabolic process;positive regulation of angiogenesis;positive regulation of gene expression;positive regulation of miRNA mediated inhibition of translation;positive regulation of NIK/NF-kappaB signaling;positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;positive regulation of nuclear-transcribed mRNA poly(A) tail shortening;positive regulation of transcription by RNA polymerase II;positive regulation of trophoblast cell migration;post-embryonic development;posttranscriptional gene silencing by RNA;pre-miRNA processing;production of miRNAs involved in gene silencing by miRNA;production of siRNA involved in RNA interference;regulation of cell morphogenesis;regulation of gene silencing by miRNA;regulation of megakaryocyte differentiation;regulation of stem cell proliferation;RNA phosphodiester bond hydrolysis, endonucleolytic;RNA secondary structure unwinding;siRNA loading onto RISC involved in RNA interference;synaptonemal complex assembly;translation;Wnt signaling pathway, calcium modulating pathway core promoter binding;double-stranded RNA binding;endoribonuclease activity;endoribonuclease activity, cleaving miRNA-paired mRNA;endoribonuclease activity, cleaving siRNA-paired mRNA;metal ion binding;miRNA binding;mRNA cap binding;protein C-terminus binding;RNA 7-methylguanosine cap binding;RNA binding;RNA polymerase II complex binding;RNA polymerase II proximal promoter sequence-specific DNA binding;single-stranded RNA binding;siRNA binding;translation initiation factor activity cell junction;condensed nuclear chromosome;cytoplasm;cytoplasmic ribonucleoprotein granule;cytosol;dendrite;extracellular exosome;membrane;micro-ribonucleoprotein complex;mRNA cap binding complex;nuclear body;nucleoplasm;nucleus;P-body;polysome;ribonucleoprotein complex;RISC complex;RISC-loading complex Ca2+ pathway;Competing endogenous RNAs (ceRNAs) regulate PTEN translation;Estrogen-dependent gene expression;MAPK6/MAPK4 signaling;MicroRNA (miRNA) biogenesis;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Post-transcriptional silencing by small RNAs;Pre-NOTCH Transcription and Translation;Regulation of MECP2 expression and activity;Regulation of PTEN mRNA translation;Regulation of RUNX1 Expression and Activity;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Small interfering RNA (siRNA) biogenesis;TP53 Regulates Metabolic Genes;Transcriptional Regulation by MECP2;Transcriptional regulation by small RNAs AGO2-FXR1-TNF(alpha)ARE-RNP complex;DICER1-NCOA6-AGO2 complex;RNA-induced silencing complex, RISC;TRBP containing complex (DICER, TRBP, AGO2, RPL7A, EIF6, MOV10);TTP-AGO2 complex;TTP-AGO4 complex -0.785404860973358 0.0683908835053444 1.03975999355316 0.739520251750946 2.17063355445862 0.754302859306335 1.9090793132782 0.754302859306335 -0.546836018562317 -0.358595192432404 -0.999224245548248 -0.49767217040062 -0.891776561737061 -0.335204035043716 -0.335204035043716 -1.18476605415344 -0.624312698841095 -0.876993894577026 + Cluster -674 22 22 19 30 30 25.4 85.595 0 214.82 21817000000 96 4.55865685621563 4.8E-05 Q01813;Q01813-2 Q01813;Q01813-2 ATP-dependent 6-phosphofructokinase, platelet type PFKP 1488 Catalyzes the phosphorylation of D-fructose 6-phosphateto fructose 1,6-bisphosphate by ATP, the first committing step ofglycolysis. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}. canonical glycolysis;cellular response to leukemia inhibitory factor;fructose 1,6-bisphosphate metabolic process;fructose 6-phosphate metabolic process;glucose catabolic process;protein complex oligomerization 6-phosphofructokinase activity;AMP binding;ATP binding;cadherin binding;fructose-6-phosphate binding;identical protein binding;metal ion binding;monosaccharide binding;protein-containing complex binding 6-phosphofructokinase complex;cytoplasm;cytosol;extracellular exosome;membrane;nucleus AMPK signaling pathway;Biosynthesis of amino acids;Carbon metabolism;Central carbon metabolism in cancer;Fructose and mannose metabolism;Galactose metabolism;Glucagon signaling pathway;Glycolysis / Gluconeogenesis;HIF-1 signaling pathway;Metabolic pathways;Pentose phosphate pathway;RNA degradation;Thyroid hormone signaling pathway Glycolysis -0.375850468873978 -0.291215479373932 1.26911520957947 0.846055090427399 2.20530438423157 1.00480175018311 1.50486850738525 0.674843609333038 -0.375850468873978 -0.489229440689087 -0.886475145816803 -0.765054285526276 -0.438393294811249 -0.136443823575974 -0.468917936086655 -0.853825092315674 -1.26537382602692 -1.1583594083786 + Cluster -674 5 5 5 7.2 7.2 7.2 113.79 0 14.305 919310000 7 5.23071971664223 1.25786163522013E-05 Q9NSE4 Q9NSE4 Isoleucine--tRNA ligase, mitochondrial IARS2 2933 Mitochondrion matrix {ECO:0000250}. isoleucyl-tRNA aminoacylation;mitochondrial translation;tRNA aminoacylation for protein translation aminoacyl-tRNA editing activity;ATP binding;isoleucine-tRNA ligase activity;tRNA binding cytosol;mitochondrial matrix;mitochondrion Aminoacyl-tRNA biosynthesis CAGSSS syndrome Mitochondrial tRNA aminoacylation -1.02908182144165 -0.0920972153544426 1.71422159671783 1.47534263134003 1.31121897697449 0.940259099006653 1.33970510959625 0.679830491542816 -1.20253837108612 -0.155796021223068 -1.33125603199005 -0.599493265151978 -0.14604277908802 -0.343445211648941 -0.383736222982407 -1.26055335998535 -0.630602717399597 -0.285934656858444 + Cluster -674 4 4 4 18 18 18 22.977 0 27.083 2205200000 12 4.89214793135623 2E-05 Q9NP72;Q9NP72-2;Q9NP72-3 Q9NP72;Q9NP72-2;Q9NP72-3 Ras-related protein Rab-18 RAB18 2871 Plays a role in apical endocytosis/recycling. May beimplicated in transport between the plasma membrane and earlyendosomes. Plays a key role in eye and brain development andneurodegeneration. Cytoplasmic side {ECO:0000305}.; Lipid-anchor{ECO:0000305};Cell membrane {ECO:0000305} brain development;endoplasmic reticulum tubular network organization;eye development;import into nucleus;intracellular protein transport;lipid droplet organization;neutrophil degranulation;Rab protein signal transduction;small GTPase mediated signal transduction GDP binding;GTP binding;GTPase activity cytosol;endoplasmic reticulum membrane;endoplasmic reticulum tubular network;Golgi apparatus;intracellular;plasma membrane;secretory granule membrane;synapse Warburg micro syndrome COPI-independent Golgi-to-ER retrograde traffic;Neutrophil degranulation;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation -0.68928462266922 -0.0310750622302294 1.75680363178253 0.730193376541138 1.30158603191376 1.54793751239777 1.47452962398529 0.774236857891083 -0.355100154876709 -0.839337110519409 -1.17334568500519 -0.352996647357941 -0.531703770160675 -0.289611339569092 -0.609702944755554 -1.45928621292114 -0.792200267314911 -0.461643218994141 + Cluster -674 1 1 1 3.7 3.7 3.7 66.194 0 35.964 735360000 4 5.61483792737645 8.47457627118644E-06 O94842;O94842-3;O94842-2 O94842;O94842-3;O94842-2 TOX high mobility group box family member 4 TOX4 386 Component of the PTW/PP1 phosphatase complex, whichplays a role in the control of chromatin structure and cell cycleprogression during the transition from mitosis into interphase Nucleus {ECO:0000305|PubMed:20516061}.Note=Associated with chromatin. DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific chromatin;nucleus;PTW/PP1 phosphatase complex -1.3658173084259 -0.0272388700395823 1.6511367559433 1.18619894981384 1.32582592964172 1.5712081193924 0.95346599817276 0.889290809631348 -0.213534995913506 -1.30058622360229 -0.456446409225464 -0.501024842262268 -0.222594290971756 -0.333797574043274 -0.599452197551727 -1.13696992397308 -0.878368496894836 -0.541295409202576 + Cluster -674 12 11 11 42.9 40.2 40.2 36.091 0 297.47 41826000000 70 5.27240090328897 1.31578947368421E-05 Q15717;Q15717-2 Q15717;Q15717-2 ELAV-like protein 1 ELAVL1 1825 RNA-binding protein that binds to the 3'-UTR region ofmRNAs and increases their stability (PubMed:14517288,PubMed:18285462). Involved in embryonic stem cells (ESCs)differentiation: preferentially binds mRNAs that are notmethylated by N6-methyladenosine (m6A), stabilizing them,promoting ESCs differentiation (By similarity). Binds to poly-Uelements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs(PubMed:8626503, PubMed:17632515, PubMed:18285462,PubMed:23519412, PubMed:14731398). Binds avidly to the AU-richelement in FOS and IL3/interleukin-3 mRNAs. In the case of the FOSAU-rich element, binds to a core element of 27 nucleotides thatcontain AUUUA, AUUUUA, and AUUUUUA motifs. Binds preferentially tothe 5'-UUUU[AG]UUU-3' motif in vitro (PubMed:8626503). WithZNF385A, binds the 3'-UTR of p53/TP53 mRNA to control theirnuclear export induced by CDKN2A. Hence, may regulate p53/TP53expression and mediate in part the CDKN2A anti-proliferativeactivity. May also bind with ZNF385A the CCNB1 mRNA (Bysimilarity). Increases the stability of the leptin mRNA harboringan AU-rich element (ARE) in its 3' UTR (PubMed:29180010) Cytoplasm {ECO:0000269|PubMed:14517288,ECO:0000269|PubMed:17632515, ECO:0000269|PubMed:18285462,ECO:0000269|PubMed:19029303}. Nucleus{ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:17632515,ECO:0000269|PubMed:18285462}. Cytoplasm, Stress granule{ECO:0000250|UniProtKB:P70372}. Note=Translocates into thecytoplasm following phosphorylation by MAPKAPK2 (PubMed:14517288).Likewise, phosphorylation by PRKCD promotes translocation from thenucleus into the cytoplasm, where it is associated with free andcytoskeleton-bound polysomes (PubMed:18285462).Localizes to thestress granules in the presence of PLEKHN1 (By similarity).{ECO:0000250|UniProtKB:P70372, ECO:0000269|PubMed:14517288,ECO:0000269|PubMed:18285462}. 3'-UTR-mediated mRNA stabilization;mRNA splicing, via spliceosome;mRNA stabilization;multicellular organism development;negative regulation of gene silencing by miRNA;positive regulation of translation;protein homooligomerization;regulation of mRNA stability;regulation of stem cell population maintenance AU-rich element binding;double-stranded RNA binding;miRNA binding;mRNA 3'-UTR AU-rich region binding;mRNA 3'-UTR binding;mRNA binding;protein homodimerization activity;protein kinase binding;RNA binding cytoplasm;cytoplasmic stress granule;cytosol;glutamatergic synapse;membrane;nucleoplasm;nucleus;postsynapse;ribonucleoprotein complex AMPK signaling pathway;IL-17 signaling pathway HuR (ELAVL1) binds and stabilizes mRNA;mRNA Splicing - Major Pathway IGF2BP1 complex -0.715250432491302 0.585802972316742 1.58211970329285 0.658205687999725 1.76884973049164 1.30738759040833 0.770370602607727 0.941070973873138 -1.00899219512939 -1.13715469837189 -1.22948145866394 -0.524679720401764 0.0957993566989899 -0.061442457139492 -0.161902502179146 -0.992241740226746 -0.992241740226746 -0.886219680309296 + Cluster -674 3 3 3 11.9 11.9 11.9 50.381 0 180.03 785390000 7 3.91380400203966 0.000177897574123989 Q5T3I0;Q5T3I0-3;Q5T3I0-2 Q5T3I0;Q5T3I0-3 G patch domain-containing protein 4 GPATCH4 1938 RNA binding -0.942665040493011 -0.467205792665482 1.78180515766144 1.11285400390625 0.77352511882782 1.34716641902924 0.569329440593719 1.34716641902924 -0.586290001869202 -0.978978037834167 -1.86306798458099 -0.80641496181488 0.132496774196625 0.569329440593719 -0.317060768604279 -0.586290001869202 -0.289031565189362 -0.796668589115143 + Cluster -674 5 5 5 14.8 14.8 14.8 57.293 0 63.364 5271900000 14 4.86283776115 1.94174757281553E-05 Q01581;P54868;P54868-3;P54868-2 Q01581 Hydroxymethylglutaryl-CoA synthase, cytoplasmic HMGCS1 1484 This enzyme condenses acetyl-CoA with acetoacetyl-CoA toform HMG-CoA, which is the substrate for HMG-CoA reductase. Cytoplasm.;Mitochondrion. acetyl-CoA metabolic process;brain development;cellular response to cholesterol;cellular response to follicle-stimulating hormone stimulus;cellular response to low-density lipoprotein particle stimulus;cholesterol biosynthetic process;farnesyl diphosphate biosynthetic process, mevalonate pathway;ketone body biosynthetic process;lipid metabolic process;liver development;male gonad development;regulation of cholesterol biosynthetic process;regulation of lipid metabolic process;response to drug;response to low light intensity stimulus;response to purine-containing compound;response to tellurium ion;response to vitamin E drug binding;hydroxymethylglutaryl-CoA synthase activity;isomerase activity;organic acid binding;protein homodimerization activity cytoplasm;cytosol;mitochondrial matrix;mitochondrion Butanoate metabolism;Metabolic pathways;PPAR signaling pathway;Synthesis and degradation of ketone bodies;Terpenoid backbone biosynthesis;Valine, leucine and isoleucine degradation HMG-CoA synthase deficiency Activation of gene expression by SREBF (SREBP);Cholesterol biosynthesis;PPARA activates gene expression;Synthesis of Ketone Bodies -0.383546620607376 1.02376127243042 1.34771537780762 0.38862869143486 1.5889003276825 1.23559522628784 1.14670944213867 0.80012571811676 -0.383546620607376 -1.19225776195526 -0.82350754737854 -0.879854202270508 0.382841676473618 -0.343846410512924 -0.325825840234756 -1.45449423789978 -0.889527976512909 -1.2378705739975 + Cluster -674 3 3 2 4.7 4.7 3 92.619 0 7.7152 1078000000 4 3.51581784418544 0.000412121212121212 P21127;Q9UQ88;P21127-4;P21127-5;P21127-10;P21127-6;Q9UQ88-4;P21127-8;Q9UQ88-3;P21127-3;Q9UQ88-10;P21127-12;Q9UQ88-2;P21127-2;P21127-9;Q9UQ88-5;Q9UQ88-9 P21127;Q9UQ88;P21127-4;P21127-5;P21127-10;P21127-6;Q9UQ88-4;P21127-8;Q9UQ88-3;P21127-3;Q9UQ88-10;P21127-12;Q9UQ88-2;P21127-2;P21127-9;Q9UQ88-5;Q9UQ88-9 Cyclin-dependent kinase 11B;Cyclin-dependent kinase 11A CDK11B;CDK11A 751 Appears to play multiple roles in cell cycleprogression, cytokinesis and apoptosis. The p110 isoforms havebeen suggested to be involved in pre-mRNA splicing, potentially byphosphorylating the splicing protein SFRS7. The p58 isoform mayact as a negative regulator of normal cell cycle progression;Plays multiple roles in cell cycle progression,cytokinesis and apoptosis. Involved in pre-mRNA splicing in akinase activity-dependent manner. Isoform 7 may act as a negativeregulator of normal cell cycle progression Cytoplasm. Nucleus. apoptotic process;cell proliferation;mitotic cell cycle;protein phosphorylation;regulation of cell growth;regulation of mRNA processing;regulation of transcription, DNA-templated ATP binding;cyclin-dependent protein serine/threonine kinase activity;protein kinase activity;protein serine/threonine kinase activity;RNA binding cytoplasm;nucleus Recruitment of mitotic centrosome proteins and complexes Parvulin-associated pre-rRNP complex -0.681555807590485 0.272798269987106 1.64770424365997 1.05002212524414 1.76971662044525 1.22814381122589 0.990134716033936 0.708529710769653 -0.490532249212265 -1.01463449001312 -0.796534359455109 -0.321976542472839 -0.418814688920975 -0.171427264809608 -0.203461021184921 -1.17154765129089 -1.09279632568359 -1.30376899242401 + Cluster -674 20 20 20 19.6 19.6 19.6 152.78 0 319.5 16968000000 71 4.8831104563818 1.98019801980198E-05 P52701;P52701-3;P52701-4;P52701-2 P52701;P52701-3;P52701-4;P52701-2 DNA mismatch repair protein Msh6 MSH6 1183 Component of the post-replicative DNA mismatch repairsystem (MMR). Heterodimerizes with MSH2 to form MutS alpha, whichbinds to DNA mismatches thereby initiating DNA repair. When bound,MutS alpha bends the DNA helix and shields approximately 20 basepairs, and recognizes single base mismatches and dinucleotideinsertion-deletion loops (IDL) in the DNA. After mismatch binding,forms a ternary complex with the MutL alpha heterodimer, which isthought to be responsible for directing the downstream MMR events,including strand discrimination, excision, and resynthesis. ATPbinding and hydrolysis play a pivotal role in mismatch repairfunctions. The ATPase activity associated with MutS alpharegulates binding similar to a molecular switch: mismatched DNAprovokes ADP-->ATP exchange, resulting in a discernibleconformational transition that converts MutS alpha into a slidingclamp capable of hydrolysis-independent diffusion along the DNAbackbone. This transition is crucial for mismatch repair. MutSalpha may also play a role in DNA homologous recombination repair.Recruited on chromatin in G1 and early S phase via its PWWP domainthat specifically binds trimethylated 'Lys-36' of histone H3(H3K36me3): early recruitment to chromatin to be replicatedallowing a quick identification of mismatch repair to initiate theDNA mismatch repair reaction. Nucleus {ECO:0000269|PubMed:23622243}.Chromosome {ECO:0000269|PubMed:23622243}. Note=Associates withH3K36me3 via its PWWP domain. determination of adult lifespan;DNA repair;interstrand cross-link repair;intrinsic apoptotic signaling pathway;intrinsic apoptotic signaling pathway in response to DNA damage;isotype switching;maintenance of DNA repeat elements;meiotic mismatch repair;mismatch repair;mitotic G2 DNA damage checkpoint;negative regulation of DNA endoreduplication;negative regulation of DNA recombination;positive regulation of helicase activity;positive regulation of isotype switching;pyrimidine dimer repair;replication fork arrest;response to UV;somatic hypermutation of immunoglobulin genes;somatic recombination of immunoglobulin gene segments;viral process ATP binding;chromatin binding;damaged DNA binding;DNA-dependent ATPase activity;enzyme binding;four-way junction DNA binding;guanine/thymine mispair binding;methylated histone binding;mismatched DNA binding cytosol;Golgi apparatus;intracellular membrane-bounded organelle;mismatch repair complex;MutSalpha complex;nuclear chromatin;nucleoplasm;nucleus Colorectal cancer;Mismatch repair;Pathways in cancer;Platinum drug resistance Colorectal cancer;Mismatch repair deficiency Defective Mismatch Repair Associated With MSH2;Defective Mismatch Repair Associated With MSH6;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) BASC (Ab 80) complex (BRCA1-associated genome surveillance complex);BASC (Ab C-20) complex (BRCA1-associated genome surveillance complex);BASC complex (BRCA1-associated genome surveillance complex);BRCA1-BARD1-BACH1-DNA damage complex I;GCN5-TRRAP histone acetyltransferase complex;MSH2/6-BLM-p53-RAD51 complex;MSH2-MSH6 complex;MSH2-MSH6-PMS1-MLH1 complex;MSH2-MSH6-PMS2-MLH1 complex;MutS-alpha-PK-zeta complex;PCNA-MSH2-MSH6 complex;PCNA-MutS-alpha-MutL-alpha-DNA complex -1.45240223407745 -0.400989979505539 1.61580920219421 2.11735916137695 1.21258282661438 0.534362375736237 0.907831132411957 0.686738193035126 -0.214941635727882 -0.49135810136795 -1.02033710479736 -0.316966116428375 -0.065007820725441 0.108880653977394 -0.344181030988693 -1.28244113922119 -0.569742619991302 -1.02519595623016 + Cluster -674 2 2 2 3.6 3.6 3.6 83.308 0 9.7129 1405400000 4 3.64432911834826 0.000331838565022422 P48449;P48449-2;P48449-3 P48449;P48449-2;P48449-3 Lanosterol synthase LSS 1073 Catalyzes the cyclization of (S)-2,3 oxidosqualene tolanosterol, a reaction that forms the sterol nucleus. Through theproduction of lanosterol may regulate lens protein aggregation andincrease transparency. Endoplasmic reticulum membrane{ECO:0000269|PubMed:14766201, ECO:0000269|PubMed:15525992};Peripheral membrane protein {ECO:0000269|PubMed:14766201,ECO:0000269|PubMed:15525992}. cholesterol biosynthetic process;regulation of cholesterol biosynthetic process;regulation of protein stability;steroid biosynthetic process lanosterol synthase activity endoplasmic reticulum membrane;lipid droplet;membrane Metabolic pathways;Steroid biosynthesis Cataract Activation of gene expression by SREBF (SREBP);Cholesterol biosynthesis -1.07623469829559 0.158151835203171 1.49745833873749 1.26038157939911 0.586524486541748 1.80005121231079 0.569591641426086 1.3238000869751 -0.597600519657135 -1.95573616027832 -0.590719938278198 0.0472743771970272 -0.245752930641174 -0.685016989707947 -0.263424187898636 -0.438945204019547 -0.825262606143951 -0.564540326595306 + Cluster -674 3 3 3 16.2 16.2 16.2 26.183 0 43.885 16322000000 26 3.68515273162562 0.000313817330210773 Q15631;Q15631-2 Q15631 Translin TSN 1818 DNA-binding protein that specifically recognizesconsensus sequences at the breakpoint junctions in chromosomaltranslocations, mostly involving immunoglobulin (Ig)/T-cellreceptor gene segments. Seems to recognize single-stranded DNAends generated by staggered breaks occurring at recombination hotspots.Exhibits both single-stranded and double-strandedendoribonuclease activity. May act as an activator of RNA-inducedsilencing complex (RISC) by facilitating endonucleolytic cleavageof the siRNA passenger strand. Cytoplasm {ECO:0000269|PubMed:11801738}.Nucleus {ECO:0000269|PubMed:11801738}. DNA recombination DNA binding;endoribonuclease activity;identical protein binding;mRNA binding;sequence-specific DNA binding;single-stranded DNA binding cytoplasm;cytosol;nucleus Small interfering RNA (siRNA) biogenesis -0.0415534302592278 0.0327884405851364 0.86721283197403 0.786892354488373 0.325849145650864 1.94061779975891 1.42345941066742 1.42345941066742 -0.535378992557526 -2.00935053825378 -0.95782470703125 0.326049029827118 -0.791623115539551 -0.71602737903595 -0.638687133789063 -0.250550210475922 -0.735616862773895 -0.449715912342072 + Cluster -674 22 22 21 45 45 45 42.331 0 323.31 128100000000 210 3.40631971909994 0.000511194029850746 P38159;P38159-2;Q96E39;P38159-3;O75526;Q8N7X1 P38159;P38159-2;Q96E39 RNA-binding motif protein, X chromosome;RNA-binding motif protein, X chromosome, N-terminally processed;RNA binding motif protein, X-linked-like-1 RBMX;RBMXL1 969 acts additively with TRA2B to promote exon 7inclusion of the survival motor neuron SMN2. Represses thesplicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in asingle-stranded conformation; maythus be involved in tumor suppression. When associated with SAFB,binds to and stimulates transcription from the SREBF1 promoter.Associates with nascent mRNAs transcribed by RNA polymerase II.Component of the supraspliceosome complex that regulates pre-mRNAalternative splice site selection. Can either activate or suppressexon inclusion; probably binds RNA as a homodimer.Binds non-specifically to pre-mRNAs. Plays also a role in thecytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomainsand the release of TNFR1 exosome-like vesicles to theextracellular compartment.;RNA-binding protein that plays several role in theregulation of pre- and post-transcriptional processes. Implicatedin tissue-specific regulation of gene transcription andalternative splicing of several pre-mRNAs. Binds to and stimulatestranscription from the tumor suppressor TXNIP gene promoter;RNA-binding protein which may be involved in pre-mRNAsplicing. Nucleus {ECO:0000250}.;Nucleus {ECO:0000269|PubMed:10958650}.;Nucleus {ECO:0000269|PubMed:19282290,ECO:0000269|PubMed:21327109}. Note=Component of ribonucleosomes.Localizes in numerous small granules in the nucleus. cellular response to interleukin-1;membrane protein ectodomain proteolysis;mRNA processing;mRNA splice site selection;mRNA splicing, via spliceosome;negative regulation of mRNA splicing, via spliceosome;osteoblast differentiation;positive regulation of mRNA splicing, via spliceosome;positive regulation of transcription by RNA polymerase II;protein complex oligomerization;protein homooligomerization;regulation of alternative mRNA splicing, via spliceosome;RNA metabolic process;RNA splicing;transcription by RNA polymerase II chromatin binding;identical protein binding;mRNA binding;protein domain specific binding;RNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;single-stranded RNA binding catalytic step 2 spliceosome;commitment complex;extracellular exosome;extracellular space;membrane;nuclear euchromatin;nucleoplasm;nucleus;ribonucleoprotein complex;spliceosomal complex;supraspliceosomal complex Spliceosome Syndromic X-linked mental retardation mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA C complex spliceosome;CDC5L complex -0.532545149326324 -0.0221890229731798 1.09313881397247 1.02875769138336 0.827663242816925 1.47842693328857 0.998650252819061 1.24967575073242 -0.159837320446968 -1.85515773296356 -0.33620685338974 1.16362857818604 -0.91811466217041 -0.936912536621094 -0.843957960605621 -0.76343846321106 -0.73579078912735 -0.73579078912735 + Cluster -674 3 3 3 6.9 6.9 6.9 52.998 0 10.111 1013600000 6 3.29291385539714 0.000597938144329897 Q05D32;Q05D32-2 Q05D32;Q05D32-2 CTD small phosphatase-like protein 2 CTDSPL2 1522 Probable phosphatase. negative regulation of BMP signaling pathway;positive regulation of protein export from nucleus phosphoprotein phosphatase activity nucleoplasm -1.78376436233521 1.07932734489441 1.35218465328217 0.770463824272156 1.07932734489441 1.68239092826843 1.2645149230957 0.682794094085693 -0.762452125549316 -0.709017693996429 -0.850121855735779 -0.297945320606232 -0.531752049922943 -0.531752049922943 -0.709017693996429 -0.762452125549316 -0.210275560617447 -0.762452125549316 + Cluster -674 49 49 49 44.6 44.6 44.6 140.96 0 323.31 321020000000 491 3.11312628644358 0.000890282131661442 Q08211;Q08211-2 Q08211 ATP-dependent RNA helicase A DHX9 1546 Multifunctional ATP-dependent nucleic acid helicase thatunwinds DNA and RNA in a 3' to 5' direction and that playsimportant roles in many processes, such as DNA replication,transcriptional activation, post-transcriptional RNA regulation,mRNA translation and RNA-mediated gene silencing (PubMed:9111062,PubMed:11416126, PubMed:12711669, PubMed:15355351,PubMed:16680162, PubMed:17531811, PubMed:20669935,PubMed:21561811, PubMed:24049074, PubMed:25062910,PubMed:24990949, PubMed:28221134). Requires a 3'-single-strandedtail as entry site for acid nuclei unwinding activities as well asthe binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerousnucleic acid substrates such as double-stranded (ds) DNA and RNA,DNA:RNA hybrids, DNA and RNA forks composed of either partiallycomplementary DNA duplexes or DNA:RNA hybrids, respectively, andalso DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes(PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA,single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containingRNA (PubMed:9111062, PubMed:10198287). Binds also to circulardsDNA or dsRNA of either linear and/or circular forms andstimulates the relaxation of supercoiled DNAs catalyzed bytopoisomerase TOP2A (PubMed:12711669). Plays a role in DNAreplication at origins of replication and cell cycle progression(PubMed:24990949). Plays a role as a transcriptional coactivatoracting as a bridging factor between polymerase II holoenzyme andtranscription factors or cofactors, such as BRCA1, CREBBP, RELAand SMN1 (PubMed:11149922, PubMed:9323138, PubMed:9662397,PubMed:11038348, PubMed:11416126, PubMed:15355351,PubMed:28221134). Binds to the CDKN2A promoter (PubMed:11038348).Plays several roles in post-transcriptional regulation of geneexpression (PubMed:28221134, PubMed:28355180). In cooperation withNUP98, promotes pre-mRNA alternative splicing activities of asubset of genes (PubMed:11402034, PubMed:16680162,PubMed:28221134, PubMed:28355180). As component of a large PERcomplex, is involved in the negative regulation of 3'transcriptional termination of circadian target genes such as PER1and NR1D1 and the control of the circadian rhythms (Bysimilarity). Acts also as a nuclear resolvase that is able to bindand neutralize harmful massive secondary double-stranded RNAstructures formed by inverted-repeat Alu retrotransposon elementsthat are inserted and transcribed as parts of genes during theprocess of gene transposition (PubMed:28355180). Involved in thepositive regulation of nuclear export of constitutive transportelement (CTE)-containing unspliced mRNA (PubMed:9162007,PubMed:10924507, PubMed:11402034). Component of the coding regiondeterminant (CRD)-mediated complex that promotes cytoplasmic MYCmRNA stability (PubMed:19029303). Plays a role in mRNA translation(PubMed:28355180). Positively regulates translation of selectedmRNAs through its binding to post-transcriptional control element(PCE) in the 5'-untranslated region (UTR) (PubMed:16680162).Involved with LARP6 in the translation stimulation of type Icollagen mRNAs for CO1A1 and CO1A2 through binding of a specificstem-loop structure in their 5'-UTRs (PubMed:22190748). StimulatesLIN28A-dependent mRNA translation probably by facilitatingribonucleoprotein remodeling during the process of translation(PubMed:21247876). Plays also a role as a small interfering(siRNA)-loading factor involved in the RNA-induced silencingcomplex (RISC) loading complex (RLC) assembly, and hence functionsin the RISC-mediated gene silencing process (PubMed:17531811).Binds preferentially to short double-stranded RNA, such as thoseproduced during rotavirus intestinal infection (PubMed:28636595).This interaction may mediate NLRP9 inflammasome activation andtrigger inflammatory response, including IL18 release andpyroptosis (PubMed:28636595). Finally, mediates the attachment ofheterogeneous nuclear ribonucleoproteins (hnRNPs) to actinfilaments in the nucleus (PubMed:11687588) Nucleus {ECO:0000269|PubMed:10198287,ECO:0000269|PubMed:10207077, ECO:0000269|PubMed:11687588,ECO:0000269|PubMed:16375861, ECO:0000269|PubMed:17303075,ECO:0000269|PubMed:9162007}. Nucleus, nucleoplasm{ECO:0000269|PubMed:28221134}. Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. Cytoplasm{ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10207077,ECO:0000269|PubMed:16375861, ECO:0000269|PubMed:17289661,ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20696886,ECO:0000269|PubMed:8690889, ECO:0000269|PubMed:9162007}.Cytoplasm, cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:14654843, ECO:0000269|PubMed:17498979}.Note=Nucleoplasmic shuttling protein (PubMed:10198287,PubMed:16375861, PubMed:10207077, PubMed:9162007). Its nuclearimport involves the nucleocytoplasmic transport receptor Importinalpha/Importin beta receptor pathway in a Ran-dependent manner(PubMed:16375861). In interphase, localizes in nuclear stressgranules and at perichromatin fibrils and in cytoplasmicribonucleoprotein granules (PubMed:10198287). Colocalizes with WRNand H2AFX at centrosomes in a microtubule-dependent mannerfollowing DNA damaging agent treatment (PubMed:17498979). Excludedfrom the mitotic nucleus as early as prophase and re-entered thenucleus at telophase (PubMed:10198287). Recruited in diffuse anddiscrete intranuclear foci (GLFG-body) in a NUP98-dependent manner(PubMed:28221134). Colocalizes with SP7 in the nucleus(PubMed:17303075). Colocalizes with ACTB at nuclear actinfilaments inside the nucleus or at the nuclear pore(PubMed:11687588). Colocalizes with HNRNPC at nuclearribonucleoprotein complex proteins in the nucleus(PubMed:11687588). Localized in cytoplasmic mRNP granulescontaining untranslated mRNAs (PubMed:17289661).{ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10207077,ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:16375861,ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:17303075,ECO:0000269|PubMed:17498979, ECO:0000269|PubMed:28221134,ECO:0000269|PubMed:9162007}. alternative mRNA splicing, via spliceosome;cellular response to exogenous dsRNA;cellular response to tumor necrosis factor;CRD-mediated mRNA stabilization;DNA duplex unwinding;DNA replication;DNA-templated transcription, termination;DNA-templated viral transcription;G-quadruplex DNA unwinding;inflammatory response;innate immune response;mRNA splicing, via spliceosome;mRNA transport;osteoblast differentiation;positive regulation of cytoplasmic translation;positive regulation of DNA repair;positive regulation of DNA replication;positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity;positive regulation of fibroblast proliferation;positive regulation of gene silencing by miRNA;positive regulation of inflammatory response;positive regulation of innate immune response;positive regulation of interferon-alpha secretion;positive regulation of interferon-beta secretion;positive regulation of interleukin-18 production;positive regulation of interleukin-6 secretion;positive regulation of NF-kappaB transcription factor activity;positive regulation of polysome binding;positive regulation of response to cytokine stimulus;positive regulation of RNA export from nucleus;positive regulation of transcription by RNA polymerase II;positive regulation of tumor necrosis factor secretion;positive regulation of type I interferon production;positive regulation of viral transcription;positive regulation of viral translation;protein localization to cytoplasmic stress granule;pyroptosis;regulation of cytoplasmic translation;regulation of defense response to virus by host;regulation of mRNA processing;regulation of transcription by RNA polymerase II;rhythmic process;RNA secondary structure unwinding;small RNA loading onto RISC;targeting of mRNA for destruction involved in RNA interference ATP binding;ATPase activity;ATP-dependent 3'-5' DNA helicase activity;ATP-dependent 3'-5' DNA/RNA helicase activity;ATP-dependent 3'-5' RNA helicase activity;ATP-dependent DNA helicase activity;ATP-dependent RNA helicase activity;chromatin DNA binding;DNA binding;DNA replication origin binding;double-stranded DNA binding;double-stranded RNA binding;importin-alpha family protein binding;metal ion binding;mRNA binding;nucleoside-triphosphatase activity;nucleoside-triphosphate diphosphatase activity;polysome binding;promoter-specific chromatin binding;regulatory region RNA binding;RISC complex binding;RNA binding;RNA helicase activity;RNA polymerase binding;RNA polymerase II complex binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II transcription factor binding;RNA stem-loop binding;sequence-specific mRNA binding;single-stranded DNA binding;single-stranded DNA-dependent ATP-dependent 3'-5' DNA helicase activity;single-stranded RNA binding;siRNA binding;transcription coactivator activity;transcription coregulator activity;triplex DNA binding actin cytoskeleton;centrosome;CRD-mediated mRNA stability complex;cytoplasm;cytoplasmic ribonucleoprotein granule;cytosol;membrane;micro-ribonucleoprotein complex;nuclear body;nuclear stress granule;nucleolus;nucleoplasm;nucleus;perichromatin fibrils;polysomal ribosome;polysome;protein-containing complex;ribonucleoprotein complex;RISC-loading complex DEx/H-box helicases activate type I IFN and inflammatory cytokines production;mRNA Splicing - Major Pathway;RIP-mediated NFkB activation via ZBP1 DGCR8 multiprotein complex;DHX9-ADAR-vigilin-DNA-PK-Ku antigen complex;GammaH2AFX-NDHII-Ku70-DNA complex;IGF2BP1 complex;Nop56p-associated pre-rRNA complex;SMN-PolII-RHA complex;Spliceosome;STAT6-p100-RHA complex;Toposome -1.06969594955444 0.335570424795151 1.0414057970047 1.13226199150085 0.828445434570313 1.3788982629776 0.81488299369812 1.26684033870697 -0.139514327049255 -2.00975632667542 -1.58431696891785 0.380611270666122 -0.405468851327896 0.10119890421629 0.0570789575576782 -0.723182678222656 -0.459509521722794 -0.945749819278717 + Cluster -674 6 6 6 25.3 25.3 25.3 20.252 0 51.365 63600000000 59 3.05906941858099 0.000968229954614221 P62913;P62913-2 P62913;P62913-2 60S ribosomal protein L11 RPL11 1383 Component of the ribosome, a large ribonucleoproteincomplex responsible for the synthesis of proteins in the cell. Thesmall ribosomal subunit (SSU) binds messenger RNAs (mRNAs) andtranslates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) containsthe ribosomal catalytic site termed the peptidyl transferasecenter (PTC), which catalyzes the formation of peptide bonds,thereby polymerizing the amino acids delivered by tRNAs into apolypeptide chain. The nascent polypeptides leave the ribosomethrough a tunnel in the LSU and interact with protein factors thatfunction in enzymatic processing, targeting, and the membraneinsertion of nascent chains at the exit of the ribosomal tunnel.As part of the 5S RNP/5S ribonucleoprotein particle it is anessential component of the LSU, required for its formation and thematuration of rRNAs (PubMed:19061985, PubMed:12962325,PubMed:24120868). It also couples ribosome biogenesis to p53/TP53activation. As part of the 5S RNP it accumulates in thenucleoplasm and inhibits MDM2, when ribosome biogenesis isperturbed, mediating the stabilization and the activation of TP53(PubMed:24120868). Promotes nucleolar location of PML (Bysimilarity). Nucleus, nucleolus{ECO:0000269|PubMed:27829214}. Cytoplasm{ECO:0000250|UniProtKB:Q9CXW4}. cytoplasmic translation;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;negative regulation of protein neddylation;negative regulation of ubiquitin protein ligase activity;negative regulation of ubiquitin-dependent protein catabolic process;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;positive regulation of gene expression;positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator;positive regulation of protein binding;protein localization to nucleus;protein stabilization;protein targeting;regulation of signal transduction by p53 class mediator;ribosomal large subunit assembly;ribosomal large subunit biogenesis;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation 5S rRNA binding;RNA binding;structural constituent of ribosome;ubiquitin ligase inhibitor activity;ubiquitin protein ligase binding cytoplasm;cytosol;cytosolic large ribosomal subunit;extracellular exosome;membrane;nucleolus;nucleoplasm;polysomal ribosome;protein-containing complex Ribosome Diamond-Blackfan anemia Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle) -1.39136123657227 0.227770045399666 1.01331031322479 0.324828058481216 1.2864875793457 1.77369070053101 1.26466453075409 1.09528577327728 -0.382184892892838 -1.63955652713776 -0.875950515270233 0.180075258016586 -0.550251185894012 -0.447453796863556 -0.800582051277161 -0.714224278926849 0.497966349124908 -0.862514138221741 + Cluster -674 7 7 7 13.8 13.8 13.8 80.954 0 78.601 7836400000 23 3.06356299233238 0.000954476479514416 P35611;P35611-2;P35611-4;P35611-6;P35611-3;P35611-5 P35611;P35611-2;P35611-4;P35611-6;P35611-3;P35611-5 Alpha-adducin ADD1 938 Membrane-cytoskeleton-associated protein that promotesthe assembly of the spectrin-actin network. Binds to calmodulin. Cytoplasmic side.;Cytoplasm, cytoskeleton. Cell membrane;Peripheral membrane protein actin cytoskeleton organization;actin filament bundle assembly;barbed-end actin filament capping;cell morphogenesis;cell volume homeostasis;cellular response to calcium ion;erythrocyte differentiation;hemoglobin metabolic process;homeostasis of number of cells within a tissue;in utero embryonic development;IRE1-mediated unfolded protein response;multicellular organism growth;positive regulation of adherens junction organization;positive regulation of establishment of endothelial barrier;positive regulation of protein binding;transmembrane transport actin binding;actin filament binding;cadherin binding;calmodulin binding;protein heterodimerization activity;protein homodimerization activity;RNA binding;spectrin binding;structural molecule activity;transcription factor binding cell-cell adherens junction;cytoplasm;cytoskeleton;cytosol;F-actin capping protein complex;focal adhesion;nuclear body;nucleoplasm;nucleus;plasma membrane;plasma membrane raft;postsynaptic density Caspase-mediated cleavage of cytoskeletal proteins;Miscellaneous transport and binding events;XBP1(S) activates chaperone genes -1.48125958442688 -0.0608292259275913 1.38862609863281 0.769140601158142 1.0237330198288 1.50139439105988 1.13650131225586 1.50139439105988 -0.537719488143921 -1.36849129199982 -0.424951195716858 -0.859892666339874 -1.36849129199982 -0.169279277324677 0.0519390888512135 -0.537719488143921 -0.282047599554062 -0.282047599554062 + Cluster -674 32 32 1 47.2 47.2 1.8 62.656 0 323.31 356310000000 430 4.65376155903062 4.149377593361E-05 O60506-3;O60506-4;O60506-5 O60506-3;O60506-4;O60506-5 Heterogeneous nuclear ribonucleoprotein Q SYNCRIP 272 seems not to beessential for GAIT complex function.;Heterogenous nuclear ribonucleoprotein (hnRNP)implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1,isoform 2 and isoform 3 are associated in vitro with pre-mRNA,splicing intermediates and mature mRNA protein complexes. Isoform1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of theAPOB mRNA editosome complex and may modulate thepostranscriptional C to U RNA-editing of the APOB mRNA througheither by binding to A1CF (APOBEC1 complementation factor), toAPOBEC1 or to RNA itself. May be involved in translationallycoupled mRNA turnover. Implicated with other RNA-binding proteinsin the cytoplasmic deadenylation/translational and decay interplayof the FOS mRNA mediated by the major coding-region determinant ofinstability (mCRD) domain. Interacts in vitro preferentially withpoly(A) and poly(U) RNA sequences. Isoform 3 may be involved incytoplasmic vesicle-based mRNA transport through interaction withsynaptotagmins. Component of the GAIT (gamma interferon-activatedinhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition ininflammation processes. Upon interferon-gamma activation assemblesinto the GAIT complex which binds to stem loop-containing GAITelements in the 3'-UTR of diverse inflammatory mRNAs (such asceruplasmin) and suppresses their translation Cytoplasm {ECO:0000269|PubMed:11574476,ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:19029303}.Microsome {ECO:0000250|UniProtKB:Q7TMK9}. Endoplasmic reticulum{ECO:0000250}. Nucleus {ECO:0000250|UniProtKB:Q7TMK9}. Note=Thetyrosine phosphorylated form bound to RNA is found in microsomes(By similarity). Localized in cytoplasmic mRNP granules containinguntranslated mRNAs (By similarity). {ECO:0000250|UniProtKB:O43390,ECO:0000250|UniProtKB:Q7TMK9}.Isoform 1: Nucleus, nucleoplasm{ECO:0000250|UniProtKB:Q7TMK9}. Note=Expressed predominantly inthe nucleoplasm. {ECO:0000250|UniProtKB:Q7TMK9}.Isoform 2: Nucleus, nucleoplasm{ECO:0000250|UniProtKB:Q7TMK9}. Note=Expressed predominantly inthe nucleoplasm. {ECO:0000250|UniProtKB:Q7TMK9}.Isoform 3: Nucleus, nucleoplasm{ECO:0000250|UniProtKB:Q7TMK9}. Note=Expressed predominantly inthe nucleoplasm. {ECO:0000250|UniProtKB:Q7TMK9}. cellular response to interferon-gamma;CRD-mediated mRNA stabilization;mRNA splicing, via spliceosome;negative regulation of translation;osteoblast differentiation;RNA processing;RNA splicing;viral process mRNA 5'-UTR binding;mRNA binding;poly(A) binding;RNA binding catalytic step 2 spliceosome;CRD-mediated mRNA stability complex;endoplasmic reticulum;GAIT complex;histone pre-mRNA 3'end processing complex;membrane;nucleoplasm;nucleus;ribonucleoprotein complex C complex spliceosome;GAIT complex;IGF2BP1 complex;Multiprotein complex (mRNA turnover) -1.29436564445496 0.290744215250015 1.61306238174438 0.113488011062145 0.911573648452759 2.0531313419342 1.11960744857788 0.767691493034363 -1.1415753364563 -1.42547655105591 -0.986251890659332 -0.199143186211586 -0.986251890659332 -0.144110813736916 -0.199143186211586 -0.584855377674103 0.113488011062145 -0.0216125752776861 + Cluster -674 29 22 22 22.7 18.9 18.9 174.38 0 247.44 55123000000 119 3.04506955974475 0.000992537313432836 P11388;P11388-2;P11388-3;P11388-4 P11388;P11388-2;P11388-3;P11388-4 DNA topoisomerase 2-alpha TOP2A 625 Control of topological states of DNA by transientbreakage and subsequent rejoining of DNA strands. Topoisomerase IImakes double-strand breaks. Essential during mitosis and meiosisfor proper segregation of daughter chromosomes. May play a role inregulating the period length of ARNTL/BMAL1 transcriptionaloscillation (By similarity). Cytoplasm {ECO:0000269|PubMed:22013166}.Nucleus, nucleoplasm {ECO:0000269|PubMed:22013166}. Note=Generallylocated in the nucleoplasm. apoptotic chromosome condensation;cellular response to DNA damage stimulus;chromosome segregation;DNA ligation;DNA topological change;embryonic cleavage;female meiotic nuclear division;hematopoietic progenitor cell differentiation;mitotic DNA integrity checkpoint;negative regulation of DNA duplex unwinding;positive regulation of apoptotic process;positive regulation of single stranded viral RNA replication via double stranded DNA intermediate;positive regulation of transcription by RNA polymerase II;regulation of circadian rhythm;resolution of meiotic recombination intermediates;rhythmic process;sister chromatid segregation ATP binding;chromatin binding;DNA binding;DNA binding, bending;DNA topoisomerase type II (ATP-hydrolyzing) activity;DNA-dependent ATPase activity;drug binding;enzyme binding;histone deacetylase binding;magnesium ion binding;protein C-terminus binding;protein heterodimerization activity;protein homodimerization activity;protein kinase C binding;RNA binding;ubiquitin binding condensed chromosome;cytoplasm;DNA topoisomerase complex (ATP-hydrolyzing);nucleolus;nucleoplasm;nucleus;protein-containing complex;ribonucleoprotein complex;viral integration complex Platinum drug resistance Aclarubicin;Aldoxorubicin;Amonafide;Amrubicin;Amsacrine;Becatecarin;Berubicin hydrochloride;Crisnatol mesylate;Daunorubicin;Dexrazoxane;Doxorubicin;Elsamitrucin;Epirubicin;Etoposide;Fostriecin sodium;Idarubicin;Idronoxil;Ledoxantrone trihydrochloride;Losoxantrone hydrochloride;Menogaril;Mitindomide;Mitoxantrone;Pirarubicin;Piroxantrone hydrochloride;Pixantrone;Quarfloxin;Sobuzoxane;Teloxantrone hydrochloride;Teniposide;Tirapazamine;Topixantrone;Valrubicin;Vosaroxin;Zorubicin SUMOylation of DNA replication proteins;Transcription of E2F targets under negative control by DREAM complex CDC5L complex;CTCF-nucleophosmin-PARP-HIS-KPNA-LMNA-TOP complex;DNA synthesome complex (13 subunits);DNA synthesome complex (17 subunits);Toposome -0.628363609313965 0.71226567029953 1.3662930727005 0.0610030703246593 1.26432204246521 1.8293981552124 1.2937798500061 1.17496860027313 -0.534008324146271 -0.974090039730072 -1.0522586107254 0.10375702381134 -1.18685448169708 -0.488740891218185 -0.699997246265411 -0.927792131900787 -0.742097675800323 -0.571584522724152 + Cluster -674 24 24 24 41.4 41.4 41.4 76.715 0 282.22 52168000000 96 3.94814271277865 0.000162983425414365 P49915;P49915-2 P49915;P49915-2 GMP synthase [glutamine-hydrolyzing] GMPS 1127 Involved in the de novo synthesis of guanine nucleotideswhich are not only essential for DNA and RNA synthesis, but alsoprovide GTP, which is involved in a number of cellular processesimportant for cell division. Cytoplasm. glutamine metabolic process;GMP biosynthetic process;purine nucleobase biosynthetic process;purine ribonucleoside monophosphate biosynthetic process ATP binding;GMP synthase (glutamine-hydrolyzing) activity;GMP synthase activity;pyrophosphatase activity cytosol Drug metabolism - other enzymes;Metabolic pathways;Purine metabolism Purine ribonucleoside monophosphate biosynthesis -1.27095830440521 0.728730201721191 0.322129398584366 0.728730201721191 0.728730201721191 1.56753718852997 1.56753718852997 1.56753718852997 0.322129398584366 -0.2331722676754 -0.702495336532593 -0.2331722676754 -1.69054102897644 -0.702495336532593 -1.14074420928955 -0.832709431648254 -0.363386392593384 -0.363386392593384 + Cluster -674 42 42 42 42.5 42.5 42.5 90.583 0 323.31 803250000000 583 3.17065792154437 0.000787096774193548 Q00839;Q00839-2 Q00839;Q00839-2 Heterogeneous nuclear ribonucleoprotein U HNRNPU 1475 this binding is direct and bridges theXist RNA and the inactive chromosome X (Xi) (By similarity). Alsonegatively regulates embryonic stem cell differentiation upon LIFsignaling (By similarity). Required for embryonic development (Bysimilarity). Binds to brown fat long non-coding RNA 1 (Blnc1);DNA- and RNA-binding protein involved in severalcellular processes such as nuclear chromatin organization,telomere-length regulation, transcription, mRNA alternativesplicing and stability, Xist-mediated transcriptional silencingand mitotic cell progression (PubMed:10490622, PubMed:18082603,PubMed:19029303, PubMed:22325991, PubMed:25986610,PubMed:28622508). Plays a role in the regulation of interphaselarge-scale gene-rich chromatin organization through chromatin-associated RNAs (caRNAs) in a transcription-dependent manner, andthereby maintains genomic stability (PubMed:1324173,PubMed:8174554, PubMed:28622508). Required for the localization ofthe long non-coding Xist RNA on the inactive chromosome X (Xi) andthe subsequent initiation and maintenance of X-linkedtranscriptional gene silencing during X-inactivation (Bysimilarity). Plays a role as a RNA polymerase II (Pol II)holoenzyme transcription regulator (PubMed:8174554,PubMed:9353307, PubMed:10490622, PubMed:15711563, PubMed:19617346,PubMed:23811339). Promotes transcription initiation by directassociation with the core-TFIIH basal transcription factor complexfor the assembly of a functional pre-initiation complex with PolII in a actin-dependent manner (PubMed:10490622, PubMed:15711563).Blocks Pol II transcription elongation activity by inhibiting theC-terminal domain (CTD) phosphorylation of Pol II and dissociatesfrom Pol II pre-initiation complex prior to productivetranscription elongation (PubMed:10490622). Positively regulatesCBX5-induced transcriptional gene silencing and retention of CBX5in the nucleus (PubMed:19617346). Negatively regulatesglucocorticoid-mediated transcriptional activation(PubMed:9353307). Key regulator of transcription initiation andelongation in embryonic stem cells upon leukemia inhibitory factor(LIF) signaling (By similarity). Involved in the long non-codingRNA H19-mediated Pol II transcriptional repression(PubMed:23811339). Participates in the circadian regulation of thecore clock component ARNTL/BMAL1 transcription (By similarity).Plays a role in the regulation of telomere length(PubMed:18082603). Plays a role as a global pre-mRNA alternativesplicing modulator by regulating U2 small nuclearribonucleoprotein (snRNP) biogenesis (PubMed:22325991). Plays arole in mRNA stability (PubMed:17174306, PubMed:17289661,PubMed:19029303). Component of the CRD-mediated complex thatpromotes MYC mRNA stabilization (PubMed:19029303). Enhances theexpression of specific genes, such as tumor necrosis factor TNFA,by regulating mRNA stability, possibly through binding to the 3'-untranslated region (UTR) (PubMed:17174306). Plays a role inmitotic cell cycle regulation (PubMed:21242313, PubMed:25986610).Involved in the formation of stable mitotic spindle microtubules(MTs) attachment to kinetochore, spindle organization andchromosome congression (PubMed:21242313). Phosphorylation at Ser-59 by PLK1 is required for chromosome alignement and segregationand progression through mitosis (PubMed:25986610). Contributesalso to the targeting of AURKA to mitotic spindle MTs(PubMed:21242313). Binds to double- and single-stranded DNA andRNA, poly(A), poly(C) and poly(G) oligoribonucleotides(PubMed:1628625, PubMed:8068679, PubMed:8174554, PubMed:9204873,PubMed:9405365). Binds to chromatin-associated RNAs (caRNAs)(PubMed:28622508). Associates with chromatin to scaffold/matrixattachment region (S/MAR) elements in a chromatin-associated RNAs(caRNAs)-dependent manner (PubMed:7509195, PubMed:1324173,PubMed:9204873, PubMed:9405365, PubMed:10671544, PubMed:11003645,PubMed:11909954, PubMed:28622508). Binds to the Xist RNA(PubMed:26244333). Binds the long non-coding H19 RNA(PubMed:23811339). Binds to SMN1/2 pre-mRNAs at G/U-rich regions(PubMed:22325991). Binds to small nuclear RNAs (snRNAs)(PubMed:22325991). Binds to the 3'-UTR of TNFA mRNA(PubMed:17174306). Binds (via RNA-binding RGG-box region) to thelong non-coding Xist RNA;facilitates the recruitment of Blnc1 by ZBTB7B required to drivebrown and beige fat development and thermogenesis (By similarity) Nucleus {ECO:0000269|PubMed:10671544,ECO:0000269|PubMed:11003645, ECO:0000269|PubMed:1324173,ECO:0000269|PubMed:14608463, ECO:0000269|PubMed:15563465,ECO:0000269|PubMed:19617346, ECO:0000269|PubMed:21242313,ECO:0000269|PubMed:8174554, ECO:0000269|PubMed:9353307,ECO:0000269|PubMed:9405365}. Nucleus matrix{ECO:0000269|PubMed:1324173, ECO:0000269|PubMed:14608463,ECO:0000269|PubMed:8174554}. Chromosome{ECO:0000269|PubMed:11003645, ECO:0000269|PubMed:14608463,ECO:0000269|PubMed:15563465}. Nucleus speckle{ECO:0000269|PubMed:9353307}. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:14654843,ECO:0000269|PubMed:25986610}. Chromosome, centromere, kinetochore{ECO:0000269|PubMed:21242313}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:21242313, ECO:0000269|PubMed:25986610}.Cytoplasm, cytoskeleton, spindle pole{ECO:0000269|PubMed:21242313}. Midbody{ECO:0000269|PubMed:25986610}. Cytoplasm{ECO:0000269|PubMed:19029303}. Cell surface{ECO:0000269|PubMed:7993898}. Cytoplasmic granule{ECO:0000269|PubMed:17289661}. Note=Localizes at inactive Xchromosome (Xi) regions (PubMed:11003645, PubMed:14608463,PubMed:15563465). Localizes in the nucleus during interphase(PubMed:21242313). At metaphase, localizes with mitotic spindlemicrotubules (MTs) (PubMed:21242313). At anaphase, localizes inthe mitotic spindle midzone (PubMed:21242313). Localizes inspindle MTs proximal to spindle poles in a TPX2- and AURKA-dependent manner (PubMed:21242313). The Ser-59 phosphorylated formlocalizes to centrosomes during prophase and metaphase, to mitoticspindles in anaphase and to the midbody during cytokinesis(PubMed:25986610). Colocalizes with SMARCA4 in the nucleus (Bysimilarity). Colocalizes with CBX5 in the nucleus(PubMed:19617346). Colocalizes with NR3C1 in nuclear speckles(PubMed:9353307). Localized in cytoplasmic ribonucleoprotein (RNP)granules containing untranslated mRNAs (PubMed:17289661).{ECO:0000250|UniProtKB:Q8VEK3, ECO:0000269|PubMed:11003645,ECO:0000269|PubMed:14608463, ECO:0000269|PubMed:15563465,ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:19617346,ECO:0000269|PubMed:21242313, ECO:0000269|PubMed:25986610,ECO:0000269|PubMed:9353307}. adaptive thermogenesis;cardiac muscle cell development;cell cycle;cell division;cellular response to glucocorticoid stimulus;cellular response to leukemia inhibitory factor;chromatin organization;circadian regulation of gene expression;CRD-mediated mRNA stabilization;dendritic transport of messenger ribonucleoprotein complex;dosage compensation by inactivation of X chromosome;maintenance of protein location in nucleus;mRNA splicing, via spliceosome;mRNA stabilization;negative regulation of kinase activity;negative regulation of stem cell differentiation;negative regulation of telomere maintenance via telomerase;negative regulation of transcription by RNA polymerase II;negative regulation of transcription elongation from RNA polymerase II promoter;osteoblast differentiation;positive regulation of attachment of mitotic spindle microtubules to kinetochore;positive regulation of brown fat cell differentiation;positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity;positive regulation of stem cell proliferation;positive regulation of transcription by RNA polymerase II;protein localization to spindle microtubule;regulation of alternative mRNA splicing, via spliceosome;regulation of chromatin organization;regulation of mitotic cell cycle;regulation of mitotic spindle assembly;RNA localization to chromatin;RNA metabolic process;RNA processing actin binding;ATP binding;chromatin binding;chromatin DNA binding;DNA binding;double-stranded DNA binding;double-stranded RNA binding;identical protein binding;mRNA 3'-UTR binding;poly(A) binding;poly(C) RNA binding;poly(G) binding;pre-mRNA binding;promoter-specific chromatin binding;protein-containing complex binding;ribonucleoprotein complex binding;RNA binding;RNA polymerase II complex binding;RNA polymerase II C-terminal domain binding;RNA polymerase II proximal promoter sequence-specific DNA binding;sequence-specific double-stranded DNA binding;single-stranded DNA binding;single-stranded RNA binding;snRNA binding;telomerase RNA binding;TFIIH-class transcription factor complex binding;transcription corepressor activity catalytic step 2 spliceosome;cell surface;centrosome;condensed chromosome kinetochore;CRD-mediated mRNA stability complex;cytoplasmic ribonucleoprotein granule;dendrite cytoplasm;inactive sex chromosome;kinetochore;membrane;midbody;mitotic spindle;mitotic spindle microtubule;mitotic spindle midzone;nuclear chromosome;nuclear matrix;nuclear speck;nucleoplasm;nucleus;protein-containing complex;ribonucleoprotein complex;spindle pole;telomerase holoenzyme complex Spliceosome mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA Actin-ribonucleoprotein complex (POLR2A, GTF2F1, HNRNPU);C complex spliceosome;DGCR8 multiprotein complex;Emerin complex 24;Emerin complex 52;HNRNPU-NR3C1 complex;IGF2BP1 complex;Large Drosha complex;Nop56p-associated pre-rRNA complex;SNW1 complex -0.763178646564484 0.0360615961253643 0.711132943630219 0.801188409328461 0.395960867404938 2.06901597976685 1.5422877073288 1.18061459064484 0.176092460751534 -1.06111073493958 -0.26600456237793 0.269534349441528 -1.73931932449341 -0.93384861946106 -1.06111073493958 -0.641487240791321 -0.541199266910553 -0.174629732966423 + Cluster -674 13 13 12 45.1 45.1 44.8 38.449 0 323.31 19800000000 54 3.45688428036561 0.00046242774566474 Q9UBE0;Q9UBE0-3;Q9UBE0-2 Q9UBE0;Q9UBE0-3;Q9UBE0-2 SUMO-activating enzyme subunit 1;SUMO-activating enzyme subunit 1, N-terminally processed SAE1 3067 The heterodimer acts as an E1 ligase for SUMO1, SUMO2,SUMO3, and probably SUMO4. It mediates ATP-dependent activation ofSUMO proteins followed by formation of a thioester bond between aSUMO protein and a conserved active site cysteine residue onUBA2/SAE2. Nucleus {ECO:0000269|PubMed:11481243}. positive regulation of protein targeting to mitochondrion;protein modification by small protein conjugation;protein sumoylation;protein ubiquitination ATP-dependent protein binding;enzyme activator activity;protein C-terminus binding;protein heterodimerization activity;small protein activating enzyme binding;SUMO activating enzyme activity;ubiquitin activating enzyme activity cytoplasm;nucleoplasm;nucleus;SUMO activating enzyme complex Ubiquitin mediated proteolysis SUMO is conjugated to E1 (UBA2:SAE1);SUMO is transferred from E1 to E2 (UBE2I, UBC9) SUA1-UBA2 complex;SUMO1-SUA1-UBA2 complex -0.333977103233337 -0.164951682090759 0.951437175273895 0.731211125850677 0.824132084846497 2.00222682952881 1.32517385482788 1.4167400598526 0.0286948047578335 -0.615885436534882 -0.424780547618866 0.0816742852330208 -1.63671159744263 -0.948811769485474 -1.19961392879486 -0.695977509021759 -0.699022769927979 -0.64155787229538 + Cluster -674 1 1 1 6.1 6.1 6.1 36.648 0 5.7303 1999000000 4 5.73358772838256 9.80392156862745E-06 O15127 O15127 Secretory carrier-associated membrane protein 2 SCAMP2 166 Functions in post-Golgi recycling pathways. Acts as arecycling carrier to the cell surface. Multi-pass membrane protein{ECO:0000269|PubMed:15840657}.; Multi-pass membraneprotein {ECO:0000269|PubMed:15840657}. Recycling endosome membrane{ECO:0000269|PubMed:15840657};Golgi apparatus, trans-Golgi networkmembrane {ECO:0000269|PubMed:15840657} post-Golgi vesicle-mediated transport;protein transport extracellular exosome;Golgi apparatus;Golgi membrane;integral component of membrane;intracellular membrane-bounded organelle;recycling endosome membrane;trans-Golgi network membrane;transport vesicle SCAMP1-SCAMP2 complex;SCAMP1-SCAMP2-SCAMP3 complex -0.522471487522125 -0.344673871994019 0.310053557157516 0.439553588628769 0.550267338752747 2.04097127914429 2.04097127914429 1.37484705448151 0.0285377781838179 -0.606812715530396 -0.900246500968933 -0.747292637825012 -1.5135098695755 -0.747292637825012 -0.94168746471405 -0.561225354671478 0.0285377781838179 0.0714728161692619 + Cluster -674 10 10 10 20.3 20.3 20.3 64.121 0 98.423 7249100000 31 3.15707459500932 0.000798076923076923 Q9P2K5;Q9P2K5-2;Q9P2K5-3;Q9P2K5-4 Q9P2K5;Q9P2K5-2 Myelin expression factor 2 MYEF2 3056 Transcriptional repressor of the myelin basic proteingene (MBP). Binds to the proximal MB1 element 5'-TTGTCC-3' of theMBP promoter. Its binding to MB1 and function are inhibited byPURA (By similarity). Nucleus. myotube differentiation;neuron differentiation;regulation of mRNA stability involved in response to oxidative stress DNA-binding transcription repressor activity, RNA polymerase II-specific;mRNA binding;RNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;single-stranded DNA binding cytoplasm;nucleus;post-mRNA release spliceosomal complex;ribonucleoprotein complex -0.627591907978058 0.398025959730148 0.398025959730148 0.398025959730148 1.57523262500763 1.5415426492691 1.5415426492691 1.5415426492691 0.398025959730148 -0.661281764507294 -0.661281764507294 -0.661281764507294 -1.31823492050171 -0.661281764507294 -0.661281764507294 -1.28454506397247 -0.627591907978058 -0.627591907978058 + Cluster -674 44 44 44 45.5 45.5 45.5 76.613 0 323.31 791380000000 649 4.76436295939709 2.67857142857143E-05 P19338 P19338 Nucleolin NCL 729 Nucleolin is the major nucleolar protein of growingeukaryotic cells. It is found associated with intranucleolarchromatin and pre-ribosomal particles. It induces chromatindecondensation by binding to histone H1. It is thought to play arole in pre-rRNA transcription and ribosome assembly. May play arole in the process of transcriptional elongation. Binds RNAoligonucleotides with 5'-UUAGGG-3' repeats more tightly than thetelomeric single-stranded DNA 5'-TTAGGG-3' repeats Nucleus, nucleolus. Cytoplasm.Note=Localized in cytoplasmic mRNP granules containinguntranslated mRNAs. angiogenesis;cellular response to epidermal growth factor stimulus;cellular response to leukemia inhibitory factor;negative regulation of translation;positive regulation of transcription by RNA polymerase II;positive regulation of transcription of nucleolar large rRNA by RNA polymerase I DNA topoisomerase binding;identical protein binding;mRNA 5'-UTR binding;protein C-terminus binding;RNA binding;telomeric DNA binding cell cortex;cytoplasmic ribonucleoprotein granule;extracellular exosome;membrane;nucleolus;nucleoplasm;nucleus;ribonucleoprotein complex Pathogenic Escherichia coli infection Major pathway of rRNA processing in the nucleolus and cytosol CD28-transactivation complex;DGCR8 multiprotein complex;DGCR8-NCL complex;Nop56p-associated pre-rRNA complex;POLR2A-CCNT1-CDK9-NCL-LEM6-CPSF2 complex;RNA pol II containing coactivator complex Tat-SF;TLE1 corepressor complex (MASH1 promoter-corepressor complex) -0.850184321403503 0.460460901260376 0.842106282711029 0.723071575164795 1.57902681827545 0.824131309986115 1.01631593704224 1.55774891376495 0.795195043087006 -0.461354225873947 -1.10622870922089 0.167979702353477 -0.290526360273361 -0.621418178081512 -1.0865957736969 -1.58718371391296 -1.04390859603882 -0.918636560440063 + Cluster -674 1 1 1 16.2 16.2 16.2 15.131 0 30.888 3079700000 6 3.93091748939752 0.000167582417582418 Q6EEV4;Q6EEV4-2 Q6EEV4;Q6EEV4-2 DNA-directed RNA polymerase II subunit GRINL1A, isoforms 4/5 POLR2M 1970 -0.0152450185269117 0.15913999080658 1.06173431873322 0.631587743759155 0.922751367092133 1.80103397369385 1.87750101089478 1.08506286144257 -0.42726668715477 -0.81608921289444 -0.869451344013214 -0.389086127281189 -1.23101890087128 -0.489917904138565 -0.968040347099304 -1.16082692146301 -0.875861883163452 -0.296007007360458 + Cluster -674 10 10 9 18.3 18.3 16.7 86.16 0 105.42 9856300000 30 5.66525386454692 9.09090909090909E-06 Q15436;Q15436-2 Q15436;Q15436-2 Protein transport protein Sec23A SEC23A 1808 Component of the coat protein complex II (COPII) whichpromotes the formation of transport vesicles from the endoplasmicreticulum (ER). The coat has two main functions, the physicaldeformation of the endoplasmic reticulum membrane into vesiclesand the selection of cargo molecules for their transport to theGolgi complex. Required for the translocation of insulin-inducedglucose transporter SLC2A4/GLUT4 to the cell membrane (Bysimilarity). Cytoplasmic side{ECO:0000269|PubMed:8898360}. Cytoplasm, cytosol{ECO:0000269|PubMed:8898360}. Note=Enriched at endoplasmicreticulum exit sites, also known as transitional endoplasmicreticulum (tER). {ECO:0000269|PubMed:28442536,ECO:0000269|PubMed:8898360}.; Cytoplasmic side{ECO:0000269|PubMed:8898360}. Endoplasmic reticulum membrane{ECO:0000269|PubMed:8898360}; Peripheral membrane protein{ECO:0000269|PubMed:8898360};Cytoplasmic vesicle, COPII-coated vesiclemembrane {ECO:0000305|PubMed:8898360} antigen processing and presentation of exogenous peptide antigen via MHC class II;antigen processing and presentation of peptide antigen via MHC class I;cargo loading into COPII-coated vesicle;COPII vesicle coating;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi organization;intracellular protein transport;macroautophagy;protein localization to plasma membrane;regulation of cell shape;regulation of COPII vesicle coating GTPase activator activity;zinc ion binding COPII vesicle coat;cytosol;endoplasmic reticulum;endoplasmic reticulum exit site;endoplasmic reticulum membrane;ER to Golgi transport vesicle membrane;extrinsic component of membrane;Golgi membrane;perinuclear region of cytoplasm Protein processing in endoplasmic reticulum Cranio-lenticulo-sutural dysplasia Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Cargo concentration in the ER;COPII-mediated vesicle transport;MHC class II antigen presentation;Regulation of cholesterol biosynthesis by SREBP (SREBF) Coat protein complex II (SAR1B, PREB, SEC23A , SEC24B, SEC23IP);SEC23-SEC24 adaptor complex;SEC23-SEC24-SCAP-SREBP1c complex 0.499935239553452 -0.094710186123848 0.612274885177612 0.311278074979782 0.885822474956512 1.97338330745697 1.91429150104523 1.25685346126556 -0.094710186123848 -1.19182896614075 -0.689022839069366 -0.384178847074509 -0.904250621795654 -0.904250621795654 -1.07103621959686 -0.788156986236572 -0.711014151573181 -0.620679199695587 + Cluster -674 21 17 17 50.9 44.8 44.8 46.871 0 172.88 34703000000 92 4.78006962140099 2.7027027027027E-05 P38919 P38919 Eukaryotic initiation factor 4A-III;Eukaryotic initiation factor 4A-III, N-terminally processed EIF4A3 973 specifically inhibits formation of proapoptotic isoformssuch as Bcl-X(S); the function is different from the establishedEJC assembly (PubMed:22203037). Involved in craniofacialdevelopment (PubMed:24360810).;ATP-dependent RNA helicase (PubMed:16170325). Involvedin pre-mRNA splicing as component of the spliceosome(PubMed:11991638, PubMed:22961380, PubMed:28502770,PubMed:28076346). Core component of the splicing-dependentmultiprotein exon junction complex (EJC) deposited at splicejunctions on mRNAs. The EJC is a dynamic structure consisting ofcore proteins and several peripheral nuclear and cytoplasmicassociated factors that join the complex only transiently eitherduring EJC assembly or during subsequent mRNA metabolism. The EJCmarks the position of the exon-exon junction in the mature mRNAfor the gene expression machinery and the core components remainbound to spliced mRNAs throughout all stages of mRNA metabolismthereby influencing downstream processes including nuclear mRNAexport, subcellular mRNA localization, translation efficiency andnonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase andRNA-helicase activities are induced by CASC3, but abolished inpresence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. Theinhibition of ATPase activity by the MAGOH-RBM8A heterodimerincreases the RNA-binding affinity of the EJC. Involved intranslational enhancement of spliced mRNAs after formation of the80S ribosome complex. Binds spliced mRNA in sequence-independentmanner, 20-24 nucleotides upstream of mRNA exon-exon junctions.Shows higher affinity for single-stranded RNA in an ATP-bound coreEJC complex than after the ATP is hydrolyzed. Involved in thesplicing modulation of BCL2L1/Bcl-X (and probably other apoptoticgenes) Nucleus {ECO:0000269|PubMed:11991638,ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:28076346,ECO:0000269|PubMed:28502770}. Nucleus speckle{ECO:0000269|PubMed:10623621}. Cytoplasm{ECO:0000250|UniProtKB:Q3B8Q2}. Note=Nucleocytoplasmic shuttlingprotein. Travels to the cytoplasm as part of the exon junctioncomplex (EJC) bound to mRNA. Detected in dendritic layer as wellas the nuclear and cytoplasmic (somatic) compartments of neurons.Colocalizes with STAU1 and FMR1 in dendrites (By similarity).{ECO:0000250|UniProtKB:Q3B8Q2}. associative learning;cellular response to brain-derived neurotrophic factor stimulus;cellular response to selenite ion;embryonic cranial skeleton morphogenesis;exploration behavior;mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;negative regulation of excitatory postsynaptic potential;negative regulation of selenocysteine incorporation;negative regulation of selenocysteine insertion sequence binding;negative regulation of translation;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;positive regulation of translation;regulation of translation at postsynapse, modulating synaptic transmission;response to organic cyclic compound;RNA export from nucleus;rRNA processing ATP binding;ATP-dependent RNA helicase activity;mRNA binding;poly(A) binding;ribonucleoprotein complex binding;RNA binding;RNA stem-loop binding;selenocysteine insertion sequence binding;translation regulator activity catalytic step 2 spliceosome;cytoplasm;cytosol;dendrite;exon-exon junction complex;glutamatergic synapse;membrane;neuronal cell body;nuclear speck;nucleoplasm;postsynaptic cytosol mRNA surveillance pathway;RNA transport;Spliceosome Cleavage of Growing Transcript in the Termination Region;Deadenylation of mRNA;ISG15 antiviral mechanism;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Regulation of expression of SLITs and ROBOs;Transport of Mature mRNA derived from an Intron-Containing Transcript C complex spliceosome;CBP80/20- dependent translation complex;EIF4A3-MLN51 complex;Exon junction complex;Exon junction complex (EIF4A3, MLN51, MAGOH, Y14);Exon junction complex (EIF4A3, MLN51, UPF3B, MAGOH, Y14);Exon junction complex (EIF4A3, MLN51, UPF3B, MAGOH, Y14, PYM);SMG1-UPF2-Y14-MAGOH-UPF3B-EIF4A3 complex;Spliceosome 0.200604632496834 -0.406754791736603 1.0461106300354 1.0461106300354 1.0461106300354 2.20423817634583 1.50507664680481 0.659570693969727 -0.406754791736603 -0.792002975940704 -0.408803761005402 -0.792002975940704 -0.792002975940704 -0.792002975940704 -0.792002975940704 -0.867769777774811 -1.25096905231476 -0.406754791736603 + Cluster -674 35 35 33 75.3 75.3 70.3 47.168 0 323.31 2081100000000 1270 5.80894971593444 1.05263157894737E-05 P06733;P06733-2 P06733;P06733-2 Alpha-enolase ENO1 519 Multifunctional enzyme that, as well as its role inglycolysis, plays a part in various processes such as growthcontrol, hypoxia tolerance and allergic responses. May alsofunction in the intravascular and pericellular fibrinolytic systemdue to its ability to serve as a receptor and activator ofplasminogen on the cell surface of several cell-types such asleukocytes and neurons. Stimulates immunoglobulin production.MBP1 binds to the myc promoter and acts as atranscriptional repressor. May be a tumor suppressor. Cytoplasm {ECO:0000269|PubMed:10802057}.Cell membrane {ECO:0000269|PubMed:10802057}. Cytoplasm, myofibril,sarcomere, M line {ECO:0000269|PubMed:10802057}. Note=Cantranslocate to the plasma membrane in either the homodimeric(alpha/alpha) or heterodimeric (alpha/gamma) form. ENO1 islocalized to the M line.Isoform MBP-1: Nucleus. canonical glycolysis;gluconeogenesis;negative regulation of cell growth;negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;positive regulation of ATP biosynthetic process;positive regulation of muscle contraction;positive regulation of plasminogen activation;response to virus cadherin binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;GTPase binding;magnesium ion binding;phosphopyruvate hydratase activity;protein homodimerization activity;RNA binding;RNA polymerase II regulatory region sequence-specific DNA binding cell cortex region;cell surface;cytoplasm;cytosol;extracellular exosome;extracellular space;M band;membrane;nucleus;phosphopyruvate hydratase complex;plasma membrane Biosynthesis of amino acids;Carbon metabolism;Glycolysis / Gluconeogenesis;HIF-1 signaling pathway;Metabolic pathways;RNA degradation Gluconeogenesis;Glycolysis 0.498827189207077 0.330023169517517 0.851967930793762 0.476773113012314 1.10863959789276 1.26771652698517 1.95065927505493 1.30680215358734 -0.204211890697479 -0.957036316394806 -1.03266263008118 -0.356559455394745 -1.01972377300262 -0.356559455394745 -0.802633225917816 -1.26137053966522 -1.18801999092102 -0.612631618976593 + Cluster -674 3 3 3 10.3 10.3 10.3 43.239 0 173.89 1792500000 11 5.51141255974286 8E-06 P18615;P18615-3;P18615-4 P18615;P18615-3 Negative elongation factor E NELFE 720 Essential component of the NELF complex, a complex thatnegatively regulates the elongation of transcription by RNApolymerase II (PubMed:10199401). The NELF complex, which acts viaan association with the DSIF complex and causes transcriptionalpausing, is counteracted by the P-TEFb kinase complex(PubMed:11940650, PubMed:12612062). Provides the strongest RNAbinding activity of the NELF complex and may initially recruit theNELF complex to RNA (PubMed:18303858, PubMed:27282391) Nucleus. negative regulation of mRNA polyadenylation;negative regulation of transcription elongation from RNA polymerase II promoter;positive regulation of ERK1 and ERK2 cascade;positive regulation of histone H3-K4 methylation;positive regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter chromatin binding;RNA binding NELF complex;nuclear body;nucleoplasm;nucleus;plasma membrane Abortive elongation of HIV-1 transcript in the absence of Tat;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;HIV elongation arrest and recovery;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Elongation;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes NELF complex (Negative elongation factor complex) 0.0540861710906029 0.525041282176971 1.17370021343231 0.578183352947235 0.973625481128693 1.63573741912842 1.53989672660828 1.31963908672333 -0.31015682220459 -1.28731095790863 -1.09221971035004 -0.452879071235657 -0.68895024061203 -0.432785987854004 -0.541120171546936 -0.964241206645966 -0.718189060688019 -1.31205630302429 + Cluster -674 1 1 1 17.4 17.4 17.4 16.297 0 50.598 6223200000 8 6.03742443732319 1.21951219512195E-05 Q9Y547 Q9Y547 Intraflagellar transport protein 25 homolog HSPB11 3302 Component of the IFT complex B required for sonichedgehog/SHH signaling. May mediate transport of SHH components:required for the export of SMO and PTCH1 receptors out of thecilium and the accumulation of GLI2 at the ciliary tip in responseto activation of the SHH pathway, suggesting it is involved in thedynamic transport of SHH signaling molecules within the cilium.Not required for ciliary assembly. Its role in intraflagellartransport is mainly seen in tissues rich in ciliated cells such askidney and testis. Essential for male fertility, spermiogenesisand sperm flagella formation. Plays a role in the earlydevelopment of the kidney. May be involved in the regulation ofureteric bud initiation (By similarity) Cell projection, cilium{ECO:0000250|UniProtKB:Q9D6H2}. cell differentiation;heart development;intraciliary transport involved in cilium assembly;kidney development;left/right axis specification;lung development;skeletal system development;smoothened signaling pathway;spermatogenesis metal ion binding centrosome;ciliary tip;cilium;intraciliary transport particle B Charcot-Marie-Tooth disease Intraflagellar transport Intraflagellar transport complex B;Intraflagellar transport complex B core complex 0.232544958591461 0.414623707532883 1.50894343852997 0.427457749843597 0.82487279176712 1.91103112697601 1.45017218589783 1.09677839279175 -0.704237461090088 -1.03952980041504 -1.15973746776581 -0.605843126773834 -0.620661735534668 -0.421356558799744 -0.610870361328125 -0.931349754333496 -0.807115733623505 -0.965722560882568 + Cluster -674 3 3 3 5 5 5 78.576 0 40.772 3707700000 7 5.32946509158241 1.37931034482759E-05 Q6NZY4;Q6NZY4-2 Q6NZY4;Q6NZY4-2 Zinc finger CCHC domain-containing protein 8 ZCCHC8 1986 Scaffolding subunit of the trimeric nuclear exosometargeting (NEXT) complex, a complex that directs a subset of non-coding short-lived RNAs for exosomal degradation. The RNA exosomeis fundamental for the degradation of RNA in eukaryotic nuclei.Substrate targeting is facilitated by its cofactor MTREX, whichlinks to RNA-binding protein adapters (PubMed:27871484). May beinvolved in pre-mRNA splicing (Probable) Nucleus, nucleoplasm{ECO:0000269|PubMed:16263084, ECO:0000269|PubMed:21855801}.Nucleus {ECO:0000255|PROSITE-ProRule:PRU00768}. Note=Excluded fromnucleolus. {ECO:0000269|PubMed:21855801}. mRNA splicing, via spliceosome RNA binding;zinc ion binding catalytic step 2 spliceosome;nuclear body;nucleoplasm;nucleus;TRAMP complex C complex spliceosome;MTR4-RBM7-ZCCHC8 complex -0.5668044090271 0.480093091726303 1.19809150695801 0.538933336734772 0.963943004608154 2.0180401802063 1.13591015338898 1.32687473297119 -0.387489587068558 -1.37937593460083 -1.42668461799622 -0.378027826547623 -0.378027826547623 -0.299288392066956 -0.619390964508057 -0.581529259681702 -0.5668044090271 -1.07846295833588 + Cluster -674 7 7 7 37.3 37.3 37.3 31.54 0 48.625 20781000000 37 4.93500777880469 2.08333333333333E-05 P48739;P48739-2;P48739-3 P48739;P48739-2;P48739-3 Phosphatidylinositol transfer protein beta isoform PITPNB 1084 Catalyzes the transfer of PtdIns and phosphatidylcholinebetween membranes. Cytoplasm {ECO:0000250}. Golgi apparatus{ECO:0000250}. lipid metabolic process;nucleus organization;phospholipid transport;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum phosphatidylcholine binding;phosphatidylcholine transporter activity;phosphatidylinositol binding;phosphatidylinositol transporter activity cytoplasm;endoplasmic reticulum membrane;Golgi membrane PI and PC transport between ER and Golgi membranes 0.0869753956794739 0.428553134202957 1.08553659915924 0.636314928531647 0.812513947486877 1.81065845489502 1.79744231700897 1.10264611244202 -0.668016493320465 -1.05109190940857 -1.31738269329071 -0.9933962225914 -0.261438339948654 -0.630841791629791 -0.456647932529449 -0.817327380180359 -0.773954689502716 -0.7905433177948 + Cluster -674 8 8 8 10.7 10.7 10.7 102.36 0 66.144 4682300000 21 5.80524617968277 1.04166666666667E-05 P78344;P78344-2 P78344;P78344-2 Eukaryotic translation initiation factor 4 gamma 2 EIF4G2 1426 Appears to play a role in the switch from cap-dependentto IRES-mediated translation during mitosis, apoptosis and viralinfection. Cleaved by some caspases and viral proteases cell cycle arrest;cell death;cellular macromolecule biosynthetic process;negative regulation of autophagy;positive regulation of cell growth;regulation of translational initiation cadherin binding;mRNA binding;RNA binding;translation factor activity, RNA binding;translation initiation factor activity cell-cell adherens junction;cytosol;eukaryotic translation initiation factor 4F complex;membrane RNA transport;Viral myocarditis ISG15 antiviral mechanism 0.135299503803253 0.517902374267578 0.734149515628815 0.79692280292511 0.939678370952606 1.57470464706421 1.60221910476685 1.40293622016907 0.0429934896528721 -1.04672825336456 -1.19613492488861 -0.220652803778648 -1.01464211940765 -0.629409313201904 -0.472273468971252 -0.847957611083984 -1.09688723087311 -1.22212040424347 + Cluster -674 3 3 3 7.9 7.9 7.9 64.681 0 13.414 1108700000 9 6.22199523891851 0 Q96ME7;Q96ME7-2;Q96ME7-3 Q96ME7;Q96ME7-2;Q96ME7-3 Zinc finger protein 512 ZNF512 2506 May be involved in transcriptional regulation. Nucleus {ECO:0000305}. DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;metal ion binding nucleus 0.0227681044489145 -0.0166222751140594 1.24891138076782 0.924838125705719 0.874599039554596 1.39208233356476 1.60754084587097 1.60754084587097 -0.240217328071594 -0.937645614147186 -1.26296329498291 -0.340631693601608 -0.665885508060455 -0.700011074542999 -0.700011074542999 -0.922808408737183 -0.922808408737183 -0.968676090240479 + Cluster -674 25 25 25 30.7 30.7 30.7 117.36 0 323.31 37791000000 121 7.86121402037256 0 Q7L014 Q7L014 Probable ATP-dependent RNA helicase DDX46 DDX46 2048 Plays an essential role in splicing, either prior to, orduring splicing A complex formation Lipid-anchor {ECO:0000305}. Note=Present in Cajal bodies (CBs) andnuclear speckles.;Nucleus speckle{ECO:0000269|PubMed:12234937}. Nucleus, Cajal body{ECO:0000269|PubMed:12234937}. Membrane {ECO:0000305} mRNA splicing, via spliceosome ATP binding;helicase activity;RNA binding Cajal body;fibrillar center;membrane;nuclear speck;nucleoplasm;nucleus Spliceosome mRNA Splicing - Major Pathway 17S U2 snRNP;Spliceosome 0.128798052668571 0.0624755397439003 1.08634412288666 0.566294252872467 0.871345162391663 1.71196901798248 1.65218245983124 1.40263330936432 -0.430213779211044 -1.51833510398865 -1.20614910125732 -0.167810469865799 -0.883777737617493 -0.29902121424675 -0.691636681556702 -0.725061237812042 -0.895597040653229 -0.664439558982849 + Cluster -674 28 28 28 28.8 28.8 28.8 135.58 0 323.31 70027000000 151 5.4214471168836 7.69230769230769E-06 Q15393;Q15393-3;Q15393-2 Q15393 Splicing factor 3B subunit 3 SF3B3 1798 Involved in pre-mRNA splicing as a component of thesplicing factor SF3B complex, a constituent of the spliceosome(PubMed:10490618, PubMed:10882114, PubMed:27720643,PubMed:28781166). SF3B complex is required for 'A' complexassembly formed by the stable binding of U2 snRNP to thebranchpoint sequence (BPS) in pre-mRNA. Sequence independentbinding of SF3A/SF3B complex upstream of the branch site isessential, it may anchor U2 snRNP to the pre-mRNA(PubMed:12234937). May also be involved in the assembly of the 'E'complex (PubMed:10882114). Belongs also to the minor U12-dependentspliceosome, which is involved in the splicing of rare class ofnuclear pre-mRNA intron (PubMed:15146077) Nucleus {ECO:0000269|PubMed:10490618,ECO:0000269|PubMed:11564863, ECO:0000269|PubMed:27720643,ECO:0000269|PubMed:28541300, ECO:0000269|PubMed:28781166}. mRNA splicing, via spliceosome;negative regulation of protein catabolic process;RNA splicing, via transesterification reactions nucleic acid binding;protein-containing complex binding catalytic step 2 spliceosome;nucleolus;nucleoplasm;nucleus;small nuclear ribonucleoprotein complex;spliceosomal complex;U12-type spliceosomal complex;U2-type precatalytic spliceosome Spliceosome mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway 17S U2 snRNP;18S U11/U12 snRNP;C complex spliceosome;NCOR1 complex;SF3b complex;Spliceosome;STAGA complex;TFTC complex (TATA-binding protein-free TAF-II-containing complex) -0.0809986144304276 0.0145960990339518 1.51738619804382 0.831263959407806 1.12812530994415 1.0113273859024 1.6160614490509 1.5211877822876 -0.757059991359711 -0.285919338464737 -1.2918758392334 -0.120242580771446 -0.940498948097229 -0.607670724391937 -0.902418375015259 -0.973221361637115 -0.922982513904572 -0.757059991359711 + Cluster -674 13 13 13 30 30 30 67.877 0 235.3 43763000000 81 6.38333449596299 0 P29401;P29401-2 P29401;P29401-2 Transketolase TKT 852 Catalyzes the transfer of a two-carbon ketol group froma ketose donor to an aldose acceptor, via a covalent intermediatewith the cofactor thiamine pyrophosphate glyceraldehyde-3-phosphate biosynthetic process;pentose-phosphate shunt;pentose-phosphate shunt, non-oxidative branch;regulation of growth;xylulose biosynthetic process cofactor binding;metal ion binding;protein homodimerization activity;transketolase activity cytosol;extracellular exosome;myelin sheath;nuclear body;nuclear speck;nucleoplasm;peroxisome;vesicle Biosynthesis of amino acids;Carbon metabolism;Metabolic pathways;Pentose phosphate pathway Insulin effects increased synthesis of Xylulose-5-Phosphate;Pentose phosphate pathway -0.213928207755089 0.0901929810643196 0.872560143470764 0.378943502902985 0.70257979631424 1.61320447921753 2.02599239349365 1.6295964717865 -0.109017789363861 -0.985508024692535 -1.45816624164581 -0.577826976776123 -0.780329644680023 -0.780329644680023 -0.686628580093384 -0.40127968788147 -0.760114014148712 -0.559940993785858 + Cluster -674 3 3 3 18.4 18.4 18.4 28.433 0 51.065 3294500000 14 5.22066787365111 1.25E-05 P25788;P25788-2 P25788;P25788-2 Proteasome subunit alpha type-3 PSMA3 808 Component of the 20S core proteasome complex involved inthe proteolytic degradation of most intracellular proteins. Thiscomplex plays numerous essential roles within the cell byassociating with different regulatory particles. Associated withtwo 19S regulatory particles, forms the 26S proteasome and thusparticipates in the ATP-dependent degradation of ubiquitinatedproteins. The 26S proteasome plays a key role in the maintenanceof protein homeostasis by removing misfolded or damaged proteinsthat could impair cellular functions, and by removing proteinswhose functions are no longer required. Associated with the PA200or PA28, the 20S proteasome mediates ubiquitin-independent proteindegradation. This type of proteolysis is required in severalpathways including spermatogenesis (20S-PA200 complex) orgeneration of a subset of MHC class I-presented antigenic peptides(20S-PA28 complex). Binds to the C-terminus of CDKN1A and therebymediates its degradation. Negatively regulates the membranetrafficking of the cell-surface thromboxane A2 receptor (TBXA2R)isoform 2. Cytoplasm {ECO:0000269|PubMed:12181345}.Nucleus {ECO:0000269|PubMed:12181345}. post-translational protein modification;proteasomal protein catabolic process;proteasomal ubiquitin-independent protein catabolic process;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination;regulation of endopeptidase activity;viral process endopeptidase activity;threonine-type endopeptidase activity;ubiquitin protein ligase binding cytoplasm;cytosol;extracellular exosome;nucleoplasm;nucleus;proteasome complex;proteasome core complex;proteasome core complex, alpha-subunit complex;synapse Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 20S proteasome;26S proteasome;ANP32A-ANP32B-PSMA3-PTMA-SLC25A5 complex;DNAJB2-HSPA8-PSMA3 complex;PA28-20S proteasome;PA28gamma-20S proteasome;PA700-20S-PA28 complex -0.230452969670296 0.291074812412262 0.934433579444885 0.812484622001648 0.812484622001648 1.57451236248016 1.63456666469574 1.57451236248016 0.0506455898284912 -0.318103790283203 -1.31455540657043 -0.955563366413116 -0.468982636928558 -0.758646905422211 -0.967727541923523 -0.545542895793915 -1.00721704959869 -1.11792206764221 + Cluster -674 9 9 9 21 21 21 62.942 0 150.76 20786000000 46 6.30038181357027 0 O43776;O43776-2 O43776 Asparagine--tRNA ligase, cytoplasmic NARS 244 Cytoplasm. asparaginyl-tRNA aminoacylation;tRNA aminoacylation for protein translation asparagine-tRNA ligase activity;ATP binding;nucleic acid binding cytoplasm;cytosol;extracellular exosome Aminoacyl-tRNA biosynthesis Cytosolic tRNA aminoacylation 0.472677558660507 0.188712164759636 0.734198808670044 0.560747027397156 0.897391855716705 1.24732065200806 2.21213030815125 1.35649907588959 0.0143308453261852 -0.915528178215027 -1.08200001716614 -0.543882012367249 -0.776503145694733 -0.664755761623383 -0.833323240280151 -0.956951797008514 -0.897681057453156 -1.01338315010071 + Cluster -674 34 34 23 37.1 37.1 27.9 121.9 0 323.31 54277000000 170 5.88360031185741 1.13636363636364E-05 O60264 O60264 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 SMARCA5 260 thismay require intact histone H4 tails. Also required for replicationof pericentric heterochromatin in S-phase specifically inconjunction with BAZ1A. Probably plays a role in repression ofpolI dependent transcription of the rDNA locus, through therecruitment of the SIN3/HDAC1 corepressor complex to the rDNApromoter. Essential component of the WICH complex, a chromatinremodeling complex that mobilizes nucleosomes and reconfiguresirregular chromatin to a regular nucleosomal array structure. TheWICH complex regulates the transcription of various genes, has arole in RNA polymerase I and RNA polymerase III transcription,mediates the histone H2AX phosphorylation at 'Tyr-142', and isinvolved in the maintenance of chromatin structures during DNAreplication processes. Essential component of the NoRC (nucleolarremodeling complex) complex, a complex that mediates silencing ofa fraction of rDNA by recruiting histone-modifying enzymes and DNAmethyltransferases, leading to heterochromatin formation andtranscriptional silencing.;Helicase that possesses intrinsic ATP-dependentnucleosome-remodeling activity. Complexes containing SMARCA5 arecapable of forming ordered nucleosome arrays on chromatin Nucleus {ECO:0000255|PROSITE-ProRule:PRU00624, ECO:0000269|PubMed:12434153}. ATP-dependent chromatin remodeling;cellular response to leukemia inhibitory factor;CENP-A containing nucleosome assembly;chromatin remodeling;chromatin silencing at rDNA;DNA-templated transcription, initiation;nucleosome assembly;nucleosome positioning;positive regulation of gene expression, epigenetic;positive regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II ATP binding;ATPase activity;DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;helicase activity;nucleosome binding chromatin silencing complex;condensed chromosome;fibrillar center;nucleoplasm;nucleus;NURF complex;RSF complex B-WICH complex positively regulates rRNA expression;Deposition of new CENPA-containing nucleosomes at the centromere;NoRC negatively regulates rRNA expression;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks ALL-1 supercomplex;B-WICH complex;CEN complex;DNMT3B complex;HuCHRAC complex;Nucleolar remodeling complex (NoRC complex);Polycomb repressive complex 1 (PRC1, hPRC-H);Remodeling and spacing factor (RSF) complex;RSF complex;SNF2H-BAZ1A complex;SNF2h-cohesin-NuRD complex;SNF2h-HDAC12 complex;WICH complex -0.15922549366951 0.028972702100873 1.13323974609375 1.00477528572083 1.09648704528809 1.21375846862793 1.71493554115295 1.46619594097137 -0.438696205615997 -1.07386326789856 -0.95306396484375 0.0175813473761082 -1.18611919879913 -0.466636180877686 -0.732831120491028 -1.18172693252563 -0.725421071052551 -0.758362531661987 + Cluster -674 11 10 10 9.9 9.3 9.3 123.9 0 95.385 9634100000 37 6.71948752490246 0 O14776;O14776-2 O14776;O14776-2 Transcription elongation regulator 1 TCERG1 132 Transcription factor that binds RNA polymerase II andinhibits the elongation of transcripts from target promoters.Regulates transcription elongation in a TATA box-dependent manner.Necessary for TAT-dependent activation of the humanimmunodeficiency virus type 1 (HIV-1) promoter Nucleus {ECO:0000269|PubMed:10908677,ECO:0000269|PubMed:15485897, ECO:0000269|PubMed:9315662}. negative regulation of transcription by RNA polymerase II;transcription by RNA polymerase II identical protein binding;proline-rich region binding;RNA binding;RNA polymerase binding;RNA polymerase II repressing transcription factor binding;transcription coactivator activity;transcription corepressor activity nucleoplasm;nucleus Spliceosome Spliceosome -0.310671031475067 0.490650177001953 0.843319296836853 0.805307686328888 1.05167555809021 1.23521029949188 1.67054915428162 1.32317245006561 -0.627154231071472 -1.41083371639252 -1.28851139545441 -0.391002118587494 -1.30966091156006 -0.221867829561234 0.393026143312454 -1.09513008594513 -0.310671031475067 -0.847408294677734 + Cluster -674 6 6 6 16.6 16.6 16.6 39.611 0 23.819 9044200000 25 4.08105649975734 0.000126126126126126 P48556 P48556 26S proteasome non-ATPase regulatory subunit 8 PSMD8 1076 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair post-translational protein modification;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination cytosol;nucleoplasm;nucleus;proteasome accessory complex;proteasome complex;proteasome regulatory particle;proteasome regulatory particle, lid subcomplex Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 PA700 complex;PA700-20S-PA28 complex;SNARE complex (RINT1, ZW10, p31);SNARE complex (RINT1, ZW10, p31, Stx18) 0.398196518421173 0.446911722421646 0.299532264471054 0.530326068401337 1.09736955165863 0.892518937587738 2.16148447990417 1.56347596645355 -0.220143511891365 -1.30142951011658 -1.45813858509064 -0.0761138275265694 -0.501270592212677 -0.517034590244293 -0.763505816459656 -0.788989067077637 -0.902297079563141 -0.860892951488495 + Cluster -674 2 2 2 16.7 16.7 16.7 27.835 0 44.312 3014700000 12 4.01191097168379 0.00013953488372093 Q8WY22 Q8WY22 BRI3-binding protein BRI3BP 2316 Involved in tumorigenesis and may function bystabilizing p53/TP53. Multi-pass membrane protein{ECO:0000305|PubMed:17943721}.;Mitochondrion outer membrane{ECO:0000305|PubMed:17943721} integral component of membrane;mitochondrial outer membrane;mitochondrion 0.280010879039764 0.146299093961716 0.873889923095703 0.570793509483337 0.960452377796173 1.52743768692017 1.57589554786682 1.55427634716034 -0.187997922301292 -1.23866999149323 -0.849011123180389 0.197830438613892 -0.586806893348694 -0.966939628124237 -1.21399235725403 -0.477973341941833 -1.09010243415833 -1.07539212703705 + Cluster -674 14 14 14 48.6 48.6 48.6 37.106 0 122.83 30837000000 77 5.24622056994811 1.29032258064516E-05 O43852;O43852-3;O43852-4;O43852-2;O43852-10;O43852-6;O43852-15;O43852-5;O43852-13;O43852-14;O43852-11;O43852-9;O43852-12;O43852-7;O43852-8 O43852;O43852-3;O43852-4;O43852-2;O43852-10;O43852-6;O43852-15;O43852-5 Calumenin CALU 252 Involved in regulation of vitamin K-dependentcarboxylation of multiple N-terminal glutamate residues. Seems toinhibit gamma-carboxylase GGCX. Binds 7 calcium ions with a lowaffinity (By similarity). Endoplasmic reticulum membrane{ECO:0000269|PubMed:10222138}. Golgi apparatus{ECO:0000269|PubMed:10222138}. Secreted {ECO:0000305}. Melanosome{ECO:0000269|PubMed:12643545}. Sarcoplasmic reticulum lumen{ECO:0000305}. Note=Identified by mass spectrometry in melanosomefractions from stage I to stage IV. {ECO:0000269|PubMed:12643545}. cellular protein metabolic process;post-translational protein modification calcium ion binding endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;extracellular region;Golgi apparatus;melanosome;membrane;sarcoplasmic reticulum lumen Platelet degranulation;Post-translational protein phosphorylation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) 0.15588290989399 -0.0626961141824722 0.781823694705963 0.881793320178986 1.4804322719574 1.24707853794098 1.83354675769806 1.11873805522919 -0.223025768995285 -0.243008732795715 -1.26263296604156 -0.564024388790131 -0.564024388790131 -0.850227475166321 -0.71555495262146 -0.371842622756958 -1.4195910692215 -1.22266709804535 + Cluster -674 18 18 18 40.9 40.9 40.9 57.136 0 241.57 54368000000 116 5.78788270280245 1.02040816326531E-05 P14868;P14868-2 P14868;P14868-2 Aspartate--tRNA ligase, cytoplasmic DARS 678 Catalyzes the specific attachment of an amino acid toits cognate tRNA in a 2 step reaction: the amino acid (AA) isfirst activated by ATP to form AA-AMP and then transferred to theacceptor end of the tRNA. Cytoplasm, cytosol{ECO:0000269|PubMed:19289464}. aspartyl-tRNA aminoacylation;protein-containing complex assembly;translation;tRNA aminoacylation for protein translation aminoacylase activity;aspartate-tRNA ligase activity;ATP binding;RNA binding aminoacyl-tRNA synthetase multienzyme complex;cytoplasm;cytosol;extracellular exosome;membrane;synapse Aminoacyl-tRNA biosynthesis Cytosolic tRNA aminoacylation;SeMet incorporation into proteins Multisynthetase complex -0.285773038864136 0.302920907735825 0.892436504364014 1.23458480834961 1.58382534980774 1.28124725818634 1.26008546352386 1.36070466041565 -0.650135338306427 -0.450410723686218 -1.22631680965424 -0.380885511636734 -0.428427308797836 -0.469064176082611 -0.946961760520935 -0.678129971027374 -1.23575878143311 -1.1639416217804 + Cluster -674 7 7 7 20 20 20 58.281 0 30.182 3571900000 16 6.42190152940702 0 Q9C0B1;Q9C0B1-4;Q9C0B1-2;Q9C0B1-3 Q9C0B1 Alpha-ketoglutarate-dependent dioxygenase FTO FTO 2737 RNA demethylase that mediates oxidative demethylation ofdifferent RNA species, such as mRNAs, tRNAs and snRNAs, and actsas a regulator of fat mass, adipogenesis and energy homeostasis(PubMed:22002720, PubMed:26458103, PubMed:28002401,PubMed:30197295, PubMed:26457839, PubMed:25452335). Specificallydemethylates N(6)-methyladenosine (m6A) RNA, the most prevalentinternal modification of messenger RNA (mRNA) in higher eukaryotes(PubMed:22002720, PubMed:26458103, PubMed:30197295,PubMed:26457839, PubMed:25452335). M6A demethylation by FTOaffects mRNA expression and stability (PubMed:30197295). Also ableto demethylate m6A in U6 small nuclear RNA (snRNA)(PubMed:30197295). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m)in the 5'-cap by FTO affects mRNA stability by promotingsusceptibility to decapping (PubMed:28002401). Also acts as a tRNAdemethylase by removing N(1)-methyladenine from various tRNAs(PubMed:30197295). Has no activity towards 1-methylguanine(PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able to repair alkylated DNAand RNA by oxidative demethylation: demethylates single-strandedRNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine(PubMed:18775698, PubMed:20376003). Ability to repair alkylatedDNA and RNA is however unsure in vivo (PubMed:18775698,PubMed:20376003). Involved in the regulation of fat mass,adipogenesis and body weight, thereby contributing to theregulation of body size and body fat accumulation(PubMed:18775698, PubMed:20376003). Involved in the regulation ofthermogenesis and the control of adipocyte differentiation intobrown or white fat cells (PubMed:26287746). Regulates activity ofthe dopaminergic midbrain circuitry via its ability to demethylatem6A in mRNAs (By similarity). Plays an oncogenic role in a numberof acute myeloid leukemias by enhancing leukemic oncogene-mediatedcell transformation: acts by mediating m6A demethylation of targettranscripts such as MYC, CEBPA, ASB2 and RARA, leading to promotetheir expression (PubMed:28017614, PubMed:29249359) Nucleus {ECO:0000269|PubMed:22002720,ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:28002401,ECO:0000269|PubMed:30197295}. Nucleus speckle{ECO:0000269|PubMed:22002720}. Cytoplasm{ECO:0000269|PubMed:30197295}. Note=Localizes mainly in thenucleus, where it is able to demethylate N(6)-methyladenosine(m6A) and N(6),2'-O-dimethyladenosine cap (m6A(m)) in U6 smallnuclear RNA (snRNA), N(1)-methyladenine from tRNAs and internalm6A in mRNAs (PubMed:30197295). In the cytoplasm, mediatesdemethylation of m6A and m6A(m) in mRNAs and N(1)-methyladeninefrom tRNAs (PubMed:30197295). {ECO:0000269|PubMed:30197295}. adipose tissue development;DNA dealkylation involved in DNA repair;DNA demethylation;mRNA destabilization;oxidative demethylation;oxidative single-stranded DNA demethylation;oxidative single-stranded RNA demethylation;regulation of brown fat cell differentiation;regulation of lipid storage;regulation of multicellular organism growth;regulation of respiratory system process;regulation of white fat cell proliferation;RNA repair;temperature homeostasis DNA-N1-methyladenine dioxygenase activity;ferrous iron binding;oxidative DNA demethylase activity;oxidative RNA demethylase activity;RNA N6-methyladenosine dioxygenase activity;tRNA demethylase activity cytoplasm;nuclear speck;nucleoplasm;nucleus Genetic obesity;Growth retardation, developmental delay, coarse facies, and early death;Type 2 diabetes mellitus Reversal of alkylation damage by DNA dioxygenases -0.373033612966537 0.210532128810883 1.1950044631958 1.3146516084671 1.41160929203033 1.06377899646759 1.45642459392548 0.734435319900513 0.0335573852062225 0.152302756905556 -1.33871340751648 -0.74385929107666 -0.3321313560009 -0.712731719017029 -0.279473721981049 -1.28615236282349 -1.33803701400757 -1.16816389560699 + Cluster -674 15 15 15 26.3 26.3 26.3 109.93 0 284.17 21724000000 54 5.01235928647795 2.22222222222222E-05 Q15020;Q15020-4;Q15020-2 Q15020;Q15020-4 Squamous cell carcinoma antigen recognized by T-cells 3 SART3 1753 U6 snRNP-binding protein that functions as a recyclingfactor of the splicing machinery. Promotes the initial reassemblyof U4 and U6 snRNPs following their ejection from the spliceosomeduring its maturation (PubMed:12032085). Also binds U6atac snRNPsand may function as a recycling factor for U4atac/U6atacspliceosomal snRNP, an initial step in the assembly of U12-typespliceosomal complex. The U12-type spliceosomal complex plays arole in the splicing of introns with non-canonical splice sites(PubMed:14749385). May also function as a substrate-targetingfactor for deubiquitinases like USP4 and USP15. Recruits USP4 toubiquitinated PRPF3 within the U4/U5/U6 tri-snRNP complex,promoting PRPF3 deubiquitination and thereby regulating thespliceosome U4/U5/U6 tri-snRNP spliceosomal complex disassembly(PubMed:20595234). May also recruit the deubiquitinase USP15 tohistone H2B and mediate histone deubiquitination, therebyregulating gene expression and/or DNA repair (PubMed:24526689).May play a role in hematopoiesis probably through transcriptionregulation of specific genes including MYC (By similarity) Nucleus, nucleoplasm{ECO:0000269|PubMed:10463607, ECO:0000269|PubMed:11959860,ECO:0000269|PubMed:12578909}. Nucleus, Cajal body{ECO:0000269|PubMed:12578909}. Nucleus speckle{ECO:0000269|PubMed:11959860}. Cytoplasm{ECO:0000269|PubMed:10463607, ECO:0000269|PubMed:11959860}. cell morphogenesis;hematopoietic stem cell proliferation;homeostasis of number of cells;mRNA splicing, via spliceosome;nucleosome assembly;positive regulation of histone deubiquitination;regulation of alternative mRNA splicing, via spliceosome;regulation of gene expression;RNA splicing;spliceosomal snRNP assembly;spliceosomal tri-snRNP complex assembly histone binding;RNA binding;U4 snRNA binding;U6 snRNA binding;U6atac snRNA binding;ubiquitin-specific protease binding ASAP complex;Cajal body;cytoplasm;nuclear speck;nucleoplasm;nucleus Disseminated superficial actinic porokeratosis (DSAP) 0.0791827291250229 0.266475468873978 1.12623023986816 0.911634266376495 1.56176519393921 0.595500469207764 1.74673342704773 1.08659529685974 -0.430287539958954 -0.275057345628738 -1.57683992385864 -0.576487600803375 0.0397132821381092 -0.352822154760361 -0.687307775020599 -1.15719044208527 -1.15719044208527 -1.20064699649811 + Cluster -674 3 3 3 29.9 29.9 29.9 17.247 0 12.429 4624400000 5 4.43692804735979 6.22710622710623E-05 Q9NQT5-2;Q9NQT5 Q9NQT5-2;Q9NQT5 Exosome complex component RRP40 EXOSC3 2900 Non-catalytic component of the RNA exosome complex whichhas 3'->5' exoribonuclease activity and participates in amultitude of cellular RNA processing and degradation events. Inthe nucleus, the RNA exosome complex is involved in propermaturation of stable RNA species such as rRNA, snRNA and snoRNA,in the elimination of RNA processing by-products and non-coding'pervasive' transcripts, such as antisense RNA species andpromoter-upstream transcripts (PROMPTs), and of mRNAs withprocessing defects, thereby limiting or excluding their export tothe cytoplasm. The RNA exosome may be involved in Ig class switchrecombination (CSR) and/or Ig variable region somatichypermutation (SHM) by targeting AICDA deamination activity totranscribed dsDNA substrates. In the cytoplasm, the RNA exosomecomplex is involved in general mRNA turnover and specificallydegrades inherently unstable mRNAs containing AU-rich elements(AREs) within their 3' untranslated regions, and in RNAsurveillance pathways, preventing translation of aberrant mRNAs.It seems to be involved in degradation of histone mRNA. Thecatalytic inactive RNA exosome core complex of 9 subunits (Exo-9)is proposed to play a pivotal role in the binding and presentationof RNA for ribonucleolysis, and to serve as a scaffold for theassociation with catalytic subunits and accessory proteins orcomplexes. EXOSC3 as peripheral part of the Exo-9 complexstabilizes the hexameric ring of RNase PH-domain subunits throughcontacts with EXOSC9 and EXOSC5. Cytoplasm {ECO:0000269|PubMed:17545563}.Nucleus, nucleolus {ECO:0000269|PubMed:20531389}. Nucleus{ECO:0000269|PubMed:17545563}. CUT catabolic process;DNA deamination;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);isotype switching;nuclear polyadenylation-dependent rRNA catabolic process;nuclear polyadenylation-dependent tRNA catabolic process;nuclear retention of pre-mRNA with aberrant 3'-ends at the site of transcription;nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5';polyadenylation-dependent snoRNA 3'-end processing;positive regulation of isotype switching;regulation of mRNA stability;rRNA processing;U4 snRNA 3'-end processing 3'-5'-exoribonuclease activity;RNA binding cytoplasm;cytoplasmic exosome (RNase complex);cytosol;exosome (RNase complex);nuclear exosome (RNase complex);nucleolus;nucleoplasm;nucleus;transcriptionally active chromatin RNA degradation Pontocerebellar hypoplasia ATF4 activates genes;Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;KSRP (KHSRP) binds and destabilizes mRNA;Major pathway of rRNA processing in the nucleolus and cytosol;mRNA decay by 3' to 5' exoribonuclease;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA Exosome -0.00990592781454325 0.335530161857605 0.979630470275879 0.979630470275879 1.17532193660736 1.47954535484314 1.69894683361053 0.846858084201813 -0.151871621608734 -0.734840452671051 -1.33517444133759 -0.253469318151474 -0.0533187091350555 -0.456095039844513 -1.19238364696503 -1.19436764717102 -0.84462958574295 -1.269406914711 + Cluster -674 56 56 56 32.7 32.7 32.7 284.54 0 323.31 72161000000 228 5.40559549277773 7.57575757575758E-06 Q13813;Q13813-3;Q13813-2 Q13813;Q13813-3;Q13813-2 Spectrin alpha chain, non-erythrocytic 1 SPTAN1 1663 Fodrin, which seems to be involved in secretion,interacts with calmodulin in a calcium-dependent manner and isthus candidate for the calcium-dependent movement of thecytoskeleton at the membrane. Cytoplasm, cytoskeleton. Cytoplasm, cellcortex. Note=Expressed along the cell membrane in podocytes andpresumptive tubule cells during glomerulogenesis and is expressedalong lateral cell margins in tubule cells. {ECO:0000250}. actin filament capping;axon guidance;endoplasmic reticulum to Golgi vesicle-mediated transport;MAPK cascade;neutrophil degranulation actin binding;cadherin binding;calcium ion binding;calmodulin binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton cytosol;extracellular exosome;extracellular region;extracellular vesicle;intracellular membrane-bounded organelle;membrane;microtubule cytoskeleton;specific granule lumen;spectrin;tertiary granule lumen Apoptosis Early infantile epileptic encephalopathy Caspase-mediated cleavage of cytoskeletal proteins;COPI-mediated anterograde transport;Interaction between L1 and Ankyrins;NCAM signaling for neurite out-growth;Nephrin family interactions;Neutrophil degranulation;RAF/MAP kinase cascade Emerin architectural complex;Emerin complex 1;Emerin complex 32;Emerin-actin-NMI-(alphaII)spectrin complex -0.271440505981445 0.334419518709183 1.22029995918274 0.671641945838928 1.43708801269531 1.32244789600372 1.89054310321808 0.591797530651093 -0.104457624256611 -0.696931481361389 -0.899942994117737 -0.988036870956421 -0.536770105361938 -0.256749629974365 -0.426393330097198 -0.96024751663208 -0.577534735202789 -1.74973320960999 + Cluster -674 2 2 2 3.5 3.5 3.5 100.45 0 42.836 1068000000 7 4.91000016137031 2.06185567010309E-05 Q12959;Q12959-2;Q12959-9;Q12959-5;Q12959-8;Q12959-3;Q12959-6;Q12959-4;Q12959-7 Q12959;Q12959-2;Q12959-9;Q12959-5;Q12959-8;Q12959-3;Q12959-6;Q12959-4;Q12959-7 Disks large homolog 1 DLG1 1579 Essential multidomain scaffolding protein required fornormal development (By similarity). Recruits channels, receptorsand signaling molecules to discrete plasma membrane domains inpolarized cells. May play a role in adherens junction assembly,signal transduction, cell proliferation, synaptogenesis andlymphocyte activation. Regulates the excitability of cardiacmyocytes by modulating the functional expression of Kv4 channels.Functional regulator of Kv1.5 channel. Membrane {ECO:0000269|PubMed:10859302,ECO:0000269|PubMed:11723125, ECO:0000269|PubMed:8922391};Peripheral membrane protein {ECO:0000269|PubMed:8922391}.Basolateral cell membrane {ECO:0000269|PubMed:12807908}.Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q62696}.Cell junction, synapse, postsynaptic cell membrane, postsynapticdensity {ECO:0000250|UniProtKB:Q62696}. Cell junction, synapse{ECO:0000250|UniProtKB:Q62696}. Cell membrane, sarcolemma{ECO:0000269|PubMed:12445884}. Apical cell membrane{ECO:0000269|PubMed:12445884}. Cell junction{ECO:0000269|PubMed:10859302, ECO:0000269|PubMed:11723125,ECO:0000269|PubMed:7937897}. Cytoplasm{ECO:0000269|PubMed:10859302}. Note=Colocalizes with EPB41 atregions of intercellular contacts. Basolateral in epithelial cells(PubMed:12807908). May also associate with endoplasmic reticulummembranes. Mainly found in neurons soma, moderately found atpostsynaptic densities (By similarity).{ECO:0000250|UniProtKB:Q62696, ECO:0000269|PubMed:10859302,ECO:0000269|PubMed:12807908, ECO:0000269|PubMed:8922391,ECO:0000269|PubMed:9192623}. actin filament organization;activation of protein kinase activity;amyloid precursor protein metabolic process;astral microtubule organization;bicellular tight junction assembly;branching involved in ureteric bud morphogenesis;cell-cell adhesion;cellular protein-containing complex localization;chemical synaptic transmission;cortical actin cytoskeleton organization;cortical microtubule organization;embryonic skeletal system morphogenesis;endothelial cell proliferation;establishment of centrosome localization;establishment or maintenance of cell polarity;establishment or maintenance of epithelial cell apical/basal polarity;hard palate development;immunological synapse formation;lens development in camera-type eye;MAPK cascade;membrane raft organization;mitotic cell cycle checkpoint;negative regulation of epithelial cell proliferation;negative regulation of ERK1 and ERK2 cascade;negative regulation of mitotic cell cycle;negative regulation of p38MAPK cascade;negative regulation of protein kinase B signaling;negative regulation of T cell proliferation;negative regulation of transcription by RNA polymerase II;neurotransmitter receptor localization to postsynaptic specialization membrane;peristalsis;positive regulation of actin filament polymerization;positive regulation of cell proliferation;positive regulation of potassium ion transport;positive regulation of protein localization to plasma membrane;protein localization to plasma membrane;receptor clustering;receptor localization to synapse;regulation of cell shape;regulation of membrane potential;regulation of myelination;regulation of potassium ion export across plasma membrane;regulation of potassium ion import;regulation of sodium ion transmembrane transport;regulation of ventricular cardiac muscle cell action potential;regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization;reproductive structure development;smooth muscle tissue development;T cell activation;T cell cytokine production;viral process cadherin binding;cytoskeletal protein binding;guanylate kinase activity;ion channel binding;ionotropic glutamate receptor binding;L27 domain binding;mitogen-activated protein kinase kinase binding;phosphatase binding;phosphoprotein phosphatase activity;potassium channel regulator activity;protein C-terminus binding;protein kinase binding;protein-containing complex scaffold activity;Ras guanyl-nucleotide exchange factor activity;structural constituent of postsynaptic density apical plasma membrane;basement membrane;basolateral plasma membrane;bicellular tight junction;cell junction;cell projection membrane;cell-cell junction;cytoplasm;cytoplasmic side of plasma membrane;cytosol;endoplasmic reticulum;endoplasmic reticulum membrane;extracellular exosome;glutamatergic synapse;Golgi apparatus;immunological synapse;intercalated disc;lateral loop;lateral plasma membrane;membrane raft;microtubule;MPP7-DLG1-LIN7 complex;myelin sheath abaxonal region;neuromuscular junction;neuron projection;node of Ranvier;nucleus;perinuclear region of cytoplasm;plasma membrane;postsynaptic density membrane;sarcolemma Hippo signaling pathway;Human papillomavirus infection;Human T-cell leukemia virus 1 infection;T cell receptor signaling pathway;Tight junction;Viral carcinogenesis Activation of Ca-permeable Kainate Receptor;CREB phosphorylation through the activation of CaMKII;NrCAM interactions;RAF/MAP kinase cascade;Ras activation upon Ca2+ influx through NMDA receptor;Synaptic adhesion-like molecules;Trafficking of AMPA receptors;Unblocking of NMDA receptors, glutamate binding and activation beta(1)-AR receptosome (ADRB1-SAP97-AKAP79-PRKAR2A);LIN2-LIN7-SAP97 complex;LIN2-LIN7-SAP97-MINT1 complex;LIN2-SAP97 complex;MPP7-DLG1-LIN7A complex;MPP7-DLG1-LIN7C complex -0.564887225627899 0.734392702579498 0.688479840755463 0.667091846466064 1.637535572052 1.5315146446228 1.6805967092514 0.74245673418045 -0.203953266143799 -1.18968546390533 -1.34779810905457 -0.643959403038025 -0.246871814131737 -0.203984960913658 -0.322331756353378 -0.986990809440613 -0.924823105335236 -1.04678213596344 + Cluster -674 11 11 11 30.6 30.6 30.6 46.089 0 167.02 7254500000 35 4.56361696030672 4.83870967741935E-05 Q9BY77;Q9BY77-2 Q9BY77;Q9BY77-2 Polymerase delta-interacting protein 3 POLDIP3 2715 probably mediated by association with the TREXcomplex.;Is involved in regulation of translation. Ispreferentially associated with CBC-bound spliced mRNA-proteincomplexes during the pioneer round of mRNA translation.Contributes to enhanced translational efficiency of spliced overnonspliced mRNAs. Recruits activated ribosomal protein S6 kinasebeta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclearmRNA export Nucleus. Nucleus speckle. Cytoplasm.Note=Nucleocytoplasmic shuttling protein. mRNA 3'-end processing;mRNA export from nucleus;poly(A)+ mRNA export from nucleus;positive regulation of translation;RNA export from nucleus protein-containing complex binding;RNA binding cytoplasm;cytoplasmic ribonucleoprotein granule;cytosol;nuclear speck;nucleoplasm Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;Transport of Mature mRNA derived from an Intron-Containing Transcript -0.481331616640091 -0.131302729249001 0.644630491733551 1.3930401802063 1.3930401802063 0.871532499790192 1.75680792331696 1.27946996688843 -0.732904851436615 -0.934273481369019 -1.08966553211212 -0.0296095572412014 -0.375923991203308 -0.486834496259689 -0.991494238376617 -0.597644090652466 0.136063739657402 -1.62360060214996 + Cluster -674 1 1 1 7.1 7.1 7.1 35.273 0 15.025 216750000 3 4.41226345369945 6.15942028985507E-05 Q96S97 Q96S97 Myeloid-associated differentiation marker MYADM 2539 Multi-pass membraneprotein {ECO:0000305}.;Membrane {ECO:0000305} establishment of endothelial barrier;membrane raft organization;negative regulation of actin filament polymerization;negative regulation of gene expression;negative regulation of heterotypic cell-cell adhesion;negative regulation of protein kinase C signaling;negative regulation of protein phosphorylation;positive regulation of cell migration;positive regulation of substrate adhesion-dependent cell spreading;protein localization to plasma membrane cell-cell junction;cortical actin cytoskeleton;integral component of membrane;membrane raft;plasma membrane;ruffle -0.073450930416584 0.243425637483597 0.551473438739777 0.861851572990417 1.31539416313171 1.55857789516449 1.42581355571747 1.31599342823029 -0.464566290378571 -0.750029504299164 -1.71898257732391 -0.271558701992035 -0.421248108148575 -0.421248108148575 -0.717351138591766 -0.606212615966797 -0.123480565845966 -1.70440113544464 + Cluster -674 3 3 3 9.5 9.5 9.5 26.21 0 43.187 3417300000 10 4.28787444136722 8.25082508250825E-05 Q9BVC6 Q9BVC6 Transmembrane protein 109 TMEM109 2681 May mediate cellular response to DNA damage byprotecting against ultraviolet C-induced cell death(PubMed:23542032). Can form voltage-gated calcium and potassiumchannels in vitro (By similarity). Multi-pass membrane protein{ECO:0000250|UniProtKB:O77751}.; Multi-pass membrane protein{ECO:0000250|UniProtKB:O77751}. Endoplasmic reticulum membrane{ECO:0000250|UniProtKB:O77751}; Multi-pass membrane protein{ECO:0000250|UniProtKB:O77751}. Sarcoplasmic reticulum membrane{ECO:0000250|UniProtKB:O77751};Nucleus outer membrane{ECO:0000250|UniProtKB:O77751} cellular response to gamma radiation;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;negative regulation of cell death;regulation of ion transmembrane transport voltage-gated ion channel activity extracellular exosome;integral component of membrane;nuclear outer membrane;sarcoplasmic reticulum membrane 0.0526880957186222 0.325005888938904 0.894030451774597 1.1950341463089 0.653028190135956 0.881053924560547 1.71139633655548 1.68650889396667 0.000575779238715768 -0.418746173381805 -1.31214928627014 -0.168600186705589 -1.24319326877594 -0.205226629972458 -0.930983424186707 -0.837930679321289 -1.11473441123962 -1.16775763034821 + Cluster -674 4 4 4 43.4 43.4 43.4 27.335 0 50.6 11880000000 21 5.36943089216512 7.2463768115942E-06 Q9UKY7;Q9UKY7-2;Q9UKY7-3 Q9UKY7;Q9UKY7-2;Q9UKY7-3 Protein CDV3 homolog CDV3 3155 Cytoplasm {ECO:0000250}. cell proliferation cytosol;plasma membrane 0.4068643450737 0.326943188905716 0.750065326690674 0.0800555720925331 0.795527160167694 1.539391040802 1.70156335830688 1.539391040802 0.127184942364693 -0.241579473018646 -1.59933853149414 -0.192834705114365 -1.33710837364197 -0.283058673143387 -1.12641453742981 -0.731520891189575 -0.945281744003296 -0.80984902381897 + Cluster -674 6 6 6 8.8 8.8 8.8 65.601 0 49.868 996630000 17 3.97388098060387 0.000148876404494382 Q13123 Q13123 Protein Red IK 1595 Involved in pre-mRNA splicing as a component of thespliceosome (PubMed:28781166). Auxiliary spliceosomal protein thatregulates selection of alternative splice sites in a small set oftarget pre-mRNA species (Probable). Required for normal mitoticcell cycle progression (PubMed:22351768, PubMed:24252166).Recruits MAD1L1 and MAD2L1 to kinetochores, and is required totrigger the spindle assembly checkpoint (PubMed:22351768).Required for normal accumulation of SMU1 (PubMed:24945353) Nucleus {ECO:0000269|PubMed:24945353,ECO:0000269|PubMed:28781166}. Nucleus, nucleoplasm{ECO:0000269|PubMed:24252166, ECO:0000269|PubMed:24945353}.Chromosome {ECO:0000269|PubMed:24252166}. Cytoplasm, cytoskeleton,spindle pole {ECO:0000269|PubMed:22351768}. Note=Predominantlypresent throughout the nucleoplasm during prometaphase, metaphaseand anaphase. Is also detected in nuclear foci that are notidentical with Cajal bodies. Starts to accumulate at chromosomesduring telophase, and is nearly exclusively associated withchromosomes in newly divided cells (PubMed:24252166). Colocalizeswith MAD1L1 at mitotic spindle poles during metaphase and anaphase(PubMed:22351768). {ECO:0000269|PubMed:24252166}. mitotic cell cycle;mitotic spindle assembly checkpoint;mRNA splicing, via spliceosome;protein localization to kinetochore;viral process identical protein binding chromosome;cytoplasm;nuclear speck;nucleoplasm;nucleus;spindle pole;U2-type precatalytic spliceosome Spliceosome 0.109253659844398 0.770968794822693 0.900846421718597 0.511547267436981 0.643494188785553 1.32216441631317 1.80175709724426 1.36308348178864 0.215834766626358 0.0637286230921745 -1.32491850852966 -0.960339963436127 -1.12962365150452 -0.526094317436218 -0.609846115112305 -1.2251238822937 -0.81535404920578 -1.11137807369232 + Cluster -674 4 4 4 4.6 4.6 4.6 134.68 0 41.279 1222700000 11 4.88524651450575 1.99004975124378E-05 P20020;P20020-5;P20020-2;P20020-6;P20020-4;P20020-1 P20020;P20020-5;P20020-2;P20020-6;P20020-4;P20020-1 Plasma membrane calcium-transporting ATPase 1 ATP2B1 737 This magnesium-dependent enzyme catalyzes the hydrolysisof ATP coupled with the transport of calcium out of the cell. Multi-pass membrane protein.;Cell membrane aging;brain development;calcium ion export across plasma membrane;cellular calcium ion homeostasis;cellular response to corticosterone stimulus;cellular response to vitamin D;ion transmembrane transport;neural retina development;regulation of cardiac conduction;regulation of cytosolic calcium ion concentration;response to cold ATP binding;calcium ion transmembrane transporter activity;calcium-transporting ATPase activity;calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration;calmodulin binding;metal ion binding;PDZ domain binding apical plasma membrane;basolateral plasma membrane;cytoplasmic side of plasma membrane;dendritic spine membrane;extracellular exosome;GABA-ergic synapse;glutamatergic synapse;integral component of plasma membrane;integral component of presynaptic active zone membrane;membrane;membrane raft;neuronal cell body membrane;nucleus;plasma membrane Adrenergic signaling in cardiomyocytes;Aldosterone synthesis and secretion;Calcium signaling pathway;cAMP signaling pathway;cGMP-PKG signaling pathway;Endocrine and other factor-regulated calcium reabsorption;Mineral absorption;Pancreatic secretion;Salivary secretion Ion homeostasis;Ion transport by P-type ATPases;Reduction of cytosolic Ca++ levels -0.623155534267426 -0.195916712284088 1.53532671928406 1.0045850276947 1.28134119510651 1.53752839565277 1.2825516462326 1.17760145664215 -0.476786673069 -0.610489547252655 -0.770182192325592 -0.610489547252655 -0.190785422921181 -0.469936162233353 -1.34580731391907 -1.04799973964691 -0.323128759860992 -1.15425682067871 + Cluster -674 4 4 4 29.3 29.3 29.3 28.38 0 57.916 4955600000 9 6.88798297273198 0 P13984 P13984 General transcription factor IIF subunit 2 GTF2F2 662 TFIIF is a general transcription initiation factor thatbinds to RNA polymerase II and helps to recruit it to theinitiation complex in collaboration with TFIIB. It promotestranscription elongation. This subunit shows ATP-dependent DNA-helicase activity. Nucleus {ECO:0000269|PubMed:10454543}. 7-methylguanosine mRNA capping;fibroblast growth factor receptor signaling pathway;mRNA splicing, via spliceosome;positive regulation of transcription by RNA polymerase II;positive regulation of transcription elongation from RNA polymerase II promoter;RNA metabolic process;snRNA transcription by RNA polymerase II;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;transcription initiation from RNA polymerase II promoter ATP binding;DNA binding;helicase activity microtubule cytoskeleton;nucleoplasm;nucleus;transcription factor TFIIF complex;transcriptional preinitiation complex Basal transcription factors Abortive elongation of HIV-1 transcript in the absence of Tat;Estrogen-dependent gene expression;FGFR2 alternative splicing;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;HIV elongation arrest and recovery;HIV Transcription Initiation;mRNA Capping;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;Processing of Capped Intron-Containing Pre-mRNA;RNA Pol II CTD phosphorylation and interaction with CE;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Promoter Escape;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription Elongation;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;Signaling by FGFR2 IIIa TM;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes;Transcription of the HIV genome;Viral Messenger RNA Synthesis BRCA1-RNA polymerase II complex;RNA polymerase II (RNAPII);RNA polymerase II holoenzyme complex;TFIIF complex (transcription factor IIF) -0.16996955871582 -0.586020469665527 1.14489912986755 1.03376936912537 1.14489912986755 1.8228155374527 1.8228155374527 0.620652139186859 -0.00375020503997803 -0.610957443714142 -0.505477845668793 -0.434660077095032 -0.822351336479187 -0.980910301208496 -0.911966860294342 -1.02325963973999 -0.331299304962158 -1.20922756195068 + Cluster -674 55 55 55 35.5 35.5 35.5 238.26 0 323.31 114280000000 306 6.41797431680233 0 Q14980;Q14980-2;Q14980-4;Q14980-3;Q14980-5 Q14980;Q14980-2;Q14980-4;Q14980-3 Nuclear mitotic apparatus protein 1 NUMA1 1741 Microtubule (MT)-binding protein that plays a role inthe formation and maintenance of the spindle poles and thealignement and the segregation of chromosomes during mitotic celldivision (PubMed:7769006, PubMed:17172455, PubMed:19255246,PubMed:24996901, PubMed:26195665, PubMed:27462074). Functions totether the minus ends of MTs at the spindle poles, which iscritical for the establishment and maintenance of the spindlepoles (PubMed:12445386, PubMed:11956313). Plays a role in theestablishment of the mitotic spindle orientation during metaphaseand elongation during anaphase in a dynein-dynactin-dependentmanner (PubMed:23870127, PubMed:24109598, PubMed:24996901,PubMed:26765568). In metaphase, part of a ternary complex composedof GPSM2 and G(i) alpha proteins, that regulates the recruitmentand anchorage of the dynein-dynactin complex in the mitotic cellcortex regions situated above the two spindle poles, and henceregulates the correct oritentation of the mitotic spindle(PubMed:23027904, PubMed:22327364, PubMed:23921553). Duringanaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical regionthrough direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulationof the spindle elongation and chromosome segregation(PubMed:22327364, PubMed:23921553, PubMed:24996901,PubMed:24371089). Binds also to other polyanionicphosphoinositides, such as phosphatidylinositol 3-phosphate (PIP),lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate(PIP3), in vitro (PubMed:24996901, PubMed:24371089). Also requiredfor proper orientation of the mitotic spindle during asymmetriccell divisions (PubMed:21816348). Plays a role in mitotic MT asterassembly (PubMed:11163243, PubMed:11229403, PubMed:12445386).Involved in anastral spindle assembly (PubMed:25657325).Positively regulates TNKS protein localization to spindle poles inmitosis (PubMed:16076287). Highly abundant component of thenuclear matrix where it may serve a non-mitotic structural role,occupies the majority of the nuclear volume (PubMed:10075938).Required for epidermal differentiation and hair folliclemorphogenesis (By similarity). Lipid-anchor{ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901};Cytoplasmic side {ECO:0000269|PubMed:24371089,ECO:0000269|PubMed:24996901}. Lateral cell membrane{ECO:0000250|UniProtKB:E9Q7G0}. Note=Mitotic cell cycle-dependentshuttling protein that relocalizes from the interphase nucleus tothe spindle poles and cell cortex (PubMed:1541636,PubMed:10811826). In interphase, resides in the nuclear matrix(PubMed:1541630, PubMed:1541636, PubMed:23921553). In prophase,restricted to the interchromatin or condensed chromosome space(PubMed:10811826). In prometaphase, after nuclear envelopedisassembly, forms aggregates both in the spindle midzone and atduplicated centrosomes and astral microtubules (MTs) of thebipolar spindle apparatus (PubMed:10811826). Translocates from thespindle midzone towards the spindle poles along spindle fibers ina MT- and dynein-dynactin-dependent manner until the anaphaseonset (PubMed:1541636, PubMed:10811826). In metaphase, recruitedto the polar cortical region in a GPSM2- and GNAI1-dependentmanner (PubMed:23870127, PubMed:24109598, PubMed:24996901).Excluded from the metaphase equatorial cortical region in aRanGTP-dependent manner (PubMed:22327364, PubMed:23870127).Phosphorylation on Thr-2055 by CDK1 results in its localization atspindle poles in metaphase, but not at the cell cortex(PubMed:23921553). In anaphase, recruited and anchored at the cellmembrane of the polar cortical region in a EPB41-, EPB41L2-,phosphatidylinositol-dependent and GPSM2- and G(i) alpha proteins-independent manner (PubMed:23870127, PubMed:24996901,PubMed:24109598, PubMed:24371089). Excluded from the anaphaseequatorial region of the cell cortex in a RACGAP1- and KIF23-dependent and RanGTP-independent manner (PubMed:24996901).Associated with astral MTs emanating from the spindle poles duringanaphase (PubMed:12445386, PubMed:24996901). NonphosphorylatedThr-2055 localizes at the cell cortex, weakly during metaphase andmore prominently during anaphase in a phosphatase PPP2CA-dependentmanner (PubMed:23921553). As mitosis progresses it reassociateswith telophase chromosomes very early during nuclear reformation,before substantial accumulation of lamins on chromosomal surfacesis evident (PubMed:1541636). Localizes to the tips of cortical MTsin prometaphase (PubMed:26765568). Localizes along MTs andspecifically to both MT plus and minus ends (PubMed:26765568).Accumulates also at MT tips near the cell periphery(PubMed:26765568). Colocalizes with GPSM2 at mitotic spindle polesduring mitosis (PubMed:11781568, PubMed:21816348). Colocalizeswith SPAG5 at mitotic spindle at prometaphase and at mitoticspindle poles at metaphase and anaphase (PubMed:27462074).Colocalizes with ABRO1 at mitotic spindle poles (PubMed:26195665).Colocalized with TNKS from prophase through to anaphase in mitosis(PubMed:16076287). Colocalizes with tubulin alpha(PubMed:12445386). CCSAP is essential for its centrosomallocalization (PubMed:26562023). In horizontally retinal progenitordividing cells, localized to the lateral cortical region (Bysimilarity). {ECO:0000250|UniProtKB:E9Q7G0,ECO:0000269|PubMed:10811826, ECO:0000269|PubMed:11781568,ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:1541630,ECO:0000269|PubMed:1541636, ECO:0000269|PubMed:16076287,ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364,ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553,ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089,ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:26195665,ECO:0000269|PubMed:26562023, ECO:0000269|PubMed:26765568,ECO:0000269|PubMed:27462074}.Isoform 3: Cytoplasm, cytosol{ECO:0000269|PubMed:7962183}. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:7962183}.Cytoplasm, cytoskeleton, spindle pole{ECO:0000269|PubMed:7962183}. Note=During interphase, mainlyclustered at the centrosomal region in the cytosol. After entryinto mitosis, detected at mitotic spindle poles.{ECO:0000269|PubMed:7962183}.Isoform 4: Cytoplasm, cytosol{ECO:0000269|PubMed:7962183}. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:7962183}.Cytoplasm, cytoskeleton, spindle pole{ECO:0000269|PubMed:7962183}. Note=During interphase, mainlyclustered at the centrosomal region in the cytosol. After entryinto mitosis, detected at mitotic spindle poles.{ECO:0000269|PubMed:7962183}.;Nucleus {ECO:0000269|PubMed:1541630,ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:27462074}.Nucleus, nucleoplasm {ECO:0000269|PubMed:10811826}. Nucleus matrix{ECO:0000269|PubMed:10075938, ECO:0000269|PubMed:11956313,ECO:0000269|PubMed:1541636, ECO:0000269|PubMed:7962183}.Chromosome {ECO:0000269|PubMed:1541630}. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386,ECO:0000269|PubMed:26765568}. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:10811826,ECO:0000269|PubMed:1541630, ECO:0000269|PubMed:1541636,ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26562023,ECO:0000269|PubMed:26765568}. Cytoplasm, cytoskeleton, spindlepole {ECO:0000269|PubMed:10811826, ECO:0000269|PubMed:11781568,ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386,ECO:0000269|PubMed:1541630, ECO:0000269|PubMed:1541636,ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:21816348,ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23870127,ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598,ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325,ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26562023,ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006,ECO:0000269|PubMed:7962183}. Cytoplasm, cell cortex{ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364,ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553,ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24996901}. Cellmembrane {ECO:0000269|PubMed:24371089,ECO:0000269|PubMed:24996901} anastral spindle assembly;astral microtubule organization;cell division;chromosome segregation;establishment of mitotic spindle orientation;meiotic cell cycle;microtubule bundle formation;nucleus organization;positive regulation of BMP signaling pathway;positive regulation of chromosome segregation;positive regulation of chromosome separation;positive regulation of hair follicle development;positive regulation of intracellular transport;positive regulation of keratinocyte differentiation;positive regulation of microtubule polymerization;positive regulation of mitotic spindle elongation;positive regulation of protein localization to cell cortex;positive regulation of protein localization to spindle pole body;positive regulation of spindle assembly;regulation of metaphase plate congression;regulation of mitotic spindle organization disordered domain specific binding;dynein complex binding;microtubule binding;microtubule minus-end binding;microtubule plus-end binding;phosphatidylinositol binding;protein C-terminus binding;protein domain specific binding;protein-containing complex binding;structural molecule activity;tubulin binding cell cortex;cell cortex region;centrosome;chromosome;cortical microtubule;cytoplasm;cytoplasmic microtubule bundle;cytosol;dendrite;extracellular exosome;extrinsic component of plasma membrane;Golgi membrane;lateral cell cortex;lateral plasma membrane;microtubule bundle;microtubule minus-end;microtubule plus-end;mitotic spindle;mitotic spindle astral microtubule;mitotic spindle midzone;mitotic spindle pole;neuronal cell body;nuclear matrix;nucleoplasm;nucleus;protein-containing complex;spindle;spindle microtubule;spindle pole;spindle pole centrosome Mitotic Prophase;Recruitment of NuMA to mitotic centrosomes NuMA-LGN-G-alpha-i-1 complex -0.372997522354126 -0.00817864201962948 1.09752118587494 1.27601051330566 0.872917771339417 2.0844361782074 1.05864417552948 1.02553951740265 -0.101009517908096 -0.0633817836642265 -0.803314983844757 -0.722373306751251 -1.19249391555786 -0.637080907821655 -0.749942600727081 -0.792416512966156 -0.435954540967941 -1.53592503070831 + Cluster -674 12 12 12 14.4 14.4 14.4 147.18 0 97.185 7730800000 27 5.80381651026864 1.03092783505155E-05 Q9NTJ3;Q9NTJ3-2 Q9NTJ3;Q9NTJ3-2 Structural maintenance of chromosomes protein 4 SMC4 2937 Central component of the condensin complex, a complexrequired for conversion of interphase chromatin into mitotic-likecondense chromosomes. The condensin complex probably introducespositive supercoils into relaxed DNA in the presence of type Itopoisomerases and converts nicked DNA into positive knotted formsin the presence of type II topoisomerases Nucleus {ECO:0000269|PubMed:10958694}.Cytoplasm {ECO:0000269|PubMed:10958694}. Chromosome{ECO:0000269|PubMed:10958694}. Note=In interphase cells, themajority of the condensin complex is found in the cytoplasm, whilea minority of the complex is associated with chromatin. Asubpopulation of the complex however remains associated withchromosome foci in interphase cells. During mitosis, most of thecondensin complex is associated with the chromatin. At the onsetof prophase, the regulatory subunits of the complex arephosphorylated by CDC2, leading to condensin's association withchromosome arms and to chromosome condensation. Dissociation fromchromosomes is observed in late telophase. cell division;kinetochore organization;meiotic chromosome condensation;meiotic chromosome segregation;mitotic chromosome condensation;mitotic sister chromatid segregation ATP binding;protein heterodimerization activity;single-stranded DNA binding condensin complex;cytosol;nuclear speck;nucleoplasm;nucleus Condensation of Prometaphase Chromosomes;Condensation of Prophase Chromosomes CAP(C)-CAP(E) complex;Condensin I complex;Condensin II;Condensin I-PARP-1-XRCC1 complex;DNA ligase IV-condensin complex;DNMT3B complex 0.386468678712845 -0.1488176882267 0.967519104480743 1.94911158084869 0.584681749343872 1.91056644916534 0.458201676607132 0.0475987941026688 -0.225777149200439 0.346747666597366 -0.482624441385269 0.103521794080734 -0.417555153369904 -0.303683906793594 -1.66275656223297 -1.52281844615936 -0.727744877338409 -1.26263928413391 + Cluster -674 5 5 4 29.1 29.1 25.1 23.818 0 220.77 8122400000 29 3.07815121653512 0.000938461538461538 O15173;O15173-2 O15173;O15173-2 Membrane-associated progesterone receptor component 2 PGRMC2 172 Receptor for steroids. Single-pass membraneprotein {ECO:0000305}.;Membrane {ECO:0000305} steroid binding;steroid hormone receptor activity integral component of membrane;membrane;nuclear envelope -0.855327963829041 -0.0489454157650471 1.33902490139008 1.8639965057373 1.00021767616272 1.72944915294647 0.933658182621002 0.837939143180847 -0.658341348171234 -0.4744952917099 -0.589661419391632 -0.305756390094757 -0.727274060249329 -0.602593123912811 -0.801238775253296 -1.29874277114868 -0.345079004764557 -0.996829986572266 + Cluster -674 4 4 4 4.8 4.8 4.8 166.8 0 39.772 698210000 5 6.23032703171524 0 Q86X10;Q86X10-3;Q86X10-2;Q86X10-4 Q86X10;Q86X10-3;Q86X10-2;Q86X10-4 Ral GTPase-activating protein subunit beta RALGAPB 2122 Non-catalytic subunit of the heterodimeric RalGAP1 andRalGAP2 complexes which act as GTPase activators for the Ras-likesmall GTPases RALA and RALB. activation of GTPase activity;regulation of small GTPase mediated signal transduction GTPase activator activity;protein heterodimerization activity Translocation of SLC2A4 (GLUT4) to the plasma membrane -1.43492436408997 0.322373747825623 1.25896763801575 0.921069443225861 1.51519203186035 1.27210855484009 1.43956077098846 0.948333859443665 -0.267138957977295 0.0420347303152084 -0.825052917003632 -0.223914504051208 -1.27629697322845 -0.524694919586182 -0.852041780948639 -1.04685020446777 -0.331842452287674 -0.936883628368378 + Cluster -674 4 4 4 8.1 8.1 8.1 100.01 0 57.661 4149400000 16 4.91796778510091 2.07253886010363E-05 Q9HCS7 Q9HCS7 Pre-mRNA-splicing factor SYF1 XAB2 2862 Involved in pre-mRNA splicing as component of thespliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346).Involved in transcription-coupled repair (TCR), transcription andpre-mRNA splicing (PubMed:10944529, PubMed:17981804) Nucleus {ECO:0000269|PubMed:11991638,ECO:0000269|PubMed:25599396, ECO:0000269|PubMed:28076346,ECO:0000269|PubMed:28502770}. Note=Detected in the splicingcomplex carrying pre-mRNA. {ECO:0000250|UniProtKB:Q99PK0}. blastocyst development;cerebral cortex development;generation of catalytic spliceosome for first transesterification step;mRNA splicing, via spliceosome;transcription, DNA-templated;transcription-coupled nucleotide-excision repair catalytic step 2 spliceosome;membrane;nucleoplasm;nucleus;post-mRNA release spliceosomal complex;Prp19 complex;U2-type catalytic step 2 spliceosome Spliceosome Dual incision in TC-NER;Formation of TC-NER Pre-Incision Complex;Gap-filling DNA repair synthesis and ligation in TC-NER;mRNA Splicing - Major Pathway;Transcription-Coupled Nucleotide Excision Repair (TC-NER) C complex spliceosome;Spliceosome -1.74218082427979 0.125069230794907 1.09224379062653 0.893888294696808 1.8425133228302 1.46591985225677 1.38487827777863 0.602031707763672 -0.314368814229965 -0.265430241823196 -0.386864960193634 -0.265430241823196 -1.02199637889862 -0.577732622623444 -0.935411870479584 -1.07258808612823 -0.412270218133926 -0.412270218133926 + Cluster -674 4 4 4 5.8 5.8 5.8 86.191 0 27.866 536220000 5 4.46844909955733 6.0377358490566E-05 O14964;O14964-2 O14964;O14964-2 Hepatocyte growth factor-regulated tyrosine kinase substrate HGS 146 Involved in intracellular signal transduction mediatedby cytokines and growth factors. When associated with STAM, itsuppresses DNA signaling upon stimulation by IL-2 and GM-CSF.Could be a direct effector of PI3-kinase in vesicular pathway viaearly endosomes and may regulate trafficking to early and lateendosomes by recruiting clathrin. May concentrate ubiquitinatedreceptors within clathrin-coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body(MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0complex binds ubiquitin and acts as sorting machinery thatrecognizes ubiquitinated receptors and transfers them to furthersequential lysosomal sorting/trafficking processes. May contributeto the efficient recruitment of SMADs to the activin receptorcomplex. Involved in receptor recycling via its association withthe CART complex, a multiprotein complex required for efficienttransferrin receptor recycling but not for EGFR degradation. Peripheral membrane protein{ECO:0000305|PubMed:23166352, ECO:0000305|PubMed:24790097}; Peripheral membraneprotein {ECO:0000250|UniProtKB:Q9JJ50}. Note=Colocalizes withUBQLN1 in ubiquitin-rich cytoplasmic aggregates that are notendocytic compartments. {ECO:0000269|PubMed:16159959}.;Cytoplasm {ECO:0000250|UniProtKB:Q9JJ50}.Early endosome membrane {ECO:0000269|PubMed:23166352,ECO:0000269|PubMed:24790097};Cytoplasmic side {ECO:0000305|PubMed:23166352,ECO:0000305|PubMed:24790097}. Endosome, multivesicular bodymembrane {ECO:0000250|UniProtKB:Q9JJ50} endosomal transport;macroautophagy;membrane invagination;membrane organization;multivesicular body assembly;negative regulation of angiogenesis;negative regulation of cell proliferation;negative regulation of epidermal growth factor receptor signaling pathway;negative regulation of JAK-STAT cascade;negative regulation of platelet-derived growth factor receptor signaling pathway;negative regulation of vascular endothelial growth factor receptor signaling pathway;positive regulation of exosomal secretion;positive regulation of gene expression;protein localization to membrane;protein targeting to lysosome;regulation of MAP kinase activity;regulation of protein catabolic process;signal transduction metal ion binding;protein domain specific binding;ubiquitin-like protein ligase binding cytosol;early endosome;early endosome membrane;endosome;ESCRT-0 complex;extracellular exosome;intracellular membrane-bounded organelle;lysosome;multivesicular body membrane Endocytosis;Phagosome Cargo recognition for clathrin-mediated endocytosis;Clathrin-mediated endocytosis;EGFR downregulation;Endosomal Sorting Complex Required For Transport (ESCRT);InlB-mediated entry of Listeria monocytogenes into host cell;Lysosome Vesicle Biogenesis;Negative regulation of MET activity;Ub-specific processing proteases CART complex;RIN1-STAM2-HRS complex;SIMPLE-HRS-STAM1 complex;SNARE complex (HGS, SNAP25, STX13) -1.33563506603241 -0.0317918621003628 1.16583621501923 0.816250324249268 1.6093578338623 1.24968242645264 1.87799918651581 0.72697639465332 -0.595675528049469 -0.322949916124344 -1.30680406093597 -0.00778394937515259 -0.951092004776001 -0.684304594993591 -0.581703364849091 -0.903170228004456 -0.475944936275482 -0.249246850609779 + Cluster -674 16 16 16 28.1 28.1 28.1 80.592 0 263.11 20467000000 54 4.69851087265002 3.01724137931034E-05 P49959;P49959-2;P49959-3 P49959;P49959-2;P49959-3 Double-strand break repair protein MRE11A MRE11A 1129 Component of the MRN complex, which plays a central rolein double-strand break (DSB) repair, DNA recombination,maintenance of telomere integrity and meiosis. The complexpossesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11.RAD50 may be required to bind DNA ends and hold them in closeproximity. This could facilitate searches for short or longregions of sequence homology in the recombining DNA templates, andmay also stimulate the activity of DNA ligases and/or restrict thenuclease activity of MRE11 to prevent nucleolytic degradation pasta given point (PubMed:9651580, PubMed:9590181, PubMed:9705271,PubMed:11741547, PubMed:29670289). The complex may also berequired for DNA damage signaling via activation of the ATM kinase(PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). Nucleus {ECO:0000269|PubMed:10783165,ECO:0000269|PubMed:26215093}. Chromosome, telomere{ECO:0000269|PubMed:10888888}. Chromosome{ECO:0000269|PubMed:26215093}. Note=Localizes to discrete nuclearfoci after treatment with genotoxic agents.{ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:26215093}. cell proliferation;cellular response to DNA damage stimulus;DNA double-strand break processing;DNA duplex unwinding;DNA recombination;DNA repair;DNA replication;DNA strand resection involved in replication fork processing;double-strand break repair;double-strand break repair via homologous recombination;double-strand break repair via nonhomologous end joining;intra-S DNA damage checkpoint;meiotic DNA double-strand break formation;mitochondrial double-strand break repair via homologous recombination;mitotic G2 DNA damage checkpoint;negative regulation of apoptotic process;negative regulation of DNA endoreduplication;positive regulation of kinase activity;positive regulation of protein autophosphorylation;positive regulation of telomere maintenance;positive regulation of type I interferon production;reciprocal meiotic recombination;regulation of mitotic recombination;sister chromatid cohesion;synapsis;telomere maintenance;telomere maintenance via telomerase;telomeric 3' overhang formation;viral process 3'-5' exonuclease activity;3'-5'-exodeoxyribonuclease activity;5'-3' exonuclease activity;cadherin binding;double-stranded DNA binding;endodeoxyribonuclease activity;identical protein binding;manganese ion binding;nuclease activity;protein C-terminus binding;single-stranded DNA endodeoxyribonuclease activity cytoplasm;cytosol;Mre11 complex;nuclear chromosome, telomeric region;nucleoplasm;nucleus;PML body;site of double-strand break Cellular senescence;Homologous recombination;Non-homologous end-joining Ataxia-telangiectasia-like syndrome;Immunodeficiency associated with DNA repair defects Cytosolic sensors of pathogen-associated DNA;DNA Damage/Telomere Stress Induced Senescence;G2/M DNA damage checkpoint;HDR through Homologous Recombination (HRR);HDR through MMEJ (alt-NHEJ);HDR through Single Strand Annealing (SSA);Homologous DNA Pairing and Strand Exchange;IRF3-mediated induction of type I IFN;Meiotic recombination;Nonhomologous End-Joining (NHEJ);Presynaptic phase of homologous DNA pairing and strand exchange;Processing of DNA double-strand break ends;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;Regulation of TP53 Activity through Phosphorylation;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Sensing of DNA Double Strand Breaks BASC complex (BRCA1-associated genome surveillance complex);BRCA1-BARD1-BACH1-DNA damage complex II;BRCA1-RAD50-MRE11-NBS1 complex;CF IIAm complex (Cleavage factor IIAm complex);DNA double-strand break end-joining complex;MDC1-MRE11-RAD50-NBS1 complex;MDC1-MRN-ATM-FANCD2 complex;MRE11A-RAD50-NBN-TRF2 complex;MRN complex (MRE11-RAD50-NBN complex);MRN-TRRAP complex (MRE11A-RAD50-NBN-TRRAP complex);PTIP-DNA damage response complex;R/M complex (RAD50-MRE11 complex);RAD50-MRE11-NBN-p200-p350 complex;Rap1 complex;TERF2-RAP1 complex -0.865259289741516 0.257128894329071 0.932750701904297 1.01051914691925 0.932750701904297 1.66586220264435 1.61132109165192 1.35480630397797 0.160510718822479 -0.564315617084503 -0.654927909374237 -0.433724582195282 -1.16158998012543 -1.00836849212646 -0.809072017669678 -1.22978889942169 -0.646190524101257 -0.552412450313568 + Cluster -674 23 23 23 24.7 24.7 24.7 134.46 0 323.31 49676000000 108 6.42820436192958 0 Q9P2J5;Q9P2J5-2;Q9P2J5-3 Q9P2J5;Q9P2J5-2 Leucine--tRNA ligase, cytoplasmic LARS 3055 Catalyzes the specific attachment of an amino acid toits cognate tRNA in a two step reaction: the amino acid (AA) isfirst activated by ATP to form AA-AMP and then transferred to theacceptor end of the tRNA. Exhibits a post-transfer editingactivity to hydrolyze mischarged tRNAs Cytoplasm {ECO:0000250}. cellular response to amino acid starvation;cellular response to amino acid stimulus;cellular response to leucine;cellular response to leucine starvation;glutaminyl-tRNA aminoacylation;leucyl-tRNA aminoacylation;negative regulation of autophagy;positive regulation of GTPase activity;positive regulation of TORC1 signaling;protein targeting to lysosome;regulation of cell size;tRNA aminoacylation for protein translation aminoacyl-tRNA editing activity;ATP binding;glutamine-tRNA ligase activity;GTPase activator activity;leucine-tRNA ligase activity aminoacyl-tRNA synthetase multienzyme complex;cytoplasm;cytosol;endomembrane system;endoplasmic reticulum;lysosome;nuclear body Aminoacyl-tRNA biosynthesis Infantile liver failure Cytosolic tRNA aminoacylation;SeMet incorporation into proteins Multisynthetase complex -0.752661883831024 -0.0770823508501053 1.02327656745911 1.03762662410736 1.13251078128815 1.52861726284027 1.49186635017395 1.37911593914032 -0.299134910106659 -0.200944930315018 -1.06090986728668 0.0473164990544319 -1.0522346496582 -0.762823700904846 -1.36999273300171 -1.13752043247223 -0.393978327512741 -0.533046305179596 + Cluster -674 2 2 2 16.7 16.7 16.7 20.324 0 16.443 1424900000 8 6.21653757358301 0 P53801 P53801 Pituitary tumor-transforming gene 1 protein-interacting protein PTTG1IP 1211 May facilitate PTTG1 nuclear translocation. Single-pass type Imembrane protein {ECO:0000305}. Cytoplasm{ECO:0000269|PubMed:10781616}. Nucleus{ECO:0000269|PubMed:10781616}. Note=According to PubMed:10781616,it is found in the cytoplasm and the nucleus.;Membrane {ECO:0000305} negative regulation of DNA damage response, signal transduction by p53 class mediator;negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator;positive regulation of cellular protein catabolic process;positive regulation of protein ubiquitination;protein import into nucleus p53 binding cytoplasm;extracellular exosome;integral component of membrane;membrane;nucleoplasm;nucleus -1.57648944854736 0.51713103055954 0.51713103055954 1.40591251850128 1.13326811790466 1.08115684986115 1.54963231086731 1.33693027496338 0.281828969717026 -0.99914014339447 -0.422079920768738 0.0861556529998779 -0.99914014339447 -0.765414834022522 -0.868034303188324 -0.858074545860291 -0.796424031257629 -0.624349236488342 + Cluster -674 13 13 8 18.6 18.6 13.1 102.35 0 226.81 29225000000 80 3.98074482701647 0.000140845070422535 Q92973;Q92973-2;Q92973-3 Q92973;Q92973-2;Q92973-3 Transportin-1 TNPO1 2370 Functions in nuclear protein import as nuclear transportreceptor. Serves as receptor for nuclear localization signals(NLS) in cargo substrates (PubMed:24753571). Is thought to mediatedocking of the importin/substrate complex to the nuclear porecomplex (NPC) through binding to nucleoporin and the complex issubsequently translocated through the pore by an energy requiring,Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ranbinds to the importin, the importin/substrate complex dissociatesand importin is re-exported from the nucleus to the cytoplasmwhere GTP hydrolysis releases Ran. The directionality of nuclearimport is thought to be conferred by an asymmetric distribution ofthe GTP- and GDP-bound forms of Ran between the cytoplasm andnucleus (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region ofthe heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2and mediates their nuclear import. Appears also to be involved inhnRNP A1/A2 nuclear export. Mediates the nuclear import ofribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-likeimport receptor binding (BIB) domain of RPL23A. In vitro, mediatesnuclear import of H2A, H2B, H3 and H4 histones, and SRP19 (Bysimilarity). Mediates nuclear import of ADAR/ADAR1 isoform 1 andisoform 5 in a RanGTP-dependent manner (PubMed:19124606,PubMed:24753571). Cytoplasm. Nucleus. intraciliary transport involved in cilium assembly;NLS-bearing protein import into nucleus;protein import into nucleus, translocation;regulation of mRNA stability;ribosomal protein import into nucleus;viral process nuclear localization sequence binding;protein transporter activity;Ran GTPase binding;RNA binding cilium;cytoplasm;cytosol;extracellular exosome;nuclear membrane;nuclear periphery;nucleus Intraflagellar transport;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA -0.948718726634979 0.250422120094299 1.34137094020844 1.02638912200928 1.19379806518555 1.3736652135849 1.46038711071014 0.950264811515808 0.14129164814949 -0.723452091217041 -0.742689490318298 0.267442911863327 -0.99594658613205 -0.399911373853683 -1.18980896472931 -1.0621691942215 -1.1811044216156 -0.761231124401093 + Cluster -674 10 10 10 35.9 35.9 35.9 34.852 0 84.174 27139000000 42 5.72373813236951 9.70873786407767E-06 Q99848 Q99848 Probable rRNA-processing protein EBP2 EBNA1BP2 2599 Required for the processing of the 27S pre-rRNA Nucleus, nucleolus{ECO:0000269|PubMed:19170763, ECO:0000269|PubMed:2879624}.Note=Associated with the nucleolus in an RNA-dependent manner. ribosomal large subunit biogenesis;rRNA processing RNA binding nuclear periphery;nucleolus;nucleus;preribosome, large subunit precursor Major pathway of rRNA processing in the nucleolus and cytosol Nop56p-associated pre-rRNA complex -0.732546746730804 0.366340070962906 1.1818128824234 1.42491436004639 1.52563488483429 1.27909803390503 0.958948731422424 1.04614055156708 -0.269975960254669 -0.262578219175339 -0.636812031269073 0.135916069149971 -0.868675053119659 -0.644209742546082 -1.00779283046722 -1.26375424861908 -0.910852193832397 -1.321608543396 + Cluster -674 8 8 8 7.8 7.8 7.8 178.7 0 48.322 1403600000 15 6.96297273574835 0 Q9NRL2;Q9NRL2-2 Q9NRL2;Q9NRL2-2 Bromodomain adjacent to zinc finger domain protein 1A BAZ1A 2920 Component of the ACF complex, an ATP-dependent chromatinremodeling complex, that regulates spacing of nucleosomes usingATP to generate evenly spaced nucleosomes along the chromatin. TheATPase activity of the complex is regulated by the length offlanking DNA. Also involved in facilitating the DNA replicationprocess. BAZ1A is the accessory, non-catalytic subunit of thecomplex which can enhance and direct the process provided by theATPase subunit, SMARCA5, probably through targetingpericentromeric heterochromatin in late S phase. Moves end-positioned nucleosomes to a predominantly central position. Mayhave a role in nuclear receptor-mediated transcription repression.Component of the histone-fold protein complex CHRACcomplex which facilitates nucleosome sliding by the ACF complexand enhances ACF-mediated chromatin assembly. The C-terminalregions of both CHRAC1 and POLE1 are required for these functions. Nucleus. Note=May target the CHRAC complexto heterochromatin. chromatin remodeling;DNA-dependent DNA replication;histone acetylation;regulation of transcription by RNA polymerase II metal ion binding ACF complex;CHRAC HuCHRAC complex;SNF2H-BAZ1A complex;SNF2h-cohesin-NuRD complex -0.0113538419827819 -0.134205177426338 1.25288462638855 1.03481793403625 1.60900378227234 1.3062778711319 1.10488843917847 1.25534129142761 -0.296487301588058 -0.383341699838638 -0.750729322433472 0.13342872262001 -0.704011023044586 -0.939666748046875 -1.02218234539032 -1.00903880596161 -1.20093190670013 -1.24469459056854 + Cluster -674 1 1 1 5 5 5 36.853 0 10.047 110750000 2 8.71410173435065 0 P42330;P42330-2 P42330;P42330-2 Aldo-keto reductase family 1 member C3 AKR1C3 1011 Catalyzes the conversion of aldehydes and ketones toalcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and20-alpha HSD. Can interconvert active androgens, estrogens andprogestins with their cognate inactive metabolites. Preferentiallytransforms androstenedione (4-dione) to testosterone. Cytoplasm. cellular response to cadmium ion;cellular response to calcium ion;cellular response to corticosteroid stimulus;cellular response to jasmonic acid stimulus;cellular response to prostaglandin D stimulus;cellular response to prostaglandin stimulus;cellular response to reactive oxygen species;cellular response to starvation;cyclooxygenase pathway;daunorubicin metabolic process;doxorubicin metabolic process;farnesol catabolic process;G protein-coupled receptor signaling pathway;keratinocyte differentiation;macromolecule metabolic process;male gonad development;negative regulation of retinoic acid biosynthetic process;oxidation-reduction process;positive regulation of cell death;positive regulation of cell proliferation;positive regulation of endothelial cell apoptotic process;positive regulation of protein kinase B signaling;positive regulation of reactive oxygen species metabolic process;progesterone metabolic process;prostaglandin metabolic process;protein import into nucleus, translocation;regulation of retinoic acid receptor signaling pathway;regulation of testosterone biosynthetic process;renal absorption;response to nutrient;retinal metabolic process;retinoid metabolic process;steroid metabolic process;testosterone biosynthetic process 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity;alcohol dehydrogenase (NADP+) activity;alditol:NADP+ 1-oxidoreductase activity;aldo-keto reductase (NADP) activity;androsterone dehydrogenase activity;delta4-3-oxosteroid 5beta-reductase activity;dihydrotestosterone 17-beta-dehydrogenase activity;geranylgeranyl reductase activity;indanol dehydrogenase activity;ketoreductase activity;ketosteroid monooxygenase activity;NADP-retinol dehydrogenase activity;oxidoreductase activity;oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor;phenanthrene 9,10-monooxygenase activity;prostaglandin D2 11-ketoreductase activity;prostaglandin H2 endoperoxidase reductase activity;prostaglandin-F synthase activity;retinal dehydrogenase activity;retinol dehydrogenase activity;steroid dehydrogenase activity;testosterone 17-beta-dehydrogenase (NADP+) activity;testosterone dehydrogenase (NAD+) activity;trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity cytoplasm;cytosol;extracellular exosome;intracellular;nucleus Arachidonic acid metabolism;Folate biosynthesis;Metabolic pathways;Ovarian steroidogenesis;Steroid hormone biosynthesis RA biosynthesis pathway;Retinoid metabolism and transport;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of Prostaglandins (PG) and Thromboxanes (TX) -1.10260462760925 0.532463252544403 1.55229556560516 1.10155665874481 1.52016353607178 0.846916496753693 0.996830761432648 1.04057776927948 -0.272576063871384 -0.246081963181496 -1.22755086421967 0.352494060993195 -0.405746042728424 -0.556253790855408 -0.801144063472748 -1.46813857555389 -0.931601047515869 -0.931601047515869 + Cluster -674 10 10 10 10.4 10.4 10.4 155.34 0 92.501 9656400000 32 4.17210064063986 0.00010410094637224 Q7Z3K3;Q7Z3K3-5;Q7Z3K3-7;Q7Z3K3-2;Q7Z3K3-6;Q7Z3K3-3;Q7Z3K3-4 Q7Z3K3;Q7Z3K3-5;Q7Z3K3-7;Q7Z3K3-2;Q7Z3K3-6;Q7Z3K3-3 Pogo transposable element with ZNF domain POGZ 2074 Plays a role in mitotic cell cycle progression and isinvolved in kinetochore assembly and mitotic sister chromatidcohesion. Probably through its association with CBX5 plays a rolein mitotic chromosome segregation by regulating aurora kinaseB/AURKB activation and AURKB and CBX5 dissociation from chromosomearms. Nucleus. Chromosome. Cytoplasm.Note=According to some authors, it is not localized to mitoticchromatin (PubMed:19244240). Recruited to trimethylated 'Lys-9' ofhistone H3 (H3K9me3). {ECO:0000269|PubMed:19244240}. cell division;kinetochore assembly;mitotic sister chromatid cohesion;regulation of gene expression DNA-binding transcription factor activity, RNA polymerase II-specific;metal ion binding;RNA polymerase II core promoter sequence-specific DNA binding cytoplasm;cytosol;nuclear chromatin;nucleoplasm;nucleus -0.504230439662933 0.471739590167999 0.940858960151672 2.12733173370361 1.16899907588959 0.880790174007416 0.845908403396606 1.20921957492828 -0.521212816238403 -0.678328335285187 -0.732779979705811 -0.61342853307724 -0.225143238902092 -0.33060747385025 -0.355565160512924 -0.783006489276886 -1.59377110004425 -1.30677402019501 + Cluster -674 5 5 5 22.4 22.4 22.4 29.669 0 48.498 3247100000 17 4.40483004023406 6.07142857142857E-05 Q6DKI1;Q6DKI1-2 Q6DKI1;Q6DKI1-2 60S ribosomal protein L7-like 1 RPL7L1 1968 blastocyst formation;maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) RNA binding;structural constituent of ribosome cytosolic large ribosomal subunit;nucleolus -0.508416295051575 0.350360512733459 1.29268276691437 1.29268276691437 1.29268276691437 1.46507143974304 1.25185263156891 1.25185263156891 -0.627112150192261 -0.626225054264069 -0.925564289093018 -0.673227846622467 -0.581255197525024 -0.581255197525024 -0.581255197525024 -0.984678089618683 -1.16416335105896 -0.944032728672028 + Cluster -674 14 14 13 30.6 30.6 30.6 59.379 0 323.31 67496000000 106 8.17836291649178 0 Q14498;Q14498-2;Q14498-3 Q14498;Q14498-2;Q14498-3 RNA-binding protein 39 RBM39 1711 Transcriptional coactivator for steroid nuclearreceptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1 (Bysimilarity). May be involved in pre-mRNA splicing process Nucleus speckle. Note=Concentrated innuclear speckles. Colocalizes with the core spliceosomal snRNPproteins. mRNA processing;RNA processing;RNA splicing RNA binding microtubule cytoskeleton;microtubule organizing center;nuclear speck;nucleoplasm;protein-containing complex Spliceosome -0.901484966278076 -0.130647674202919 1.31310343742371 1.49960613250732 1.25659871101379 1.65778601169586 1.30433189868927 0.956073701381683 -0.888195395469666 -0.837485551834106 -0.776788711547852 -0.290007650852203 -0.798920333385468 -0.632611751556396 -0.582351088523865 -0.915003478527069 -0.841219663619995 -0.392783612012863 + Cluster -674 3 3 1 8 8 2.1 41.59 0 6.2835 3478200000 13 8.00752734964068 0 Q01085;Q01085-2 Q01085;Q01085-2 Nucleolysin TIAR TIAL1 1477 RNA-binding protein. Possesses nucleolytic activityagainst cytotoxic lymphocyte target cells. May be involved inapoptosis. Cytoplasm {ECO:0000250}. Nucleus{ECO:0000250}. Cytoplasmic granule. Note=The cytoplasmic granulesare stress granules which are a dense aggregation in the cytosolcomposed of proteins and RNAs that appear when the cell is understress. Colocalizes with NANOS3 in the stress granules (Bysimilarity). Cytoplasmic granules of cytolytic T-lymphocytes.{ECO:0000250}. apoptotic process;defense response;fibroblast growth factor receptor signaling pathway;germ cell development;positive regulation of cell proliferation;regulation of transcription by RNA polymerase II;stem cell division AU-rich element binding;DNA binding;RNA binding cytoplasm;cytoplasmic stress granule;lysosome;nucleoplasm;nucleus FGFR2 alternative splicing -0.855361878871918 0.45739683508873 1.37219274044037 1.42143380641937 1.04044103622437 1.48255801200867 1.22123026847839 1.06456482410431 -0.108101055026054 -0.508070886135101 -0.597213625907898 -0.597213625907898 -0.839921832084656 -0.797099173069 -0.428863823413849 -1.27313637733459 -0.954619109630585 -1.1002162694931 + Cluster -674 17 17 17 41.8 41.8 41.8 55.52 0 165.64 39279000000 86 6.96854923986504 0 P43490 P43490 Nicotinamide phosphoribosyltransferase NAMPT 1031 Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamidemononucleotide, an intermediate in the biosynthesis of NAD. It isthe rate limiting component in the mammalian NAD biosynthesispathway. The secreted form behaves both as a cytokine withimmunomodulating properties and an adipokine with anti-diabeticproperties, it has no enzymatic activity, partly because of lackof activation by ATP, which has a low level in extracellular spaceand plasma. Plays a role in the modulation of circadian clockfunction. NAMPT-dependent oscillatory production of NAD regulatesoscillation of clock target gene expression by releasing the coreclock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependentSIRT1-mediated suppression (By similarity) Nucleus {ECO:0000269|PubMed:24130902}.Cytoplasm {ECO:0000250|UniProtKB:Q99KQ4}. Secreted{ECO:0000269|PubMed:21741723}. Note=Under non-inflammatoryconditions, visfatin predominantly exhibits a granular patternwithin the nucleus. Secreted by endothelial cells upon IL-1betastimulation. Abundantly secreted in milk, reaching 100-fold higherconcentrations compared to maternal serum.{ECO:0000269|PubMed:21741723, ECO:0000269|PubMed:24130902}. aging;cell-cell signaling;cellular response to amyloid-beta;cellular response to ionizing radiation;cellular response to oxygen-glucose deprivation;circadian regulation of gene expression;circadian rhythm;female pregnancy;microglial cell activation;NAD biosynthesis via nicotinamide riboside salvage pathway;negative regulation of autophagy;negative regulation of cellular senescence;neuron death;positive regulation of cell proliferation;positive regulation of nitric-oxide synthase biosynthetic process;positive regulation of smooth muscle cell proliferation;positive regulation of transcription by RNA polymerase II;regulation of lung blood pressure;response to D-galactose;response to organic cyclic compound;signal transduction cytokine activity;drug binding;identical protein binding;nicotinamide phosphoribosyltransferase activity;nicotinate-nucleotide diphosphorylase (carboxylating) activity;protein homodimerization activity cell junction;cytosol;extracellular exosome;nuclear speck;plasma membrane Metabolic pathways;Nicotinate and nicotinamide metabolism;NOD-like receptor signaling pathway Teglarinad chloride BMAL1:CLOCK,NPAS2 activates circadian gene expression;Nicotinamide salvaging -0.748508334159851 0.370099186897278 1.21302449703217 1.38022208213806 1.02649080753326 1.54211223125458 1.16565322875977 1.36152470111847 -0.611900508403778 -0.362579613924026 -1.43044650554657 -0.362579613924026 -0.797729432582855 -0.591463267803192 -0.52446973323822 -0.748508334159851 -0.877232015132904 -1.00370931625366 + Cluster -674 10 10 10 33.8 33.8 33.8 35.936 0 138.12 24564000000 54 6.29907855277399 0 P08758 P08758 Annexin A5 ANXA5 563 This protein is an anticoagulant protein that acts as anindirect inhibitor of the thromboplastin-specific complex, whichis involved in the blood coagulation cascade. blood coagulation;cellular response to gonadotropin-releasing hormone;cellular response to lead ion;negative regulation of apoptotic process;negative regulation of blood coagulation;negative regulation of prolactin secretion;negative regulation of sequestering of calcium ion;platelet degranulation;positive regulation of apoptotic process;protein homooligomerization;regulation of flagellated sperm motility;response to calcium ion;response to organic substance;response to thyroid hormone;signal transduction calcium ion binding;calcium-dependent phospholipid binding;calcium-transporting ATPase activity;heparin binding;molecular adaptor activity;peptide hormone binding;phospholipase inhibitor activity;phospholipid binding;receptor tyrosine kinase binding collagen-containing extracellular matrix;cytoplasm;cytosol;endothelial microparticle;external side of plasma membrane;extracellular exosome;extracellular region;focal adhesion;intracellular;membrane Platelet degranulation -0.269472509622574 0.233616441488266 1.10850203037262 1.10850203037262 1.39289724826813 1.49917733669281 1.49917733669281 1.26703906059265 -0.687527537345886 -0.641269147396088 -0.764784276485443 -0.531259834766388 -0.641269147396088 -0.764784276485443 -0.921996533870697 -0.962182760238647 -0.962182760238647 -0.962182760238647 + Cluster -674 36 34 34 53.4 53.4 53.4 72.332 0 323.31 299940000000 400 9.18321888726735 0 P11021 P11021 78 kDa glucose-regulated protein HSPA5 614 Endoplasmic reticulum chaperone that plays a key role inprotein folding and quality control in the endoplasmic reticulumlumen (PubMed:2294010, PubMed:23769672, PubMed:23990668,PubMed:28332555). Involved in the correct folding of proteins anddegradation of misfolded proteins via its interaction withDNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5from its substrate (By similarity). Acts as a key repressor of theERN1/IRE1-mediated unfolded protein response (UPR)(PubMed:1550958, PubMed:19538957). In the unstressed endoplasmicreticulum, recruited by DNAJB9/ERdj4 to the luminal region ofERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1,thereby inactivating ERN1/IRE1 (By similarity). Accumulation ofmisfolded protein in the endoplasmic reticulum causes release ofHSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequentactivation of ERN1/IRE1 (By similarity). Plays an auxiliary rolein post-translational transport of small presecretory proteinsacross endoplasmic reticulum (ER). May function as an allostericmodulator for SEC61 channel-forming translocon complex, likelycooperating with SEC62 to enable the productive insertion of theseprecursors into SEC61 channel. Appears to specifically regulatetranslocation of precursors having inhibitory residues in theirmature region that weaken channel gating Endoplasmic reticulum lumen{ECO:0000269|PubMed:21080038, ECO:0000269|PubMed:21289099,ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:29497057}.Melanosome {ECO:0000269|PubMed:12643545}. Cytoplasm{ECO:0000250|UniProtKB:P20029}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV.{ECO:0000269|PubMed:12643545}. ATF6-mediated unfolded protein response;cellular response to antibiotic;cellular response to calcium ion;cellular response to cAMP;cellular response to drug;cellular response to gamma radiation;cellular response to glucose starvation;cellular response to heat;cellular response to interleukin-4;cellular response to manganese ion;cellular response to nerve growth factor stimulus;cellular response to unfolded protein;cerebellar Purkinje cell layer development;cerebellum structural organization;chaperone cofactor-dependent protein refolding;endoplasmic reticulum unfolded protein response;ER overload response;IRE1-mediated unfolded protein response;luteolysis;maintenance of protein localization in endoplasmic reticulum;negative regulation of apoptotic process;negative regulation of IRE1-mediated unfolded protein response;negative regulation of protein homodimerization activity;negative regulation of transforming growth factor beta receptor signaling pathway;neuron apoptotic process;neuron differentiation;PERK-mediated unfolded protein response;positive regulation of cell migration;positive regulation of neuron projection development;positive regulation of protein ubiquitination;positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress;protein folding in endoplasmic reticulum;protein refolding;regulation of ATF6-mediated unfolded protein response;regulation of IRE1-mediated unfolded protein response;regulation of PERK-mediated unfolded protein response;regulation of protein folding in endoplasmic reticulum;response to cocaine;response to methamphetamine hydrochloride;response to unfolded protein;stress response to metal ion;substantia nigra development;toxin transport;ubiquitin-dependent ERAD pathway ATP binding;ATPase activity;ATPase activity, coupled;cadherin binding;calcium ion binding;chaperone binding;enzyme binding;heat shock protein binding;misfolded protein binding;protein binding involved in protein folding;protein domain specific binding;ribosome binding;ubiquitin protein ligase binding;unfolded protein binding cell surface;cytoplasm;cytosol;endoplasmic reticulum;endoplasmic reticulum chaperone complex;endoplasmic reticulum lumen;endoplasmic reticulum membrane;endoplasmic reticulum-Golgi intermediate compartment;extracellular exosome;focal adhesion;integral component of endoplasmic reticulum membrane;intracellular membrane-bounded organelle;melanosome;membrane;midbody;mitochondrion;myelin sheath;nucleus;plasma membrane;protein-containing complex;smooth endoplasmic reticulum Antigen processing and presentation;Prion diseases;Protein export;Protein processing in endoplasmic reticulum;Thyroid hormone synthesis Antigen Presentation: Folding, assembly and peptide loading of class I MHC;ATF6 (ATF6-alpha) activates chaperone genes;ATF6 (ATF6-alpha) activates chaperones;IRE1alpha activates chaperones;PERK regulates gene expression;Platelet degranulation;Regulation of HSF1-mediated heat shock response CEN complex;DGCR8 multiprotein complex;H2AX complex I;H2AX complex II;H2AX complex, isolated from cells without IR exposure;HCF-1 complex;HRD1 complex;SNW1 complex -0.534912109375 1.09582960605621 1.11492741107941 0.811463057994843 1.3371776342392 0.918821334838867 1.19579648971558 0.783663988113403 0.10946112126112 0.312044858932495 0.0936122164130211 -0.179301664233208 -1.24877285957336 -0.878917634487152 -0.996946811676025 -1.69347620010376 -0.918565273284912 -1.3219051361084 + Cluster -674 18 18 18 32.9 32.9 32.9 83.165 0 241.51 51221000000 90 5.74354399528568 1E-05 P41250 P41250 Glycine--tRNA ligase GARS 1001 Catalyzes the ligation of glycine to the 3'-end of itscognate tRNA. Also produces diadenosine tetraphosphate (Ap4A), auniversal pleiotropic signaling molecule needed for cellregulation pathways, by direct condensation of 2 ATPs Cytoplasm {ECO:0000269|PubMed:17035524}.Cell projection, axon {ECO:0000269|PubMed:17035524,ECO:0000269|PubMed:25168514}. Secreted{ECO:0000250|UniProtKB:Q9CZD3}. Secreted, exosome{ECO:0000250|UniProtKB:Q9CZD3}. Note=Secreted by motor neuron,possibly through the exosome pathway (By similarity). Intransfected COS7 cells, not detected in mitochondria, nor in Golgiapparatus (PubMed:17035524). {ECO:0000250|UniProtKB:Q9CZD3,ECO:0000269|PubMed:17035524}. diadenosine tetraphosphate biosynthetic process;glycyl-tRNA aminoacylation;mitochondrial glycyl-tRNA aminoacylation;tRNA aminoacylation for protein translation ATP binding;bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity;glycine-tRNA ligase activity;identical protein binding;protein dimerization activity axon;cytoplasm;cytosol;extracellular exosome;mitochondrial matrix;mitochondrion;secretory granule Aminoacyl-tRNA biosynthesis Charcot-Marie-Tooth disease;Distal hereditary motor neuropathies Cytosolic tRNA aminoacylation;Mitochondrial tRNA aminoacylation -0.308890283107758 0.687459230422974 1.28747999668121 1.28747999668121 1.06956303119659 1.5007392168045 0.773891627788544 0.773891627788544 0.321706533432007 -0.509895801544189 -0.822498023509979 -0.191881880164146 -0.191881880164146 -0.509895801544189 -0.822498023509979 -1.62161087989807 -1.10154783725739 -1.62161087989807 + Cluster -674 37 37 37 53.3 53.3 53.3 82.704 0 323.31 403920000000 539 4.96124592434286 2.16216216216216E-05 P13010 P13010 X-ray repair cross-complementing protein 5 XRCC5 648 Single-stranded DNA-dependent ATP-dependent helicase.Has a role in chromosome translocation. The DNA helicase IIcomplex binds preferentially to fork-like ends of double-strandedDNA in a cell cycle-dependent manner. It works in the 3'-5'direction. Binding to DNA may be mediated by XRCC6. Involved inDNA non-homologous end joining (NHEJ) required for double-strandbreak repair and V(D)J recombination. The XRCC5/6 dimer acts asregulatory subunit of the DNA-dependent protein kinase complexDNA-PK by increasing the affinity of the catalytic subunit PRKDCto DNA by 100-fold. The XRCC5/6 dimer is probably involved instabilizing broken DNA ends and bringing them together(PubMed:12145306, PubMed:20383123, PubMed:7957065,PubMed:8621488). The assembly of the DNA-PK complex to DNA ends isrequired for the NHEJ ligation step. In association with NAA15,the XRCC5/6 dimer binds to the osteocalcin promoter and activatesosteocalcin expression (PubMed:20383123). The XRCC5/6 dimerprobably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRPlyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5probably acts as the catalytic subunit of 5'-dRP activity, andallows to 'clean' the termini of abasic sites, a class ofnucleotide damage commonly associated with strand breaks, beforesuch broken ends can be joined. The XRCC5/6 dimer together withAPEX1 acts as a negative regulator of transcription(PubMed:8621488). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNPcomplex, a complex that serves as a platform for IRF3phosphorylation and subsequent innate immune response activationthrough the cGAS-STING pathway. Nucleus {ECO:0000269|PubMed:22442688}.Nucleus, nucleolus {ECO:0000269|PubMed:22002106}. Chromosome{ECO:0000269|PubMed:22442688}. activation of innate immune response;brain development;cell proliferation;cellular hyperosmotic salinity response;cellular response to DNA damage stimulus;cellular response to fatty acid;cellular response to gamma radiation;cellular response to leukemia inhibitory factor;cellular response to X-ray;DNA recombination;double-strand break repair;double-strand break repair via nonhomologous end joining;establishment of integrated proviral latency;hematopoietic stem cell differentiation;innate immune response;negative regulation of t-circle formation;negative regulation of transcription, DNA-templated;neutrophil degranulation;positive regulation of catalytic activity;positive regulation of neurogenesis;positive regulation of protein kinase activity;positive regulation of telomerase activity;positive regulation of telomere maintenance via telomerase;positive regulation of type I interferon production;protein localization to chromosome, telomeric region;regulation of smooth muscle cell proliferation;regulation of telomere maintenance;response to drug;telomere maintenance ATP binding;ATP-dependent DNA helicase activity;damaged DNA binding;DNA binding;DNA end binding;double-stranded DNA binding;enzyme activator activity;protein C-terminus binding;protein-containing complex binding;RNA binding;telomeric DNA binding;transcription regulatory region DNA binding;ubiquitin protein ligase binding cytosol;extracellular region;Ku70:Ku80 complex;membrane;nonhomologous end joining complex;nuclear chromosome, telomeric region;nuclear telomere cap complex;nucleolus;nucleoplasm;nucleus;plasma membrane;protein-containing complex;protein-DNA complex;ribonucleoprotein complex;secretory granule lumen;site of DNA damage Non-homologous end-joining 2-LTR circle formation;Cytosolic sensors of pathogen-associated DNA;IRF3-mediated induction of type I IFN;Neutrophil degranulation;Nonhomologous End-Joining (NHEJ) 53BP1-containing complex;DEAF1- complex;DHX9-ADAR-vigilin-DNA-PK-Ku antigen complex;DNA double-strand break end-joining complex;DNA-PK-Ku complex;DNA-PK-Ku-eIF2-NF90-NF45 complex;Dysbindin 1-A-DNA-PK-complex;HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex;Ku antigen complex;Ku antigen-NARG1 complex;Ku antigen-YY1-alphaMyHC promoter complex;Ku-ORC complex;MGC1-DNA-PKcs-Ku complex;NCOA6-DNA-PK-Ku-PARP1 complex;PCNA-KU antigen complex;Rap1 complex;TERF2-RAP1 complex;TRF2-Ku complex;Vigilin-DNA-PK-Ku antigen complex;WRN-Ku70-Ku80-PARP1 complex;XRCC6-XRCC5-WRN complex -0.10749688744545 0.815586447715759 1.01722359657288 1.17619955539703 1.01722359657288 0.891357004642487 1.41355407238007 1.26458716392517 0.278333485126495 -0.0947781354188919 -0.671305119991302 -0.529959321022034 -0.77297043800354 -0.671305119991302 -0.829247951507568 -1.4931126832962 -1.2107766866684 -1.4931126832962 + Cluster -674 37 37 37 32.7 32.7 32.7 170.59 0 323.31 105640000000 188 6.94933904020708 0 P07814 P07814 Bifunctional glutamate/proline--tRNA ligase;Glutamate--tRNA ligase;Proline--tRNA ligase EPRS 541 Multifunctional protein which is primarily part of theaminoacyl-tRNA synthetase multienzyme complex, also know asmultisynthetase complex, that catalyzes the attachment of thecognate amino acid to the corresponding tRNA in a two-stepreaction: the amino acid is first activated by ATP to form acovalent intermediate with AMP and is then transferred to theacceptor end of the cognate tRNA (PubMed:1756734, PubMed:24100331,PubMed:23263184). The phosphorylation of EPRS, induced byinterferon-gamma, dissociates the protein from the aminoacyl-tRNAsynthetase multienzyme complex and recruits it to the GAIT complexthat binds to stem loop-containing GAIT elements in the 3'-UTR ofdiverse inflammatory mRNAs (such as ceruplasmin), suppressingtheir translation. Interferon-gamma can therefore redirect, inspecific cells, the EPRS function from protein synthesis totranslation inhibition (PubMed:15479637, PubMed:23071094). Alsofunctions as an effector of the mTORC1 signaling pathway bypromoting, through SLC27A1, the uptake of long-chain fatty acid byadipocytes. Thereby, it also plays a role in fat metabolism andmore indirectly influences lifespan (PubMed:28178239) Peripheral membrane protein{ECO:0000305|PubMed:19289464, ECO:0000305|PubMed:28178239}.Note=Translocates from cytosol to membranes upon phosphorylationat Ser-999. {ECO:0000269|PubMed:19289464,ECO:0000269|PubMed:28178239}.;Cytoplasm, cytosol{ECO:0000269|PubMed:19289464}. Membrane{ECO:0000269|PubMed:28178239} cellular response to insulin stimulus;cellular response to interferon-gamma;glutamyl-tRNA aminoacylation;long-chain fatty acid import;negative regulation of translation;prolyl-tRNA aminoacylation;protein-containing complex assembly;tRNA aminoacylation for protein translation ATP binding;glutamate-tRNA ligase activity;GTPase binding;identical protein binding;proline-tRNA ligase activity;protein homodimerization activity;RNA stem-loop binding;zinc ion binding aminoacyl-tRNA synthetase multienzyme complex;cytoplasm;cytosol;GAIT complex;membrane;plasma membrane;ribonucleoprotein complex Aminoacyl-tRNA biosynthesis;Metabolic pathways;Porphyrin and chlorophyll metabolism Cytosolic tRNA aminoacylation;SeMet incorporation into proteins;tRNA modification in the nucleus and cytosol GAIT complex;Multisynthetase complex 0.112739443778992 0.696224391460419 0.963973224163055 1.25046706199646 1.25046706199646 0.910221934318542 1.63131856918335 0.835687160491943 -0.147792592644691 -0.783763527870178 -0.783763527870178 -0.123166352510452 -0.345646053552628 -0.670403122901917 -0.670403122901917 -1.02107512950897 -1.31738674640656 -1.78769874572754 + Cluster -674 34 34 34 40.5 40.5 40.5 113.08 0 323.31 136740000000 276 5.39912020494233 7.5187969924812E-06 P09874 P09874 Poly [ADP-ribose] polymerase 1 PARP1 585 HPF1 conferring serinespecificity (PubMed:28190768). Probably also catalyzes tyrosineADP-ribosylation of target proteins following interaction withHPF1 (PubMed:30257210). Catalyzes the poly-ADP-ribosylation ofhistones in a HPF1-dependent manner (PubMed:27067600). Involved inthe base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved inchromatin architecture and in DNA metabolism (PubMed:17177976,PubMed:18172500, PubMed:19344625, PubMed:19661379,PubMed:23230272). ADP-ribosylation follows DNA damage and appearsas an obligatory step in a detection/signaling pathway leading tothe reparation of DNA strand breaks (PubMed:17177976,PubMed:18172500, PubMed:19344625, PubMed:19661379,PubMed:23230272). In addition to base excision repair (BER)pathway, also involved in double-strand breaks (DSBs) repair:together with TIMELESS, accumulates at DNA damage sites andpromotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). In addition toproteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminalphosphates and a 2'-OH group in single- and double-stranded DNA,respectively (PubMed:27471034). Required for PARP9 and DTX3Lrecruitment to DNA damage sites (PubMed:23230272). PARP1-dependentPARP9-DTX3L-mediated ubiquitination promotes the rapid andspecific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 toDNA damage sites (PubMed:23230272). Acts as a regulator oftranscription: positively regulates the transcription of MTUS1 andnegatively regulates the transcription of MTUS2/TIP150(PubMed:19344625). With EEF1A1 and TXK, forms a complex that actsas a T-helper 1 (Th1) cell-specific transcription factor and bindsthe promoter of IFN-gamma to directly regulate its transcription,and is thus involved importantly in Th1 cytokine production(PubMed:17177976). Involved in the synthesis of ATP in thenucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257).Nuclear ATP generation is required for extensive chromatinremodeling events that are energy-consuming (PubMed:27257257);Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair(PubMed:17177976, PubMed:18172500, PubMed:19344625,PubMed:19661379, PubMed:23230272, PubMed:25043379,PubMed:26344098). Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+)is transferred to the acceptor carboxyl group of glutamate andaspartate residues and further ADP-ribosyl groups are transferredto the 2'-position of the terminal adenosine moiety, building up apolymer with an average chain length of 20-30 units(PubMed:7852410, PubMed:9315851, PubMed:19764761,PubMed:25043379). Mediates the poly(ADP-ribosyl)ation of a numberof proteins, including itself, APLF and CHFR (PubMed:17396150,PubMed:19764761). Also mediates serine ADP-ribosylation of targetproteins following interaction with HPF1 Nucleus {ECO:0000269|PubMed:17177976,ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:23230272}.Nucleus, nucleolus {ECO:0000269|PubMed:9518481}. Chromosome{ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26344098}.Note=Localizes to sites of DNA damage.{ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26344098}. apoptotic process;ATP generation from poly-ADP-D-ribose;cellular response to amyloid-beta;cellular response to DNA damage stimulus;cellular response to insulin stimulus;cellular response to oxidative stress;cellular response to UV;cellular response to zinc ion;DNA damage response, detection of DNA damage;DNA repair;double-strand break repair;double-strand break repair via homologous recombination;global genome nucleotide-excision repair;macrophage differentiation;mitochondrial DNA metabolic process;mitochondrial DNA repair;mitochondrion organization;negative regulation of ATP biosynthetic process;negative regulation of telomere maintenance via telomere lengthening;negative regulation of transcription by RNA polymerase II;nucleotide-excision repair, DNA damage recognition;nucleotide-excision repair, DNA incision;nucleotide-excision repair, DNA incision, 5'-to lesion;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, preincision complex stabilization;peptidyl-serine ADP-ribosylation;positive regulation of cardiac muscle hypertrophy;positive regulation of intracellular estrogen receptor signaling pathway;positive regulation of mitochondrial depolarization;positive regulation of myofibroblast differentiation;positive regulation of neuron death;positive regulation of protein localization to nucleus;positive regulation of single strand break repair;positive regulation of SMAD protein signal transduction;positive regulation of transcription by RNA polymerase II;positive regulation of transcription regulatory region DNA binding;protein ADP-ribosylation;protein autoprocessing;protein modification process;protein poly-ADP-ribosylation;regulation of catalytic activity;regulation of cellular protein localization;regulation of DNA methylation;regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway;regulation of SMAD protein complex assembly;response to aldosterone;response to gamma radiation;signal transduction involved in regulation of gene expression;telomere maintenance;transcription by RNA polymerase II;transforming growth factor beta receptor signaling pathway DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;enzyme binding;estrogen receptor binding;histone deacetylase binding;identical protein binding;NAD binding;NAD+ ADP-ribosyltransferase activity;protein ADP-ribosylase activity;protein kinase binding;protein N-terminus binding;RNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;R-SMAD binding;transcription factor binding;zinc ion binding membrane;mitochondrion;nuclear chromosome, telomeric region;nuclear envelope;nucleolus;nucleoplasm;nucleus;protein-containing complex;protein-DNA complex;site of DNA damage;transcription factor complex Apoptosis;Base excision repair;Necroptosis;NF-kappa B signaling pathway Iniparib;Niraparib;Olaparib;Pamiparib;Rucaparib;Talazoparib;Veliparib DNA Damage Recognition in GG-NER;Downregulation of SMAD2/3:SMAD4 transcriptional activity;Dual Incision in GG-NER;Formation of Incision Complex in GG-NER;HDR through MMEJ (alt-NHEJ);POLB-Dependent Long Patch Base Excision Repair;SUMOylation of DNA damage response and repair proteins CAMK2-delta-MASH1 promoter-coactivator complex;CDK8-MED6-PARP1 complex;Condensin I-PARP-1-XRCC1 complex;CTCF-nucleophosmin-PARP-HIS-KPNA-LMNA-TOP complex;H2AX complex I;MASH1 promoter-coactivator complex;NCOA6-DNA-PK-Ku-PARP1 complex;PARP1-LIG3 complex;Rap1 complex;RC complex during G2/M-phase of cell cycle;RC complex during S-phase of cell cycle;TLE1 corepressor complex (MASH1 promoter-corepressor complex);WRN-Ku70-Ku80-PARP1 complex -0.0493432134389877 0.181040495634079 1.20419538021088 0.791788041591644 1.13812136650085 1.33637726306915 1.12805187702179 1.25306057929993 -0.0493432134389877 -0.733910501003265 -0.630993902683258 0.551014959812164 -1.22951674461365 -0.160931646823883 -1.51319408416748 -1.46463203430176 -0.548653841018677 -1.20313084125519 + Cluster -674 5 5 5 17.7 17.7 17.7 48.586 0 20.265 4434700000 8 5.11738776643693 1.75438596491228E-05 Q9BXS5;Q9BXS5-2;Q9Y6Q5;Q9Y6Q5-2 Q9BXS5;Q9BXS5-2 AP-1 complex subunit mu-1 AP1M1 2707 Subunit of clathrin-associated adaptor protein complex 1that plays a role in protein sorting in the trans-Golgi network(TGN) and endosomes. The AP complexes mediate the recruitment ofclathrin to membranes and the recognition of sorting signalswithin the cytosolic tails of transmembrane cargo molecules. Peripheral membrane protein;Cytoplasmic side. Note=Component of the coat surrounding thecytoplasmic face of coated vesicles located at the Golgi complex.;Golgi apparatus. Cytoplasmic vesicle,clathrin-coated vesicle membrane antigen processing and presentation of exogenous peptide antigen via MHC class II;endosome to melanosome transport;intracellular protein transport;melanosome organization;neutrophil degranulation;protein targeting;regulation of defense response to virus by virus;vesicle targeting clathrin adaptor complex;clathrin-coated vesicle membrane;cytoplasmic vesicle membrane;cytosol;extracellular exosome;Golgi membrane;intracellular membrane-bounded organelle;lysosomal membrane;membrane;plasma membrane;specific granule membrane;trans-Golgi network membrane Human immunodeficiency virus 1 infection;Lysosome Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;MHC class II antigen presentation;Nef mediated downregulation of MHC class I complex cell surface expression;Neutrophil degranulation AP1 adaptor complex;AP1B1-AP1G2-AP1M-1AP1S1 complex;Gamma-BAR-AP1 complex -0.696584939956665 0.750184834003448 1.19338297843933 0.719708383083344 1.37541270256042 1.37735366821289 1.47713911533356 0.922029376029968 -0.671279966831207 -0.447568863630295 -0.531122505664825 0.288024365901947 -1.54681360721588 -0.703500032424927 -0.835571229457855 -1.25839912891388 -0.650514960289001 -0.761880338191986 + Cluster -674 7 7 7 15.4 15.4 15.4 75.035 0 60.641 2874800000 13 4.94392548723856 2.12765957446809E-05 Q96PZ0;Q96PZ0-2 Q96PZ0;Q96PZ0-2 Pseudouridylate synthase 7 homolog PUS7 2525 Pseudouridylate synthase that catalyzespseudouridylation of RNAs (PubMed:28073919, PubMed:29628141). Actsas a regulator of protein synthesis in embryonic stem cells bymediating pseudouridylation of RNA fragments derived from tRNAs(tRFs): pseudouridylated tRFs inhibit translation by targeting thetranslation initiation complex (PubMed:29628141). Also catalyzespseudouridylation of mRNAs: mediates pseudouridylation of mRNAswith the consensus sequence 5'-UGUAG-3' (PubMed:28073919). Inaddition to mRNAs and tRNAs, binds other types of RNAs, such assnRNAs, Y RNAs and vault RNAs, suggesting that it can catalyzepseudouridylation of many RNA types (PubMed:29628141) Nucleus {ECO:0000269|PubMed:29628141}. mRNA pseudouridine synthesis;negative regulation of translation;regulation of hematopoietic stem cell differentiation;regulation of mesoderm development;tRNA pseudouridine synthesis enzyme binding;pseudouridine synthase activity;RNA binding nucleus tRNA modification in the nucleus and cytosol -0.332574456930161 0.368723958730698 1.31727373600006 1.13777136802673 1.13777136802673 1.32602739334106 1.6264671087265 0.937126874923706 -1.08454477787018 -0.858564376831055 -0.656672537326813 0.339409083127975 -0.996729254722595 -0.858564376831055 -0.858564376831055 -0.651618242263794 -0.990363001823425 -0.902375400066376 + Cluster -674 32 32 32 55.7 55.7 55.7 85.237 0 323.31 241330000000 331 5.69957834042308 9.43396226415094E-06 P49321;P49321-3;P49321-4;P49321-2 P49321;P49321-3;P49321-4;P49321-2 Nuclear autoantigenic sperm protein NASP 1090 Required for DNA replication, normal cell cycleprogression and cell proliferation. Forms a cytoplasmic complexwith HSP90 and H1 linker histones and stimulates HSP90 ATPaseactivity. NASP and H1 histone are subsequently released from thecomplex and translocate to the nucleus where the histone isreleased for binding to DNA. Cytoplasm {ECO:0000250|UniProtKB:Q99MD9}.Nucleus {ECO:0000250|UniProtKB:Q99MD9}. blastocyst development;cell proliferation;CENP-A containing nucleosome assembly;DNA replication;DNA replication-dependent nucleosome assembly;DNA replication-independent nucleosome assembly;G1/S transition of mitotic cell cycle;histone exchange;male gonad development;nucleosome assembly;protein transport;response to testosterone histone binding;protein-containing complex binding cytoplasm;nuclear chromatin;nucleoplasm;nucleus;protein-containing complex ASF1-histone containing complex;Histone H3.1 complex;Histone H3.3 complex -0.454323083162308 0.339004844427109 1.0984103679657 0.948114037513733 1.43569648265839 1.37478077411652 1.57865631580353 1.17826354503632 -0.369129925966263 -0.768542766571045 -0.847977578639984 -0.0928550139069557 -1.06182479858398 -0.503520250320435 -0.856994926929474 -1.16608393192291 -0.656782031059265 -1.17489206790924 + Cluster -674 2 2 2 3.5 3.5 3.5 92.499 0 7.141 1398700000 4 7.13187693047904 0 Q6IA86;Q6IA86-5;Q6IA86-4;Q6IA86-2;Q6IA86-3;Q6IA86-6;Q6IA86-7 Q6IA86;Q6IA86-5;Q6IA86-4;Q6IA86-2;Q6IA86-3;Q6IA86-6;Q6IA86-7 Elongator complex protein 2 ELP2 1975 Regulates the ligand-dependent activation of STAT3 Cytoplasm. Nucleus. regulation of JAK-STAT cascade;regulation of transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;tRNA wobble uridine modification protein kinase binding cytoplasm;cytosol;Elongator holoenzyme complex;transcription elongation factor complex Autosomal recessive mental retardation HATs acetylate histones Elongator complex (ELP1, ELP2, ELP3, ELP4, ELP5, ELP6);Elongator core complex;Elongator holo complex -0.490207403898239 0.37739497423172 1.10471451282501 0.903320968151093 1.62156319618225 0.952573835849762 1.7208411693573 1.13264095783234 -0.176327899098396 -0.151710510253906 -0.727827429771423 -0.283268451690674 -1.07282853126526 -0.772291660308838 -0.798139870166779 -1.05000686645508 -1.03169929981232 -1.25874161720276 + Cluster -674 9 2 2 41.5 13.8 13.8 14.105 0 48.414 7347700000 5 7.2436558841714 0 Q93077;Q7L7L0;P04908 Q93077;Q7L7L0;P04908 Histone H2A type 1-C;Histone H2A type 3;Histone H2A type 1-B/E HIST1H2AC;HIST3H2A;HIST1H2AB 2380 Core component of nucleosome. Nucleosomes wrap andcompact DNA into chromatin, limiting DNA accessibility to thecellular machineries which require DNA as a template. Histonesthereby play a central role in transcription regulation, DNArepair, DNA replication and chromosomal stability. DNAaccessibility is regulated via a complex set of post-translationalmodifications of histones, also called histone code, andnucleosome remodeling. Nucleus. Chromosome. chromatin organization;negative regulation of cell proliferation;nucleosome disassembly;UV-damage excision repair DNA binding;protein heterodimerization activity extracellular exosome;nuclear chromatin;nuclear nucleosome;nucleoplasm;nucleosome;nucleus Alcoholism;Necroptosis;Systemic lupus erythematosus Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;Activation of anterior HOX genes in hindbrain development during early embryogenesis;Amyloid fiber formation;B-WICH complex positively regulates rRNA expression;Condensation of Prophase Chromosomes;Deposition of new CENPA-containing nucleosomes at the centromere;DNA Damage/Telomere Stress Induced Senescence;DNA methylation;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Estrogen-dependent gene expression;Formation of the beta-catenin:TCF transactivating complex;HATs acetylate histones;HDACs deacetylate histones;Meiotic recombination;Meiotic synapsis;Metalloprotease DUBs;NoRC negatively regulates rRNA expression;Oxidative Stress Induced Senescence;Packaging Of Telomere Ends;PRC2 methylates histones and DNA;Pre-NOTCH Transcription and Translation;RMTs methylate histone arginines;RNA Polymerase I Chain Elongation;RNA Polymerase I Promoter Opening;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Senescence-Associated Secretory Phenotype (SASP);SIRT1 negatively regulates rRNA expression;Transcriptional regulation by small RNAs;Ub-specific processing proteases;UCH proteinases -0.192311823368073 0.416526705026627 1.21696758270264 0.794297218322754 1.3999035358429 1.08510982990265 1.69577670097351 1.12206220626831 -0.106169015169144 -0.358950972557068 -0.769156694412231 -0.221594035625458 -1.1054379940033 -0.56556236743927 -0.882243871688843 -1.43839931488037 -0.887383699417114 -1.20343399047852 + Cluster -674 2 2 2 16.4 16.4 16.4 20.332 0 18.797 2159100000 8 7.31939985384951 0 O00193 O00193 Small acidic protein SMAP 69 -0.504092395305634 0.439863622188568 1.50637924671173 0.278261035680771 1.26829838752747 1.78572714328766 1.28713154792786 0.831555426120758 -0.12604396045208 -0.621837735176086 0.109244585037231 -0.586819350719452 -1.46735322475433 -0.621837735176086 -0.715839564800262 -1.40333425998688 -0.401790916919708 -1.05751192569733 + Cluster -674 7 7 6 15.3 15.3 13.6 60.13 0 50.152 4887100000 21 4.65306352197315 4.13223140495868E-05 O75131;Q96A23;Q9UBL6;Q8IYJ1;Q96FN4;Q9HCH3;Q9HCH3-2;Q96FN4-2;O95741;Q9UBL6-2;Q96A23-2;O95741-2 O75131 Copine-3 CPNE3 307 Calcium-dependent phospholipid-binding protein that mayplay a role in calcium-mediated intracellular processes;Calcium-dependent phospholipid-binding protein thatplays a role in calcium-mediated intracellular processes. Bindsphospholipid membranes in a calcium-dependent manner (Bysimilarity). Plays a role in dendrite formation by melanocytes(PubMed:23999003).;Calcium-dependent phospholipid-binding protein thatplays a role in calcium-mediated intracellular processes. Exhibitscalcium-dependent cell membrane binding properties;Calcium-dependent phospholipid-binding protein thatplays a role in ERBB2-mediated tumor cell migration in response togrowth factor heregulin stimulation (PubMed:20010870);Probable calcium-dependent phospholipid-binding proteinthat may play a role in calcium-mediated intracellular processes;Probable calcium-dependent phospholipid-binding proteinthat may play a role in calcium-mediated intracellular processes(By similarity). Plays a role in dendrite formation by melanocytes(PubMed:23999003). Cytoplasm {ECO:0000250|UniProtKB:P59108}.Nucleus {ECO:0000250|UniProtKB:P59108}. Cell membrane{ECO:0000250|UniProtKB:P59108}. Note=Translocates to the cellmembrane and the nucleus in a calcium-dependent manner.Colocalizes with CD2 at the cell membrane.{ECO:0000250|UniProtKB:P59108}.;Cytoplasm {ECO:0000250|UniProtKB:Q9Z140}.Cell membrane {ECO:0000250|UniProtKB:Q9Z140}. Endosome{ECO:0000250|UniProtKB:Q9Z140}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000250|UniProtKB:Q9Z140}. Perikaryon{ECO:0000250|UniProtKB:Q9Z140}. Cell projection, dendrite{ECO:0000250|UniProtKB:Q9Z140}. Note=Mainly cytoplasmic in absenceof calcium. Associated predominantly with membranes in presence ofcalcium. Translocates to the cell membrane in a calcium-dependentmanner. Colocalized with transferrin in intracellular clathrin-coated membrane vesicles in a calcium-dependent manner.{ECO:0000250|UniProtKB:Q9Z140}.;Cytoplasm {ECO:0000269|PubMed:21087455}.Nucleus {ECO:0000269|PubMed:21087455}. Cell membrane{ECO:0000269|PubMed:21087455}. Note=Translocates to the cellmembrane in a calcium-dependent manner (PubMed:21087455).{ECO:0000269|PubMed:21087455}.;Nucleus {ECO:0000269|PubMed:20010870,ECO:0000269|PubMed:21087455}. Cytoplasm{ECO:0000269|PubMed:12949241, ECO:0000269|PubMed:20010870,ECO:0000269|PubMed:21087455}. Cell membrane{ECO:0000269|PubMed:20010870, ECO:0000269|PubMed:21087455}. Celljunction {ECO:0000269|PubMed:20010870}. Cell junction, focaladhesion {ECO:0000269|PubMed:20010870}. Note=Associates to themembrane in a calcium-dependent manner (PubMed:20010870).Translocates to the cell membrane and the nucleus in a calcium- orgrowth factor heregulin-dependent manner (PubMed:21087455,PubMed:20010870). Colocalizes with the tyrosine phosphorylatedERBB2 form at cell membrane and focal adhesions in a calcium- orgrowth factor heregulin-dependent manner (PubMed:20010870).{ECO:0000269|PubMed:20010870, ECO:0000269|PubMed:21087455}.;Perikaryon {ECO:0000250|UniProtKB:Q8JZW4}.Cell projection {ECO:0000250|UniProtKB:Q8JZW4}. cellular response to calcium ion;cellular response to growth factor stimulus;chemical synaptic transmission;ERBB2 signaling pathway;glycerophospholipid biosynthetic process;lipid metabolic process;nervous system development;neutrophil degranulation;positive regulation of cell migration;positive regulation of dendrite extension;vesicle-mediated transport calcium ion binding;calcium-dependent phospholipid binding;calcium-dependent protein binding;phosphatidylserine binding;protein serine/threonine kinase activity;receptor tyrosine kinase binding;RNA binding;transporter activity axon;azurophil granule membrane;cell junction;clathrin-coated endocytic vesicle;cytoplasm;cytosol;dendrite;endosome;extracellular exosome;extracellular space;focal adhesion;membrane;mitochondrion;neuron projection;nucleolus;nucleus;perikaryon;plasma membrane Glycerophospholipid biosynthesis;Neutrophil degranulation 0.603669762611389 0.27122238278389 1.14570713043213 0.603669762611389 1.0718879699707 1.46869051456451 1.46869051456451 1.19140815734863 -0.084081768989563 -0.814782381057739 -1.04379832744598 0.00636778166517615 -0.921277105808258 -0.498031497001648 -0.857289373874664 -1.31671607494354 -1.00240588188171 -1.29293155670166 + Cluster -674 23 23 21 73.9 73.9 73.9 29.999 0 323.31 96378000000 146 6.32000319296089 0 Q15691 Q15691 Microtubule-associated protein RP/EB family member 1 MAPRE1 1824 Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubulecytoskeleton (PubMed:12388762, PubMed:16109370, PubMed:19632184,PubMed:21646404, PubMed:28726242, PubMed:28814570). Promotescytoplasmic microtubule nucleation and elongation(PubMed:12388762, PubMed:16109370, PubMed:19632184,PubMed:21646404, PubMed:28726242, PubMed:28814570). May beinvolved in spindle function by stabilizing microtubules andanchoring them at centrosomes (PubMed:12388762). Also acts as aregulator of minus-end microtubule organization: interacts withthe complex formed by AKAP9 and PDE4DIP, leading to recruitCAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomalminus-end microtubules to the Golgi, an important step forpolarized cell movement (PubMed:28814570). Promotes elongation ofCAMSAP2-decorated microtubule stretches on the minus-end ofmicrotubules (PubMed:28814570). Acts as a regulator ofautophagosome transport via interaction with CAMSAP2(PubMed:28726242). May play a role in cell migration (Bysimilarity). Cytoplasm, cytoskeleton{ECO:0000269|PubMed:10188731, ECO:0000269|PubMed:12388762,ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:28814570,ECO:0000269|PubMed:9724749}. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:12388762,ECO:0000269|PubMed:14654843}. Golgi apparatus{ECO:0000269|PubMed:25217626}. Note=Associated with themicrotubule growing distal tips (PubMed:28814570). Recruitment tothe Golgi apparatus requires the presence of PDE4DIP isoform13/MMG8/SMYLE (PubMed:25217626). {ECO:0000269|PubMed:25217626,ECO:0000269|PubMed:28814570}. cell division;cell migration;cell proliferation;ciliary basal body-plasma membrane docking;G2/M transition of mitotic cell cycle;negative regulation of microtubule polymerization;positive regulation of cell migration;positive regulation of microtubule plus-end binding;positive regulation of microtubule polymerization;protein localization;protein localization to microtubule;protein localization to microtubule plus-end;regulation of G2/M transition of mitotic cell cycle;regulation of microtubule polymerization or depolymerization;spindle assembly cadherin binding;identical protein binding;microtubule binding;microtubule plus-end binding;protein C-terminus binding;protein kinase binding;RNA binding cell projection membrane;centrosome;cortical microtubule cytoskeleton;cytoplasmic microtubule;cytosol;focal adhesion;Golgi apparatus;microtubule;microtubule organizing center;microtubule plus-end;spindle midzone Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Mitotic Prometaphase;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint 0.128513172268867 0.163287565112114 1.29794490337372 0.842252314090729 1.10889708995819 1.76972258090973 1.33276414871216 1.04570150375366 -0.390105545520782 -0.441503822803497 -0.912866175174713 0.0944459587335587 -1.03313970565796 -0.942219018936157 -0.912866175174713 -1.22227740287781 -0.964275717735291 -0.964275717735291 + Cluster -674 16 16 16 16.9 16.9 16.9 151.86 0 246.39 28359000000 71 7.40561096935949 0 Q9UKV3;Q9UKV3-5;Q9UKV3-2;Q9UKV3-3 Q9UKV3;Q9UKV3-5;Q9UKV3-2;Q9UKV3-3 Apoptotic chromatin condensation inducer in the nucleus ACIN1 3152 ACIN1confers RNA-binding to the complex. The ASAP complex can inhibitRNA processing during in vitro splicing reactions. The ASAPcomplex promotes apoptosis and is disassembled after induction ofapoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X(and probably other apoptotic genes); specifically inhibitsformation of proapoptotic isoforms such as Bcl-X(S); the activityis different from the established EJC assembly and function.Induces apoptotic chromatin condensation after activation byCASP3. Regulates cyclin A1, but not cyclin A2, expression inleukemia cells.;Auxiliary component of the splicing-dependentmultiprotein exon junction complex (EJC) deposited at splicejunction on mRNAs. The EJC is a dynamic structure consisting ofcore proteins and several peripheral nuclear and cytoplasmicassociated factors that join the complex only transiently eitherduring EJC assembly or during subsequent mRNA metabolism.Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJCprior to or during the splicing process and to regulate specificexcision of introns in specific transcription subsets Nucleus. Nucleus speckle. Nucleus,nucleoplasm. Note=Phosphorylation on Ser-1180 by SRPK2redistributes it from the nuclear speckles to the nucleoplasm. apoptotic chromosome condensation;erythrocyte differentiation;mRNA processing;negative regulation of mRNA splicing, via spliceosome;positive regulation of apoptotic process;positive regulation of monocyte differentiation;RNA splicing ATPase activity;enzyme binding;nucleic acid binding;RNA binding ASAP complex;cytosol;nuclear speck;nucleolus;nucleoplasm;nucleus;plasma membrane mRNA surveillance pathway;RNA transport;Spliceosome Apoptotic cleavage of cellular proteins Apoptosis- and splicing-associated protein complex (ASAP-L), SAP18, RNPS1, Acinus-L;Spliceosome -0.217165738344193 0.329608201980591 0.983811020851135 0.923302292823792 1.03279709815979 1.3579968214035 1.5608047246933 1.28207576274872 0.17729914188385 -0.432784199714661 -1.19458878040314 -0.0541207157075405 -1.39362788200378 -0.325657844543457 -0.800123870372772 -1.41358709335327 -0.751837968826294 -1.06420111656189 + Cluster -674 15 15 15 59.6 59.6 59.6 24.205 0 323.31 153450000000 163 5.99858694568117 1.17647058823529E-05 P62241 P62241 40S ribosomal protein S8 RPS8 1338 Lipid-anchor {ECO:0000305}. Note=Localizedin cytoplasmic mRNP granules containing untranslated mRNAs.;Cytoplasm {ECO:0000269|PubMed:17289661}.Membrane {ECO:0000305} maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;endoplasmic reticulum;extracellular exosome;focal adhesion;membrane;nucleoplasm;nucleus;ribonucleoprotein complex Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic 0.0266213491559029 0.25300395488739 0.986468255519867 0.744392096996307 1.35660719871521 1.22512006759644 1.76782786846161 0.88617730140686 -0.0414427705109119 -0.300087451934814 -0.681112766265869 0.186709806323051 -1.5912139415741 -0.755522668361664 -0.73790830373764 -1.49194371700287 -0.991901695728302 -0.841794550418854 + Cluster -674 3 3 3 0.9 0.9 0.9 293.51 0 3.085 677320000 8 6.29505658176711 0 Q9UMN6;Q03164;Q9UMN6-2;Q03164-2;Q03164-3 Q9UMN6 Histone-lysine N-methyltransferase 2B KMT2B 3171 Histone methyltransferase that plays an essential rolein early development and hematopoiesis. Catalytic subunit of theMLL1/MLL complex, a multiprotein complex that mediates bothmethylation of 'Lys-4' of histone H3 (H3K4me) complex andacetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLLcomplex, it specifically mediates H3K4me, a specific tag forepigenetic transcriptional activation (PubMed:12453419,PubMed:20677832, PubMed:26886794). Has weak methyltransferaseactivity by itself, and requires other component of the MLL1/MLLcomplex to obtain full methyltransferase activity(PubMed:19187761, PubMed:26886794). Has no activity toward histoneH3 phosphorylated on 'Thr-3', less activity toward H3 dimethylatedon 'Arg-8' or 'Lys-9', while it has higher activity toward H3acetylated on 'Lys-9'. Binds to unmethylated CpG elements in thepromoter of target genes and helps maintain them in thenonmethylated state (PubMed:20010842). Required fortranscriptional activation of HOXA9 (PubMed:12453419,PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-inducedapoptosis. Plays a critical role in the control of circadian geneexpression and is essential for the transcriptional activationmediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes apermissive chromatin state for circadian transcription bymediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me)and this histone modification directs the circadian acetylation atH3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 tochromatin (By similarity).;Histone methyltransferase. Methylates 'Lys-4' of histoneH3. H3 'Lys-4' methylation represents a specific tag forepigenetic transcriptional activation. Plays a central role inbeta-globin locus transcription regulation by being recruited byNFE2. Plays an important role in controlling bulk H3K4me duringoocyte growth and preimplantation development. Required during thetranscriptionally active period of oocyte growth for theestablishment and/or maintenance of bulk H3K4 trimethylation(H3K4me3), global transcriptional silencing that preceedsresumption of meiosis, oocyte survival and normal zygotic genomeactivation. Nucleus {ECO:0000250}.;Nucleus {ECO:0000269|PubMed:12482972}.MLL cleavage product N320: Nucleus.MLL cleavage product C180: Nucleus.Note=Localizes to a diffuse nuclear pattern when not associatedwith MLL cleavage product N320. apoptotic process;chromatin-mediated maintenance of transcription;circadian regulation of gene expression;embryonic hemopoiesis;gene silencing;histone H3-K4 methylation;histone H3-K4 trimethylation;histone H4-K16 acetylation;memory;negative regulation of DNA methylation;oocyte differentiation;ovarian follicle development;ovulation;positive regulation of cellular response to drug;positive regulation of histone H3-K4 methylation;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;positive regulation of transporter activity;protein-containing complex assembly;regulation of hematopoietic stem cell differentiation;regulation of histone H3-K14 acetylation;regulation of histone H3-K4 methylation;regulation of histone H3-K9 acetylation;regulation of megakaryocyte differentiation;transcription by RNA polymerase II AT DNA binding;DNA binding;DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;histone methyltransferase activity (H3-K4 specific);histone-lysine N-methyltransferase activity;identical protein binding;lysine-acetylated histone binding;protein homodimerization activity;RNA polymerase II distal enhancer sequence-specific DNA binding;transcription regulatory region DNA binding;unmethylated CpG binding;zinc ion binding cytosol;histone methyltransferase complex;MLL1 complex;nucleoplasm;nucleus Cushing syndrome;Lysine degradation;Transcriptional misregulation in cancer B-cell acute lymphoblastic leukemia;Follicular lymphoma;Primary dystonia;T-cell acute lymphoblastic leukemia;Wiedemann-Steiner syndrome PKMTs methylate histone lysines;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RUNX1 regulates transcription of genes involved in differentiation of HSCs ALL-1 supercomplex;Menin-associated histone methyltransferase complex;MLL1 complex;MLL1 core complex;MLL1-WDR5 complex;MLL-HCF complex;MOF complex;MWRAD complex (MLL1, WDR5, RBBP5, ASH2L, DPY30);PTIP-HMT complex -0.11590938270092 0.576704025268555 1.0081729888916 0.697604894638062 1.2838944196701 1.35657930374146 1.63338315486908 1.08433556556702 0.0054675810970366 -0.463523954153061 -1.15613734722137 0.025090740993619 -1.04818487167358 -0.588198184967041 -0.843334317207336 -1.41477620601654 -0.907289981842041 -1.13387835025787 + Cluster -674 8 8 8 45.4 45.4 45.4 12.855 0 79.812 32966000000 60 6.20076260421339 0 O75347;O75347-2 O75347;O75347-2 Tubulin-specific chaperone A TBCA 321 involved in the early step ofthe tubulin folding pathway.;Tubulin-folding protein Cytoplasm, cytoskeleton. post-chaperonin tubulin folding pathway;protein folding;tubulin complex assembly beta-tubulin binding;chaperone binding;RNA binding cytoplasm;microtubule;microtubule cytoskeleton;nucleolus Post-chaperonin tubulin folding pathway -0.17219965159893 0.554129183292389 0.89124459028244 0.743253529071808 1.34607601165771 1.1742936372757 1.77025258541107 1.06493496894836 0.0585184134542942 -0.462728291749954 -1.05891454219818 0.0846263617277145 -1.13958668708801 -0.521240949630737 -0.911637127399445 -1.4341903924942 -0.793803155422211 -1.1930285692215 + Cluster -674 1 1 1 31.1 31.1 31.1 5.2288 0 18.36 5295800000 11 5.86160264410716 1.0989010989011E-05 P0CG34;P0CG35 P0CG34;P0CG35 Thymosin beta-15A;Thymosin beta-15B TMSB15A;TMSB15B 593 Plays an important role in the organization of thecytoskeleton. Binds to and sequesters actin monomers (G actin) andtherefore inhibits actin polymerization (By similarity);Plays an important role in the organization of thecytoskeleton. Binds to and sequesters actin monomers (G actin) andtherefore inhibits actin polymerization (By similarity). May beinvolved in cell migration. Cytoplasm, cytoskeleton {ECO:0000250}. actin filament organization;positive regulation of cell migration;regulation of cell migration;sequestering of actin monomers actin monomer binding;DNA-binding transcription factor activity, RNA polymerase II-specific cytoplasm;cytoskeleton -0.216765105724335 0.349218994379044 0.961719989776611 1.37895143032074 0.843989908695221 1.2540830373764 0.418571472167969 1.42540061473846 0.120186574757099 -1.48094284534454 0.287140041589737 0.622704684734344 -0.842290818691254 -0.842290818691254 -0.842290818691254 -0.434295147657394 -1.4362188577652 -1.56687223911285 + Cluster -674 78 78 78 20.7 20.7 20.7 469.08 0 323.31 126210000000 377 3.69305210553833 0.000298823529411765 P78527;P78527-2 P78527;P78527-2 DNA-dependent protein kinase catalytic subunit PRKDC 1433 negatively regulates CRY1phosphorylation. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNPcomplex, a complex that serves as a platform for IRF3phosphorylation and subsequent innate immune response activationthrough the cGAS-STING pathway.;Serine/threonine-protein kinase that acts as a molecularsensor for DNA damage. Involved in DNA non-homologous end joining(NHEJ) required for double-strand break (DSB) repair and V(D)Jrecombination. Must be bound to DNA to express its catalyticproperties. Promotes processing of hairpin DNA structures in V(D)Jrecombination by activation of the hairpin endonuclease artemis(DCLRE1C). The assembly of the DNA-PK complex at DNA ends is alsorequired for the NHEJ ligation step. Required to protect and alignbroken ends of DNA. May also act as a scaffold protein to aid thelocalization of DNA repair proteins to the site of damage. Foundat the ends of chromosomes, suggesting a further role in themaintenance of telomeric stability and the prevention ofchromosomal end fusion. Also involved in modulation oftranscription. Recognizes the substrate consensus sequence [ST]-Q.Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, therebyregulating DNA damage response mechanism. Phosphorylates DCLRE1C,c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1,DHX9, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2.Can phosphorylate C1D not only in the presence of linear DNA butalso in the presence of supercoiled DNA. Ability to phosphorylatep53/TP53 in the presence of supercoiled DNA is dependent on C1D.Contributes to the determination of the circadian period length byantagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1protein stability, most likely through an indirect mechanism.Interacts with CRY1 and CRY2 Nucleus {ECO:0000269|PubMed:12231622,ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:22002106}.Nucleus, nucleolus {ECO:0000269|PubMed:22002106}. activation of innate immune response;B cell lineage commitment;brain development;cell proliferation;cellular protein modification process;cellular response to DNA damage stimulus;cellular response to insulin stimulus;double-strand break repair;double-strand break repair via alternative nonhomologous end joining;double-strand break repair via nonhomologous end joining;ectopic germ cell programmed cell death;heart development;immunoglobulin V(D)J recombination;innate immune response;intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of apoptotic process;negative regulation of cellular senescence;negative regulation of immunoglobulin production;negative regulation of protein phosphorylation;negative regulation of response to gamma radiation;peptidyl-serine phosphorylation;positive regulation of apoptotic process;positive regulation of developmental growth;positive regulation of fibroblast proliferation;positive regulation of transcription by RNA polymerase II;positive regulation of type I interferon production;pro-B cell differentiation;protein destabilization;protein phosphorylation;protein ubiquitination;regulation of circadian rhythm;regulation of smooth muscle cell proliferation;response to activity;response to gamma radiation;rhythmic process;signal transduction involved in mitotic G1 DNA damage checkpoint;somitogenesis;spleen development;T cell differentiation in thymus;T cell lineage commitment;T cell receptor V(D)J recombination;telomere capping;telomere maintenance;thymus development ATP binding;DNA-dependent protein kinase activity;double-stranded DNA binding;enzyme binding;protein domain specific binding;protein kinase activity;protein serine/threonine kinase activity;RNA binding;transcription factor binding cytosol;DNA-dependent protein kinase-DNA ligase 4 complex;membrane;nonhomologous end joining complex;nuclear chromosome, telomeric region;nucleolus;nucleoplasm;nucleus;protein-containing complex;protein-DNA complex;transcription factor complex Cell cycle;Non-homologous end-joining T-B-Severe combined immunodeficiency Cytosolic sensors of pathogen-associated DNA;E3 ubiquitin ligases ubiquitinate target proteins;IRF3-mediated induction of type I IFN;Nonhomologous End-Joining (NHEJ) Artemis-DNA-PK complex;CDC5L complex;DHX9-ADAR-vigilin-DNA-PK-Ku antigen complex;DNA-PK-Ku complex;DNA-PK-Ku-eIF2-NF90-NF45 complex;Dysbindin 1-A-DNA-PK-complex;HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex;MGC1-DNA-PKcs-Ku complex;NCOA6-DNA-PK-Ku-PARP1 complex;Vigilin-DNA-PK-Ku antigen complex -0.966114819049835 1.10789954662323 0.861017167568207 1.61957716941833 1.09901392459869 1.09945213794708 0.640124142169952 1.09945213794708 -0.131197944283485 -0.747797191143036 -0.0189412832260132 0.103104375302792 -0.998630225658417 -0.451929301023483 -0.724814593791962 -1.78476393222809 -0.508930683135986 -1.29652059078217 + Cluster -674 4 4 4 21.5 21.5 21.5 21.868 0 4.2412 1106600000 6 3.63641153397794 0.000334821428571429 O75340;O75340-2 O75340;O75340-2 Programmed cell death protein 6 PDCD6 320 the function involves inhibition of VEGF-inducedphosphorylation of the Akt signaling pathway (PubMed:21893193). Incase of infection by HIV-1 virus, indirectly inhibits HIV-1production by affecting viral Gag expression and distribution(PubMed:27784779).;Calcium sensor that plays a key role in processes suchas endoplasmic reticulum (ER)-Golgi vesicular transport, endosomalbiogenesis or membrane repair. Acts as an adapter that bridgesunrelated proteins or stabilizes weak protein-protein complexes inresponse to calcium: calcium-binding triggers exposure of apolarsurface, promoting interaction with different sets of proteinsthanks to 3 different hydrophobic pockets, leading totranslocation to membranes (PubMed:20691033, PubMed:25667979).Involved in ER-Golgi transport by promoting the associationbetween PDCD6IP and TSG101, thereby bridging together the ESCRT-III and ESCRT-I complexes (PubMed:19520058). Together with PEF1,acts as calcium-dependent adapter for the BCR(KLHL12) complex, acomplex involved in ER-Golgi transport by regulating the size ofCOPII coats (PubMed:27716508). In response to cytosolic calciumincrease, the heterodimer formed with PEF1 interacts with, andbridges together the BCR(KLHL12) complex and SEC31 (SEC31A orSEC31B), promoting monoubiquitination of SEC31 and subsequentcollagen export, which is required for neural crest specification(PubMed:27716508). Involved in the regulation of the distributionand function of MCOLN1 in the endosomal pathway (PubMed:19864416).Promotes localization and polymerization of TFG at endoplasmicreticulum exit site (PubMed:27813252). Required for T-cellreceptor-, Fas-, and glucocorticoid-induced apoptosis (Bysimilarity). May mediate Ca(2+)-regulated signals along the deathpathway: interaction with DAPK1 can accelerate apoptotic celldeath by increasing caspase-3 activity (PubMed:16132846). Its rolein apoptosis may however be indirect, as suggested by knockoutexperiments (By similarity). May inhibit KDR/VEGFR2-dependentangiogenesis Endoplasmic reticulum membrane{ECO:0000269|PubMed:16957052, ECO:0000269|PubMed:27813252};Peripheral membrane protein {ECO:0000269|PubMed:16957052}.Cytoplasmic vesicle, COPII-coated vesicle membrane{ECO:0000269|PubMed:27716508}. Cytoplasm{ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27784779}.Nucleus {ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:21122810,ECO:0000269|PubMed:27784779}. Endosome{ECO:0000269|PubMed:19864416}. Note=Interaction with RBM22 inducesrelocalization from the cytoplasm to the nucleus(PubMed:17045351). Translocated from the cytoplasm to the nucleusafter heat shock cell treatment. Accumulates in cytoplasmicvesicle-like organelles after heat shock treatment, which mayrepresent stress granules (PubMed:21122810). In response tocalcium increase, relocates from cytoplasm to COPII vesicle coat(PubMed:27716508). Localizes to endoplasmic reticulum exit site(ERES) (PubMed:27813252). {ECO:0000269|PubMed:17045351,ECO:0000269|PubMed:21122810, ECO:0000269|PubMed:27716508,ECO:0000269|PubMed:27813252}. activation of cysteine-type endopeptidase activity involved in apoptotic process;angiogenesis;apoptotic signaling pathway;cellular response to heat;COPII vesicle coating;endoplasmic reticulum to Golgi vesicle-mediated transport;intracellular protein transport;negative regulation of protein kinase B signaling;negative regulation of TOR signaling;negative regulation of vascular endothelial growth factor receptor signaling pathway;neural crest cell development;neural crest formation;positive regulation of angiogenesis;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of endothelial cell migration;positive regulation of endothelial cell proliferation;positive regulation of protein monoubiquitination;response to calcium ion;vascular endothelial growth factor receptor-2 signaling pathway calcium ion binding;calcium-dependent protein binding;identical protein binding;magnesium ion binding;molecular adaptor activity;protein dimerization activity;protein homodimerization activity;protein membrane anchor COPII vesicle coat;cytoplasm;cytoplasmic vesicle;endoplasmic reticulum;endoplasmic reticulum exit site;endoplasmic reticulum membrane;endosome;extracellular exosome;Golgi membrane;nucleus PEF1-ALG2 complex;Ubiquitin E3 ligase (CUL3, KLHL12, PEF1, PDCD6) -0.495164066553116 0.457285553216934 1.24775803089142 1.21671509742737 1.51352739334106 0.84033614397049 0.999105095863342 1.38064277172089 -0.430581003427505 -0.779252946376801 -0.12483686953783 0.242847219109535 -1.21199405193329 -0.486924856901169 -0.859858691692352 -1.37112748622894 -0.816274702548981 -1.32220256328583 + Cluster -674 12 12 12 18.8 18.8 18.8 107.14 0 163.58 35030000000 62 6.0200478037345 1.20481927710843E-05 P53618 P53618 Coatomer subunit beta COPB1 1206 the complexalso influences the Golgi structural integrity, as well as theprocessing, activity, and endocytic recycling of LDL receptors.Plays a functional role in facilitating the transport of kappa-type opioid receptor mRNAs into axons and enhances translation ofthese proteins. Required for limiting lipid storage in lipiddroplets. Involved in lipid homeostasis by regulating the presenceof perilipin family members PLIN2 and PLIN3 at the lipid dropletsurface and promoting the association of adipocyte surfacetriglyceride lipase (PNPLA2) with the lipid droplet to mediatelipolysis (By similarity). Involved in the Golgi disassembly andreassembly processes during cell cycle. Involved in autophagy byplaying a role in early endosome function. Plays a role inorganellar compartmentalization of secretory compartmentsincluding endoplasmic reticulum (ER)-Golgi intermediatecompartment (ERGIC), Golgi, trans-Golgi network (TGN) andrecycling endosomes, and in biosynthetic transport of CAV1.Promotes degradation of Nef cellular targets CD4 and MHC class Iantigens by facilitating their trafficking to degradativecompartments.;The coatomer is a cytosolic protein complex that bindsto dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosyntheticprotein transport from the ER, via the Golgi up to the trans Golginetwork. Coatomer complex is required for budding from Golgimembranes, and is essential for the retrograde Golgi-to-ERtransport of dilysine-tagged proteins. In mammals, the coatomercan only be recruited by membranes associated to ADP-ribosylationfactors (ARFs), which are small GTP-binding proteins Cytoplasmic side {ECO:0000305}.Cell membrane {ECO:0000269|PubMed:20362547}. Endoplasmicreticulum-Golgi intermediate compartment{ECO:0000250|UniProtKB:Q9JIF7}. Note=The coatomer is cytoplasmicor polymerized on the cytoplasmic side of the Golgi, as well as onthe vesicles/buds originating from it (By similarity). Proteolyticcleavage by CAPN8 triggers translocation from Golgi to cytoplasm(By similarity). Found in perinuclear vesicular-tubular clusters(VTCs) and in the Golgi region where associated with vesicles,buds and rims of the Golgi stack (By similarity). Occasionallypresent at the trans-side of Golgi, but mainly present at the cis-Golgi side in transitional areas (TA), on so-called peripheralelements (PE) consisting of tubules and vesicles located betweenthe cup-shaped transitional elements (TE) of the rough endoplasmicreticulum (RER) and the cis-most Golgi cisternae (By similarity).Present in cytoplasm, not associated with visible coats ormembranes, with a minor fraction present on small clusters oftubules and vesicles (By similarity). Some association with high-density and low-density microsomes and mitochondria/nucleifraction (By similarity). Very little found in plasma membranefraction (PubMed:20362547). {ECO:0000250|UniProtKB:P23514,ECO:0000269|PubMed:20362547}.; Cytoplasmic side {ECO:0000305}.Cytoplasmic vesicle, COPI-coated vesicle membrane; Peripheral membrane protein{ECO:0000269|PubMed:17451557, ECO:0000269|PubMed:18385291,ECO:0000269|PubMed:20056612}; Peripheralmembrane protein {ECO:0000305};Cytoplasm. Golgi apparatus membrane{ECO:0000269|PubMed:11056392, ECO:0000269|PubMed:17451557,ECO:0000269|PubMed:7573041} endoplasmic reticulum to Golgi vesicle-mediated transport;intracellular protein transport;intra-Golgi vesicle-mediated transport;neutrophil degranulation;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;viral process structural molecule activity COPI vesicle coat;cytosol;endoplasmic reticulum membrane;endoplasmic reticulum-Golgi intermediate compartment;ficolin-1-rich granule membrane;Golgi apparatus;Golgi membrane;Golgi-associated vesicle;intracellular membrane-bounded organelle;membrane;plasma membrane;secretory granule membrane;tertiary granule membrane;transport vesicle COPI-dependent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;Neutrophil degranulation -0.671854674816132 0.176373332738876 1.90717661380768 1.36911070346832 1.03696668148041 1.49370634555817 0.765318036079407 1.00340890884399 -0.90891832113266 -0.847376704216003 -0.201750919222832 -0.0605856776237488 -0.786282122135162 -0.59565532207489 -0.77080637216568 -1.23540270328522 -0.725862920284271 -0.947564899921417 + Cluster -674 2 2 2 18 18 18 16.694 0 146.09 2702400000 22 5.88959133957585 1.14942528735632E-05 O43169 O43169 Cytochrome b5 type B CYB5B 199 Cytochrome b5 is a membrane bound hemoprotein whichfunction as an electron carrier for several membrane boundoxygenases. Mitochondrion outer membrane {ECO:0000250}. oxidation-reduction process heme binding;metal ion binding integral component of membrane;membrane;mitochondrial outer membrane Phase I - Functionalization of compounds 0.621288120746613 -0.93771356344223 1.4996041059494 0.821463882923126 1.91197085380554 0.576134622097015 1.03190124034882 0.65441507101059 -0.974121510982513 0.412740141153336 0.293707251548767 0.130425930023193 -1.02475094795227 -1.04977715015411 -1.02475094795227 -0.957399666309357 -0.896044731140137 -1.08909273147583 + Cluster -674 4 4 4 12.1 12.1 12.1 53.254 0 31.867 5177000000 12 4.71847110110118 3.04347826086957E-05 P37198 P37198 Nuclear pore glycoprotein p62 NUP62 963 Essential component of the nuclear pore complex(PubMed:1915414). The N-terminal is probably involved innucleocytoplasmic transport (PubMed:1915414). The C-terminal isinvolved in protein-protein interaction probably via coiled-coilformation, promotes its association with centrosomes and mayfunction in anchorage of p62 to the pore complex (PubMed:1915414,PubMed:24107630). Plays a role in mitotic cell cycle progressionby regulating centrosome segregation, centriole maturation andspindle orientation (PubMed:24107630). It might be involved inprotein recruitment to the centrosome after nuclear breakdown(PubMed:24107630). Nucleus, nuclear pore complex{ECO:0000269|PubMed:1915414}. Cytoplasm, cytoskeleton, spindlepole {ECO:0000269|PubMed:24107630}. Nucleus envelope{ECO:0000269|PubMed:24107630}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome{ECO:0000269|PubMed:14654843, ECO:0000269|PubMed:24107630}.Note=Central region of the nuclear pore, within the transporter(PubMed:1915414). During mitotic cell division, it associates withthe poles of the mitotic spindle (PubMed:24107630).{ECO:0000269|PubMed:1915414, ECO:0000269|PubMed:24107630}. cell aging;cell death;cell surface receptor signaling pathway;centriole assembly;centrosome cycle;hormone-mediated signaling pathway;mitotic centrosome separation;mitotic metaphase plate congression;mRNA export from nucleus;negative regulation of apoptotic process;negative regulation of cell proliferation;negative regulation of epidermal growth factor receptor signaling pathway;negative regulation of MAP kinase activity;negative regulation of programmed cell death;negative regulation of Ras protein signal transduction;positive regulation of centriole replication;positive regulation of epidermal growth factor receptor signaling pathway;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of mitotic cytokinetic process;positive regulation of mitotic nuclear division;positive regulation of protein localization to centrosome;positive regulation of transcription, DNA-templated;protein heterotrimerization;protein import into nucleus;regulation of mitotic spindle organization;regulation of protein import into nucleus;regulation of Ras protein signal transduction;regulation of signal transduction;spermatogenesis;transcription, DNA-templated;viral process chromatin binding;Hsp70 protein binding;Hsp90 protein binding;kinesin binding;phospholipid binding;PTB domain binding;receptor signaling complex scaffold activity;SH2 domain binding;structural constituent of nuclear pore;thyroid hormone receptor binding;ubiquitin binding annulate lamellae;centrosome;cytoplasm;Flemming body;mitotic spindle;nuclear envelope;nuclear membrane;nuclear pore;nuclear pore central transport channel;nucleus;ribonucleoprotein complex;spindle pole RNA transport Infantile bilateral striatal necrosis ISG15 antiviral mechanism;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Rev-mediated nuclear export of HIV RNA;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs 0.464074850082397 -0.575912892818451 1.39823424816132 1.47999668121338 1.75851356983185 0.0515292100608349 0.632814049720764 0.812722384929657 -0.858625888824463 -0.180521935224533 0.812722384929657 -0.134704098105431 -1.28807938098907 -0.454811871051788 -0.251608997583389 -1.49418258666992 -0.78442257642746 -1.38773703575134 + Cluster -674 16 16 6 30.3 30.3 10.9 71.368 0 137.18 15719000000 52 3.29252806446915 0.000598627787307033 Q9NVI7;Q9NVI7-2;Q9NVI7-3;Q5T9A4-2 Q9NVI7;Q9NVI7-2;Q9NVI7-3 ATPase family AAA domain-containing protein 3A ATAD3A 2964 Essential for mitochondrial network organization,mitochondrial metabolism and cell growth at organism and cellularlevel. May play an important role in mitochondrial proteinsynthesis. May also participate in mitochondrial DNA replication.May bind to mitochondrial DNA D-loops and contribute to nucleoidstability. Required for enhanced channeling of cholesterol forhormone-dependent steroidogenesis.;May play a role in a mitochondrial network organizationtypical for stem cells, characterized by reduced mitochondrialmetabolism, low mtDNA copies and fragmentated mitochondrialnetwork. may act by suppressing ATAD3A function, interfering withATAD3A interaction with matrix nucleoid complexes Single-pass membrane protein {ECO:0000269|PubMed:20154147,ECO:0000269|PubMed:20349121}. Mitochondrion matrix, mitochondrionnucleoid {ECO:0000269|PubMed:17210950,ECO:0000269|PubMed:18063578}. Note=In the mitochondrial innermembrane, enriched in sites with the potential to form contactswith the outer membrane (PubMed:20349121, PubMed:20154147). The N-terminal domain interacts with the inner surface of themitochondrial outer membrane and the C-terminal domain localizesin a specific matrix compartment, where it is associated withnucleoids (PubMed:18063578). {ECO:0000269|PubMed:18063578,ECO:0000269|PubMed:20154147, ECO:0000269|PubMed:20349121}.;Mitochondrion inner membrane{ECO:0000269|PubMed:16909202, ECO:0000269|PubMed:18063578};Mitochondrion inner membrane{ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:20154147,ECO:0000269|PubMed:20332122, ECO:0000269|PubMed:20349121};Peripheral membrane protein {ECO:0000269|PubMed:16909202,ECO:0000269|PubMed:18063578}. Note=Has been found to co-purifywith nucleoids (PubMed:22453275). Since it does not face themitochondrial matrix, the association with nucleoids could bemediated by ATAD3A. {ECO:0000269|PubMed:22453275}. mitochondrion organization;negative regulation of apoptotic process;neutrophil degranulation;regulation of cell growth ATP binding;zinc ion binding ficolin-1-rich granule membrane;integral component of membrane;mitochondrial inner membrane;mitochondrial nucleoid;mitochondrion;plasma membrane;secretory granule membrane Neutrophil degranulation 0.8252774477005 0.000702667224686593 0.795922696590424 -0.202845349907875 1.21458125114441 1.2467440366745 2.10919213294983 0.583407819271088 -0.60576468706131 0.314944356679916 -0.36911004781723 0.234100922942162 -1.56142103672028 -1.30744612216949 -1.2505065202713 -0.445658832788467 -0.85053676366806 -0.731584072113037 + Cluster -674 10 10 10 46.7 46.7 46.7 27.843 0 186.94 6401600000 31 3.18852238132606 0.000759803921568627 P38117;P38117-2 P38117;P38117-2 Electron transfer flavoprotein subunit beta ETFB 968 Heterodimeric electron transfer flavoprotein thataccepts electrons from several mitochondrial dehydrogenases,including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosinedehydrogenase (PubMed:25416781, PubMed:15159392, PubMed:15975918).It transfers the electrons to the main mitochondrial respiratorychain via ETF-ubiquinone oxidoreductase (Probable). Required fornormal mitochondrial fatty acid oxidation and normal amino acidmetabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMPmolecule that probably has a purely structural role(PubMed:8962055, PubMed:15159392, PubMed:15975918) Mitochondrion matrix{ECO:0000305|PubMed:25023281, ECO:0000305|PubMed:8504797}. fatty acid beta-oxidation using acyl-CoA dehydrogenase electron transfer activity cytosol;mitochondrial matrix;mitochondrion Glutaric acidemia;Secondary hyperammonemia Protein methylation;Respiratory electron transport 0.869052469730377 0.21948653459549 0.16951584815979 0.0569360852241516 1.16866457462311 1.55793786048889 1.92975056171417 0.582953095436096 0.373028486967087 0.305941671133041 -0.71551638841629 -0.110118627548218 -1.71919596195221 -1.01671826839447 -0.814980864524841 -1.26572382450104 -0.673494398593903 -0.917518794536591 + Cluster -674 14 14 14 64.6 64.6 64.6 36.573 0 209.74 37127000000 73 3.683957611178 0.000313084112149533 P14550 P14550 Alcohol dehydrogenase [NADP(+)] AKR1A1 669 Catalyzes the NADPH-dependent reduction of a variety ofaromatic and aliphatic aldehydes to their corresponding alcohols.Catalyzes the reduction of mevaldate to mevalonic acid and ofglyceraldehyde to glycerol. Has broad substrate specificity. Invitro substrates include succinic semialdehyde, 4-nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-glucuronic acid. Plays a role in the activation of procarcinogens,such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and inthe metabolism of various xenobiotics and drugs, including theanthracyclines doxorubicin (DOX) and daunorubicin (DAUN) aldehyde catabolic process;cellular aldehyde metabolic process;D-glucuronate catabolic process;glucose metabolic process;glucuronate catabolic process to xylulose 5-phosphate;glutathione derivative biosynthetic process;L-ascorbic acid biosynthetic process alcohol dehydrogenase (NADP+) activity;alditol:NADP+ 1-oxidoreductase activity;aldo-keto reductase (NADP) activity;electron transfer activity;L-glucuronate reductase activity;oxidoreductase activity apical plasma membrane;cytosol;extracellular exosome;extracellular space;synapse Glycerolipid metabolism;Glycolysis / Gluconeogenesis;Metabolic pathways;Pentose and glucuronate interconversions Formation of xylulose-5-phosphate;Glutathione conjugation 0.24676288664341 -0.358887732028961 0.815696716308594 0.504290401935577 1.15087473392487 1.73449921607971 1.83042967319489 1.21142220497131 -0.471019089221954 0.0955218598246574 -0.951044142246246 -0.61812162399292 -1.27969086170197 -0.87621796131134 -1.14671015739441 -0.218493059277534 -1.00890445709229 -0.660408735275269 + Cluster -674 23 23 23 32 32 32 90.725 0 286.15 52201000000 125 4.89466047507415 2.01005025125628E-05 P11387;Q969P6;Q969P6-2 P11387 DNA topoisomerase 1 TOP1 624 Releases the supercoiling and torsional tension of DNAintroduced during duplication of mitochondrial DNA by transientlycleaving and rejoining one strand of the DNA duplex. Introduces asingle-strand break via transesterification at a target site induplex DNA. The scissile phosphodiester is attacked by thecatalytic tyrosine of the enzyme, resulting in the formation of aDNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a5'-OH DNA strand. The free DNA strand then rotates around theintact phosphodiester bond on the opposing strand, thus removingDNA supercoils. Finally, in the religation step, the DNA 5'-OHattacks the covalent intermediate to expel the active-sitetyrosine and restore the DNA phosphodiester backbone (Bysimilarity).;Releases the supercoiling and torsional tension of DNAintroduced during the DNA replication and transcription bytransiently cleaving and rejoining one strand of the DNA duplex.Introduces a single-strand break via transesterification at atarget site in duplex DNA. The scissile phosphodiester is attackedby the catalytic tyrosine of the enzyme, resulting in theformation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and theexpulsion of a 5'-OH DNA strand. The free DNA strand then rotatesaround the intact phosphodiester bond on the opposing strand, thusremoving DNA supercoils. Finally, in the religation step, the DNA5'-OH attacks the covalent intermediate to expel the active-sitetyrosine and restore the DNA phosphodiester backbone (Bysimilarity). Regulates the alternative splicing of tissue factor(F3) pre-mRNA in endothelial cells. Involved in the circadiantranscription of the core circadian clock component ARNTL/BMAL1 byaltering the chromatin structure around the ROR response elements(ROREs) on the ARNTL/BMAL1 promoter Mitochondrion {ECO:0000269|PubMed:11526219}.;Nucleus, nucleolus{ECO:0000269|PubMed:12149243}. Nucleus, nucleoplasm{ECO:0000269|PubMed:12149243}. Note=Diffuse nuclear localizationwith some enrichment in nucleoli. On CPT treatment, cleared fromnucleoli into nucleoplasm. Sumoylated forms found in bothnucleoplasm and nucleoli. chromatin remodeling;chromosome segregation;circadian regulation of gene expression;circadian rhythm;DNA replication;DNA topological change;embryonic cleavage;peptidyl-serine phosphorylation;phosphorylation;programmed cell death;response to drug;viral process ATP binding;chromatin binding;DNA binding;DNA topoisomerase type I activity;double-stranded DNA binding;protein domain specific binding;protein serine/threonine kinase activity;RNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;single-stranded DNA binding;supercoiled DNA binding chromosome;DNA topoisomerase complex (ATP-hydrolyzing);fibrillar center;mitochondrial nucleoid;mitochondrion;nucleolus;nucleoplasm;nucleus;P-body;perikaryon;protein-DNA complex;replication fork protection complex Aclarubicin;Belotecan hydrochloride;Cositecan;Edotecarin;Elsamitrucin;Etirinotecan pegol;Exatecan mesylate;Firtecan pegol;Irinotecan;Lurtotecan dihydrochloride;Pegamotecan;Rubitecan;Sacituzumab govitecan;Tenifatecan;Topotecan;Trastuzumab deruxtecan SUMOylation of DNA replication proteins DNA synthesome complex (13 subunits);DNA synthesome complex (17 subunits);Nop56p-associated pre-rRNA complex;RC complex during G2/M-phase of cell cycle;RC complex during S-phase of cell cycle;TFIIIC containing-TOP1-SUB1 complex;TOP1-PSF-P54 complex -0.0831012800335884 -0.151821449398994 0.781664907932281 0.863112211227417 1.13760924339294 1.35422646999359 1.99132704734802 1.16208016872406 -0.271793961524963 -0.464883595705032 -0.503608644008636 0.194081827998161 -1.6060733795166 -0.999135792255402 -1.1279901266098 -0.684426784515381 -0.749293684959412 -0.841973185539246 + Cluster -674 10 10 10 31.8 31.8 31.8 58.232 0 157.39 5221400000 17 6.2849434940944 0 Q96GM5;Q96GM5-2;Q92925;Q6STE5;Q6STE5-2;Q92925-3;Q92925-2 Q96GM5;Q96GM5-2 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 SMARCD1 2464 Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner (PubMed:22952240, PubMed:26601204).Critical regulator of myeloid differentiation, controllinggranulocytopoiesis and the expression of genes involved inneutrophil granule formation (PubMed:28369036);Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner (PubMed:8804307, PubMed:29374058). Belongsto the neural progenitors-specific chromatin remodeling complex(npBAF complex) and the neuron-specific chromatin remodelingcomplex (nBAF complex). During neural development a switch from astem/progenitor to a postmitotic chromatin remodeling mechanismoccurs as neurons exit the cell cycle and become committed totheir adult state. The transition from proliferating neuralstem/progenitor cells to postmitotic neurons requires a switch insubunit composition of the npBAF and nBAF complexes. As neuralprogenitors exit mitosis and differentiate into neurons, npBAFcomplexes which contain ACTL6A/BAF53A and PHF10/BAF45A, areexchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45Bor DPF3/BAF45C subunits in neuron-specific complexes (nBAF). ThenpBAF complex is essential for the self-renewal/proliferativecapacity of the multipotent neural stem cells. The nBAF complexalong with CREST plays a role regulating the activity of genesessential for dendrite growth (By similarity). Has a stronginfluence on vitamin D-mediated transcriptional activity from anenhancer vitamin D receptor element (VDRE). May be a link betweenmammalian SWI-SNF-like chromatin remodeling complexes and thevitamin D receptor (VDR) heterodimer (PubMed:14698202). Mediatescritical interactions between nuclear receptors and theBRG1/SMARCA4 chromatin-remodeling complex for transactivation(PubMed:12917342).;Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner. Stimulates nuclear receptor mediatedtranscription. Belongs to the neural progenitors-specificchromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). Duringneural development a switch from a stem/progenitor to apostmitotic chromatin remodeling mechanism occurs as neurons exitthe cell cycle and become committed to their adult state. Thetransition from proliferating neural stem/progenitor cells topostmitotic neurons requires a switch in subunit composition ofthe npBAF and nBAF complexes. As neural progenitors exit mitosisand differentiate into neurons, npBAF complexes which containACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologousalternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunitsin neuron-specific complexes (nBAF). The npBAF complex isessential for the self-renewal/proliferative capacity of themultipotent neural stem cells. The nBAF complex along with CRESTplays a role regulating the activity of genes essential fordendrite growth (By similarity). Nucleus {ECO:0000269|PubMed:14701856}.;Nucleus {ECO:0000269|PubMed:8804307,ECO:0000305}.;Nucleus {ECO:0000305}. ATP-dependent chromatin remodeling;cardiac right ventricle formation;cellular response to fatty acid;chromatin remodeling;chromatin-mediated maintenance of transcription;muscle cell differentiation;nervous system development;neural retina development;nucleosome disassembly;positive regulation of G2/M transition of mitotic cell cycle;positive regulation of neuroblast proliferation;positive regulation of smooth muscle cell differentiation;positive regulation of transcription, DNA-templated;regulation of lipid metabolic process;regulation of protein binding;regulation of transcription by RNA polymerase II;secondary heart field specification;transcription, DNA-templated chromatin binding;nuclear hormone receptor binding;nuclear receptor binding;nuclear receptor transcription coactivator activity;protein-containing complex scaffold activity;signaling receptor binding;transcription coactivator activity;transcription factor binding cytoplasm;intracellular membrane-bounded organelle;nBAF complex;npBAF complex;nuclear chromatin;nucleoplasm;nucleus;protein-containing complex;SWI/SNF complex Hepatocellular carcinoma;Thermogenesis Neutrophil specific granule deficiency Activation of gene expression by SREBF (SREBP);BMAL1:CLOCK,NPAS2 activates circadian gene expression;Circadian Clock;PPARA activates gene expression;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);RMTs methylate histone arginines;RORA activates gene expression;RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Transcriptional activation of mitochondrial biogenesis;Transcriptional regulation of white adipocyte differentiation BAF complex;BRD7-BAF60A-MEP50 complex;BRD7-SWI\u2013SNF complex;BRG1-associated complex;Brg1-associated complex I;BRG1-SIN3A complex;BRG1-SIN3A-HDAC containing SWI/SNF remodeling complex I;Brm-associated complex;BRM-associated complex;BRM-SIN3A complex;BRM-SIN3A-HDAC complex;EBAFa complex;EBAFb complex;LARC complex (LCR-associated remodeling complex);NUMAC complex (nucleosomal methylation activator complex);PBAF complex (Polybromo- and BAF containing complex);RNA polymerase II complex, chromatin structure modifying;SIN3-ING1b complex II;SWI-SNF chromatin remodeling-related-BRCA1 complex;WINAC complex -0.103245884180069 -0.187521129846573 0.939676880836487 1.05661714076996 0.501141607761383 0.731183528900146 1.69925618171692 1.40223109722137 -0.300299823284149 0.560276746749878 -0.203806102275848 0.247821792960167 -2.11078286170959 -1.35637223720551 -0.969789206981659 -1.12427794933319 -0.427900344133377 -0.354209393262863 + Cluster -674 3 3 3 7.2 7.2 7.2 66.319 0 10.745 2246400000 9 4.45758257189314 6.31970260223048E-05 Q5JTV8-3;Q5JTV8;Q5JTV8-2 Q5JTV8-3;Q5JTV8;Q5JTV8-2 Torsin-1A-interacting protein 1 TOR1AIP1 1921 Required for nuclear membrane integrity. Induces TOR1Aand TOR1B ATPase activity and is required for their location onthe nuclear membrane. Binds to A- and B-type lamins. Possible rolein membrane attachment and assembly of the nuclear lamina Nucleus inner membrane{ECO:0000269|PubMed:12061773, ECO:0000269|PubMed:24275647};Single-pass membrane protein {ECO:0000269|PubMed:12061773,ECO:0000269|PubMed:24275647}. nuclear membrane organization;positive regulation of ATPase activity;protein localization to nucleus ATPase activator activity;ATPase binding;cytoskeletal protein binding;lamin binding integral component of membrane;nuclear inner membrane;nuclear membrane;nucleus Limb-girdle muscular dystrophy LAP1-TOR1A complex -0.155155673623085 0.344890922307968 1.2577155828476 0.613341808319092 1.13653266429901 1.33646726608276 1.45913970470428 0.947196364402771 -0.36713981628418 0.520650088787079 -0.688944816589355 0.307615637779236 -1.37139594554901 -1.21568751335144 -1.29499304294586 -1.21446537971497 -0.851298570632935 -0.76446932554245 + Cluster -674 27 27 26 53.8 53.8 53.8 55.992 0 323.31 110020000000 180 6.22018019073148 0 P34897;P34897-3;P34897-2 P34897;P34897-3;P34897-2 Serine hydroxymethyltransferase, mitochondrial SHMT2 915 5,10-methylenetetrahydrofolateproviding methyl donors to produce the taurinomethyluridine baseat the wobble position of some mitochondrial tRNAs(PubMed:29452640, PubMed:29364879). Associates with mitochondrialDNA (PubMed:18063578). In addition to its role in mitochondria,also plays a role in the deubiquitination of target proteins ascomponent of the BRISC complex: required for IFNAR1deubiquitination by the BRISC complex (PubMed:24075985);Catalyzes the cleavage of serine to glycine accompaniedwith the production of 5,10-methylenetetrahydrofolate, anessential intermediate for purine biosynthesis (PubMed:24075985,PubMed:29364879, PubMed:25619277). Serine provides the majorsource of folate one-carbon in cells by catalyzing the transfer ofone carbon from serine to tetrahydrofolate (PubMed:25619277).Contributes to the de novo mitochondrial thymidylate biosynthesispathway via its role in glycine and tetrahydrofolate metabolism:thymidylate biosynthesis is required to prevent uracilaccumulation in mtDNA (PubMed:21876188). Also required formitochondrial translation by producing 5,10-methylenetetrahydrofolate Mitochondrion {ECO:0000269|PubMed:21876188,ECO:0000269|PubMed:24075985}. Mitochondrion matrix, mitochondrionnucleoid {ECO:0000269|PubMed:18063578}. Mitochondrion innermembrane {ECO:0000269|PubMed:21876188}. Cytoplasm{ECO:0000269|PubMed:24075985}. Nucleus{ECO:0000269|PubMed:24075985}. Note=Mainly localizes in themitochondrion. Also found in the cytoplasm and nucleus as part ofthe BRISC complex (PubMed:24075985).{ECO:0000269|PubMed:24075985}. cellular response to tetrahydrofolate;folic acid metabolic process;glycine biosynthetic process from serine;glycine metabolic process;L-serine biosynthetic process;L-serine catabolic process;L-serine metabolic process;one-carbon metabolic process;positive regulation of cell proliferation;protein homotetramerization;protein K63-linked deubiquitination;protein tetramerization;regulation of aerobic respiration;regulation of mitochondrial translation;regulation of oxidative phosphorylation;response to type I interferon;tetrahydrofolate interconversion;tetrahydrofolate metabolic process amino acid binding;chromatin binding;cobalt ion binding;glycine hydroxymethyltransferase activity;identical protein binding;L-allo-threonine aldolase activity;pyridoxal phosphate binding;serine binding;zinc ion binding BRISC complex;cytoplasm;extracellular exosome;microtubule cytoskeleton;mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrial matrix;mitochondrial nucleoid;mitochondrion;nucleus Antifolate resistance;Biosynthesis of amino acids;Carbon metabolism;Glycine, serine and threonine metabolism;Glyoxylate and dicarboxylate metabolism;Metabolic pathways;One carbon pool by folate Metabolism of folate and pterines ABRAXAS2-SHMT2 complex -0.496392458677292 0.633509695529938 0.5834139585495 0.724723637104034 1.11138963699341 1.552485704422 1.66892862319946 1.2293553352356 0.0388036258518696 -0.0999181792140007 -0.679022610187531 0.0895383581519127 -1.40347290039063 -1.16820168495178 -1.18973529338837 -1.07925617694855 -0.758074641227722 -0.758074641227722 + Cluster -674 12 12 12 52.7 52.7 52.7 29.062 0 107.83 16652000000 51 5.7048474334875 9.52380952380952E-06 O75822;O75822-2;O75822-3 O75822;O75822-2;O75822-3 Eukaryotic translation initiation factor 3 subunit J EIF3J 358 Component of the eukaryotic translation initiationfactor 3 (eIF-3) complex, which is required for several steps inthe initiation of protein synthesis (PubMed:25849773,PubMed:27462815). The eIF-3 complex associates with the 40Sribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiationcomplex (43S PIC). The eIF-3 complex stimulates mRNA recruitmentto the 43S PIC and scanning of the mRNA for AUG recognition. TheeIF-3 complex is also required for disassembly and recycling ofpost-termination ribosomal complexes and subsequently preventspremature joining of the 40S and 60S ribosomal subunits prior toinitiation. The eIF-3 complex specifically targets and initiatestranslation of a subset of mRNAs involved in cell proliferation,including cell cycling, differentiation and apoptosis, and usesdifferent modes of RNA stem-loop binding to exert eithertranslational activation or repression (PubMed:25849773) Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03009}. formation of cytoplasmic translation initiation complex;translational initiation translation initiation factor activity cytosol;eukaryotic 43S preinitiation complex;eukaryotic 48S preinitiation complex;eukaryotic translation initiation factor 3 complex RNA transport Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Ribosomal scanning and start codon recognition;Translation initiation complex formation EIF3 complex (EIF3A, EIF3B, EIF3G, EIF3I, EIF3J);EIF3 complex (EIF3B, EIF3J, EIF3I);eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7);eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7, PCID1) -0.434941530227661 0.330625534057617 0.64329731464386 0.587655961513519 1.4454470872879 1.39002060890198 1.46993780136108 1.0336766242981 0.330625534057617 0.531063258647919 -1.14775216579437 0.0142709435895085 -0.725577712059021 -1.22232937812805 -1.34337151050568 -0.491288721561432 -1.13900542259216 -1.27235436439514 + Cluster -674 29 20 20 71.6 49.7 49.7 50.582 0 229.5 44765000000 94 4.55083821461121 4.74308300395257E-05 P31150 P31150 Rab GDP dissociation inhibitor alpha GDI1 884 Regulates the GDP/GTP exchange reaction of most Rabproteins by inhibiting the dissociation of GDP from them, and thesubsequent binding of GTP to them. Promotes the dissociation ofGDP-bound Rab proteins from the membrane and inhibits theiractivation. Promotes the dissociation of RAB1A, RAB3A, RAB5A andRAB10 from membranes. Cytoplasm {ECO:0000269|PubMed:19570034}.Golgi apparatus, trans-Golgi network{ECO:0000269|PubMed:19570034}. negative regulation of axonogenesis;negative regulation of protein targeting to membrane;positive regulation of axon extension;protein transport;Rab protein signal transduction;regulation of small GTPase mediated signal transduction;response to calcium ion;signal transduction GDP-dissociation inhibitor activity;GTPase activator activity;Rab GDP-dissociation inhibitor activity;Rab GTPase binding axon;cytoplasm;cytosol;Golgi apparatus;midbody;myelin sheath;neuronal cell body;protein-containing complex X-linked mental retardation RAB GEFs exchange GTP for GDP on RABs;Rho GTPase cycle 0.812083542346954 0.289352774620056 0.669181048870087 0.669181048870087 0.755030989646912 1.09925413131714 1.54515159130096 1.46894097328186 -0.662467002868652 0.229308038949966 -1.05988693237305 0.413217693567276 -1.69579899311066 -1.20724761486053 -0.792898654937744 -0.646200716495514 -1.15943276882172 -0.726769089698792 + Cluster -674 3 3 3 5.9 5.9 5.9 62.606 0 9.9215 1591800000 11 3.95780385194731 0.000155988857938719 Q13555;Q13555-8;Q13555-5;Q13555-9;Q13555-11;Q13555-6;Q13555-10;Q13555-7;Q13555-4;Q13555-2;Q13555-3;Q13554;Q13554-2;Q13554-5;Q13554-8;Q13554-6;Q13554-4;Q13554-3;Q13554-7;Q13557-8;Q13557-6;Q13557-4;Q13557-11;Q13557-3;Q13557-5;Q13557-10;Q13557-9;Q9UQM7-2;Q9UQM7;Q13557;Q13557-12 Q13555;Q13555-8;Q13555-5;Q13555-9;Q13555-11;Q13555-6;Q13555-10;Q13555-7;Q13555-4;Q13555-2;Q13555-3;Q13554;Q13554-2;Q13554-5;Q13554-8;Q13554-6;Q13554-4;Q13554-3;Q13554-7 Calcium/calmodulin-dependent protein kinase type II subunit gamma;Calcium/calmodulin-dependent protein kinase type II subunit beta CAMK2G;CAMK2B 1646 Calcium/calmodulin-dependent protein kinase involved inthe regulation of Ca(2+) homeostatis and excitation-contractioncoupling (ECC) in heart by targeting ion channels, transportersand accessory proteins involved in Ca(2+) influx into the myocyte,Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+)uptake and Na(+) and K(+) channel transport. Targets alsotranscription factors and signaling molecules to regulate heartfunction. In its activated form, is involved in the pathogenesisof dilated cardiomyopathy and heart failure. Contributes tocardiac decompensation and heart failure by regulating SR Ca(2+)release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4,promoting its nuclear export and binding to 14-3-3 protein, andexpression of MEF2 and genes involved in the hypertrophic program.Is essential for left ventricular remodeling responses tomyocardial infarction. In pathological myocardial remodeling actsdownstream of the beta adrenergic receptor signaling cascade toregulate key proteins involved in ECC. Regulates Ca(2+) influx tomyocytes by binding and phosphorylating the L-type Ca(2+) channelsubunit beta-2 CACNB2. In addition to Ca(2+) channels, can targetand regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5Aand the K+ channel Kv4.3/KCND3, which contribute toarrhythmogenesis in heart failure. Phosphorylates phospholamban(PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributingto the enhancement of SR Ca(2+) uptake that may be important infrequency-dependent acceleration of relaxation (FDAR) andmaintenance of contractile function during acidosis. Mayparticipate in the modulation of skeletal muscle function inresponse to exercise, by regulating SR Ca(2+) transport throughphosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor.;Calcium/calmodulin-dependent protein kinase thatfunctions autonomously after Ca(2+)/calmodulin-binding andautophosphorylation, and is involved in dendritic spine andsynapse formation, neuronal plasticity and regulation ofsarcoplasmic reticulum Ca(2+) transport in skeletal muscle. Inneurons, plays an essential structural role in the reorganizationof the actin cytoskeleton during plasticity by binding andbundling actin filaments in a kinase-independent manner. Thisstructural function is required for correct targeting of CaMK2A,which acts downstream of NMDAR to promote dendritic spine andsynapse formation and maintain synaptic plasticity which enableslong-term potentiation (LTP) and hippocampus-dependent learning.In developing hippocampal neurons, promotes arborization of thedendritic tree and in mature neurons, promotes dendriticremodeling. Also regulates the migration of developing neurons(PubMed:29100089). Participates in the modulation of skeletalmuscle function in response to exercise. In slow-twitch muscles,is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+)transport and in fast-twitch muscle participates in the control ofCa(2+) release from the SR through phosphorylation of triadin, aryanodine receptor-coupling factor, and phospholamban (PLN/PLB),an endogenous inhibitor of SERCA2A/ATP2A2;Calcium/calmodulin-dependent protein kinase thatfunctions autonomously after Ca(2+)/calmodulin-binding andautophosphorylation, and is involved in sarcoplasmic reticulumCa(2+) transport in skeletal muscle and may function in dendriticspine and synapse formation and neuronal plasticity. In slow-twitch muscles, is involved in regulation of sarcoplasmicreticulum (SR) Ca(2+) transport and in fast-twitch muscleparticipates in the control of Ca(2+) release from the SR throughphosphorylation of the ryanodine receptor-coupling factor triadin.In neurons, may participate in the promotion of dendritic spineand synapse formation and maintenance of synaptic plasticity whichenables long-term potentiation (LTP) and hippocampus-dependentlearning.;Calcium/calmodulin-dependent protein kinase thatfunctions autonomously after Ca(2+)/calmodulin-binding andautophosphorylation, and is involved in synaptic plasticity,neurotransmitter release and long-term potentiation. Member of theNMDAR signaling complex in excitatory synapses, it regulatesNMDAR-dependent potentiation of the AMPAR and therefore excitatorysynaptic transmission (By similarity). Regulates dendritic spinedevelopment (PubMed:28130356). Also regulates the migration ofdeveloping neurons (PubMed:29100089). Phosphorylates thetranscription factor FOXO3 to activate its transcriptionalactivity (PubMed:23805378). Cytoplasmic side{ECO:0000305}.; Cytoplasmic side{ECO:0000305}. Sarcoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305};Cell junction, synapse{ECO:0000250|UniProtKB:P11275}. Cell junction, synapse,postsynaptic cell membrane, postsynaptic density{ECO:0000250|UniProtKB:P11275}. Cell projection, dendritic spine{ECO:0000269|PubMed:28130356}. Cell projection, dendrite{ECO:0000269|PubMed:28130356}. Note=Postsynaptic lipid rafts.{ECO:0000250|UniProtKB:P11275}.;Cell membrane, sarcolemma {ECO:0000305};Cytoplasm, cytoskeleton{ECO:0000269|PubMed:21529938}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome {ECO:0000250}.Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:21529938};Cytoplasmic side {ECO:0000269|PubMed:21529938}. Cell junction,synapse {ECO:0000250|UniProtKB:P08413}. Note=In slow-twitchmuscle, evenly distributed between longitudinal SR and junctionalSR.;Cytoplasmic side {ECO:0000305}.;Peripheral membrane protein {ECO:0000269|PubMed:21529938};Peripheral membrane protein {ECO:0000305};Sarcoplasmic reticulum membrane{ECO:0000305} angiotensin-activated signaling pathway;calcium ion transport;cardiac muscle cell contraction;cell differentiation;cellular response to calcium ion;dendrite morphogenesis;dendritic spine development;endoplasmic reticulum calcium ion homeostasis;G1/S transition of mitotic cell cycle;insulin secretion;interferon-gamma-mediated signaling pathway;MAPK cascade;negative regulation of sodium ion transmembrane transport;negative regulation of sodium ion transmembrane transporter activity;nervous system development;peptidyl-serine phosphorylation;peptidyl-threonine autophosphorylation;peptidyl-threonine phosphorylation;positive regulation of calcium ion transport;positive regulation of cardiac muscle cell apoptotic process;positive regulation of cardiac muscle hypertrophy;positive regulation of dendritic spine morphogenesis;positive regulation of neuron projection development;positive regulation of NF-kappaB transcription factor activity;positive regulation of synapse maturation;protein autophosphorylation;protein complex oligomerization;protein phosphorylation;regulation of calcium ion transmembrane transport via high voltage-gated calcium channel;regulation of calcium ion transport;regulation of cardiac muscle cell action potential;regulation of cardiac muscle cell action potential involved in regulation of contraction;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;regulation of cell communication by electrical coupling;regulation of cell communication by electrical coupling involved in cardiac conduction;regulation of cell growth;regulation of cellular localization;regulation of dendritic spine development;regulation of heart contraction;regulation of heart rate by cardiac conduction;regulation of histone deacetylase activity;regulation of long-term neuronal synaptic plasticity;regulation of membrane depolarization;regulation of mitochondrial membrane permeability involved in apoptotic process;regulation of neuron migration;regulation of neuronal synaptic plasticity;regulation of neurotransmitter secretion;regulation of relaxation of cardiac muscle;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;regulation of ryanodine-sensitive calcium-release channel activity;regulation of skeletal muscle adaptation;regulation of synapse structural plasticity;regulation of synaptic vesicle docking;regulation of the force of heart contraction;regulation of transcription by RNA polymerase II;relaxation of cardiac muscle;response to ischemia;signal transduction;Wnt signaling pathway, calcium modulating pathway actin binding;ATP binding;calcium-dependent protein serine/threonine kinase activity;calcium-dependent protein serine/threonine phosphatase activity;calmodulin binding;calmodulin-dependent protein kinase activity;glutamate receptor binding;identical protein binding;ion channel binding;kinase activity;metal ion binding;protein homodimerization activity;protein serine/threonine kinase activity;Ras guanyl-nucleotide exchange factor activity;sodium channel inhibitor activity;titin binding calcium- and calmodulin-dependent protein kinase complex;cell junction;cytoplasm;cytosol;dendritic spine;endocytic vesicle membrane;membrane;microtubule organizing center;mitochondrion;neuron projection;nucleoplasm;nucleus;plasma membrane;postsynaptic density;postsynaptic membrane;sarcolemma;sarcoplasmic reticulum membrane;Schaffer collateral - CA1 synapse;synapse Adrenergic signaling in cardiomyocytes;Aldosterone synthesis and secretion;Amphetamine addiction;Axon guidance;Calcium signaling pathway;cAMP signaling pathway;Cholinergic synapse;Circadian entrainment;Cushing syndrome;Dopaminergic synapse;ErbB signaling pathway;Gastric acid secretion;Glioma;Glucagon signaling pathway;GnRH signaling pathway;HIF-1 signaling pathway;Inflammatory mediator regulation of TRP channels;Insulin secretion;Long-term potentiation;Melanogenesis;Necroptosis;Neurotrophin signaling pathway;Olfactory transduction;Oocyte meiosis;Oxytocin signaling pathway;Pathways in cancer;Proteoglycans in cancer;Tuberculosis;Wnt signaling pathway Autosomal dominant mental retardation Ca2+ pathway;CREB phosphorylation through the activation of CaMKII;CREB phosphorylation through the activation of Ras;HSF1-dependent transactivation;Interferon gamma signaling;Ion homeostasis;Ion transport by P-type ATPases;Phase 0 - rapid depolarisation;RAF/MAP kinase cascade;Ras activation upon Ca2+ influx through NMDA receptor;Regulation of MECP2 expression and activity;Trafficking of AMPA receptors;Unblocking of NMDA receptors, glutamate binding and activation CAMK2-delta-MASH1 promoter-coactivator complex;SERCA2a-alphaKAP-CaM-CaMKII complex;Ternary complex (LRRC7, CAMK2a, ACTN4) 0.101193659007549 0.74261063337326 1.42125928401947 0.314107477664948 0.480598956346512 0.850744128227234 0.850744128227234 1.22995829582214 -0.548354148864746 0.525787770748138 0.266052007675171 0.353128641843796 -2.63053131103516 -0.361396551132202 -1.08453905582428 -0.963913977146149 -0.736597418785095 -0.810852348804474 + Cluster -674 3 3 3 25.4 25.4 25.4 23.025 0 33.759 4191800000 13 3.35703913942648 0.000552536231884058 Q15286;Q15286-2 Q15286;Q15286-2 Ras-related protein Rab-35 RAB35 1784 The small GTPases Rab are key regulators ofintracellular membrane trafficking, from the formation oftransport vesicles to their fusion with membranes. Rabs cyclebetween an inactive GDP-bound form and an active GTP-bound formthat is able to recruit to membranes different sets of downstreameffectors directly responsible for vesicle formation, movement,tethering and fusion. That Rab is involved in the process ofendocytosis and is an essential rate-limiting regulator of thefast recycling pathway back to the plasma membrane. Duringcytokinesis, required for the postfurrowing terminal steps, namelyfor intercellular bridge stability and abscission, possibly bycontrolling phosphatidylinositol 4,5-bis phosphate (PIP2) andSEPT2 localization at the intercellular bridge. May indirectlyregulate neurite outgrowth. Together with TBC1D13 may be involvedin regulation of insulin-induced glucose transporter SLC2A4/GLUT4translocation to the plasma membrane in adipocytes Lipid-anchor {ECO:0000305};Cell membrane {ECO:0000269|PubMed:16950109,ECO:0000269|PubMed:21951725};Cytoplasmic side {ECO:0000305}. Membrane, clathrin-coated pit{ECO:0000269|PubMed:16950109}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269|PubMed:16950109}. Endosome{ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725}.Melanosome {ECO:0000269|PubMed:17081065}. Note=Present on sortingendosomes and recycling endosome tubules (PubMed:16950109). Tendsto be enriched in PIP2-positive cell membrane domains(PubMed:16950109). During mitosis, associated with the plasmamembrane and present at the ingressing furrow during earlycytokinesis as well as at the intercellular bridge later duringcytokinesis (PubMed:16950109). Identified in stage I to stage IVmelanosomes (PubMed:17081065). {ECO:0000269|PubMed:16950109,ECO:0000269|PubMed:17081065}. antigen processing and presentation;cellular response to nerve growth factor stimulus;endocytic recycling;endosomal transport;intracellular protein transport;mitotic cytokinesis;neuron projection development;plasma membrane to endosome transport;protein localization;protein localization to endosome;Rab protein signal transduction GDP binding;GTP binding;GTPase activity;phosphatidylinositol-4,5-bisphosphate binding anchored component of synaptic vesicle membrane;cell projection membrane;clathrin-coated endocytic vesicle;clathrin-coated pit;clathrin-coated vesicle membrane;cytosol;endosome membrane;extracellular exosome;Golgi membrane;intercellular bridge;melanosome;plasma membrane;recycling endosome membrane Endocytosis RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation;TBC/RABGAPs 1.1433287858963 -0.280371516942978 1.95649778842926 0.29501610994339 0.782966017723083 0.608256697654724 1.51028084754944 1.09300136566162 -0.681113660335541 -0.0656914114952087 -0.153461098670959 -0.0963399261236191 -1.26978230476379 -0.605335175991058 -1.02091634273529 -0.653619349002838 -1.21982514858246 -1.34289181232452 + Cluster -674 10 10 10 14.6 14.6 14.6 118.32 0 116.55 3184000000 27 3.78715990246568 0.000252475247524752 P53992;P53992-2 P53992 Protein transport protein Sec24C SEC24C 1214 Component of the coat protein complex II (COPII) whichpromotes the formation of transport vesicles from the endoplasmicreticulum (ER). The coat has two main functions, the physicaldeformation of the endoplasmic reticulum membrane into vesiclesand the selection of cargo molecules for their transport to theGolgi complex (PubMed:10214955, PubMed:17499046, PubMed:18843296,PubMed:20427317). Plays a central role in cargo selection withinthe COPII complex and together with SEC24D may have a differentspecificity compared to SEC24A and SEC24B (PubMed:17499046,PubMed:20427317, PubMed:18843296). May more specifically packageGPI-anchored proteins through the cargo receptor TMED10(PubMed:20427317). May also be specific for IxM motif-containingcargos like the SNAREs GOSR2 and STX5 (PubMed:18843296) Cytoplasmic side{ECO:0000269|PubMed:10075675}. Endoplasmic reticulum membrane{ECO:0000269|PubMed:10075675, ECO:0000269|PubMed:10329445}; Peripheral membrane protein{ECO:0000269|PubMed:10075675};Cytoplasmic side {ECO:0000269|PubMed:10075675}. Cytoplasm, cytosol{ECO:0000269|PubMed:10075675}.;Cytoplasmic vesicle, COPII-coated vesiclemembrane {ECO:0000269|PubMed:10075675,ECO:0000269|PubMed:10329445};Peripheral membrane protein {ECO:0000269|PubMed:10075675} antigen processing and presentation of exogenous peptide antigen via MHC class II;antigen processing and presentation of peptide antigen via MHC class I;cargo loading into COPII-coated vesicle;COPII vesicle coating;endoplasmic reticulum to Golgi vesicle-mediated transport;intracellular protein transport SNARE binding;zinc ion binding COPII vesicle coat;cytosol;endoplasmic reticulum membrane;ER to Golgi transport vesicle membrane;Golgi membrane Protein processing in endoplasmic reticulum Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Cargo concentration in the ER;COPII-mediated vesicle transport;MHC class II antigen presentation;Regulation of cholesterol biosynthesis by SREBP (SREBF) 0.985108077526093 -0.229890406131744 1.65977275371552 -0.203964740037918 1.20901083946228 0.646611571311951 0.750314235687256 0.903938114643097 -0.331280052661896 0.427840292453766 0.21138970553875 0.794659733772278 -1.97240912914276 -0.777890801429749 -0.98443067073822 -0.623899281024933 -1.05962657928467 -1.40525364875793 + Cluster -674 7 7 7 7.4 7.4 7.4 164.98 0 26.447 826860000 8 3.67773302053064 0.000320930232558139 Q14C86;Q14C86-6;Q14C86-5;Q14C86-4;Q14C86-2;Q14C86-3 Q14C86;Q14C86-6;Q14C86-5;Q14C86-4;Q14C86-2;Q14C86-3 GTPase-activating protein and VPS9 domain-containing protein 1 GAPVD1 1744 Acts both as a GTPase-activating protein (GAP) and aguanine nucleotide exchange factor (GEF), and participates invarious processes such as endocytosis, insulin receptorinternalization or LC2A4/GLUT4 trafficking. Acts as a GEF for theRas-related protein RAB31 by exchanging bound GDP for free GTP,leading to regulate LC2A4/GLUT4 trafficking. In the absence ofinsulin, it maintains RAB31 in an active state and promotes afutile cycle between LC2A4/GLUT4 storage vesicles and earlyendosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulinstimulation, it is translocated to the plasma membrane, releasingLC2A4/GLUT4 from intracellular storage vesicles. Also involved inEGFR trafficking and degradation, possibly by promoting EGFRubiquitination and subsequent degradation by the proteasome. HasGEF activity for Rab5 and GAP activity for Ras Membrane {ECO:0000269|PubMed:16410077};Peripheral membrane protein {ECO:0000269|PubMed:16410077}.Endosome {ECO:0000269|PubMed:16410077}. Note=Recruited to theplasma membrane by TRIP10/CIP4 in response to insulin. endocytosis;membrane organization;regulation of protein transport;signal transduction cadherin binding;GTPase activating protein binding;GTPase activator activity;guanyl-nucleotide exchange factor activity;Rab guanyl-nucleotide exchange factor activity cytosol;endosome;membrane Clathrin-mediated endocytosis;RAB GEFs exchange GTP for GDP on RABs -0.0344510599970818 -0.0344510599970818 1.4550313949585 0.721527218818665 1.16346061229706 1.2018758058548 0.910875916481018 0.628523111343384 -0.110668353736401 0.839796125888824 -0.12502384185791 0.528711199760437 -1.64414751529694 -1.35428929328918 -0.986289799213409 -0.584124684333801 -1.56590056419373 -1.01045525074005 + Cluster -674 5 3 3 31.2 24.2 24.2 13.509 0 58.756 64446000000 77 6.34821432053321 0 Q71UI9;P0C0S5;Q71UI9-3;Q71UI9-4;Q71UI9-2 Q71UI9;P0C0S5;Q71UI9-3;Q71UI9-4;Q71UI9-2 Histone H2A.V;Histone H2A.Z H2AFV;H2AFZ 590 Variant histone H2A which replaces conventional H2A in asubset of nucleosomes. Nucleosomes wrap and compact DNA intochromatin, limiting DNA accessibility to the cellular machinerieswhich require DNA as a template. Histones thereby play a centralrole in transcription regulation, DNA repair, DNA replication andchromosomal stability. DNA accessibility is regulated via acomplex set of post-translational modifications of histones, alsocalled histone code, and nucleosome remodeling. May be involved inthe formation of constitutive heterochromatin. May be required forchromosome segregation during cell division;Variant histone H2A which replaces conventional H2A in asubset of nucleosomes. Nucleosomes wrap and compact DNA intochromatin, limiting DNA accessibility to the cellular machinerieswhich require DNA as a template. Histones thereby play a centralrole in transcription regulation, DNA repair, DNA replication andchromosomal stability. DNA accessibility is regulated via acomplex set of post-translational modifications of histones, alsocalled histone code, and nucleosome remodeling. May be involved inthe formation of constitutive heterochromatin. May be required forchromosome segregation during cell division (By similarity) Nucleus {ECO:0000250}. Chromosome{ECO:0000250}.;Nucleus. Chromosome. cellular response to estradiol stimulus;chromatin organization;positive regulation of transcription by RNA polymerase II chromatin DNA binding;DNA binding;nucleosomal DNA binding;protein heterodimerization activity;RNA polymerase II core promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding extracellular exosome;nuclear chromatin;nuclear euchromatin;nuclear heterochromatin;nucleosome;nucleus Alcoholism;Necroptosis;Systemic lupus erythematosus Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;Activation of anterior HOX genes in hindbrain development during early embryogenesis;Amyloid fiber formation;B-WICH complex positively regulates rRNA expression;Condensation of Prophase Chromosomes;Deposition of new CENPA-containing nucleosomes at the centromere;DNA Damage/Telomere Stress Induced Senescence;DNA methylation;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Estrogen-dependent gene expression;Formation of the beta-catenin:TCF transactivating complex;Meiotic recombination;Meiotic synapsis;NoRC negatively regulates rRNA expression;Oxidative Stress Induced Senescence;Packaging Of Telomere Ends;PRC2 methylates histones and DNA;Pre-NOTCH Transcription and Translation;RMTs methylate histone arginines;RNA Polymerase I Chain Elongation;RNA Polymerase I Promoter Opening;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Senescence-Associated Secretory Phenotype (SASP);SIRT1 negatively regulates rRNA expression;Transcriptional regulation by small RNAs CTCF-nucleophosmin-PARP-HIS-KPNA-LMNA-TOP complex;SRCAP-associated chromatin remodeling complex 1.17630076408386 0.480451643466949 0.968705534934998 0.653540790081024 1.7042715549469 0.638816356658936 0.253675490617752 0.275873929262161 -0.594936370849609 0.178474619984627 0.253675490617752 1.08251965045929 -0.744765341281891 -0.912587761878967 -1.02567553520203 -1.62549436092377 -1.22895395755768 -1.53389263153076 + Cluster -674 6 6 6 18.7 18.7 18.7 40.513 0 46.05 5365600000 18 3.83604032350143 0.00022879177377892 Q9UBS4 Q9UBS4 DnaJ homolog subfamily B member 11 DNAJB11 3077 As a co-chaperone for HSPA5 it is required for properfolding, trafficking or degradation of proteins (PubMed:10827079,PubMed:15525676, PubMed:29706351). Binds directly to both unfoldedproteins that are substrates for ERAD and nascent unfolded peptidechains, but dissociates from the HSPA5-unfolded protein complexbefore folding is completed (PubMed:15525676). May help recruitingHSPA5 and other chaperones to the substrate. Stimulates HSPA5ATPase activity (PubMed:10827079). It is necessary for maturationand correct trafficking of PKD1 (PubMed:29706351) Endoplasmic reticulum lumen{ECO:0000269|PubMed:10827079, ECO:0000269|PubMed:15195998,ECO:0000269|PubMed:15525676, ECO:0000269|PubMed:15544163}.Note=Associated with the ER membrane in a C-terminally epitope-tagged construct. IRE1-mediated unfolded protein response;positive regulation of ATPase activity;protein folding;protein maturation unfolded protein binding endoplasmic reticulum;endoplasmic reticulum lumen;membrane Protein processing in endoplasmic reticulum Polycystic kidney disease XBP1(S) activates chaperone genes 0.726390659809113 0.496057838201523 1.2485659122467 0.828534007072449 1.35732507705688 0.966989994049072 0.888523697853088 0.329141765832901 -0.442364484071732 0.609719276428223 -0.0169237237423658 0.488980054855347 -1.03090679645538 -1.20460259914398 -1.03090679645538 -1.38184475898743 -1.39735627174377 -1.43532288074493 + Cluster -674 26 26 26 50.5 50.5 50.5 66.022 0 323.31 40780000000 99 6.32123527481065 0 Q07065;Q96K21;Q96K21-3;Q96K21-4;Q96K21-2 Q07065 Cytoskeleton-associated protein 4 CKAP4 1536 High-affinity epithelial cell surface receptor for APF.Mediates the anchoring of the endoplasmic reticulum tomicrotubules.;Key regulator of abscission step in cytokinesis: part ofthe cytokinesis checkpoint, a process required to delay abscissionto prevent both premature resolution of intercellular chromosomebridges and accumulation of DNA damage. Together with CHMP4C,required to retain abscission-competent VPS4 (VPS4A and/or VPS4B)at the midbody ring until abscission checkpoint signaling isterminated at late cytokinesis. Deactivation of AURKB results indephosphorylation of CHMP4C followed by its dissociation fromZFYVE19/ANCHR and VPS4 and subsequent abscission Single-pass type IImembrane protein. Cytoplasm, cytoskeleton. Cytoplasm, perinuclearregion. Note=Translocates to the perinuclear region upon APF-stimulation.; Single-passtype II membrane protein. Cell membrane;Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:24814515}.Cleavage furrow {ECO:0000269|PubMed:24814515}. Midbody, Midbodyring {ECO:0000269|PubMed:24814515}. Note=Localizes mainly oncentrosomes in interphase and early mitosis. Localizes at thecleavage furrow and midbody ring in late mitosis and cytokinesis.{ECO:0000269|PubMed:24814515}.;Endoplasmic reticulum membrane abscission;cell division;cellular protein metabolic process;mitotic cytokinesis checkpoint;negative regulation of cytokinesis;neutrophil degranulation;post-translational protein modification metal ion binding;phosphatidylinositol-3-phosphate binding;RNA binding azurophil granule membrane;centrosome;cleavage furrow;cytoplasm;cytoplasmic ribonucleoprotein granule;cytoskeleton;cytosol;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;extracellular exosome;Flemming body;integral component of membrane;lamellar body;lipid droplet;membrane;midbody;nuclear speck;perinuclear region of cytoplasm;plasma membrane;rough endoplasmic reticulum;specific granule membrane Protein processing in endoplasmic reticulum Neutrophil degranulation;Post-translational protein phosphorylation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Surfactant metabolism 1.27172601222992 0.868813574314117 0.960355460643768 0.447179853916168 0.816322922706604 0.72295868396759 0.569145560264587 0.278048008680344 0.447179853916168 0.569145560264587 0.657498419284821 0.278048008680344 -1.02930688858032 -0.947403252124786 -1.09818398952484 -1.60384261608124 -1.63413822650909 -1.57354688644409 + Cluster -674 21 21 21 40.3 40.3 40.3 56.65 0 323.31 185710000000 220 7.45641632506853 0 O43175 O43175 D-3-phosphoglycerate dehydrogenase PHGDH 201 Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of thephosphorylated L-serine biosynthesis pathway. Also catalyzes thereversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate andthe reversible oxidation of (S)-malate to oxaloacetate brain development;cellular amino acid metabolic process;G1 to G0 transition;gamma-aminobutyric acid metabolic process;glial cell development;glutamine metabolic process;glycine metabolic process;L-serine biosynthetic process;neural tube development;neuron projection development;regulation of gene expression;spinal cord development;taurine metabolic process;threonine metabolic process electron transfer activity;L-malate dehydrogenase activity;NAD binding;phosphoglycerate dehydrogenase activity cytosol;extracellular exosome;myelin sheath Biosynthesis of amino acids;Carbon metabolism;Cysteine and methionine metabolism;Glycine, serine and threonine metabolism;Metabolic pathways 3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency;Neu-Laxova syndrome Serine biosynthesis 1.21025800704956 1.01962411403656 0.514353454113007 0.464242100715637 0.362639278173447 0.505545675754547 0.552796423435211 0.890728056430817 0.743865251541138 0.0578726157546043 0.881075501441956 0.716747760772705 -1.48977422714233 -1.03694033622742 -1.07801806926727 -1.43866753578186 -1.537024974823 -1.33932316303253 + Cluster -674 18 18 18 36.5 36.5 36.5 64.369 0 138.17 21702000000 60 8.513191494336 0 P08243;P08243-2;P08243-3 P08243;P08243-2;P08243-3 Asparagine synthetase [glutamine-hydrolyzing] ASNS 553 asparagine biosynthetic process;cellular amino acid biosynthetic process;cellular response to glucose starvation;cellular response to hormone stimulus;glutamine metabolic process;L-asparagine biosynthetic process;liver development;negative regulation of apoptotic process;PERK-mediated unfolded protein response;positive regulation of mitotic cell cycle;response to amino acid;response to follicle-stimulating hormone;response to light stimulus;response to mechanical stimulus;response to methotrexate;response to toxic substance asparagine synthase (glutamine-hydrolyzing) activity;ATP binding;cofactor binding;protein homodimerization activity cytosol Alanine, aspartate and glutamate metabolism;Biosynthesis of amino acids;Metabolic pathways Asparagine synthetase deficiency Amino acid synthesis and interconversion (transamination);ATF4 activates genes 0.456122130155563 0.508847713470459 1.38736271858215 0.819108843803406 2.03593301773071 0.775133669376373 0.582572042942047 0.41469869017601 -0.417193710803986 -0.156691744923592 -0.0417140573263168 -0.0705488547682762 -0.680949211120605 -0.373930901288986 -0.448548376560211 -1.67465460300446 -1.47943484783173 -1.63611245155334 + Cluster -674 12 12 9 5.8 5.8 4.5 358.2 0 144.17 11531000000 37 3.77467184846052 0.000256723716381418 P49792;Q7Z3J3;Q99666;O14715;Q99666-2 P49792 E3 SUMO-protein ligase RanBP2 RANBP2 1121 E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2conjugation by UBE2I (PubMed:11792325, PubMed:12032081,PubMed:15378033, PubMed:22194619, PubMed:15931224). Involved intransport factor (Ran-GTP, karyopherin)-mediated protein importvia the F-G repeat-containing domain which acts as a docking sitefor substrates (PubMed:7775481). Binds single-stranded RNA (invitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Componentof the nuclear export pathway (PubMed:10078529). Specific dockingsite for the nuclear export factor exportin-1 (PubMed:10078529).Sumoylates PML at 'Lys-490' which is essential for the properassembly of PML-NB (PubMed:22155184). Recruits BICD2 to thenuclear envelope and cytoplasmic stacks of nuclear pore complexknown as annulate lamellae during G2 phase of cell cycle(PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357,PubMed:23353830). Cytoplasm {ECO:0000269|PubMed:15710750}.;Nucleus {ECO:0000269|PubMed:7775481}.Nucleus membrane {ECO:0000269|PubMed:11839768}. Nucleus, nuclearpore complex {ECO:0000269|PubMed:11839768,ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:23353830,ECO:0000269|PubMed:7603572}. Nucleus envelope{ECO:0000269|PubMed:20386726}. Note=Detected in diffuse anddiscrete intranuclear foci (PubMed:11839768). Cytoplasmicfilaments (PubMed:7775481). {ECO:0000269|PubMed:11839768,ECO:0000269|PubMed:7775481}. centrosome localization;mRNA export from nucleus;NLS-bearing protein import into nucleus;positive regulation of glucokinase activity;positive regulation of GTPase activity;protein folding;protein peptidyl-prolyl isomerization;protein sumoylation;regulation of gluconeogenesis;response to amphetamine;viral process metal ion binding;protein-containing complex binding;Ran GTPase binding;RNA binding;SUMO transferase activity annulate lamellae;cytoplasm;cytoplasmic periphery of the nuclear pore complex;cytosol;membrane;mitochondrion;nuclear envelope;nuclear inclusion body;nuclear membrane;nuclear pore;nuclear pore cytoplasmic filaments;nuclear pore nuclear basket;nucleus RNA transport Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;ISG15 antiviral mechanism;Mitotic Prometaphase;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Resolution of Sister Chromatid Cohesion;Rev-mediated nuclear export of HIV RNA;RHO GTPases Activate Formins;Separation of Sister Chromatids;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs -0.146952331066132 0.459453970193863 1.37844955921173 0.758316218852997 1.63484835624695 0.299732863903046 0.517672955989838 0.725554227828979 0.452243626117706 0.339904874563217 0.378878682851791 0.351372092962265 -1.52401614189148 -0.653222858905792 -0.435850381851196 -1.92444360256195 -1.08895587921143 -1.52298617362976 + Cluster -674 6 6 6 17.6 17.6 17.6 42.966 0 41.806 9506300000 19 4.62208445591176 4.0983606557377E-05 P54687;P54687-5;P54687-3;P54687-4;P54687-2 P54687;P54687-5;P54687-3;P54687-4;P54687-2 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 1223 Catalyzes the first reaction in the catabolism of theessential branched chain amino acids leucine, isoleucine, andvaline. Cytoplasm. branched-chain amino acid biosynthetic process;branched-chain amino acid catabolic process;cell proliferation;G1/S transition of mitotic cell cycle;leucine biosynthetic process;valine biosynthetic process branched-chain-amino-acid transaminase activity;identical protein binding;L-isoleucine transaminase activity;L-leucine transaminase activity;L-valine transaminase activity cytosol;mitochondrion 2-Oxocarboxylic acid metabolism;Biosynthesis of amino acids;Cysteine and methionine metabolism;Metabolic pathways;Pantothenate and CoA biosynthesis;Valine, leucine and isoleucine biosynthesis;Valine, leucine and isoleucine degradation Branched-chain amino acid catabolism 1.0616899728775 0.89939820766449 0.52640175819397 0.580028235912323 0.395668238401413 1.57765519618988 1.17283654212952 1.05180406570435 0.497364521026611 -0.46103572845459 -0.40308004617691 0.254204094409943 -1.07799768447876 -1.07799768447876 -1.03640854358673 -1.28132438659668 -1.28132438659668 -1.39788246154785 + Cluster -674 9 9 9 19.9 19.9 19.9 46.53 0 48.648 12143000000 40 6.62291151574683 0 P00966 P00966 Argininosuccinate synthase ASS1 475 One of the enzymes of the urea cycle, the metabolicpathway transforming neurotoxic amonia produced by proteincatabolism into inocuous urea in the liver of ureotelic animals.Catalyzes the formation of arginosuccinate from aspartate,citrulline and ATP and together with ASL it is responsible for thebiosynthesis of arginine in most body tissues Cytoplasm, cytosol{ECO:0000269|PubMed:28985504, ECO:0000305|PubMed:27287393}. acute-phase response;aging;arginine biosynthetic process;argininosuccinate metabolic process;aspartate metabolic process;cellular response to amine stimulus;cellular response to amino acid stimulus;cellular response to ammonium ion;cellular response to cAMP;cellular response to dexamethasone stimulus;cellular response to glucagon stimulus;cellular response to interferon-gamma;cellular response to laminar fluid shear stress;cellular response to lipopolysaccharide;cellular response to oleic acid;cellular response to tumor necrosis factor;circadian rhythm;citrulline metabolic process;diaphragm development;kidney development;liver development;midgut development;negative regulation of leukocyte cell-cell adhesion;positive regulation of nitric oxide biosynthetic process;response to estradiol;response to growth hormone;response to mycotoxin;response to nutrient;response to zinc ion;urea cycle amino acid binding;argininosuccinate synthase activity;ATP binding;identical protein binding;RNA binding;toxic substance binding cell body fiber;cytoplasm;cytosol;endoplasmic reticulum;extracellular exosome;lysosome;mitochondrial outer membrane;myelin sheath;nucleus;perikaryon Alanine, aspartate and glutamate metabolism;Arginine biosynthesis;Biosynthesis of amino acids;Fluid shear stress and atherosclerosis;Metabolic pathways Citrullinemia;Primary hyperammonemic disorders (Urea cycle disorders) Urea cycle 0.204959362745285 0.495387494564056 1.02621269226074 0.93973845243454 0.594890832901001 1.54235982894897 1.22838127613068 1.38605189323425 0.448014050722122 -0.610610783100128 -0.016234839335084 -0.496129512786865 -0.808922350406647 -0.983233749866486 -1.24164807796478 -1.09925508499146 -1.39569354057312 -1.21426796913147 + Cluster -674 26 26 26 36.2 36.2 36.2 106.81 0 322.05 56076000000 160 8.00600081159779 0 P49588;P49588-2 P49588;P49588-2 Alanine--tRNA ligase, cytoplasmic AARS 1103 Catalyzes the attachment of alanine to tRNA(Ala) in atwo-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala)(PubMed:27622773, PubMed:27911835, PubMed:28493438). Also editsincorrectly charged tRNA(Ala) via its editing domain(PubMed:27622773, PubMed:27911835, PubMed:28493438) Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03133,ECO:0000269|PubMed:27911835}. alanyl-tRNA aminoacylation;cerebellar Purkinje cell layer development;negative regulation of neuron apoptotic process;neuromuscular process controlling balance;regulation of cytoplasmic translational fidelity;tRNA aminoacylation for protein translation;tRNA modification;tRNA processing alanine-tRNA ligase activity;amino acid binding;aminoacyl-tRNA editing activity;ATP binding;Ser-tRNA(Ala) hydrolase activity;translation regulator activity;tRNA binding;zinc ion binding cytoplasm;cytosol;extracellular exosome;membrane Aminoacyl-tRNA biosynthesis Charcot-Marie-Tooth disease;Early infantile epileptic encephalopathy Cytosolic tRNA aminoacylation -0.379078984260559 0.84469598531723 0.588359892368317 0.540162801742554 1.53307092189789 1.21815049648285 1.01551961898804 1.30211198329926 0.484336584806442 -0.342694282531738 0.0219910368323326 0.202078521251678 -1.2635372877121 -1.01056301593781 -1.14308214187622 -0.805911719799042 -1.25978147983551 -1.54582893848419 + Cluster -674 8 8 8 17.6 17.6 17.6 67.993 0 109.66 17516000000 32 5.94396514267089 1.16279069767442E-05 P08195;P08195-3;P08195-2;P08195-4 P08195;P08195-3;P08195-2;P08195-4 4F2 cell-surface antigen heavy chain SLC3A2 550 Required for the function of light chain amino-acidtransporters. Involved in sodium-independent, high-affinitytransport of large neutral amino acids such as phenylalanine,tyrosine, leucine, arginine and tryptophan. Involved in guidingand targeting of LAT1 and LAT2 to the plasma membrane. Whenassociated with SLC7A6 or SLC7A7 acts as an arginine/glutamineexchanger, following an antiport mechanism for amino acidtransport, influencing arginine release in exchange forextracellular amino acids. Plays a role in nitric oxide synthesisin human umbilical vein endothelial cells (HUVECs) via transportof L-arginine. Required for normal and neoplastic cell growth.When associated with SLC7A5/LAT1, is also involved in thetransport of L-DOPA across the blood-brain barrier, and that ofthyroid hormones triiodothyronine (T3) and thyroxine (T4) acrossthe cell membrane in tissues such as placenta. Involved in theuptake of methylmercury (MeHg) when administered as the L-cysteineor D,L-homocysteine complexes, and hence plays a role in metal ionhomeostasis and toxicity. When associated with SLC7A5 or SLC7A8,involved in the cellular activity of small molecular weightnitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Together withICAM1, regulates the transport activity LAT2 in polarizedintestinal cells, by generating and delivering intracellularsignals. When associated with SLC7A5, plays an important role intransporting L-leucine from the circulating blood to the retinaacross the inner blood-retinal barrier. When associated withLAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promoteleucine uptake into these organelles and is required for mTORC1activation (PubMed:25998567). Single-pass type IImembrane protein. Melanosome. Note=Identified by mass spectrometryin melanosome fractions from stage I to stage IV. Localized to theplasma membrane when associated with SLC7A5 or SLC7A8. Localizedto the placental apical membrane. Located selectively at cell-celladhesion sites (By similarity). Colocalized with SLC7A8/LAT2 atthe basolateral membrane of kidney proximal tubules and smallintestine epithelia. Expressed in both luminal and abluminalmembranes of brain capillary endothelial cells (By similarity).{ECO:0000250}.;Apical cell membrane amino acid transport;calcium ion transport;carbohydrate metabolic process;leukocyte migration;L-leucine import across plasma membrane;response to exogenous dsRNA;tryptophan transport cadherin binding;calcium:sodium antiporter activity;catalytic activity;double-stranded RNA binding;neutral amino acid transmembrane transporter activity;RNA binding apical plasma membrane;cell surface;cytosol;extracellular exosome;integral component of membrane;melanosome;membrane;nucleus;plasma membrane Ferroptosis;mTOR signaling pathway;Protein digestion and absorption Amino acid transport across the plasma membrane;Basigin interactions;Tryptophan catabolism CD98-LAT2-ITGB1 complex;ITGAV-ITGB3-SLC3A2 complex 0.194759145379066 0.785259544849396 1.26222801208496 -0.428651601076126 1.64067316055298 1.34005236625671 0.988955318927765 0.536393940448761 0.292243480682373 0.0958362594246864 0.536393940448761 -0.359122693538666 -1.22176086902618 -0.803724229335785 -1.11300802230835 -1.49268400669098 -0.845473527908325 -1.40837013721466 + Cluster -674 3 3 3 39.3 39.3 39.3 17.663 0 135.11 1842200000 8 4.1181254986125 0.000115501519756839 Q9Y3D0 Q9Y3D0 Mitotic spindle-associated MMXD complex subunit MIP18 FAM96B 3266 Component of the cytosolic iron-sulfur protein assembly(CIA) complex, a multiprotein complex that mediates theincorporation of iron-sulfur cluster into extramitochondrial Fe/Sproteins (PubMed:23891004, PubMed:22678362, PubMed:22678361). As aCIA complex component and in collaboration with CIAO1 and MMS19,binds to and facilitates the assembly of most cytosolic-nuclearFe/S proteins (PubMed:23891004). As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation,probably by facilitating iron-sulfur cluster assembly intoERCC2/XPD (PubMed:20797633). Nucleus {ECO:0000269|PubMed:20797633}.Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:20797633}. chromosome segregation;iron-sulfur cluster assembly;protein maturation by iron-sulfur cluster transfer CIA complex;cytoplasm;cytosol;MMXD complex;nucleoplasm;nucleus;spindle Cytosolic iron-sulfur cluster assembly CIA targeting (MIP18, CIAO1, MMS19) complex;CIA2B-CIA1-MMS19 complex;MMS19 complex;MMS19-FAM96B complex;MMXD complex 1.32147812843323 -0.0730964243412018 0.666818737983704 1.29668247699738 1.09874093532562 1.27680540084839 1.41547811031342 0.939098119735718 -1.3682427406311 -0.649242341518402 -0.728977739810944 -0.449286699295044 -0.62665730714798 -0.431546568870544 -0.745661735534668 -1.01190495491028 -0.546780645847321 -1.383704662323 + Cluster -674 1 1 1 4 4 4 44.049 0 5.0149 498060000 2 3.49683988106542 0.000424 Q14344 Q14344 Guanine nucleotide-binding protein subunit alpha-13 GNA13 1707 Guanine nucleotide-binding proteins (G proteins) areinvolved as modulators or transducers in various transmembranesignaling systems (PubMed:15240885, PubMed:16787920,PubMed:16705036, PubMed:27084452). Activates effector moleculeRhoA by binding and activating RhoGEFs (ARHGEF1/p115RhoGEF,ARHGEF11/PDZ-RhoGEF and ARHGEF12/LARG) (PubMed:15240885,PubMed:12515866). GNA13-dependent Rho signaling subsequentlyregulates transcription factor AP-1 (activating protein-1) (Bysimilarity). Promotes tumor cell invasion and metastasis byactivating RhoA/ROCK signaling pathway (PubMed:16787920,PubMed:16705036, PubMed:27084452). Inhibits CDH1-mediated celladhesion in process independent from Rho activation(PubMed:11976333). Cell membrane {ECO:0000269|PubMed:10747909};Lipid-anchor {ECO:0000269|PubMed:10747909}. Melanosome{ECO:0000269|PubMed:17081065}. Cytoplasm{ECO:0000269|PubMed:10747909, ECO:0000269|PubMed:18703424}.Nucleus {ECO:0000269|PubMed:18703424}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV(PubMed:17081065). Detected in the cytoplasm of Leydig cells andin the seminiferous epithelium, including differentiating cellsfrom the spermatogonia to mature spermatozoa stages(PubMed:18703424). In round spermatids, also present in the nuclei(PubMed:18703424). {ECO:0000269|PubMed:17081065,ECO:0000269|PubMed:18703424}. activation of phospholipase D activity;adenylate cyclase-activating G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;branching involved in blood vessel morphogenesis;cell differentiation;G protein-coupled receptor signaling pathway;in utero embryonic development;platelet activation;positive regulation of apoptotic process;positive regulation of cytosolic calcium ion concentration;regulation of cell migration;regulation of cell shape;regulation of small GTPase mediated signal transduction;Rho protein signal transduction;signal transduction D5 dopamine receptor binding;G protein-coupled receptor binding;G-protein beta/gamma-subunit complex binding;GTP binding;GTPase activity;guanyl-nucleotide exchange factor activity;metal ion binding;Rho guanyl-nucleotide exchange factor activity brush border membrane;cytosol;extracellular exosome;focal adhesion;heterotrimeric G-protein complex;melanosome;membrane;nucleus;plasma membrane Apelin signaling pathway;cGMP-PKG signaling pathway;Human cytomegalovirus infection;Long-term depression;Parathyroid hormone synthesis, secretion and action;Pathways in cancer;Phospholipase D signaling pathway;Platelet activation;Regulation of actin cytoskeleton;Sphingolipid signaling pathway;Vascular smooth muscle contraction G alpha (12/13) signalling events;NRAGE signals death through JNK;Rho GTPase cycle;Thrombin signalling through proteinase activated receptors (PARs);Thromboxane signalling through TP receptor G alpha-13-Hax-1-cortactin-Rac complex 1.94930601119995 0.66732931137085 0.391779571771622 0.280462652444839 0.611511528491974 0.965593099594116 1.09669947624207 1.05180621147156 0.482180446386337 0.11681018024683 -0.423763036727905 -0.454750150442123 -0.834811747074127 -0.812587022781372 -0.705036818981171 -1.36086440086365 -1.46971189975739 -1.55195343494415 + Cluster -674 16 16 16 49.7 49.7 49.7 40.422 0 189.11 56733000000 130 4.99587522681299 2.1978021978022E-05 Q9Y617;Q9Y617-2 Q9Y617;Q9Y617-2 Phosphoserine aminotransferase PSAT1 3325 Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine L-serine biosynthetic process;pyridoxine biosynthetic process O-phospho-L-serine:2-oxoglutarate aminotransferase activity cytosol;extracellular exosome Biosynthesis of amino acids;Carbon metabolism;Cysteine and methionine metabolism;Glycine, serine and threonine metabolism;Metabolic pathways;Vitamin B6 metabolism Neu-Laxova syndrome;Phosphoserine aminotransferase deficiency Serine biosynthesis 1.83763480186462 0.290011703968048 0.688815057277679 0.187244415283203 1.07283973693848 1.26632022857666 0.944433510303497 0.868248641490936 0.31290665268898 -0.588112413883209 -0.347041547298431 -0.0907587334513664 -0.347041547298431 -0.884735703468323 -0.821278810501099 -1.29323422908783 -1.6290717124939 -1.46718001365662 + Cluster -674 5 5 5 5.1 5.1 5.1 148.66 0 31.435 1088500000 10 4.3227875751502 8.02675585284281E-05 Q9UM54-6;Q9UM54;Q9UM54-5;Q9UM54-4;Q9UM54-2;Q9UM54-1 Q9UM54-6;Q9UM54;Q9UM54-5;Q9UM54-4;Q9UM54-2;Q9UM54-1 Unconventional myosin-VI MYO6 3170 Myosins are actin-based motor molecules with ATPaseactivity. Unconventional myosins serve in intracellular movements.Myosin 6 is a reverse-direction motor protein that moves towardsthe minus-end of actin filaments. Has slow rate of actin-activatedADP release due to weak ATP binding. Functions in a variety ofintracellular processes such as vesicular membrane trafficking andcell migration. Required for the structural integrity of the Golgiapparatus via the p53-dependent pro-survival pathway. Appears tobe involved in a very early step of clathrin-mediated endocytosisin polarized epithelial cells. May act as a regulator of F-actindynamics. May play a role in transporting DAB2 from the plasmamembrane to specific cellular targets. Required for structuralintegrity of inner ear hair cells (By similarity). Peripheral membrane protein. Golgi apparatus{ECO:0000250}. Nucleus. Cytoplasm, perinuclear region. Membrane,clathrin-coated pit. Cell projection, ruffle membrane; Peripheralmembrane protein. Note=Also present in endocyctic vesicles, andmembrane ruffles. Translocates from membrane ruffles, endocyticvesicles and cytoplasm to Golgi apparatus, perinuclear membraneand nucleus through induction by p53 and p53-induced DNA damage.Recruited into membrane ruffles from cell surface by EGF-stimulation. Colocalizes with DAB2 in clathrin-coatedpits/vesicles. Colocalizes with OPTN at the Golgi complex and invesicular structures close to the plasma membrane (By similarity).{ECO:0000250}.Isoform 3: Cytoplasmic vesicle, clathrin-coated vesicle membrane.Isoform 4: Cytoplasmic vesicle, clathrin-coated vesicle membrane. Cell projection, ruffle membrane.;Golgi apparatus, trans-Golgi networkmembrane actin filament-based movement;DNA damage response, signal transduction by p53 class mediator;endocytosis;intracellular protein transport;positive regulation of transcription by RNA polymerase II;regulation of secretion;response to drug;sensory perception of sound actin binding;actin filament binding;ADP binding;ATP binding;calmodulin binding;identical protein binding;minus-end directed microfilament motor activity;motor activity actin filament;apical part of cell;cell cortex;clathrin-coated pit;clathrin-coated vesicle membrane;cytoplasm;cytoplasmic vesicle;cytosol;endocytic vesicle;extracellular exosome;filamentous actin;Golgi apparatus;lysosomal membrane;membrane;microvillus;nuclear membrane;nucleoplasm;nucleus;perinuclear region of cytoplasm;plasma membrane;RNA polymerase II, holoenzyme;ruffle;ruffle membrane;unconventional myosin complex Deafness, autosomal dominant;Deafness, autosomal recessive Gap junction degradation;Trafficking of AMPA receptors 1.64024949073792 0.291568130254745 1.1711665391922 0.490174144506454 1.1711665391922 1.40618097782135 0.962638258934021 0.150925770401955 -0.33631107211113 0.150925770401955 -0.277944892644882 -0.471438825130463 -0.642854273319244 -0.806963860988617 -0.471438825130463 -1.57286894321442 -1.57286894321442 -1.28230607509613 + Cluster -674 28 28 2 49.9 49.9 3.2 68.604 0 312.69 95605000000 247 3.57525795928032 0.000379014989293362 Q96AE4-2 Q96AE4-2 Far upstream element-binding protein 1 FUBP1 2398 Regulates MYC expression by binding to a single-strandedfar-upstream element (FUSE) upstream of the MYC promoter. May actboth as activator and repressor of transcription Nucleus {ECO:0000305}. positive regulation of gene expression;transcription by RNA polymerase II DNA-binding transcription factor activity;RNA binding;single-stranded DNA binding nucleoplasm;nucleus 1.35490489006042 0.32636222243309 1.22293269634247 0.350244432687759 1.00048363208771 0.793374359607697 0.505180299282074 0.72156697511673 0.701290011405945 -0.255537152290344 -0.292692363262177 -0.0770864859223366 0.431237280368805 -0.5150266289711 -1.31108510494232 -1.64068269729614 -1.7724711894989 -1.54299521446228 + Cluster -674 8 8 8 21.9 21.9 21.9 56.5 0 95.935 7208100000 21 3.4477072157086 0.000474285714285714 P21281;P15313 P21281;P15313 V-type proton ATPase subunit B, brain isoform;V-type proton ATPase subunit B, kidney isoform ATP6V1B2;ATP6V1B1 753 Non-catalytic subunit of the peripheral V1 complex ofvacuolar ATPase. V-ATPase is responsible for acidifying a varietyof intracellular compartments in eukaryotic cells. Peripheral membraneprotein. Melanosome. Note=Endomembrane. Identified by massspectrometry in melanosome fractions from stage I to stage IV.; Peripheral membraneprotein. Note=Endomembrane.;Endomembrane system ATP hydrolysis coupled proton transport;ATP metabolic process;calcium ion homeostasis;excretion;inner ear morphogenesis;insulin receptor signaling pathway;ion transmembrane transport;ossification;pH reduction;proton transmembrane transport;regulation of macroautophagy;regulation of pH;sensory perception of sound;transferrin transport ATP binding;hydrolase activity;protein-containing complex binding;proton transmembrane transporter activity;proton-transporting ATPase activity, rotational mechanism apical plasma membrane;basolateral plasma membrane;cytoplasm;cytosol;endomembrane system;extracellular exosome;extrinsic component of synaptic vesicle membrane;integral component of membrane;intracellular membrane-bounded organelle;lateral plasma membrane;lysosomal membrane;melanosome;microvillus;myelin sheath;plasma membrane;proton-transporting V-type ATPase, V1 domain;ruffle;vacuolar proton-transporting V-type ATPase complex Collecting duct acid secretion;Epithelial cell signaling in Helicobacter pylori infection;Human papillomavirus infection;Metabolic pathways;mTOR signaling pathway;Oxidative phosphorylation;Phagosome;Rheumatoid arthritis;Synaptic vesicle cycle;Vibrio cholerae infection DDOD syndrome;Distal renal tubular acidosis (RTA type 1);Renal tubular acidosis;Zimmermann-Laband syndrome Insulin receptor recycling;Ion channel transport;ROS, RNS production in phagocytes;Transferrin endocytosis and recycling v-ATPase-Ragulator-AXIN/LKB1-AMPK complex 2.14342641830444 0.768723487854004 0.325860977172852 0.16130293905735 0.674491882324219 0.979538083076477 0.844417095184326 0.71704089641571 0.0111633036285639 0.190563455224037 -0.477484971284866 0.499540865421295 -0.778564631938934 -0.857283174991608 -1.11780297756195 -1.06031775474548 -1.16735517978668 -1.85726070404053 + Cluster -674 2 2 2 9.6 9.6 9.6 39.672 0 18.681 94325000 5 3.90938429046968 0.000182795698924731 Q13190;Q13190-3;Q13190-2;Q13190-4 Q13190;Q13190-3;Q13190-2;Q13190-4 Syntaxin-5 STX5 1608 Mediates endoplasmic reticulum to Golgi transport.Together with p115/USO1 and GM130/GOLGA2, involved in vesicletethering and fusion at the cis-Golgi membrane to maintain thestacked and inter-connected structure of the Golgi apparatus Single-passtype IV membrane protein {ECO:0000255}. Golgi apparatus membrane{ECO:0000250|UniProtKB:Q08851}. Note=Localizes throughout theGolgi apparatus, but most abundant in the cis-most cisternae.{ECO:0000250|UniProtKB:Q08851}.;Endoplasmic reticulum-Golgi intermediatecompartment membrane {ECO:0000250|UniProtKB:Q08851} COPII vesicle coating;early endosome to Golgi transport;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi disassembly;intracellular protein transport;positive regulation of protein catabolic process;regulation of Golgi organization;retrograde transport, endosome to Golgi;vesicle docking;vesicle fusion;vesicle fusion with Golgi apparatus cadherin binding;protein N-terminus binding;SNAP receptor activity;SNARE binding cytosol;endomembrane system;endoplasmic reticulum membrane;endoplasmic reticulum-Golgi intermediate compartment membrane;ER to Golgi transport vesicle membrane;Golgi apparatus;Golgi membrane;integral component of membrane;SNARE complex;vesicle SNARE interactions in vesicular transport Cargo concentration in the ER;COPII-mediated vesicle transport;COPI-mediated anterograde transport;Intra-Golgi traffic 0.840798258781433 0.68502277135849 0.336492955684662 0.68502277135849 1.14485478401184 1.005695104599 1.72851014137268 1.47271072864532 -0.15739318728447 -0.204608410596848 -1.25930094718933 -0.865511775016785 -0.599311530590057 -0.678826093673706 -0.599311530590057 -1.12536907196045 -1.28410577774048 -1.12536907196045 + Cluster -674 26 26 26 60.9 60.9 60.9 56.084 0 323.31 115330000000 196 4.89865892283829 2.02020202020202E-05 Q9P258 Q9P258 Protein RCC2 RCC2 3047 Multifunctional protein that may effect its functions byregulating the activity of small GTPases, such as RAC1 and RALA(PubMed:12919680, PubMed:25074804, PubMed:26158537,PubMed:28869598). Required for normal progress through the cellcycle, both during interphase and during mitosis (PubMed:23388455,PubMed:12919680, PubMed:26158537). Required for the presence ofnormal levels of MAD2L1, AURKB and BIRC5 on inner centromeresduring mitosis, and for normal attachment of kinetochores tomitotic spindles (PubMed:12919680, PubMed:26158537). Required fornormal organization of the microtubule cytoskeleton in interphasecells (PubMed:23388455). Functions as guanine nucleotide exchangefactor (GEF) for RALA (PubMed:26158537). Interferes with theactivation of RAC1 by guanine nucleotide exchange factors(PubMed:25074804). Prevents accumulation of active, GTP-boundRAC1, and suppresses RAC1-mediated reorganization of the actincytoskeleton and formation of membrane protrusions(PubMed:25074804, PubMed:28869598). Required for normal cellularresponses to contacts with the extracellular matrix of adjacentcells, and for directional cell migration in response to afibronectin gradient (in vitro) (PubMed:25074804,PubMed:28869598). Cytoplasmic side{ECO:0000305|PubMed:25074804}. Note=Appears in the nucleus at G2,then concentrates at the inner centromere region of chromosomesduring prophase. Redistributes to the midzone of the mitoticspindle during anaphase. Here, the protein covers the entireequatorial diameter from cortex to cortex (PubMed:12919680,PubMed:1939370, PubMed:7559776, PubMed:9914378). Colocalizes withcytoplasmic microtubules in interphase cells (PubMed:23388455).Colocalizes with RAC1 at the cell membrane (PubMed:25074804).{ECO:0000269|PubMed:12919680, ECO:0000269|PubMed:1939370,ECO:0000269|PubMed:23388455, ECO:0000269|PubMed:25074804,ECO:0000269|PubMed:7559776, ECO:0000269|PubMed:9914378}.; Peripheral membrane protein{ECO:0000305|PubMed:25074804};Nucleus, nucleolus{ECO:0000305|PubMed:12429849}. Nucleus{ECO:0000269|PubMed:23388455}. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:23388455}. Chromosome, centromere{ECO:0000269|PubMed:12919680, ECO:0000269|PubMed:1939370,ECO:0000269|PubMed:9914378}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:1939370, ECO:0000269|PubMed:9914378}.Chromosome {ECO:0000269|PubMed:12919680,ECO:0000269|PubMed:1939370, ECO:0000269|PubMed:9914378}. Midbody{ECO:0000269|PubMed:12919680, ECO:0000269|PubMed:1939370,ECO:0000269|PubMed:9914378}. Cell membrane{ECO:0000269|PubMed:25074804} activation of GTPase activity;cell cycle;cell division;chromosome passenger complex localization to kinetochore;establishment of protein localization;focal adhesion assembly;integrin-mediated signaling pathway;negative regulation of focal adhesion assembly;negative regulation of GTPase activity;negative regulation of substrate adhesion-dependent cell spreading;positive regulation of attachment of spindle microtubules to kinetochore;positive regulation of G2/M transition of mitotic cell cycle;regulation of cell migration;regulation of fibroblast migration;regulation of ruffle assembly guanyl-nucleotide exchange factor activity;microtubule binding;protein domain specific binding;protein kinase binding;Rac GTPase binding;RNA binding;small GTPase binding chromosome, centromeric core domain;cytosol;early endosome membrane;microtubule;midbody;mitotic spindle midzone;nucleolus;plasma membrane Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Mitotic Prometaphase;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Separation of Sister Chromatids 1.98625063896179 0.338213503360748 0.940434992313385 0.2303107380867 0.816108822822571 0.903783559799194 1.28395092487335 0.894045650959015 -0.103622078895569 0.0450905039906502 -0.858239054679871 -0.345666408538818 -0.751016438007355 -0.557059109210968 -0.614895164966583 -1.54402673244476 -1.43035638332367 -1.23330795764923 + Cluster -674 2 2 2 3.6 3.6 3.6 72.765 0 7.927 1433800000 4 3.69318674450663 0.000299528301886792 P48506 P48506 Glutamate--cysteine ligase catalytic subunit GCLC 1074 aging;apoptotic mitochondrial changes;cell redox homeostasis;cellular response to fibroblast growth factor stimulus;cellular response to follicle-stimulating hormone stimulus;cellular response to glucose stimulus;cellular response to hepatocyte growth factor stimulus;cellular response to insulin stimulus;cellular response to mechanical stimulus;cellular response to thyroxine stimulus;cysteine metabolic process;glutamate metabolic process;glutathione biosynthetic process;L-ascorbic acid metabolic process;negative regulation of apoptotic process;negative regulation of extrinsic apoptotic signaling pathway;negative regulation of hepatic stellate cell activation;negative regulation of neuron apoptotic process;negative regulation of protein ubiquitination;negative regulation of transcription, DNA-templated;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of blood vessel size;regulation of mitochondrial depolarization;response to activity;response to arsenic-containing substance;response to cadmium ion;response to heat;response to hormone;response to human chorionic gonadotropin;response to interleukin-1;response to nitrosative stress;response to nutrient;response to oxidative stress;response to xenobiotic stimulus ADP binding;ATP binding;coenzyme binding;glutamate binding;glutamate-cysteine ligase activity;magnesium ion binding;protein heterodimerization activity cytosol;glutamate-cysteine ligase complex Cysteine and methionine metabolism;Ferroptosis;Glutathione metabolism;Metabolic pathways Anemia due to disorders of glutathione metabolism Defective GCLC causes Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD);Glutathione synthesis and recycling Glutamate-cysteine ligase 1.50736057758331 0.41294527053833 0.693309366703033 0.581232368946075 0.95483535528183 1.2295355796814 1.52480232715607 0.887415766716003 -0.285780489444733 -0.00653114402666688 -1.2812762260437 -0.549124956130981 -0.544474601745605 -0.476199239492416 -0.784150421619415 -1.15873301029205 -1.21441960334778 -1.49074697494507 + Cluster -674 1 1 1 1.1 1.1 1.1 117.4 0.001906 1.5676 659840000 3 4.03952928781911 0.000131578947368421 Q9H4L7;Q9H4L7-2 Q9H4L7;Q9H4L7-2 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 SMARCAD1 2799 DNA helicase that possesses intrinsic ATP-dependentnucleosome-remodeling activity and is both required for DNA repairand heterochromatin organization. Promotes DNA end resection ofdouble-strand breaks (DSBs) following DNA damage: probably acts byweakening histone DNA interactions in nucleosomes flanking DSBs.Required for the restoration of heterochromatin organization afterreplication. Acts at replication sites to facilitate themaintenance of heterochromatin by directing H3 and H4 histonesdeacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restorationof silencing. Nucleus. Chromosome. Note=Colocalizes withPCNA at replication forks during S phase. Recruited to double-strand breaks (DSBs) sites of DNA damage. ATP-dependent chromatin remodeling;chromatin organization;chromatin remodeling;chromosome separation;DNA double-strand break processing;histone H3 deacetylation;histone H4 deacetylation;nucleotide metabolic process;positive regulation of transcription, DNA-templated;protein homooligomerization;regulation of DNA recombination ATP binding;DNA binding;helicase activity;nucleic acid binding heterochromatin;nuclear matrix;nuclear replication fork;nucleoplasm;site of double-strand break Signaling pathways regulating pluripotency of stem cells Adermatoglyphia;Basan syndrome 0.286653697490692 0.067638099193573 1.2342483997345 0.796523869037628 1.50815379619598 1.04592537879944 1.56983160972595 1.20234322547913 -0.379341602325439 0.0182958245277405 -0.770887911319733 -0.770887911319733 -0.829861640930176 -0.634889960289001 -0.829861640930176 -1.57366168498993 -1.02065181732178 -0.919569849967957 + Cluster -674 1 1 1 2.9 2.9 2.9 38.291 0 7.052 498580000 3 6.73983495857582 0 Q9NRS6;Q9NRS6-2 Q9NRS6;Q9NRS6-2 Sorting nexin-15 SNX15 2924 May be involved in several stages of intracellulartrafficking. Overexpression of SNX15 disrupts the normaltrafficking of proteins from the plasma membrane to recyclingendosomes or the TGN. Cytoplasmic side{ECO:0000269|PubMed:11085978}.; Cytoplasmic side{ECO:0000269|PubMed:11085978}. Cytoplasmic vesicle membrane{ECO:0000269|PubMed:11085978}; Peripheral membrane protein{ECO:0000269|PubMed:11085978}; Peripheral membraneprotein {ECO:0000269|PubMed:11085978};Cytoplasm {ECO:0000269|PubMed:11085978}.Membrane {ECO:0000269|PubMed:11085978} intracellular protein transport phosphatidylinositol binding cytoplasmic vesicle membrane;cytosol;membrane;nucleolus 1.17804515361786 -0.199583619832993 1.34032201766968 0.574705362319946 1.25217366218567 1.2505955696106 1.47086656093597 0.773234307765961 -0.271842837333679 -0.0336601845920086 -0.645136117935181 -0.807979762554169 -0.713595390319824 -0.486306816339493 -0.807979762554169 -1.35162460803986 -1.29298675060272 -1.22924661636353 + Cluster -674 20 20 18 61.7 61.7 52.4 27.744 0 310.47 143850000000 243 4.87917236517431 1.97044334975369E-05 Q07955;Q07955-3;Q07955-2 Q07955;Q07955-3;Q07955-2 Serine/arginine-rich splicing factor 1 SRSF1 1543 Plays a role in preventing exon skipping, ensuring theaccuracy of splicing and regulating alternative splicing.Interacts with other spliceosomal components, via the RS domains,to form a bridge between the 5'- and 3'-splice site bindingcomponents, U1 snRNP and U2AF. Can stimulate binding of U1 snRNPto a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNAsequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or thedecamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitutea powerful splicing enhancer in vitro, the ASF/SF2 splicingenhancer (ASE) which can specifically activate ASE-dependentsplicing. Isoform ASF-2 and isoform ASF-3 act as splicingrepressors. May function as export adapter involved in mRNAnuclear export through the TAP/NXF1 pathway Cytoplasm {ECO:0000269|PubMed:12215544,ECO:0000269|PubMed:20308322, ECO:0000269|PubMed:9420331}. Nucleusspeckle {ECO:0000269|PubMed:12215544, ECO:0000269|PubMed:20308322,ECO:0000269|PubMed:9420331}. Note=In nuclear speckles. Shuttlesbetween the nucleus and the cytoplasm.{ECO:0000269|PubMed:12215544, ECO:0000269|PubMed:20308322,ECO:0000269|PubMed:9420331}. alternative mRNA splicing, via spliceosome;cardiac muscle contraction;in utero embryonic development;liver regeneration;mRNA 3'-end processing;mRNA 5'-splice site recognition;mRNA cis splicing, via spliceosome;mRNA export from nucleus;mRNA processing;mRNA splice site selection;mRNA splicing, via spliceosome;oligodendrocyte differentiation;positive regulation of RNA splicing;regulation of alternative mRNA splicing, via spliceosome;RNA export from nucleus DNA topoisomerase binding;mRNA binding;protein kinase B binding;RNA binding;RS domain binding catalytic step 2 spliceosome;cytoplasm;nuclear speck;nucleoplasm;nucleus Herpes simplex virus 1 infection;IL-17 signaling pathway;Spliceosome Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;Transport of Mature mRNA derived from an Intron-Containing Transcript 17S U2 snRNP;C complex spliceosome;CDC5L complex;Histone-2-Histone-4-ASF1-MCM2 complex;Spliceosome 1.18797969818115 0.264597237110138 1.00758719444275 0.573524117469788 0.97171938419342 1.0469446182251 1.56263220310211 1.0469446182251 -0.60221540927887 -0.435194075107574 -0.290783822536469 0.143363207578659 -0.860414266586304 -0.716225504875183 -1.49726712703705 -1.57031607627869 -1.3027092218399 -0.530166804790497 + Cluster -674 1 1 1 7.5 7.5 7.5 19.024 0.0015985 1.6573 63340000 2 4.59318361476521 4.47154471544715E-05 Q99547 Q99547 M-phase phosphoprotein 6 MPHOSPH6 2571 this function may include C1D;RNA-binding protein that associates with the RNA exosomecomplex. Involved in the 3'-processing of the 7S pre-RNA to themature 5.8S rRNA and play a role in recruiting the RNA exosomecomplex to pre-rRNA Nucleus, nucleolus. Cytoplasm.Note=Cytoplasmic in M phase. maturation of 5.8S rRNA;rRNA processing RNA binding cytoplasm;exosome (RNase complex);nuclear exosome (RNase complex);nucleolus;nucleoplasm;nucleus RNA degradation Major pathway of rRNA processing in the nucleolus and cytosol Exosome 1.57617616653442 -0.00177903776057065 0.97186690568924 0.517835021018982 1.15281176567078 1.43168294429779 0.356436252593994 0.732032120227814 -0.023979751393199 -0.282857686281204 -0.252232164144516 0.105633854866028 -0.808088302612305 -0.647639572620392 -0.634981393814087 -0.563573062419891 -1.21189260482788 -2.41745138168335 + Cluster -674 12 12 12 13.1 13.1 13.1 157.18 0 110.84 5980700000 24 3.22079806211608 0.000712146422628952 Q15021 Q15021 Condensin complex subunit 1 NCAPD2 1754 Regulatory subunit of the condensin complex, a complexrequired for conversion of interphase chromatin into mitotic-likecondense chromosomes. The condensin complex probably introducespositive supercoils into relaxed DNA in the presence of type Itopoisomerases and converts nicked DNA into positive knotted formsin the presence of type II topoisomerases. May target thecondensin complex to DNA via its C-terminal domain(PubMed:11136719). May promote the resolution of double-strand DNAcatenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sisterchromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Requiredfor decatenation of non-centromeric ultrafine DNA bridges duringanaphase. Early in neurogenesis, may play an essential role toensure accurate mitotic chromosome condensation in neuron stemcells, ultimately affecting neuron pool and cortex size(PubMed:27737959). Nucleus {ECO:0000269|PubMed:10958694}.Cytoplasm {ECO:0000269|PubMed:10958694}. Chromosome{ECO:0000269|PubMed:10958694}. Note=In interphase cells, themajority of the condensin complex is found in the cytoplasm, whilea minority of the complex is associated with chromatin. Asubpopulation of the complex however remains associated withchromosome foci in interphase cells. During mitosis, most of thecondensin complex is associated with the chromatin. At the onsetof prophase, the regulatory subunits of the complex arephosphorylated by CDK1, leading to condensin's association withchromosome arms and to chromosome condensation. Dissociation fromchromosomes is observed in late telophase. cell division;chromosome separation;meiotic chromosome condensation;mitotic chromosome condensation chromatin binding;histone binding condensed chromosome;condensed chromosome, centromeric region;condensin complex;condensin core heterodimer;cytoplasm;cytosol;membrane;nuclear condensin complex;nucleoplasm;nucleus Condensation of Prometaphase Chromosomes Condensin I complex;Condensin I-PARP-1-XRCC1 complex 1.17068409919739 -0.230493441224098 1.85143518447876 0.0382625572383404 1.51234447956085 1.35375356674194 0.69103479385376 0.620855212211609 -0.488904148340225 -0.674942135810852 0.0411867052316666 -0.173361748456955 -0.529753625392914 -0.612981140613556 -0.715769469738007 -0.922719597816467 -1.21679604053497 -1.71383512020111 + Cluster -674 6 6 6 7.1 7.1 7.1 133.94 0 35.794 2231900000 15 3.20527656069282 0.000735632183908046 Q7L2E3;Q7L2E3-2;Q7L2E3-3 Q7L2E3;Q7L2E3-2;Q7L2E3-3 Putative ATP-dependent RNA helicase DHX30 DHX30 2054 RNA-dependent helicase (PubMed:29100085). Plays animportant role in the assembly of the mitochondrial largeribosomal subunit (PubMed:25683715, PubMed:29100085). Required foroptimal function of the zinc-finger antiviral protein ZC3HAV1 (Bysimilarity). Associates with mitochondrial DNA (PubMed:18063578).Involved in nervous system development and differentiation throughits involvement in the up-regulation of a number of genes whichare required for neurogenesis, including GSC, NCAM1, neurogenin,and NEUROD (By similarity). Cytoplasm {ECO:0000269|PubMed:29100085}.Mitochondrion {ECO:0000269|PubMed:16825194,ECO:0000269|PubMed:29100085}. Mitochondrion matrix, mitochondrionnucleoid {ECO:0000269|PubMed:16825194,ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:25683715}.Note=Localizes to mitochondrial RNA granules found in closeproximity to the mitochondrial nucleoids (PubMed:16825194,PubMed:25683715). Relocalizes to stress granules upon heat stress(PubMed:29100085). {ECO:0000269|PubMed:16825194,ECO:0000269|PubMed:25683715, ECO:0000269|PubMed:29100085}. central nervous system development;mitochondrial large ribosomal subunit assembly ATP binding;ATP-dependent 3'-5' RNA helicase activity;ATP-dependent DNA helicase activity;ATP-dependent RNA helicase activity;chromatin binding;double-stranded RNA binding;G-quadruplex RNA binding;RNA binding cytoplasm;cytosol;mitochondrial nucleoid;mitochondrion;nucleus;ribonucleoprotein granule DHX30;FASTKD2;FASTKD5);GRSF1;H2AX complex I;protein complex (DDX28 0.654015302658081 -0.339212834835052 1.62632381916046 0.854045689105988 1.25462400913239 0.578394055366516 0.942824900150299 1.35434353351593 -0.100127458572388 -0.357643812894821 -0.159387513995171 0.379965245723724 -0.942039132118225 -0.66754561662674 -1.12896084785461 -1.78133893013 -1.00706505775452 -1.16121518611908 + Cluster -674 13 13 13 10 10 10 205.11 0 128.37 5310000000 47 5.69096934186893 9.34579439252336E-06 Q8TEM1;Q8TEM1-2 Q8TEM1;Q8TEM1-2 Nuclear pore membrane glycoprotein 210 NUP210 2277 Nucleoporin essential for nuclear pore assembly andfusion, nuclear pore spacing, as well as structural integrity Single-pass type I membrane protein{ECO:0000269|PubMed:2195063}.; Single-pass type I membrane protein{ECO:0000269|PubMed:2195063}. Endoplasmic reticulum membrane{ECO:0000269|PubMed:2195063};Nucleus, nuclear pore complex{ECO:0000269|PubMed:2195063}. Nucleus membrane{ECO:0000269|PubMed:2195063} mRNA export from nucleus;viral process protein dimerization activity endoplasmic reticulum membrane;integral component of membrane;membrane;nuclear envelope;nuclear membrane;nuclear pore RNA transport ISG15 antiviral mechanism;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Rev-mediated nuclear export of HIV RNA;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs 0.507537424564362 -0.170788154006004 2.05111408233643 1.23438131809235 0.961658716201782 0.801596343517303 0.735807061195374 0.47392538189888 0.0268984921276569 0.190016537904739 0.089658685028553 -0.213301405310631 -0.69609260559082 -0.566905438899994 -0.814731121063232 -1.50163912773132 -1.57388508319855 -1.53525114059448 + Cluster -674 8 8 8 35.6 35.6 35.6 35.206 0 50.456 3815200000 26 4.84234212544713 2.38095238095238E-05 Q08257;Q08257-3;Q08257-2 Q08257;Q08257-3;Q08257-2 Quinone oxidoreductase CRYZ 1547 Does not have alcohol dehydrogenase activity. Binds NADPand acts through a one-electron transfer process. Orthoquinones,such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are thebest substrates (in vitro). May act in the detoxification ofxenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTRof target mRNA species. Enhances the stability of mRNA coding forBCL2. NADPH binding interferes with mRNA binding Cytoplasm {ECO:0000269|PubMed:20103721}. protein homotetramerization;visual perception;xenobiotic catabolic process mRNA 3'-UTR binding;NADPH binding;NADPH:quinone reductase activity;zinc ion binding cytosol;extracellular exosome 0.963422060012817 -0.0608912035822868 1.31203854084015 0.963422060012817 0.278551667928696 1.30649065971375 0.511297523975372 0.755968987941742 0.538119196891785 -0.0242188777774572 -0.916214764118195 0.592330455780029 -0.621307194232941 -0.404221922159195 -1.20017957687378 -0.19128654897213 -1.72626030445099 -2.07706093788147 + Cluster -674 3 3 3 32.2 32.2 32.2 22.492 0 99.504 8122700000 11 3.03997170765254 0.00099406528189911 P52943;P52943-2 P52943;P52943-2 Cysteine-rich protein 2 CRIP2 1193 hemopoiesis;positive regulation of cell proliferation zinc ion binding cell cortex 0.559481382369995 0.719359278678894 1.11825466156006 1.15274012088776 1.15274012088776 1.35473001003265 0.908753454685211 0.865226745605469 -0.440391212701797 -1.08665502071381 -0.215280696749687 0.137890890240669 -0.603627979755402 -0.740017116069794 -0.621054768562317 -1.22340083122253 -1.5269376039505 -1.51181137561798 + Cluster -674 4 4 4 29.6 29.6 29.6 14.688 0 20.908 14350000000 24 5.13338107966601 1.78571428571429E-05 Q9GZQ8;A6NCE7;Q9H492;Q9H492-2 Q9GZQ8;A6NCE7 Microtubule-associated proteins 1A/1B light chain 3B;Microtubule-associated proteins 1A/1B light chain 3 beta 2 MAP1LC3B;MAP1LC3B2 12 Ubiquitin-like modifier involved in formation ofautophagosomal vacuoles (autophagosomes) (PubMed:20713600,PubMed:24290141). Whereas LC3s are involved in elongation of thephagophore membrane, the GABARAP/GATE-16 subfamily is essentialfor a later stage in autophagosome maturation (PubMed:20713600);Ubiquitin-like modifier involved in formation ofautophagosomal vacuoles (autophagosomes). Plays a role inmitophagy which contributes to regulate mitochondrial quantity andquality by eliminating the mitochondria to a basal level tofulfill cellular energy requirements and preventing excess ROSproduction. Whereas LC3s are involved in elongation of thephagophore membrane, the GABARAP/GATE-16 subfamily is essentialfor a later stage in autophagosome maturation (By similarity);Ubiquitin-like modifier involved in formation ofautophagosomal vacuoles (autophagosomes). Plays a role inmitophagy which contributes to regulate mitochondrial quantity andquality by eliminating the mitochondria to a basal level tofulfill cellular energy requirements and preventing excess ROSproduction. Whereas LC3s are involved in elongation of thephagophore membrane, the GABARAP/GATE-16 subfamily is essentialfor a later stage in autophagosome maturation. Promotes primaryciliogenesis by removing OFD1 from centriolar satellites via theautophagic pathway. Lipid-anchor {ECO:0000250}. Note=LC3-II binds to the autophagicmembranes. {ECO:0000250}.; Lipid-anchor {ECO:0000250}.Cytoplasmic vesicle, autophagosome membrane {ECO:0000250}; Lipid-anchor. Cytoplasmic vesicle, autophagosome membrane;Cytoplasm, cytoskeleton {ECO:0000250}.Endomembrane system {ECO:0000250};Cytoplasm, cytoskeleton. Endomembranesystem;Lipid-anchor. Cytoplasmic vesicle, autophagosome{ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:23459205}.Note=LC3-II binds to the autophagic membranes.;Lipid-anchor. Cytoplasmic vesicle, autophagosome{ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:23459205}.Note=LC3-II binds to the autophagic membranes. Localizes also todiscrete punctae along the ciliary axoneme (By similarity).{ECO:0000250}. autophagosome assembly;autophagosome maturation;autophagy;autophagy of mitochondrion;cellular response to amino acid starvation;cellular response to copper ion;cellular response to hydrogen peroxide;cellular response to nitrogen starvation;cellular response to starvation;macroautophagy;response to iron(II) ion;response to lead ion;response to morphine microtubule binding;phosphatidylethanolamine binding;phospholipid binding;ubiquitin protein ligase binding autolysosome;autophagosome;autophagosome membrane;axoneme;cytoplasmic vesicle;cytosol;endomembrane system;intracellular;late endosome;microtubule;mitochondrion;organelle membrane;synapse Ferroptosis Macroautophagy;Pink/Parkin Mediated Mitophagy;Receptor Mediated Mitophagy;TBC/RABGAPs CHDH-SQSTM1-MAP1LC3 complex 1.15887880325317 0.117077358067036 1.27315592765808 1.27315592765808 1.15887880325317 1.00437927246094 0.533488929271698 0.880147457122803 -0.222909599542618 -0.367752999067307 -0.104331135749817 -0.104331135749817 -0.594902575016022 -0.40521913766861 -0.841469883918762 -1.6279958486557 -1.50225424766541 -1.6279958486557 + Cluster -674 21 21 21 54.6 54.6 54.6 32.337 0 323.31 260940000000 280 4.80151562464139 2.76497695852535E-05 P07910-2;P07910-4;P07910;P07910-3;O60812;B7ZW38;B2RXH8;P0DMR1;Q86SE5;Q86SE5-3 P07910-2;P07910-4;P07910;P07910-3 Heterogeneous nuclear ribonucleoproteins C1/C2 HNRNPC 544 Binds pre-mRNA and nucleates the assembly of 40S hnRNPparticles (PubMed:8264621). Interacts with poly-U tracts in the3'-UTR or 5'-UTR of mRNA and modulates the stability and the levelof translation of bound mRNA molecules (PubMed:12509468,PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPCtetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramersbind 700 nucleotides (PubMed:8264621). May play a role in theearly steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structurein mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named'm(6)A-switch', facilitating binding of HNRNPC, leading toregulation of mRNA splicing (PubMed:25719671);May play a role in nucleosome assembly by neutralizingbasic proteins such as A and B core hnRNPs. Nucleus {ECO:0000250|UniProtKB:P07910}.;Nucleus {ECO:0000250}. Note=Component ofribonucleosomes. {ECO:0000250}.;Nucleus. Note=Component of ribonucleosomes. 3'-UTR-mediated mRNA stabilization;ATP-dependent chromatin remodeling;mRNA splicing, via spliceosome;negative regulation of telomere maintenance via telomerase;osteoblast differentiation;RNA metabolic process;RNA splicing identical protein binding;mRNA 3'-UTR binding;N6-methyladenosine-containing RNA binding;nucleosomal DNA binding;poly(U) RNA binding;RNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;telomerase RNA binding actin cytoskeleton;catalytic step 2 spliceosome;cytosol;extracellular exosome;extracellular region;membrane;nuclear chromatin;nucleoplasm;nucleus;protein-containing complex;spliceosomal complex;telomerase holoenzyme complex Spliceosome mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA;SUMOylation of RNA binding proteins C complex spliceosome;LARC complex (LCR-associated remodeling complex);Toposome 0.492885798215866 0.135701537132263 1.45744800567627 1.20247185230255 1.23919975757599 1.31971478462219 1.53252184391022 -0.348176091909409 -0.648457169532776 -0.0485537052154541 -0.0248416513204575 -0.793979823589325 -0.0248416513204575 -0.69118469953537 -0.920630276203156 -1.16859018802643 -1.32266128063202 -1.38802683353424 + Cluster -674 1 1 1 6 6 6 36.032 0 11.973 2474800000 3 3.38142410889895 0.000522935779816514 P30519;P30519-2 P30519;P30519-2 Heme oxygenase 2 HMOX2 872 Heme oxygenase cleaves the heme ring at the alphamethene bridge to form biliverdin. Biliverdin is subsequentlyconverted to bilirubin by biliverdin reductase. Underphysiological conditions, the activity of heme oxygenase ishighest in the spleen, where senescent erythrocytes aresequestrated and destroyed. Heme oxygenase 2 could be implicatedin the production of carbon monoxide in brain where it could actas a neurotransmitter. Microsome. Endoplasmic reticulum. cellular iron ion homeostasis;heme catabolic process;heme oxidation;iron ion homeostasis;neutrophil degranulation;response to hypoxia;response to oxidative stress heme binding;heme oxygenase (decyclizing) activity;metal ion binding endoplasmic reticulum membrane;membrane;plasma membrane;specific granule membrane Metabolic pathways;Mineral absorption;Porphyrin and chlorophyll metabolism Stannsoporfin Heme degradation;Iron uptake and transport;Neutrophil degranulation 1.07752442359924 0.199175581336021 1.62095773220062 0.394394636154175 0.790258347988129 2.25931334495544 0.651023983955383 0.453288972377777 -0.415201336145401 -0.746180295944214 -0.433891445398331 -0.553528606891632 -0.553528606891632 -0.611464440822601 -0.464973151683807 -1.37246966362 -1.25005972385406 -1.04463994503021 + Cluster -674 11 11 11 49.5 49.5 49.5 21.397 0 149.19 66285000000 101 3.45196213699233 0.000472168905950096 P18621;P18621-3;P18621-2 P18621;P18621-3;P18621-2 60S ribosomal protein L17 RPL17 721 Component of the large ribosomal subunit cytoplasmic translation;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic large ribosomal subunit;nucleus Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic 0.148095905780792 0.131175652146339 1.55290043354034 0.731977820396423 1.30292773246765 1.6742912530899 1.19937574863434 0.886701464653015 -0.160106614232063 -0.618452250957489 -0.445744752883911 -0.922219276428223 -0.306503117084503 -0.861523866653442 -0.605882942676544 -1.40373361110687 -1.19845461845398 -1.10482513904572 + Cluster -674 9 9 8 27.3 27.3 25.6 54.173 0 65.571 3242100000 30 6.56929499428257 0 A1L020;Q6ZN04;Q5U5Q3 A1L020 RNA-binding protein MEX3A MEX3A 6 E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNAdecay. RNA binding is sufficient to prevent translation, butubiquitin ligase activity is required for mRNA degradation;RNA binding protein, may be involved in post-transcriptional regulatory mechanisms.;RNA-binding protein. May be involved in post-transcriptional regulatory mechanisms. Cytoplasm {ECO:0000269|PubMed:17267406}.Nucleus {ECO:0000269|PubMed:17267406}. Cytoplasm, P-body{ECO:0000269|PubMed:17267406}. Note=Predominantly expressed in thecytoplasm and shuttles between the cytoplasm and the nucleusthrough the CRM1 export pathway.;Cytoplasm {ECO:0000269|PubMed:17267406}.Nucleus {ECO:0000269|PubMed:17267406}. Note=Predominantlyexpressed in the cytoplasm and shuttles between the cytoplasm andthe nucleus through the CRM1 export pathway. May act as suppressorof replication stress and chromosome missegregation.;Nucleus {ECO:0000269|PubMed:18779327}.Cytoplasm {ECO:0000269|PubMed:18779327}. Cytoplasm, P-body{ECO:0000269|PubMed:18779327}. Cytoplasmic granule{ECO:0000269|PubMed:18779327}. Note=Predominantly expressed in thecytoplasm and shuttles between the cytoplasm and the nucleusthrough the CRM1 export pathway. Localization to P-bodies isdependent on 14-3-3. chondrocyte hypertrophy;energy homeostasis;protein autophosphorylation;protein phosphorylation;regulation of fat cell differentiation calcium ion binding;metal ion binding;RNA binding;transferase activity cytoplasm;cytosol;nucleoplasm;nucleus;P-body Antigen processing: Ubiquitination & Proteasome degradation 0.293459564447403 0.189695224165916 1.36638176441193 1.05547702312469 1.6096853017807 1.0552396774292 0.793919205665588 0.715831637382507 -0.089016392827034 -0.153596714138985 -0.518465757369995 -1.42882585525513 -0.235201358795166 0.0435534119606018 -0.272529780864716 -1.6099442243576 -1.50851023197174 -1.30715250968933 + Cluster -674 12 12 12 51.6 51.6 51.6 25.789 0 126.37 17503000000 55 3.77817354068161 0.00025615763546798 P09417;P09417-2 P09417;P09417-2 Dihydropteridine reductase QDPR 572 The product of this enzyme, tetrahydrobiopterin (BH-4),is an essential cofactor for phenylalanine, tyrosine, andtryptophan hydroxylases. cellular amino acid metabolic process;cellular response to drug;dihydrobiopterin metabolic process;liver development;L-phenylalanine catabolic process;response to aluminum ion;response to glucagon;response to lead ion;tetrahydrobiopterin biosynthetic process 6,7-dihydropteridine reductase activity;electron transfer activity;NADH binding;NADPH binding;protein homodimerization activity cytoplasm;cytosol;extracellular exosome;neuron projection Folate biosynthesis;Metabolic pathways Phenylketonuria Phenylalanine and tyrosine catabolism 0.82174026966095 1.24572372436523 0.62335616350174 0.419372409582138 1.18319034576416 0.984628260135651 1.32862687110901 0.605382740497589 0.325483411550522 -0.446176379919052 -1.11297333240509 -0.504747271537781 -0.0832670629024506 -0.598980307579041 -0.172446191310883 -1.34061312675476 -1.22533404827118 -2.05296659469604 + Cluster -674 3 3 3 3.8 3.8 3.8 146.56 0 19.695 583380000 7 3.7590475054464 0.000256658595641647 O60343;O60343-2;O60343-3;O60343-4;O60343-5 O60343;O60343-2;O60343-3 TBC1 domain family member 4 TBC1D4 266 May act as a GTPase-activating protein for RAB2A, RAB8A,RAB10 and RAB14. Isoform 2 promotes insulin-induced glucosetransporter SLC2A4/GLUT4 translocation at the plasma membrane,thus increasing glucose uptake. Cytoplasm {ECO:0000269|PubMed:18771725}.Note=Isoform 2 shows a cytoplasmic perinuclear localization in amyoblastic cell line in resting and insulin-stimulated cells. activation of GTPase activity;cellular response to insulin stimulus;intracellular protein transport;negative regulation of vesicle fusion;vesicle-mediated transport GTPase activator activity;Rab GTPase binding cytosol;vesicle Insulin resistance;Thyroid hormone signaling pathway Translocation of SLC2A4 (GLUT4) to the plasma membrane 1.01220786571503 0.475143492221832 1.05187690258026 0.28843629360199 0.839218258857727 1.20279443264008 1.22132766246796 0.887120246887207 0.079486720263958 0.0415566936135292 -1.93484210968018 -1.08625054359436 0.180459156632423 -0.286728352308273 -0.225449293851852 -0.941656768321991 -1.07576775550842 -1.72893285751343 + Cluster -674 4 4 3 8.5 8.5 6.6 71.456 0 159.39 6733000000 16 3.04585573463595 0.000991031390134529 Q13409;Q13409-3;Q13409-2;Q13409-6;Q13409-7;Q13409-5 Q13409;Q13409-3;Q13409-2;Q13409-6;Q13409-7;Q13409-5 Cytoplasmic dynein 1 intermediate chain 2 DYNC1I2 1629 Acts as one of several non-catalytic accessorycomponents of the cytoplasmic dynein 1 complex that are thought tobe involved in linking dynein to cargos and to adapter proteinsthat regulate dynein function. Cytoplasmic dynein 1 acts as amotor for the intracellular retrograde motility of vesicles andorganelles along microtubules. The intermediate chains mediate thebinding of dynein to dynactin via its 150 kDa component (p150-glued) DCNT1. Involved in membrane-transport, such as Golgiapparatus, late endosomes and lysosomes. Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:O88487}. Cytoplasm{ECO:0000250|UniProtKB:O88487}. Note=Detected in the cytoplasm ofpachytene spermatocytes. Localizes to the manchette in elongatingspermatids. {ECO:0000250|UniProtKB:O88487}. antigen processing and presentation of exogenous peptide antigen via MHC class II;ciliary basal body-plasma membrane docking;endoplasmic reticulum to Golgi vesicle-mediated transport;G2/M transition of mitotic cell cycle;microtubule-based movement;regulation of G2/M transition of mitotic cell cycle;viral process dynein heavy chain binding;dynein light chain binding;microtubule motor activity centrosome;cytoplasm;cytoplasmic dynein complex;cytosol;dynein complex;microtubule;vesicle Phagosome;Salmonella infection;Vasopressin-regulated water reabsorption Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;HSP90 chaperone cycle for steroid hormone receptors (SHR);Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;MHC class II antigen presentation;Mitotic Prometaphase;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Separation of Sister Chromatids 0.859764695167542 -0.0120385000482202 1.09292340278625 0.508548021316528 1.00800979137421 0.724251806735992 1.85282742977142 0.816940903663635 0.660739421844482 -0.541634380817413 -1.29189085960388 -0.767921805381775 -0.478877246379852 -0.059148907661438 -0.254589557647705 -1.38862192630768 -1.02734279632568 -1.70193958282471 + Cluster -674 2 2 2 8.7 8.7 8.7 39.436 0 9.5073 562560000 7 3.98176227625794 0.000141643059490085 Q9NWY4 Q9NWY4 UPF0609 protein C4orf27 C4orf27 2984 Acts as a cofactor for serine ADP-ribosylation byconferring serine specificity on PARP1 and PARP2: interacts withPARP1 and PARP2 and is able to change amino acid specificitytoward serine (PubMed:28190768, PubMed:29480802). Promotes histoneserine ADP-ribosylation in response to DNA damage, limiting DNAdamage-induced PARP1 hyper-automodification, and ensuring genomestability (PubMed:27067600, PubMed:28190768). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage(PubMed:29480802). HPF1 also promotes tyrosine ADP-ribosylation,probably by conferring tyrosine specificity on PARP1(PubMed:30257210). cellular response to DNA damage stimulus;peptidyl-serine ADP-ribosylation;regulation of protein ADP-ribosylation histone binding;poly-ADP-D-ribose binding;zinc ion binding nucleus 0.232884660363197 -0.520802557468414 0.913638353347778 0.433840125799179 1.26349186897278 1.88112485408783 1.35144770145416 0.712190330028534 0.232884660363197 -0.911110401153564 -0.911110401153564 -1.28369641304016 0.248570099473 0.418315708637238 -1.5057647228241 -0.76732724905014 -0.641152262687683 -1.1474244594574 + Cluster -674 1 1 1 3.2 3.2 3.2 65.071 0 5.2368 236650000 2 3.47164256321085 0.000454724409448819 Q92696 Q92696 Geranylgeranyl transferase type-2 subunit alpha RABGGTA 2347 Catalyzes the transfer of a geranylgeranyl moiety fromgeranylgeranyl diphosphate to both cysteines of Rab proteins withthe C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A,RAB3A, RAB5A and RAB7A. cellular protein modification process;post-translational protein modification;protein geranylgeranylation;protein-containing complex assembly;regulation of apoptotic process;visual perception protein heterodimerization activity;Rab geranylgeranyltransferase activity;Rab GTPase binding;zinc ion binding cytoplasm;cytosol;nucleoplasm;plasma membrane;Rab-protein geranylgeranyltransferase complex RAB geranylgeranylation;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain REP-RGGT-Rab complex 0.255778431892395 -0.150805577635765 0.991545140743256 0.455379545688629 1.94398999214172 1.15814244747162 1.67025053501129 0.814049124717712 -0.745102345943451 -0.750678777694702 -1.27623987197876 -1.20581912994385 0.139275327324867 -0.290510326623917 -0.258496046066284 -0.839366614818573 -0.605584859848022 -1.30580687522888 + Cluster -674 3 3 3 12.1 12.1 12.1 36.966 0 14.378 524660000 6 4.37602429996883 6.25E-05 Q06609;Q06609-3;Q06609-4 Q06609;Q06609-3 DNA repair protein RAD51 homolog 1 RAD51 1531 Plays an important role in homologous strand exchange, akey step in DNA repair through homologous recombination (HR)(PubMed:28575658). Binds to single and double-stranded DNA andexhibits DNA-dependent ATPase activity. Catalyzes the recognitionof homology and strand exchange between homologous DNA partners toform a joint molecule between a processed DNA break and the repairtemplate. Binds to single-stranded DNA in an ATP-dependent mannerto form nucleoprotein filaments which are essential for thehomology search and strand exchange (PubMed:26681308). Part of aPALB2-scaffolded HR complex containing BRCA2 and RAD51C and whichis thought to play a role in DNA repair by HR. Plays a role inregulating mitochondrial DNA copy number under conditions ofoxidative stress in the presence of RAD51C and XRCC3. Alsoinvolved in interstrand cross-link repair (PubMed:26253028) Nucleus {ECO:0000269|PubMed:12442171,ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:18417535,ECO:0000269|PubMed:19783859, ECO:0000269|PubMed:23401855,ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:26681308,ECO:0000269|PubMed:9192668}. Cytoplasm{ECO:0000269|PubMed:16215984, ECO:0000269|PubMed:26681308}.Cytoplasm, perinuclear region. Mitochondrion matrix{ECO:0000269|PubMed:20413593}. Chromosome{ECO:0000269|PubMed:23401855}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome{ECO:0000269|PubMed:21276791}. Note=Colocalizes with RAD51AP1 andRPA2 to multiple nuclear foci upon induction of DNA damage(PubMed:20154705). DNA damage induces an increase in nuclearlevels (PubMed:20154705). Together with FIGNL1, redistributed indiscrete nuclear DNA damage-induced foci after ionizing radiation(IR) or camptothecin (CPT) treatment (PubMed:23754376).Accumulated at sites of DNA damage in a SPIDR-dependent manner(PubMed:23509288). Recruited at sites of DNA damage in a MCM9-MCM8-dependent manner (PubMed:23401855).{ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:23401855,ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376}. cellular response to camptothecin;cellular response to DNA damage stimulus;cellular response to ionizing radiation;chromosome organization involved in meiotic cell cycle;DNA recombinase assembly;DNA recombination;DNA repair;DNA unwinding involved in DNA replication;double-strand break repair via homologous recombination;interstrand cross-link repair;meiotic cell cycle;mitotic recombination;mitotic recombination-dependent replication fork processing;negative regulation of G0 to G1 transition;positive regulation of DNA ligation;protein homooligomerization;reciprocal meiotic recombination;regulation of double-strand break repair via homologous recombination;replication fork processing;strand invasion;telomere maintenance via recombination;telomere maintenance via telomere lengthening ATP binding;chromatin binding;DNA polymerase binding;DNA-dependent ATPase activity;double-stranded DNA binding;enzyme binding;identical protein binding;protein C-terminus binding;recombinase activity;single-stranded DNA binding;single-stranded DNA-dependent ATPase activity chromatin;condensed chromosome;condensed nuclear chromosome;cytoplasm;cytosol;lateral element;microtubule organizing center;mitochondrial matrix;mitochondrion;nuclear chromatin;nuclear chromosome;nuclear chromosome, telomeric region;nucleolus;nucleoplasm;nucleus;perinuclear region of cytoplasm;PML body;protein-containing complex;site of double-strand break Fanconi anemia pathway;Homologous recombination;Pancreatic cancer;Pathways in cancer Congenital mirror movements;Fanconi anemia HDR through Homologous Recombination (HRR);HDR through Single Strand Annealing (SSA);Homologous DNA Pairing and Strand Exchange;Meiotic recombination;Presynaptic phase of homologous DNA pairing and strand exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Transcriptional Regulation by E2F6 BARD1\u2013BRCA1\u2013RAD51 complex;BRCA1-RAD51 complex;BRCC complex;hRAD51C-hXRCC3 complex;MSH2/6-BLM-p53-RAD51 complex 0.0849620923399925 -0.525372624397278 1.92034864425659 0.493980497121811 1.46184635162354 1.07539117336273 1.47754800319672 0.825968325138092 -0.834221184253693 -1.12999761104584 -1.24221289157867 -0.679734289646149 -0.173425957560539 -0.0767119973897934 -0.0767119973897934 -0.387789368629456 -1.1588716506958 -1.0549955368042 + Cluster -674 26 26 26 53.2 53.2 53.2 59.75 0 323.31 193060000000 308 4.66468520062354 3.34728033472803E-05 P25705;P25705-2;P25705-3 P25705;P25705-2;P25705-3 ATP synthase subunit alpha, mitochondrial ATP5A1 805 Mitochondrial membrane ATP synthase (F(1)F(0) ATPsynthase or Complex V) produces ATP from ADP in the presence of aproton gradient across the membrane which is generated by electrontransport complexes of the respiratory chain. F-type ATPasesconsist of two structural domains, F(1) - containing theextramembraneous catalytic core, and F(0) - containing themembrane proton channel, linked together by a central stalk and aperipheral stalk. During catalysis, ATP synthesis in the catalyticdomain of F(1) is coupled via a rotary mechanism of the centralstalk subunits to proton translocation. Subunits alpha and betaform the catalytic core in F(1). Rotation of the central stalkagainst the surrounding alpha(3)beta(3) subunits leads tohydrolysis of ATP in three separate catalytic sites on the betasubunits. Subunit alpha does not bear the catalytic high-affinityATP-binding sites (By similarity). Binds the bacterial siderophoreenterobactin and can promote mitochondrial accumulation ofenterobactin-derived iron ions (PubMed:30146159) Extracellular side{ECO:0000269|PubMed:10077593}. Note=Colocalizes with HRG on thecell surface of T-cells (PubMed:19285951).{ECO:0000269|PubMed:19285951}.; Matrixside {ECO:0000250|UniProtKB:P19483}. Cell membrane{ECO:0000269|PubMed:10077593}; Peripheral membrane protein{ECO:0000269|PubMed:10077593};Mitochondrion {ECO:0000269|PubMed:30146159}.Mitochondrion inner membrane {ECO:0000250|UniProtKB:P19483};Peripheral membrane protein {ECO:0000250|UniProtKB:P19483} ATP biosynthetic process;ATP metabolic process;ATP synthesis coupled proton transport;cristae formation;electron transport chain;lipid metabolic process;mitochondrial ATP synthesis coupled proton transport;negative regulation of endothelial cell proliferation;positive regulation of blood vessel endothelial cell migration;response to oxidative stress ADP binding;angiostatin binding;ATP binding;MHC class I protein binding;proton-transporting ATP synthase activity, rotational mechanism;RNA binding;transmembrane transporter activity extracellular exosome;membrane;mitochondrial inner membrane;mitochondrial matrix;mitochondrial proton-transporting ATP synthase complex;mitochondrial proton-transporting ATP synthase complex, catalytic core F(1);mitochondrion;myelin sheath;plasma membrane;proton-transporting ATP synthase complex Alzheimer disease;Huntington disease;Metabolic pathways;Oxidative phosphorylation;Parkinson disease;Thermogenesis ATP synthase deficiency;Combined oxidative phosphorylation deficiency Cristae formation;Formation of ATP by chemiosmotic coupling;Mitochondrial protein import F1F0-ATP synthase, mitochondrial 0.223716765642166 -0.04081866517663 1.95131683349609 0.672373354434967 1.95131683349609 0.823253512382507 0.944506168365479 0.447551637887955 -1.11816048622131 -0.366285175085068 -1.03384971618652 -0.233422458171844 -0.303779482841492 -0.170227393507957 -0.107757970690727 -1.11816048622131 -1.4034126996994 -1.11816048622131 + Cluster -674 2 2 2 6.3 6.3 6.3 88.754 0 21.198 284560000 4 3.19221381042056 0.000759016393442623 Q9UBV2 Q9UBV2 Protein sel-1 homolog 1 SEL1L 3082 Plays a role in the endoplasmic reticulum qualitycontrol (ERQC) system also called ER-associated degradation (ERAD)involved in ubiquitin-dependent degradation of misfoldedendoplasmic reticulum proteins (PubMed:16186509). Enhances SYVN1stability. Plays a role in LPL maturation and secretion. Requiredfor normal differentiation of the pancreas epithelium, and fornormal exocrine function and survival of pancreatic cells. Mayplay a role in Notch signaling. Single-pass type I membrane protein{ECO:0000269|PubMed:16186509}.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:16186509} endoplasmic reticulum mannose trimming;ERAD pathway;Notch signaling pathway;protein secretion;protein stabilization;retrograde protein transport, ER to cytosol;transmembrane transport;triglyceride metabolic process;ubiquitin-dependent ERAD pathway Derlin-1 retrotranslocation complex;endoplasmic reticulum;endoplasmic reticulum membrane;endoplasmic reticulum quality control compartment;Hrd1p ubiquitin ligase complex;Hrd1p ubiquitin ligase ERAD-L complex;integral component of membrane Protein processing in endoplasmic reticulum ABC-family proteins mediated transport;Defective CFTR causes cystic fibrosis;ER Quality Control Compartment (ERQC);Hedgehog ligand biogenesis;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Pre-NOTCH Processing in Golgi AUP1-OS9-SEL1L-UBC6e-UBXD8 complex;HRD1 complex;VCP-VIMP-DERL1-DERL2-HRD1-SEL1L complex 0.239605650305748 0.239605650305748 0.888553202152252 0.561319053173065 1.25468862056732 1.72938120365143 1.09278154373169 0.495352208614349 -0.656865000724792 -0.564626693725586 -2.00873780250549 -1.28394746780396 0.987529158592224 -0.132370695471764 -0.315412759780884 -0.630106806755066 -0.783880054950714 -1.11286902427673 + Cluster -674 7 7 7 15 15 15 85.496 0 103.86 4176700000 21 3.09995816767184 0.00090809968847352 P35222;P14923 P35222 Catenin beta-1 CTNNB1 923 Common junctional plaque protein. The membrane-associated plaques are architectural elements in an importantstrategic position to influence the arrangement and function ofboth the cytoskeleton and the cells within the tissue. Thepresence of plakoglobin in both the desmosomes and in theintermediate junctions suggests that it plays a central role inthe structure and function of submembranous plaques. Acts as asubstrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-cateninin E-cadherin/catenin adhesion complexes which are proposed tocouple cadherins to the actin cytoskeleton (By similarity);Key downstream component of the canonical Wnt signalingpathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2,APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminalSer and Thr residues and ubiquitination of CTNNB1 via BTRC and itssubsequent degradation by the proteasome. In the presence of Wntligand, CTNNB1 is not ubiquitinated and accumulates in thenucleus, where it acts as a coactivator for transcription factorsof the TCF/LEF family, leading to activate Wnt responsive genes.Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Acts as a negative regulator ofcentrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1pathway of insulin internalization. Blocks anoikis of malignantkidney and intestinal epithelial cells and promotes theiranchorage-independent growth by down-regulating DAPK2. DisruptsPML function and PML-NB formation by inhibiting RANBP2-mediatedsumoylation of PML (PubMed:17524503, PubMed:18077326,PubMed:18086858, PubMed:18957423, PubMed:21262353,PubMed:22647378, PubMed:22699938, PubMed:22155184). Promotesneurogenesis by maintaining sympathetic neuroblasts within thecell cycle (By similarity). Peripheral membrane protein{ECO:0000269|PubMed:22781308}. Note=Cytoplasmic in a soluble andmembrane-associated form.;Cell junction, adherens junction{ECO:0000269|PubMed:22781308}. Cell junction, desmosome{ECO:0000269|PubMed:22781308}. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:22781308}. Membrane{ECO:0000269|PubMed:22781308};Cytoplasm {ECO:0000269|PubMed:25183871}.Nucleus {ECO:0000269|PubMed:24342833, ECO:0000269|PubMed:25183871,ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:29367600}.Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:B6V8E6}. Celljunction, adherens junction {ECO:0000250|UniProtKB:Q02248}. Celljunction {ECO:0000250|UniProtKB:B6V8E6}. Cell membrane{ECO:0000269|PubMed:24342833}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome. Cytoplasm,cytoskeleton, spindle pole. Cell junction, synapse{ECO:0000250|UniProtKB:Q02248}. Cytoplasm, cytoskeleton, ciliumbasal body {ECO:0000250|UniProtKB:Q02248}. Note=Colocalized withRAPGEF2 and TJP1 at cell-cell contacts (By similarity).Cytoplasmic when it is unstabilized (high level ofphosphorylation) or bound to CDH1. Translocates to the nucleuswhen it is stabilized (low level of phosphorylation). Interactionwith GLIS2 and MUC1 promotes nuclear translocation. Interactionwith EMD inhibits nuclear localization. The majority of beta-catenin is localized to the cell membrane. In interphase,colocalizes with CROCC between CEP250 puncta at the proximal endof centrioles, and this localization is dependent on CROCC andCEP250. In mitosis, when NEK2 activity increases, it localizes tocentrosomes at spindle poles independent of CROCC. Colocalizeswith CDK5 in the cell-cell contacts and plasma membrane ofundifferentiated and differentiated neuroblastoma cells.Interaction with FAM53B promotes translocation to the nucleus(PubMed:25183871). {ECO:0000250|UniProtKB:B6V8E6,ECO:0000269|PubMed:25183871}. adherens junction assembly;adherens junction organization;androgen receptor signaling pathway;anterior/posterior axis specification;beta-catenin destruction complex disassembly;beta-catenin-TCF complex assembly;bone resorption;branching involved in blood vessel morphogenesis;branching involved in ureteric bud morphogenesis;bundle of His cell-Purkinje myocyte adhesion involved in cell communication;canonical Wnt signaling pathway;canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation;canonical Wnt signaling pathway involved in negative regulation of apoptotic process;canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation;canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition;cell adhesion;cell fate specification;cell maturation;cell migration;cell morphogenesis involved in differentiation;cell-cell adhesion;cell-matrix adhesion;cellular response to growth factor stimulus;cellular response to indole-3-methanol;central nervous system vasculogenesis;chemical synaptic transmission;chromatin-mediated maintenance of transcription;cornification;cranial ganglion development;cranial skeletal system development;cytoskeletal anchoring at plasma membrane;desmosome assembly;detection of mechanical stimulus;dorsal root ganglion development;dorsal/ventral axis specification;ectoderm development;embryonic axis specification;embryonic brain development;embryonic digit morphogenesis;embryonic foregut morphogenesis;embryonic forelimb morphogenesis;embryonic heart tube development;embryonic hindlimb morphogenesis;embryonic skeletal limb joint morphogenesis;endodermal cell fate commitment;endothelial cell-cell adhesion;endothelial tube morphogenesis;entry of bacterium into host cell;epithelial cell differentiation involved in prostate gland development;epithelial to mesenchymal transition;epithelial tube branching involved in lung morphogenesis;fungiform papilla formation;gastrulation with mouth forming second;genitalia morphogenesis;glial cell fate determination;hair cell differentiation;hair follicle morphogenesis;hair follicle placode formation;hindbrain development;in utero embryonic development;keratinization;layer formation in cerebral cortex;lens morphogenesis in camera-type eye;lung cell differentiation;lung induction;lung-associated mesenchyme development;male genitalia development;mesenchymal cell proliferation involved in lung development;metanephros morphogenesis;midbrain dopaminergic neuron differentiation;negative regulation of angiogenesis;negative regulation of apoptotic process;negative regulation of apoptotic signaling pathway;negative regulation of blood vessel endothelial cell migration;negative regulation of cell proliferation;negative regulation of chondrocyte differentiation;negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis;negative regulation of mitotic cell cycle, embryonic;negative regulation of oligodendrocyte differentiation;negative regulation of osteoclast differentiation;negative regulation of oxidative stress-induced neuron death;negative regulation of protein sumoylation;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;nephron tubule formation;neural plate development;neuron migration;neuron projection extension;neutrophil degranulation;odontogenesis of dentin-containing tooth;oocyte development;osteoclast differentiation;oviduct development;pancreas development;positive regulation of angiogenesis;positive regulation of apoptotic process;positive regulation of canonical Wnt signaling pathway;positive regulation of cell-matrix adhesion;positive regulation of chromatin-mediated maintenance of transcription;positive regulation of core promoter binding;positive regulation of determination of dorsal identity;positive regulation of DNA-binding transcription factor activity;positive regulation of DNA-templated transcription, initiation;positive regulation of endothelial cell differentiation;positive regulation of epithelial cell proliferation involved in prostate gland development;positive regulation of epithelial to mesenchymal transition;positive regulation of fibroblast growth factor receptor signaling pathway;positive regulation of heparan sulfate proteoglycan biosynthetic process;positive regulation of histone H3-K4 methylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of MAPK cascade;positive regulation of mesenchymal cell proliferation;positive regulation of muscle cell differentiation;positive regulation of neuroblast proliferation;positive regulation of neuron apoptotic process;positive regulation of osteoblast differentiation;positive regulation of protein import into nucleus;positive regulation of skeletal muscle tissue development;positive regulation of telomerase activity;positive regulation of telomere maintenance via telomerase;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;positive regulation of type I interferon production;protein heterooligomerization;protein localization to cell surface;protein localization to plasma membrane;proximal/distal pattern formation;regulation of angiogenesis;regulation of calcium ion import;regulation of canonical Wnt signaling pathway;regulation of cell proliferation;regulation of centriole-centriole cohesion;regulation of centromeric sister chromatid cohesion;regulation of euchromatin binding;regulation of fibroblast proliferation;regulation of heart rate by cardiac conduction;regulation of myelination;regulation of nephron tubule epithelial cell differentiation;regulation of neurogenesis;regulation of protein localization to cell surface;regulation of secondary heart field cardioblast proliferation;regulation of smooth muscle cell proliferation;regulation of T cell proliferation;regulation of timing of anagen;regulation of ventricular cardiac muscle cell action potential;renal inner medulla development;renal outer medulla development;renal vesicle formation;response to drug;response to estradiol;smooth muscle cell differentiation;stem cell population maintenance;sympathetic ganglion development;synapse organization;synaptic vesicle clustering;synaptic vesicle transport;T cell differentiation in thymus;thymus development;trachea formation;viral process;Wnt signaling pathway;Wnt signaling pathway, calcium modulating pathway alpha-catenin binding;androgen receptor binding;cadherin binding;cell adhesion molecule binding;cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication;chromatin binding;disordered domain specific binding;DNA-binding transcription factor activity;enzyme binding;estrogen receptor binding;ion channel binding;I-SMAD binding;kinase binding;nuclear hormone receptor binding;protein C-terminus binding;protein heterodimerization activity;protein homodimerization activity;protein kinase binding;protein phosphatase binding;repressing transcription factor binding;RNA polymerase II activating transcription factor binding;RNA polymerase II transcription factor binding;SMAD binding;structural constituent of cell wall;structural molecule activity;transcription coactivator activity;transcription factor binding actin cytoskeleton;adherens junction;apical part of cell;apicolateral plasma membrane;basolateral plasma membrane;beta-catenin destruction complex;beta-catenin-TCF complex;beta-catenin-TCF7L2 complex;bicellular tight junction;catenin complex;cell cortex;cell junction;cell periphery;cell-cell adherens junction;cell-cell junction;centrosome;cornified envelope;cytoplasm;cytoplasmic side of plasma membrane;cytoskeleton;cytosol;desmosome;extracellular exosome;extracellular region;fascia adherens;ficolin-1-rich granule lumen;flotillin complex;focal adhesion;gamma-catenin-TCF7L2 complex;intercalated disc;intermediate filament;intracellular;lamellipodium;lateral plasma membrane;membrane;microvillus membrane;nuclear euchromatin;nucleoplasm;nucleus;perinuclear region of cytoplasm;plasma membrane;postsynaptic density, intracellular component;postsynaptic membrane;presynaptic active zone cytoplasmic component;presynaptic membrane;protein-containing complex;protein-DNA complex;Schaffer collateral - CA1 synapse;Scrib-APC-beta-catenin complex;specific granule lumen;spindle pole;synapse;transcription factor complex;Wnt signalosome;Z disc;zonula adherens Acute myeloid leukemia;Adherens junction;Arrhythmogenic right ventricular cardiomyopathy (ARVC);Bacterial invasion of epithelial cells;Basal cell carcinoma;Breast cancer;Colorectal cancer;Cushing syndrome;Endometrial cancer;Fluid shear stress and atherosclerosis;Focal adhesion;Gastric cancer;Hepatitis C;Hepatocellular carcinoma;Hippo signaling pathway;Human cytomegalovirus infection;Human papillomavirus infection;Kaposi sarcoma-associated herpesvirus infection;Leukocyte transendothelial migration;Melanogenesis;Pathogenic Escherichia coli infection;Pathways in cancer;Prostate cancer;Proteoglycans in cancer;Rap1 signaling pathway;Signaling pathways regulating pluripotency of stem cells;Thyroid cancer;Thyroid hormone signaling pathway;Transcriptional misregulation in cancer;Wnt signaling pathway Arrhythmogenic right ventricular cardiomyopathy;Autosomal dominant mental retardation;Colorectal cancer;Endometrial cancer;Gastric cancer;Hepatoblastoma;Hepatocellular carcinoma;Medulloblastoma;Naxos disease;Nephroblastoma;Pilomatricoma;Thyroid cancer Adherens junctions interactions;Apoptotic cleavage of cell adhesion proteins;Beta-catenin phosphorylation cascade;Binding of TCF/LEF:CTNNB1 to target gene promoters;Ca2+ pathway;CDO in myogenesis;Deactivation of the beta-catenin transactivating complex;Degradation of beta-catenin by the destruction complex;Disassembly of the destruction complex and recruitment of AXIN to the membrane;Formation of the beta-catenin:TCF transactivating complex;Formation of the cornified envelope;InlA-mediated entry of Listeria monocytogenes into host cells;Keratinization;LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production;Misspliced GSK3beta mutants stabilize beta-catenin;Neutrophil degranulation;RHO GTPases activate IQGAPs;RUNX3 regulates WNT signaling;S33 mutants of beta-catenin aren't phosphorylated;S37 mutants of beta-catenin aren't phosphorylated;S45 mutants of beta-catenin aren't phosphorylated;Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1);T41 mutants of beta-catenin aren't phosphorylated;TCF dependent signaling in response to WNT;VEGFR2 mediated vascular permeability Afadin-beta-catenin complex;Amot-cadherin-11-beta-catenin-p120 complex;APC-AXIN1-CTNNB1 complex;AXIN1-APC-CTNNB1-GSK3B complex;Axin-PP2A A-PP2A C-GSK3-beta-beta-catenin complex;beta-Catenin destruction complex;beta-catenin-B-cell lymphoma 9 protein complex;Cell-cell junction complex (CDH1-CTNNB1);CTNNA1-CTNNB1 complex;CTNNAL1-CTNNB1 complex;CTNNB1-DDX5-HDGF complex;CTNNB1-DNMT1 complex;CTNNB1-EPCAM-FHL2-LEF1 complex;CTNNB1-ESR1 complex;CTNNB1-FERMT2-TCF7L2 complex;CTNNB1-FERMT2-YBX1 complex;CTNNB1-GID8 complex;CTNNB1-GLIS2 complex;CTNNB1-TBX5-YAP1 complex;DLG5-SORBS3-CTNNB1 complex;DLL1-CTNNB1-CDH2 complex;ICAT-AR-beta-catenin complex;JUN-TCF4-CTNNB1 complex;OVOL2-beta-catenin-TCF4 complex;PAR-3-VE-cadherin-beta-catenin complex;PDLIM1-E-cadherin-beta-catenin complex;Polycystin-1 multiprotein complex (ACTN1, CDH1, SRC, JUP, VCL, CTNNB1, PXN, BCAR1, PKD1, PTK2, TLN1);Polycystin-1-E-cadherin-beta-catenin complex;Polycystin-1-E-cadherin-beta-catenin-Flotillin-2 complex;RHAMM-beta-catenin complex;SETD7-YAP-AXIN1-beta-catenin complex;Sox4-beta-catenin-p300 complex;TCF4-CTNNB1 complex;TCF4-CTNNB1-CREBBP complex;TCF4-CTNNB1-EP300 complex;TCF4-CTNNB1-SUMO1-EP300-HADAC6 complex;TFC4-CTNNB1 complex;ZO1-(beta)cadherin-(VE)cadherin-VEGFR2 complex 0.452139854431152 0.263963758945465 1.22985875606537 0.452139854431152 1.12985730171204 1.33383619785309 1.41484940052032 0.413135588169098 -0.00154877442400903 -0.477218955755234 -2.18491792678833 -0.693685293197632 0.276168823242188 0.055314090102911 -0.137476325035095 -1.00795590877533 -1.18048179149628 -1.33797860145569 + Cluster -674 1 1 1 14.1 14.1 14.1 20.066 0 61.963 611220000 4 3.12777800007772 0.000862776025236593 Q9NQ92 Q9NQ92 Coordinator of PRMT5 and differentiation stimulator COPRS 2893 Histone-binding protein required for histone H4methyltransferase activity of PRMT5. Specifically required forhistone H4 'Arg-3' methylation mediated by PRMT5, but not histoneH3 'Arg-8' methylation, suggesting that it modulates the substratespecificity of PRMT5. Specifically interacts with the N-terminusof histone H4 but not with histone H3, suggesting that it acts bypromoting the association between histone H4 and PRMT5. Involvedin CCNE1 promoter repression. Plays a role in muscle celldifferentiation by modulating the recruitment of PRMT5 to thepromoter of genes involved in the coordination between cell cycleexit and muscle differentiation (By similarity). Nucleus {ECO:0000269|PubMed:18404153}. histone H4-R3 methylation;muscle organ development histone binding cytosol;nucleoplasm;nucleus;plasma membrane RMTs methylate histone arginines COPRS-PRMT5 complex;COPRS-PRMT5-RUNX1-CBFB complex 0.363296121358871 -0.307898104190826 1.37642216682434 0.342145830392838 1.07161724567413 0.952593624591827 1.56746554374695 1.08225846290588 -0.361236780881882 -0.586570262908936 -2.11607766151428 -0.882100880146027 0.176985561847687 0.0682505071163177 -0.262819647789001 0.0178073197603226 -1.01504337787628 -1.48709571361542 + Cluster -674 4 1 1 33.5 7.4 7.4 21.424 0 22.964 1792000000 4 3.38959046883592 0.000519408502772643 P01116-2 P01116-2 GTPase KRas;GTPase KRas, N-terminally processed KRAS 477 Ras proteins bind GDP/GTP and possess intrinsic GTPaseactivity. Plays an important role in the regulation of cellproliferation (PubMed:23698361, PubMed:22711838). Plays a role inpromoting oncogenic events by inducing transcriptional silencingof tumor suppressor genes (TSGs) in colorectal cancer (CRC) cellsin a ZNF304-dependent manner (PubMed:24623306) Cytoplasmic side{ECO:0000305|PubMed:23698361}. Cytoplasm, cytosol{ECO:0000269|PubMed:23698361}.; Lipid-anchor{ECO:0000305|PubMed:23698361};Cell membrane {ECO:0000269|PubMed:22431598,ECO:0000269|PubMed:23698361} actin cytoskeleton organization;cytokine-mediated signaling pathway;endocrine signaling;epithelial tube branching involved in lung morphogenesis;female pregnancy;forebrain astrocyte development;homeostasis of number of cells within a tissue;liver development;MAPK cascade;negative regulation of cell differentiation;negative regulation of neuron apoptotic process;positive regulation of cell proliferation;positive regulation of cellular senescence;positive regulation of gene expression;positive regulation of MAP kinase activity;positive regulation of NF-kappaB transcription factor activity;positive regulation of nitric-oxide synthase activity;positive regulation of protein phosphorylation;positive regulation of Rac protein signal transduction;Ras protein signal transduction;regulation of long-term neuronal synaptic plasticity;regulation of protein stability;regulation of synaptic transmission, GABAergic;response to glucocorticoid;response to isolation stress;response to mineralocorticoid;stimulatory C-type lectin receptor signaling pathway;striated muscle cell differentiation;visual learning GDP binding;GMP binding;GTP binding;GTPase activity;identical protein binding;LRR domain binding;protein-containing complex binding cytoplasm;cytosol;extrinsic component of cytoplasmic side of plasma membrane;focal adhesion;membrane;membrane raft;mitochondrion;plasma membrane Acute myeloid leukemia;AGE-RAGE signaling pathway in diabetic complications;Alcoholism;Aldosterone-regulated sodium reabsorption;Apelin signaling pathway;Apoptosis;Autophagy - animal;Axon guidance;B cell receptor signaling pathway;Bladder cancer;Breast cancer;Cellular senescence;Central carbon metabolism in cancer;Chemokine signaling pathway;Choline metabolism in cancer;Cholinergic synapse;Chronic myeloid leukemia;Colorectal cancer;C-type lectin receptor signaling pathway;EGFR tyrosine kinase inhibitor resistance;Endocrine resistance;Endometrial cancer;ErbB signaling pathway;Estrogen signaling pathway;Fc epsilon RI signaling pathway;FoxO signaling pathway;Gap junction;Gastric cancer;Glioma;GnRH signaling pathway;Hepatitis B;Hepatitis C;Hepatocellular carcinoma;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Human papillomavirus infection;Human T-cell leukemia virus 1 infection;Insulin signaling pathway;Kaposi sarcoma-associated herpesvirus infection;Longevity regulating pathway;Longevity regulating pathway - multiple species;Long-term depression;Long-term potentiation;MAPK signaling pathway;Melanogenesis;Melanoma;MicroRNAs in cancer;Mitophagy - animal;mTOR signaling pathway;Natural killer cell mediated cytotoxicity;Neurotrophin signaling pathway;Non-small cell lung cancer;Oxytocin signaling pathway;Pancreatic cancer;Pathways in cancer;PD-L1 expression and PD-1 checkpoint pathway in cancer;Phospholipase D signaling pathway;PI3K-Akt signaling pathway;Progesterone-mediated oocyte maturation;Prolactin signaling pathway;Prostate cancer;Proteoglycans in cancer;Rap1 signaling pathway;Ras signaling pathway;Regulation of actin cytoskeleton;Relaxin signaling pathway;Renal cell carcinoma;Serotonergic synapse;Signaling pathways regulating pluripotency of stem cells;Sphingolipid signaling pathway;T cell receptor signaling pathway;Thermogenesis;Thyroid cancer;Thyroid hormone signaling pathway;VEGF signaling pathway;Viral carcinogenesis Acute myeloid leukemia;Angiosarcoma;Cardiofaciocutaneous syndrome;Cervical cancer;Cholangiocarcinoma;Colorectal cancer;Endometrial cancer;Gallbladder cancer;Gastric cancer;Hepatic angiosarcoma;Kaposi sarcoma;Medullary thyroid cancer;Multiple myeloma;Non-small cell lung cancer;Noonan syndrome;Noonan syndrome and related disorders;Oral cancer;Ovarian cancer;Pancreatic cancer;Squamous cell carcinoma;Syndromic craniosynostoses;Thyroid cancer Activated NTRK2 signals through FRS2 and FRS3;Activated NTRK2 signals through RAS;Activated NTRK3 signals through RAS;Activation of RAS in B cells;CD209 (DC-SIGN) signaling;Constitutive Signaling by EGFRvIII;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;DAP12 signaling;Downstream signal transduction;EGFR Transactivation by Gastrin;Erythropoietin activates RAS;FCERI mediated MAPK activation;FRS-mediated FGFR1 signaling;FRS-mediated FGFR2 signaling;FRS-mediated FGFR3 signaling;FRS-mediated FGFR4 signaling;GRB2 events in EGFR signaling;GRB2 events in ERBB2 signaling;Insulin receptor signalling cascade;MAP2K and MAPK activation;MET activates RAS signaling;NCAM signaling for neurite out-growth;Negative regulation of MAPK pathway;p38MAPK events;Paradoxical activation of RAF signaling by kinase inactive BRAF;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;RAF activation;RAF/MAP kinase cascade;RAS signaling downstream of NF1 loss-of-function variants;Regulation of RAS by GAPs;RUNX3 regulates p14-ARF;SHC1 events in EGFR signaling;SHC1 events in ERBB2 signaling;SHC1 events in ERBB4 signaling;SHC-mediated cascade:FGFR1;SHC-mediated cascade:FGFR2;SHC-mediated cascade:FGFR3;SHC-mediated cascade:FGFR4;SHC-related events triggered by IGF1R;Signaling by BRAF and RAF fusions;Signaling by FGFR1 in disease;Signaling by FGFR2 in disease;Signaling by FGFR3 fusions in cancer;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR4 in disease;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Signaling by RAS mutants;Signaling by SCF-KIT;Signalling to RAS;SOS-mediated signalling;Tie2 Signaling;VEGFR2 mediated cell proliferation p38gamma-Hsp90-K-Ras complex 0.264455795288086 0.583633959293365 0.517626464366913 0.6440749168396 0.583633959293365 1.62725186347961 0.685519695281982 1.06884980201721 0.831633508205414 -1.83087122440338 -0.925549685955048 -1.40985298156738 0.211147904396057 0.0162433162331581 0.557215750217438 -1.08530604839325 -0.898431837558746 -1.4412750005722 + Cluster -674 15 2 2 36.2 10.4 10.4 22.35 0 4.8538 3524200000 7 3.45215179656833 0.000471153846153846 P16402 P16402 Histone H1.3 HIST1H1D 694 Histone H1 protein binds to linker DNA betweennucleosomes forming the macromolecular structure known as thechromatin fiber. Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structured fibers. Acts alsoas a regulator of individual gene transcription through chromatinremodeling, nucleosome spacing and DNA methylation (Bysimilarity). Nucleus. Chromosome. Note=According toPubMed:15911621 more commonly found in euchromatin. According toPubMed:10997781 is associated with inactive chromatin. chromosome condensation;histone H3-K27 trimethylation;histone H3-K4 trimethylation;negative regulation of chromatin silencing;negative regulation of DNA recombination;negative regulation of transcription by RNA polymerase II;nucleosome assembly;nucleosome positioning;regulation of transcription, DNA-templated chromatin DNA binding;double-stranded DNA binding;nucleosomal DNA binding;RNA binding nuclear chromatin;nuclear euchromatin;nucleosome;nucleus Activation of DNA fragmentation factor;Formation of Senescence-Associated Heterochromatin Foci (SAHF) HDAC3-H1.3-SMRT-N-Cor complex;Nop56p-associated pre-rRNA complex 0.484555691480637 0.0566118061542511 1.39971709251404 0.179138749837875 0.854270935058594 1.61664605140686 1.02079725265503 1.05719304084778 0.367164611816406 -1.01246976852417 -0.815639555454254 -1.74734246730804 0.0594131834805012 -0.237999811768532 0.0594131834805012 -1.00199794769287 -0.62888103723526 -1.71059095859528 + Cluster -674 6 6 6 23.6 23.6 23.6 38.89 0 37.144 12876000000 24 3.79944573453406 0.000246882793017456 Q15293;Q15293-2 Q15293;Q15293-2 Reticulocalbin-1 RCN1 1787 May regulate calcium-dependent activities in theendoplasmic reticulum lumen or post-ER compartment. Endoplasmic reticulum lumen. camera-type eye development;cellular protein metabolic process;in utero embryonic development;post-translational protein modification calcium ion binding endoplasmic reticulum;endoplasmic reticulum lumen Post-translational protein phosphorylation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) 0.445713639259338 0.0360305607318878 -0.00967386178672314 0.325148344039917 0.145509272813797 1.81388926506042 1.80002856254578 1.35507273674011 0.666992366313934 -1.12070071697235 -1.91713273525238 -1.22355246543884 -0.0715217217803001 -0.484836101531982 -0.151246801018715 -0.984540998935699 -0.364569425582886 -0.260609924793243 + Cluster -674 3 3 3 20.5 20.5 20.5 21.452 0 14.045 2238100000 11 3.47279501867746 0.000457425742574257 Q9Y3B2 Q9Y3B2 Exosome complex component CSL4 EXOSC1 3258 Non-catalytic component of the RNA exosome complex whichhas 3'->5' exoribonuclease activity and participates in amultitude of cellular RNA processing and degradation events. Inthe nucleus, the RNA exosome complex is involved in propermaturation of stable RNA species such as rRNA, snRNA and snoRNA,in the elimination of RNA processing by-products and non-coding'pervasive' transcripts, such as antisense RNA species andpromoter-upstream transcripts (PROMPTs), and of mRNAs withprocessing defects, thereby limiting or excluding their export tothe cytoplasm. The RNA exosome may be involved in Ig class switchrecombination (CSR) and/or Ig variable region somatichypermutation (SHM) by targeting AICDA deamination activity totranscribed dsDNA substrates. In the cytoplasm, the RNA exosomecomplex is involved in general mRNA turnover and specificallydegrades inherently unstable mRNAs containing AU-rich elements(AREs) within their 3' untranslated regions, and in RNAsurveillance pathways, preventing translation of aberrant mRNAs.It seems to be involved in degradation of histone mRNA. Thecatalytic inactive RNA exosome core complex of 9 subunits (Exo-9)is proposed to play a pivotal role in the binding and presentationof RNA for ribonucleolysis, and to serve as a scaffold for theassociation with catalytic subunits and accessory proteins orcomplexes. EXOSC1 as peripheral part of the Exo-9 complexstabilizes the hexameric ring of RNase PH-domain subunits throughcontacts with EXOSC6 and EXOSC8. Nucleus, nucleolus{ECO:0000269|PubMed:11812149}. Nucleus{ECO:0000305|PubMed:11812149}. Cytoplasm{ECO:0000305|PubMed:11812149}. exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;regulation of mRNA stability;RNA phosphodiester bond hydrolysis, exonucleolytic;rRNA processing RNA binding cytoplasm;cytosol;exosome (RNase complex);nuclear exosome (RNase complex);nucleolus;nucleoplasm RNA degradation ATF4 activates genes;Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;KSRP (KHSRP) binds and destabilizes mRNA;Major pathway of rRNA processing in the nucleolus and cytosol;mRNA decay by 3' to 5' exoribonuclease;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA Exosome 0.725810468196869 -0.320111244916916 0.372688680887222 -0.320111244916916 0.13789401948452 1.3143767118454 1.11426687240601 0.826862454414368 0.0747309252619743 -1.29056894779205 -2.29002022743225 -1.793341755867 1.27153611183167 0.606430232524872 0.240536853671074 0.0747309252619743 -0.372855454683304 -0.372855454683304 + Cluster -674 7 7 7 44.6 44.6 44.6 23.277 0 83.701 9852800000 27 3.30667813908124 0.000588132635253054 P48047 P48047 ATP synthase subunit O, mitochondrial ATP5O 1069 Mitochondrial membrane ATP synthase (F(1)F(0) ATPsynthase or Complex V) produces ATP from ADP in the presence of aproton gradient across the membrane which is generated by electrontransport complexes of the respiratory chain. F-type ATPasesconsist of two structural domains, F(1) - containing theextramembraneous catalytic core and F(0) - containing the membraneproton channel, linked together by a central stalk and aperipheral stalk. During catalysis, ATP synthesis in the catalyticdomain of F(1) is coupled via a rotary mechanism of the centralstalk subunits to proton translocation. Part of the complex F(0)domain and the peripheric stalk, which acts as a stator to holdthe catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 staticrelative to the rotary elements. Mitochondrion {ECO:0000250}. Mitochondrioninner membrane {ECO:0000250}. ATP biosynthetic process;cristae formation;mitochondrial ATP synthesis coupled proton transport;proton transmembrane transport ATPase activity;drug binding;proton-transporting ATP synthase activity, rotational mechanism;transmembrane transporter activity;transporter activity mitochondrial inner membrane;mitochondrial proton-transporting ATP synthase complex;mitochondrion;nucleus;plasma membrane Alzheimer disease;Huntington disease;Metabolic pathways;Oxidative phosphorylation;Parkinson disease;Thermogenesis Cristae formation;Formation of ATP by chemiosmotic coupling F1F0-ATP synthase, mitochondrial 1.31434369087219 0.225217193365097 0.172814354300499 -4.61853305750992E-05 0.300228536128998 1.3307124376297 1.56366801261902 0.929463863372803 -0.486912816762924 -1.67885744571686 -1.75448036193848 -1.49453020095825 0.71672785282135 0.257715731859207 0.129603996872902 -0.0772075355052948 -0.687780797481537 -0.760680317878723 + Cluster -674 3 3 3 21.7 21.7 21.7 35.079 0 9.5819 2503800000 10 3.04403843100853 0.000992548435171386 Q6UXN9 Q6UXN9 WD repeat-containing protein 82 WDR82 2024 Regulatory component of the SET1 complex implicated inthe tethering of this complex to transcriptional start sites ofactive genes. Facilitates histone H3 'Lys-4' methylation viarecruitment of the SETD1A or SETD1B to the 'Ser-5' phosphorylatedC-terminal domain (CTD) of RNA polymerase II large subunit(POLR2A). Component of PTW/PP1 phosphatase complex, which plays arole in the control of chromatin structure and cell cycleprogression during the transition from mitosis into interphase Nucleus {ECO:0000269|PubMed:16253997,ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:20516061}.Note=Associates with chromatin. histone H3-K4 methylation;histone H3-K4 trimethylation chromatin binding chromatin;histone methyltransferase complex;nucleolus;PTW/PP1 phosphatase complex;Set1C/COMPASS complex mRNA surveillance pathway Set1A complex;Set1B complex 0.279481589794159 0.0179544817656279 0.0179544817656279 0.603404521942139 1.19112634658813 0.649402916431427 1.41853153705597 1.65419149398804 -0.378621131181717 -1.24768650531769 -2.4560375213623 -0.645501613616943 0.686269044876099 0.114697247743607 -0.173889055848122 -0.182638853788376 -0.584140419960022 -0.964498519897461 + Cluster -674 9 9 6 24.2 24.2 18.4 57.886 0 120.53 9893100000 31 3.0687675861358 0.000948249619482496 O00629 O00629 Importin subunit alpha-3 KPNA4 106 Functions in nuclear protein import as an adapterprotein for nuclear receptor KPNB1. Binds specifically anddirectly to substrates containing either a simple or bipartite NLSmotif. Docking of the importin/substrate complex to the nuclearpore complex (NPC) is mediated by KPNB1 through binding tonucleoporin FxFG repeats and the complex is subsequentlytranslocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ranbinds to importin-beta and the three components separate andimportin-alpha and -beta are re-exported from the nucleus to thecytoplasm where GTP hydrolysis releases Ran from importin. Thedirectionality of nuclear import is thought to be conferred by anasymmetric distribution of the GTP- and GDP-bound forms of Ranbetween the cytoplasm and nucleus. In vitro, mediates the nuclearimport of human cytomegalovirus UL84 by recognizing a non-classical NLS. In vitro, mediates the nuclear import of humancytomegalovirus UL84 by recognizing a non-classical NLS. Cytoplasm {ECO:0000250}. Nucleus{ECO:0000250}. modulation by virus of host process;NLS-bearing protein import into nucleus;response to hydrogen peroxide nuclear import signal receptor activity;protein transporter activity cytosol;nuclear membrane;nucleoplasm;nucleus ISG15 antiviral mechanism;NS1 Mediated Effects on Host Pathways 0.022405207157135 -0.46360519528389 0.549360752105713 0.662493050098419 0.662493050098419 1.38001942634583 0.730734944343567 1.22548890113831 0.022405207157135 -1.2826681137085 -2.79483962059021 -0.667237997055054 0.679073691368103 0.191650494933128 0.537764966487885 -0.129433050751686 -0.46360519528389 -0.862500488758087 + Cluster -674 1 1 1 2.2 2.2 2.2 61.252 0 18.567 23986000000 19 3.34054672002801 0.000561278863232682 Q8IYT4;Q8IYT4-2 Q8IYT4;Q8IYT4-2 Katanin p60 ATPase-containing subunit A-like 2 KATNAL2 2168 Severs microtubules in vitro in an ATP-dependent manner.This activity may promote rapid reorganization of cellularmicrotubule arrays. Cytoplasm, cytoskeleton {ECO:0000255|HAMAP-Rule:MF_03025}. Cytoplasm {ECO:0000269|PubMed:26929214}.Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:26929214}.Cytoplasm, cytoskeleton, spindle pole{ECO:0000269|PubMed:26929214}. Note=Localizes within thecytoplasm, partially overlapping with microtubules in interphaseand to the mitotic spindle and spindle poles during mitosis.{ECO:0000269|PubMed:26929214}. cytoplasmic microtubule organization ATP binding;ATPase activity;isomerase activity;microtubule binding;microtubule-severing ATPase activity cytoplasm;microtubule;nucleus;spindle;spindle pole -0.372889995574951 0.0357098989188671 0.574641585350037 0.148833706974983 0.747940957546234 1.89246654510498 1.1981018781662 1.14931356906891 -0.0484221912920475 -1.49348151683807 -2.47575831413269 -0.55029684305191 0.351633578538895 0.373532593250275 -0.445492744445801 -0.132382199168205 -0.552107453346252 -0.401343017816544 + Cluster -674 1 1 1 18.3 18.3 18.3 14.686 0 49.703 716620000 3 3.53737714524804 0.000391393442622951 Q8N4V1;Q8N4V1-2 Q8N4V1;Q8N4V1-2 Membrane magnesium transporter 1 MMGT1 2193 Mediates Mg(2+) transport Multi-pass membrane protein{ECO:0000255}.; Multi-pass membrane protein{ECO:0000255}. Early endosome membrane{ECO:0000250|UniProtKB:Q8K273}; Multi-pass membrane protein{ECO:0000255}. Golgi apparatus membrane{ECO:0000250|UniProtKB:Q8K273};Endoplasmic reticulum membrane{ECO:0000269|PubMed:22119785} copper ion transport;magnesium ion transport cobalt ion transmembrane transporter activity;ferrous iron transmembrane transporter activity;inorganic cation transmembrane transporter activity;magnesium ion transmembrane transporter activity early endosome;early endosome membrane;ER membrane protein complex;Golgi apparatus;Golgi membrane;integral component of membrane;membrane;plasma membrane Miscellaneous transport and binding events 0.425175160169601 -0.147016942501068 0.374121397733688 -0.119100250303745 0.374121397733688 1.53427302837372 1.64843642711639 1.20976638793945 -0.225253120064735 -1.88125646114349 -2.31855130195618 -0.722573459148407 0.466442734003067 0.255285173654556 -0.191862553358078 -0.17196974158287 -0.225253120064735 -0.284784704446793 + Cluster -674 11 10 10 34.4 31.9 31.9 36.938 0 90.363 16712000000 44 3.46148195310561 0.00046484375 Q00534 Q00534 Cyclin-dependent kinase 6 CDK6 1470 promotes G1/S transition.Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclinsduring interphase at G1 to form a pRB/RB1 kinase and controls theentrance into the cell cycle. Involved in initiation andmaintenance of cell cycle exit during cell differentiation;prevents cell proliferation and regulates negatively celldifferentiation, but is required for the proliferation of specificcell types (e.g. erythroid and hematopoietic cells). Essential forcell proliferation within the dentate gyrus of the hippocampus andthe subventricular zone of the lateral ventricles. Required duringthymocyte development. Promotes the production of newborn neurons,probably by modulating G1 length. Promotes, at least inastrocytes, changes in patterns of gene expression, changes in theactin cytoskeleton including loss of stress fibers, and enhancedmotility during cell differentiation. Prevents myeloiddifferentiation by interfering with RUNX1 and reducing itstranscription transactivation activity, but promotes proliferationof normal myeloid progenitors. Delays senescence. Promotes theproliferation of beta-cells in pancreatic islets of Langerhans.May play a role in the centrosome organization during the cellcycle phases (PubMed:23918663).;Serine/threonine-protein kinase involved in the controlof the cell cycle and differentiation Cytoplasm. Nucleus. Cell projection, ruffle.Cytoplasm, cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:23918663}. Note=Localized to the ruffling edgeof spreading fibroblasts. Kinase activity only in nucleus.Localized to the cytosol of neurons and showed prominent stainingaround either side of the nucleus (By similarity). Present in thecytosol and in the nucleus in interphase cells and at thecentrosome during mitosis from prophase to telophase(PubMed:23918663). {ECO:0000250|UniProtKB:Q64261,ECO:0000269|PubMed:23918663}. astrocyte development;cell cycle arrest;cell dedifferentiation;cell division;dentate gyrus development;G1/S transition of mitotic cell cycle;generation of neurons;gliogenesis;lateral ventricle development;negative regulation of cell cycle;negative regulation of cell differentiation;negative regulation of cell proliferation;negative regulation of cellular senescence;negative regulation of epithelial cell proliferation;negative regulation of monocyte differentiation;negative regulation of myeloid cell differentiation;negative regulation of osteoblast differentiation;positive regulation of cell-matrix adhesion;positive regulation of fibroblast proliferation;protein phosphorylation;regulation of cell motility;regulation of erythrocyte differentiation;regulation of gene expression;response to virus;type B pancreatic cell development ATP binding;cyclin binding;cyclin-dependent protein serine/threonine kinase activity;FBXO family protein binding centrosome;cyclin-dependent protein kinase holoenzyme complex;cytoplasm;cytosol;nucleoplasm;nucleus;ruffle Breast cancer;Cell cycle;Cellular senescence;Chronic myeloid leukemia;Cushing syndrome;Epstein-Barr virus infection;Glioma;Hepatitis C;Hepatocellular carcinoma;Human cytomegalovirus infection;Human papillomavirus infection;Influenza A;Kaposi sarcoma-associated herpesvirus infection;Measles;Melanoma;MicroRNAs in cancer;Non-small cell lung cancer;p53 signaling pathway;Pancreatic cancer;Pathways in cancer;PI3K-Akt signaling pathway;Small cell lung cancer;Viral carcinogenesis Primary microcephaly Abemaciclib;Alvocidib;Lerociclib;Palbociclib;Ribociclib;Trilaciclib Cyclin D associated events in G1;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Regulation of RUNX1 Expression and Activity;Senescence-Associated Secretory Phenotype (SASP) CCND1-CDK6 complex;CCND2-CDK6 complex;CCND3-CDK6 complex;CyclinD1-CDK4-CDK6 complex;CyclinD3-CDK4-CDK6 complex;CyclinD3-CDK4-CDK6-p21 complex 0.283565789461136 -0.111898757517338 0.248919621109962 -0.0830697566270828 0.0359188951551914 1.79289555549622 1.51428806781769 1.01279187202454 -0.0830697566270828 -2.0936131477356 -2.0936131477356 -0.909839272499084 0.712970197200775 0.0792587026953697 -0.0151514550670981 0.228501752018929 -0.27980038523674 -0.239054545760155 + Cluster -674 9 9 9 24.5 24.5 24.5 61.585 0 120.04 13325000000 40 3.35370798000509 0.000555956678700361 Q14247;Q14247-3;Q14247-2 Q14247;Q14247-3;Q14247-2 Src substrate cortactin CTTN 1699 Contributes to the organization of the actincytoskeleton and cell shape (PubMed:21296879). Plays a role in theformation of lamellipodia and in cell migration. Plays a role inthe regulation of neuron morphology, axon growth and formation ofneuronal growth cones (By similarity). Through its interactionwith CTTNBP2, involved in the regulation of neuronal spine density(By similarity). Plays a role in the invasiveness of cancer cells,and the formation of metastases (PubMed:16636290). Plays a role infocal adhesion assembly and turnover (By similarity). In complexwith ABL1 and MYLK regulates cortical actin-based cytoskeletalrearrangement critical to sphingosine 1-phosphate (S1P)-mediatedendothelial cell (EC) barrier enhancement (PubMed:20861316). Playsa role in intracellular protein transport and endocytosis, and inmodulating the levels of potassium channels present at the cellmembrane (PubMed:17959782). Plays a role in receptor-mediatedendocytosis via clathrin-coated pits (By similarity). Required forstabilization of KCNH1 channels at the cell membrane(PubMed:23144454). Cytoplasmic side {ECO:0000305}. Cell projection,podosome {ECO:0000250|UniProtKB:Q01406}. Cell junction{ECO:0000250|UniProtKB:Q66HL2}. Cell junction, focal adhesion{ECO:0000250|UniProtKB:Q66HL2}. Membrane, clathrin-coated pit{ECO:0000250|UniProtKB:Q66HL2}. Cell projection, dendritic spine{ECO:0000250}. Cytoplasm, cell cortex{ECO:0000269|PubMed:12151401}. Note=Colocalizes transiently withPTK2/FAK1 at focal adhesions (By similarity). Associated withmembrane ruffles and lamellipodia. In the presence of CTTNBP2NL,colocalizes with stress fibers (By similarity). In the presence ofCTTNBP2, localizes at the cell cortex (By similarity). In responseto neuronal activation by glutamate, redistributes from dendriticspines to the dendritic shaft (By similarity). Colocalizes withDNM2 at the basis of filopodia in hippocampus neuron growth zones(By similarity). {ECO:0000250|UniProtKB:Q60598,ECO:0000250|UniProtKB:Q66HL2}.; Peripheral membrane protein{ECO:0000305};Cytoplasm, cytoskeleton{ECO:0000269|PubMed:12151401}. Cell projection, lamellipodium{ECO:0000269|PubMed:12151401}. Cell projection, ruffle. Cellprojection, dendrite {ECO:0000250}. Cell projection{ECO:0000250|UniProtKB:Q66HL2}. Cell membrane{ECO:0000305|PubMed:17959782} actin cytoskeleton reorganization;actin filament polymerization;cell motility;dendritic spine maintenance;focal adhesion assembly;intracellular protein transport;lamellipodium organization;membrane organization;negative regulation of extrinsic apoptotic signaling pathway;neuron projection morphogenesis;positive regulation of actin filament polymerization;positive regulation of smooth muscle contraction;receptor-mediated endocytosis;regulation of autophagy of mitochondrion;regulation of axon extension;substrate-dependent cell migration, cell extension cadherin binding;profilin binding cell cortex;clathrin-coated pit;cortical cytoskeleton;cytoplasm;cytoskeleton;cytosol;dendritic spine;focal adhesion;Golgi apparatus;intracellular membrane-bounded organelle;lamellipodium;mitotic spindle midzone;plasma membrane;podosome;ruffle;voltage-gated potassium channel complex Bacterial invasion of epithelial cells;Pathogenic Escherichia coli infection;Proteoglycans in cancer;Shigellosis;Tight junction Clathrin-mediated endocytosis;RHO GTPases activate PAKs c-Abl-cortactin-nmMLCK complex;CTTN-FER-PTK2 complex;DDEF1-CTTN-PXN complex;G alpha-13-Hax-1-cortactin-Rac complex;Hip1R-cortactin complex -0.185156181454659 0.237474426627159 0.492621898651123 0.110125213861465 0.268898695707321 1.36851096153259 1.58433783054352 1.33715450763702 0.339135199785233 -1.51310908794403 -2.28833723068237 -1.22461414337158 0.656622886657715 0.243049293756485 -0.163619250059128 -0.122841402888298 -0.359857857227325 -0.780395746231079 + Cluster -674 3 3 3 5.7 5.7 5.7 102.45 0 234.57 5118800000 14 3.92063381499306 0.000179347826086957 Q15269 Q15269 Periodic tryptophan protein 2 homolog PWP2 1781 Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);ribosomal small subunit assembly;rRNA processing RNA binding;snoRNA binding nucleoplasm;Pwp2p-containing subcomplex of 90S preribosome;small-subunit processome Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol -0.237612411379814 0.157222226262093 0.583717703819275 0.583717703819275 0.374769121408463 1.57187259197235 1.52372741699219 1.05896699428558 -0.199800699949265 -0.490653097629547 -2.56957244873047 -1.46157264709473 0.67692619562149 -0.235760673880577 -0.0738954395055771 -0.424741595983505 -0.180752396583557 -0.656558513641357 + Cluster -674 5 3 2 22.2 17.8 10.2 25.486 0 71.716 10106000000 17 3.52506886782818 0.000402439024390244 P08579 P08579 U2 small nuclear ribonucleoprotein B SNRPB2 558 Involved in pre-mRNA splicing as component of thespliceosome (PubMed:11991638, PubMed:28502770, PubMed:28781166,PubMed:28076346). Associated with sn-RNP U2, where it contributesto the binding of stem loop IV of U2 snRNA (PubMed:9716128) Nucleus {ECO:0000269|PubMed:28076346,ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166}. mRNA splicing, via spliceosome snRNA stem-loop binding;snRNP binding;U1 snRNA binding catalytic step 2 spliceosome;fibrillar center;nuclear speck;nucleoplasm;nucleus;spliceosomal complex;U1 snRNP;U2 snRNP;U2-type catalytic step 2 spliceosome;U2-type precatalytic spliceosome Spliceosome mRNA Splicing - Major Pathway 17S U2 snRNP;C complex spliceosome;SMN-PolII-RHA complex;Spliceosome -0.0731154456734657 0.0964300036430359 0.47868537902832 0.306210517883301 0.687278985977173 1.76055121421814 1.78339302539825 1.18172919750214 -0.145599201321602 -1.29146254062653 -2.17325663566589 -1.05063915252686 0.390127778053284 -0.264315724372864 -0.336149215698242 -0.288622200489044 -0.620452702045441 -0.440793246030807 + Cluster -674 3 3 3 7.8 7.8 7.8 74.89 0 20.956 2307100000 9 4.44537604097926 6.27306273062731E-05 Q15061 Q15061 WD repeat-containing protein 43 WDR43 1767 Ribosome biogenesis factor. Involved in nucleolarprocessing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I Nucleus, nucleolus{ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:24219289}.Note=Found predominantly at the fibrillar center.{ECO:0000269|PubMed:24219289}. positive regulation of rRNA processing;positive regulation of transcription by RNA polymerase I;rRNA processing RNA binding fibrillar center;nucleolus;nucleoplasm Ribosome biogenesis in eukaryotes Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol 0.536606252193451 -0.406353622674942 0.666454255580902 0.217999204993248 0.973803579807281 1.49060666561127 1.84333765506744 1.03301513195038 0.00801087636500597 -1.42235505580902 -1.93643569946289 -0.779545605182648 0.557685256004333 -0.488064020872116 -0.298302829265594 -0.813886702060699 -0.450683027505875 -0.731892347335815 + Cluster -674 17 17 17 19.8 19.8 19.8 135.65 0 97.713 10555000000 44 3.95093148843637 0.000160664819944598 O95347;O95347-2 O95347;O95347-2 Structural maintenance of chromosomes protein 2 SMC2 422 Central component of the condensin complex, a complexrequired for conversion of interphase chromatin into mitotic-likecondense chromosomes. The condensin complex probably introducespositive supercoils into relaxed DNA in the presence of type Itopoisomerases and converts nicked DNA into positive knotted formsin the presence of type II topoisomerases Nucleus {ECO:0000269|PubMed:10958694}.Cytoplasm {ECO:0000269|PubMed:10958694}. Chromosome{ECO:0000269|PubMed:10958694}. Note=In interphase cells, themajority of the condensin complex is found in the cytoplasm, whilea minority of the complex is associated with chromatin. Asubpopulation of the complex however remains associated withchromosome foci in interphase cells. During mitosis, most of thecondensin complex is associated with the chromatin. At the onsetof prophase, the regulatory subunits of the complex arephosphorylated by CDC2, leading to condensin's association withchromosome arms and to chromosome condensation. Dissociation fromchromosomes is observed in late telophase. cell division;kinetochore organization;meiotic chromosome condensation;meiotic chromosome segregation;mitotic chromosome condensation ATP binding;protein heterodimerization activity;single-stranded DNA binding condensed chromosome;condensin complex;cytoplasm;cytosol;extracellular exosome;nuclear chromosome;nucleolus;nucleoplasm;nucleus Condensation of Prometaphase Chromosomes;Condensation of Prophase Chromosomes CAP(C)-CAP(E) complex;Condensin I complex;Condensin II;Condensin I-PARP-1-XRCC1 complex;DNA ligase IV-condensin complex;DNMT3B complex 0.860352873802185 0.0762527287006378 0.539892017841339 0.447045236825943 0.79176276922226 1.01596987247467 1.77738499641418 1.38743352890015 -0.183680951595306 -1.36385834217072 -2.09817910194397 -0.402237981557846 0.224851801991463 -0.385364472866058 -0.155966252088547 -0.490080505609512 -1.10417103767395 -0.937407076358795 + Cluster -674 2 2 2 16.1 16.1 16.1 24.906 0 29.662 893360000 9 3.55986052834694 0.000387029288702929 Q9P2W1;Q9P2W1-2 Q9P2W1;Q9P2W1-2 Homologous-pairing protein 2 homolog PSMC3IP 3062 Plays an important role in meiotic recombination.Stimulates DMC1-mediated strand exchange required for pairinghomologous chromosomes during meiosis. The complex PSMC3IP/MND1binds DNA, stimulates the recombinase activity of DMC1 as well asDMC1 D-loop formation from double-strand DNA. This complexstabilizes presynaptic RAD51 and DMC1 filaments formed on singlestrand DNA to capture double-strand DNA. This complex stimulatesboth synaptic and presynaptic critical steps in RAD51 and DMC1-promoted homologous pairing. May inhibit HIV-1 viral protein TATactivity and modulate the activity of proteasomes throughassociation with PSMC3. Acts as a tissue specific coactivator ofhormone-dependent transcription mediated by nuclear receptors Nucleus {ECO:0000269|PubMed:11739747}. DNA recombination;meiotic cell cycle DNA binding;nuclear receptor transcription coactivator activity nucleoplasm 46,XX gonadal dysgenesis Meiotic recombination TBPIP/HOP2-MND1 complex 0.718236982822418 0.0153550012037158 0.225049033761024 0.0801240280270576 0.788801312446594 1.4876424074173 1.44391179084778 1.39591026306152 -0.281167507171631 -0.978858172893524 -2.27561926841736 -1.28467035293579 0.787909686565399 -0.37143287062645 -0.204779163002968 -0.281167507171631 -0.709701478481293 -0.555544257164001 + Cluster -674 13 13 13 35.3 35.3 35.3 59.681 0 264.84 22670000000 81 3.36704921447587 0.000541818181818182 P21397;P21397-2;P27338;P27338-2 P21397;P21397-2 Amine oxidase [flavin-containing] A MAOA 757 Catalyzes the oxidative deamination of biogenic andxenobiotic amines and has important functions in the metabolism ofneuroactive and vasoactive amines in the central nervous systemand peripheral tissues. MAOA preferentially oxidizes biogenicamines such as 5-hydroxytryptamine (5-HT), norepinephrine andepinephrine.;Catalyzes the oxidative deamination of biogenic andxenobiotic amines and has important functions in the metabolism ofneuroactive and vasoactive amines in the central nervous systemand peripheral tissues. MAOB preferentially degrades benzylamineand phenylethylamine. Cytoplasmic side.; Single-passtype IV membrane protein;Mitochondrion outer membrane cellular biogenic amine metabolic process;cytokine-mediated signaling pathway;dopamine catabolic process;hydrogen peroxide biosynthetic process;negative regulation of serotonin secretion;neurotransmitter catabolic process;neurotransmitter metabolic process;positive regulation of dopamine metabolic process;response to aluminum ion;response to corticosterone;response to ethanol;response to lipopolysaccharide;response to selenium ion;substantia nigra development electron transfer activity;flavin adenine dinucleotide binding;primary amine oxidase activity;protein homodimerization activity integral component of membrane;mitochondrial envelope;mitochondrial outer membrane;mitochondrion Alcoholism;Amphetamine addiction;Arginine and proline metabolism;Cocaine addiction;Dopaminergic synapse;Drug metabolism - cytochrome P450;Glycine, serine and threonine metabolism;Histidine metabolism;Metabolic pathways;Phenylalanine metabolism;Serotonergic synapse;Tryptophan metabolism;Tyrosine metabolism Brunner syndrome;Obsessive-compulsive disorder Befloxatone;Brofaromine;Caroxazone;Cimoxatone;Clorgiline;Etryptamine acetate;Iproclozide;Iproniazide;Isocarboxazid;Ladostigil tartrate;Lazabemide;Milacemide hydrochloride;Minaprine;Moclobemide;Mofegiline hydrochloride;Nialamide;Pargyline;Phenelzine;Phentermine;Pirlindole;Rasagiline;Safinamide;Safrazine hydrochloride;Selegiline;Sembragiline;Toloxatone;Tranylcypromine Biogenic amines are oxidatively deaminated to aldehydes by MAOA and MAOB;Defective MAOA causes Brunner syndrome (BRUNS);Enzymatic degradation of dopamine by COMT;Enzymatic degradation of Dopamine by monoamine oxidase;Interleukin-4 and Interleukin-13 signaling;Metabolism of serotonin;Norepinephrine Neurotransmitter Release Cycle 1.05681240558624 -0.0166869815438986 0.409127533435822 0.0662385746836662 0.515059471130371 1.52668964862823 1.44333648681641 1.34390449523926 -0.549049198627472 -1.5250152349472 -2.14416885375977 -0.863937139511108 0.485912352800369 0.0663240998983383 -0.333114355802536 -0.155854135751724 -0.64848119020462 -0.677098035812378 + Cluster -674 5 5 5 25 25 25 27.924 0 26.155 5792300000 15 3.22048802860863 0.000714285714285714 Q9NRX1 Q9NRX1 RNA-binding protein PNO1 PNO1 2926 Positively regulates dimethylation of two adjacentadenosines in the loop of a conserved hairpin near the 3'-end of18S rRNA (PubMed:25851604). Nucleus, nucleolus{ECO:0000269|PubMed:15497447}. RNA binding cytosol;nucleolus;nucleoplasm;nucleus Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol 1.00341725349426 0.0283795837312937 0.564952731132507 -0.0727586150169373 0.417474716901779 1.5155987739563 1.61035704612732 1.20132613182068 -0.424624919891357 -0.959672212600708 -2.34293365478516 -1.13370907306671 0.140464201569557 0.382401973009109 -0.413789063692093 -0.52202582359314 -0.797134578227997 -0.197724610567093 + Cluster -674 5 4 3 17.4 15 11.9 37.031 0 56.8 1556600000 7 3.05150280416585 0.000977477477477478 Q15555;Q15555-4;Q15555-5;Q15555-3;Q15555-2 Q15555;Q15555-4;Q15555-5;Q15555-3 Microtubule-associated protein RP/EB family member 2 MAPRE2 1816 May be involved in microtubule polymerization, andspindle function by stabilizing microtubules and anchoring them atcentrosomes. May play a role in cell migration (By similarity) Cytoplasm, cytoskeleton{ECO:0000269|PubMed:10188731}. Note=Associated with themicrotubule network. Accumulates at the plus end of microtubules. cell division;cell proliferation;positive regulation of adherens junction organization;positive regulation of ARF protein signal transduction;positive regulation of GTPase activity;positive regulation of keratinocyte migration;protein localization to microtubule;protein localization to microtubule plus-end;regulation of microtubule polymerization or depolymerization;signal transduction;spindle assembly identical protein binding;microtubule binding;microtubule plus-end binding;protein kinase binding cytoplasm;cytoplasmic microtubule;focal adhesion;microtubule;microtubule cytoskeleton;microtubule organizing center;microtubule plus-end;spindle midzone Congenital symmetric circumferential skin creases 0.687667489051819 0.0492315553128719 0.603248000144958 0.533065497875214 0.839510262012482 1.52107429504395 1.59902894496918 1.37673902511597 -0.906749963760376 -1.24097895622253 -1.86816966533661 -0.801917433738708 0.238724231719971 -0.375175893306732 -0.449352741241455 -0.0862567126750946 -0.971093237400055 -0.748594760894775 + Cluster -674 4 4 4 12 12 12 65.26 0 40.413 1550200000 9 3.98493145824976 0.000142045454545455 Q8WXI9 Q8WXI9 Transcriptional repressor p66-beta GATAD2B 2314 Transcriptional repressor. Enhances MBD2-mediatedrepression. Efficient repression requires the presence of GATAD2A.Targets MBD3 to discrete loci in the nucleus. May play a role insynapse development. Nucleus speckle{ECO:0000269|PubMed:11756549, ECO:0000269|PubMed:12183469,ECO:0000269|PubMed:16415179}. Note=Speckled nuclear localizationrequires both CR1 and CR2 regions. ATP-dependent chromatin remodeling;negative regulation of transcription by RNA polymerase II DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding;zinc ion binding nuclear chromatin;nuclear speck;nucleoplasm;NuRD complex;protein-containing complex Autosomal dominant mental retardation ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;HDACs deacetylate histones;Regulation of PTEN gene transcription;Regulation of TP53 Activity through Acetylation;RNA Polymerase I Transcription Initiation LARC complex (LCR-associated remodeling complex);MeCP1 complex 1.34188532829285 0.53138679265976 0.32449609041214 0.134952500462532 -0.107913210988045 1.51318371295929 0.960575044155121 1.07607305049896 0.430159032344818 -1.98193264007568 -1.53093433380127 -1.02767276763916 0.639744162559509 0.107049576938152 0.243903055787086 -0.696762919425964 -1.06721806526184 -0.890974521636963 + Cluster -674 4 4 4 33.8 33.8 33.8 15.512 0 80.219 23303000000 34 3.08152875090978 0.000938176197836167 Q9Y6H1;Q5T1J5 Q9Y6H1;Q5T1J5 Coiled-coil-helix-coiled-coil-helix domain-containing protein 2;Putative coiled-coil-helix-coiled-coil-helix domain-containing protein CHCHD2P9, mitochondrial CHCHD2;CHCHD2P9 3342 Transcription factor. Binds to the oxygen responsiveelement of COX4I2 and activates its transcription under hypoxiaconditions (4% oxygen), as well as normoxia conditions (20%oxygen) (PubMed:23303788). Mitochondrion {ECO:0000305}.;Nucleus {ECO:0000269|PubMed:23303788}.Mitochondrion {ECO:0000269|PubMed:25662902}. Mitochondrionintermembrane space {ECO:0000269|PubMed:25662902}. Note=Mainlylocalised in the intermembrane space.{ECO:0000269|PubMed:25662902}. mitochondrion organization;positive regulation of transcription by RNA polymerase II;regulation of cellular response to hypoxia sequence-specific DNA binding;transcription factor binding mitochondrial intermembrane space;mitochondrion;nucleus Parkinson disease Mitochondrial protein import 0.0113908424973488 0.380294859409332 0.662348389625549 1.08951008319855 0.598730504512787 1.48098814487457 0.419562101364136 1.7209564447403 0.249536693096161 -1.2973393201828 -1.91555368900299 -0.775332808494568 0.394598931074142 0.0528787598013878 -0.0807432681322098 -0.662998378276825 -0.842059552669525 -1.48676860332489 + Cluster -674 6 6 6 15.6 15.6 15.6 55.738 0 30.887 4624700000 19 3.6218707592666 0.000343612334801762 Q9UNF0;Q9UNF0-2 Q9UNF0;Q9UNF0-2 Protein kinase C and casein kinase substrate in neurons protein 2 PACSIN2 3180 Lipid-binding protein that is able to promote thetubulation of the phosphatidic acid-containing membranes itpreferentially binds. Plays a role in intracellular vesicle-mediated transport. Involved in the endocytosis of cell-surfacereceptors like the EGF receptor, contributing to itsinternalization in the absence of EGF stimulus. May also play arole in the formation of caveolae at the cell membrane. RecruitsDNM2 to caveolae, and thereby plays a role in caveola-mediatedendocytosis. Cytoplasmic side. Cell membrane; Cytoplasmic side. Cell projection{ECO:0000250}. Membrane, caveola. Note=Detected at the neck offlask-shaped caveolae. Localization to tubular recycling endosomesprobably requires interaction with MICALL1 and EHD1.; Cytoplasmic side. Early endosome.Recycling endosome membrane. Cell projection, ruffle membrane;Cytoplasm {ECO:0000250}. Cytoplasm,cytoskeleton {ECO:0000250}. Cytoplasmic vesicle membrane;Peripheral membrane protein actin cytoskeleton organization;caveola assembly;caveolin-mediated endocytosis;cell projection morphogenesis;cytoskeleton organization;membrane organization;modulation of chemical synaptic transmission;negative regulation of endocytosis;plasma membrane tubulation;protein localization to endosome cadherin binding;cytoskeletal protein binding;identical protein binding;phosphatidic acid binding;phospholipid binding;transporter activity caveola;cell-cell junction;cytoplasm;cytoplasmic vesicle membrane;cytoskeleton;cytosol;early endosome;extracellular exosome;extrinsic component of membrane;focal adhesion;glutamatergic synapse;intracellular membrane-bounded organelle;nuclear speck;plasma membrane;recycling endosome membrane;ruffle membrane Clathrin-mediated endocytosis 0.814973533153534 0.241978764533997 0.848340272903442 0.223605453968048 0.775448501110077 1.65256428718567 1.28361570835114 0.6999391913414 0.223605453968048 -1.6315141916275 -1.50093579292297 -1.09080195426941 0.619211852550507 0.0677245706319809 -0.0997783318161964 -0.812449216842651 -0.889119029045105 -1.42640912532806 + Cluster -674 4 4 4 12.1 12.1 12.1 57.276 0 62.525 1785600000 11 3.65364889811786 0.000331818181818182 Q9H3P2;Q9H3P2-7 Q9H3P2 Negative elongation factor A NELFA 2791 Essential component of the NELF complex, a complex thatnegatively regulates the elongation of transcription by RNApolymerase II. The NELF complex, which acts via an associationwith the DSIF complex and causes transcriptional pausing, iscounteracted by the P-TEFb kinase complex Nucleus {ECO:0000269|PubMed:11150502}. multicellular organism development;negative regulation of transcription elongation from RNA polymerase II promoter;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter cytosol;NELF complex;nuclear body;nucleoplasm Abortive elongation of HIV-1 transcript in the absence of Tat;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;HIV elongation arrest and recovery;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Elongation;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes NELF complex (Negative elongation factor complex) 0.37870717048645 0.0909875780344009 0.559301972389221 0.428022444248199 0.467499822378159 1.8238742351532 1.14424121379852 1.16846668720245 -0.0617514848709106 -1.62444698810577 -2.13627767562866 -0.927322626113892 0.884180903434753 -0.216289967298508 -0.116457186639309 -0.589910566806793 -0.454482138156891 -0.8183434009552 + Cluster -674 3 3 3 10.2 10.2 10.2 50.529 0 81.787 5225700000 13 3.86246248513499 0.000223097112860892 Q8ND56;Q8ND56-3;Q8ND56-2 Q8ND56;Q8ND56-3;Q8ND56-2 Protein LSM14 homolog A LSM14A 2233 Essential for formation of P-bodies, cytoplasmicstructures that provide storage sites for non-translating mRNAs Cytoplasm, P-body{ECO:0000269|PubMed:16484376, ECO:0000269|PubMed:17074753}.Cytoplasm, Stress granule {ECO:0000269|PubMed:16484376}. cytoplasmic mRNA processing body assembly;multicellular organism development;positive regulation of type I interferon-mediated signaling pathway;regulation of translation;RIG-I signaling pathway double-stranded DNA binding;double-stranded RNA binding;RNA binding;single-stranded RNA binding cytoplasm;cytoplasmic ribonucleoprotein granule;cytoplasmic stress granule;cytosol;P-body 0.433187067508698 0.164351209998131 0.680541694164276 0.538979172706604 0.670109629631042 1.61960387229919 1.41492688655853 0.994974732398987 0.0385376513004303 -1.69112884998322 -1.90962040424347 -0.848483026027679 0.345932930707932 0.167733624577522 -0.0939339101314545 -0.468846708536148 -0.676455140113831 -1.38041055202484 + Cluster -674 12 12 12 25.7 25.7 25.7 89.034 0 270.09 6481500000 32 4.194123029627 9.55414012738854E-05 Q12788 Q12788 Transducin beta-like protein 3 TBL3 1564 Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);rRNA processing RNA binding;snoRNA binding nucleolus;nucleoplasm;nucleus;Pwp2p-containing subcomplex of 90S preribosome;small-subunit processome Ribosome biogenesis in eukaryotes Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol Ubiquitin E3 ligase (AHR, ARNT, DDB1, TBL3, CUL4B, RBX1) 0.862674593925476 0.237745717167854 0.495758712291718 0.27954313158989 0.417534172534943 1.54316473007202 1.2988475561142 1.27500212192535 0.055414542555809 -1.67068302631378 -1.97213470935822 -0.982989966869354 0.467393428087234 0.14323590695858 -0.101838171482086 -0.457158803939819 -0.711298227310181 -1.18021178245544 + Cluster -674 2 2 2 15.6 15.6 15.6 27.083 0 39.801 967940000 8 3.8355818761679 0.000230179028132992 Q6ZN17;Q6ZN17-2 Q6ZN17;Q6ZN17-2 Protein lin-28 homolog B LIN28B 2031 Suppressor of microRNA (miRNA) biogenesis, includingthat of let-7 and possibly of miR107, miR-143 and miR-200c. Bindsprimary let-7 transcripts (pri-let-7), including pri-let-7g andpri-let-7a-1, and sequester them in the nucleolus, away from themicroprocessor complex, hence preventing their processing intomature miRNA (PubMed:22118463). Does not act on pri-miR21(PubMed:22118463). The repression of let-7 expression is requiredfor normal development and contributes to maintain the pluripotentstate of embryonic stem cells by preventing let-7-mediateddifferentiation. When overexpressed, recruits ZCCHC11/TUT4uridylyltransferase to pre-let-7 transcripts, leading to theirterminal uridylation and degradation (PubMed:19703396). Thisactivity might not be relevant in vivo, as LIN28B-mediatedinhibition of let-7 miRNA maturation appears to be ZCCHC11-independent (PubMed:22118463). Interaction with target pre-miRNAsoccurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop.Mediates MYC-induced let-7 repression (By similarity). Whenoverexpressed, isoform 1 stimulates growth of the breastadenocarcinoma cell line MCF-7. Isoform 2 has no effect on cellgrowth. however, the specificity of the polyclonal antibody used in theseexperiments has not been not documented (PubMed:16971064).{ECO:0000269|PubMed:16971064, ECO:0000269|PubMed:22118463}.;Nucleus. Nucleus, nucleolus{ECO:0000269|PubMed:22118463}. Cytoplasm{ECO:0000269|PubMed:16971064}. Note=Predominantly nucleolar(PubMed:22118463). In Huh7 cells, predominantly cytoplasmic, withonly a subset of cells exhibiting strong nuclear staining miRNA catabolic process;pre-miRNA processing;regulation of transcription, DNA-templated;RNA 3'-end processing DNA binding;RNA binding;zinc ion binding cytosol;nucleolus;nucleus 0.688749849796295 0.321864932775497 0.37234964966774 -0.108065336942673 0.565566539764404 1.51932501792908 1.15964782238007 1.15050184726715 -0.0737223997712135 -1.68763601779938 -2.24396729469299 -1.06701767444611 0.866453349590302 0.214316114783287 0.0883995816111565 -0.338146358728409 -0.649973571300507 -0.778646051883698 + Cluster -674 2 2 2 9.1 9.1 9.1 33.87 0 125.69 1099000000 6 3.47087451089625 0.000457760314341847 Q9UHR5;Q9UHR5-2 Q9UHR5;Q9UHR5-2 SAP30-binding protein SAP30BP 3114 Induces cell death. May act as a transcriptionalcorepressor of a gene related to cell survival. May be involved inthe regulation of beta-2-microglobulin genes Nucleus {ECO:0000269|PubMed:15496587}. apoptotic process;positive regulation of cell death;regulation of transcription, DNA-templated intermediate filament cytoskeleton;nucleoplasm;nucleus NoRC negatively regulates rRNA expression 0.698906540870667 0.494977027177811 0.299803346395493 -0.18621589243412 1.07259893417358 1.59559428691864 1.2664623260498 1.2664623260498 -0.399852454662323 -1.7543580532074 -1.9403600692749 -0.796076953411102 0.351513266563416 0.0543811395764351 -0.0436214469373226 -0.399852454662323 -0.969430267810822 -0.610931575298309 + Cluster -674 2 2 2 2.3 2.3 2.3 132.94 0 5.0353 760340000 2 3.3335912157609 0.000573451327433628 Q7Z5K2;Q7Z5K2-2;Q7Z5K2-3 Q7Z5K2;Q7Z5K2-2;Q7Z5K2-3 Wings apart-like protein homolog WAPAL 2085 Regulator of sister chromatid cohesion in mitosis whichnegatively regulates cohesin association with chromatin. Involvedin both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNAreplication to sister chromatid cohesion. Cohesion ensures thatchromosome partitioning is accurate in both meiotic and mitoticcells and plays an important role in DNA repair Isoform 2: Nucleus.Nucleus. Chromosome. Cytoplasm.Note=Associates with chromatin through the cohesin complex duringinterphase. Released in the cytoplasm from nuclear envelopebreakdown until anaphase, it reaccumulates in nucleus attelophase. cell division;meiotic chromosome segregation;mitotic cell cycle;negative regulation of chromatin binding;negative regulation of DNA replication;negative regulation of sister chromatid cohesion;positive regulation of fibroblast proliferation;protein localization to chromatin;regulation of chromosome condensation;regulation of cohesin loading;response to toxic substance;viral process chromatin;chromosome;chromosome, centromeric region;cohesin complex;cytoplasm;cytosol;nucleoplasm;nucleus;synaptonemal complex Cohesin Loading onto Chromatin;Establishment of Sister Chromatid Cohesion;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids 0.841179966926575 0.185719966888428 0.567699611186981 0.023579204455018 0.435351222753525 1.59286570549011 1.54325330257416 0.973569869995117 -0.155582815408707 -1.9055517911911 -1.98734080791473 -0.867282807826996 0.352387309074402 0.0451477542519569 0.252954959869385 -0.352540105581284 -0.691479384899139 -0.853931128978729 + Cluster -674 2 2 2 2.2 2.2 2.2 173.05 0 8.2642 1766600000 3 3.57602728017039 0.000380645161290323 O94913 O94913 Pre-mRNA cleavage complex 2 protein Pcf11 PCF11 394 Component of pre-mRNA cleavage complex II. Nucleus. mRNA 3'-end processing;mRNA cleavage;mRNA polyadenylation;mRNA splicing, via spliceosome;termination of RNA polymerase II transcription mRNA binding;RNA polymerase II complex binding cytoplasm;mitochondrion;mRNA cleavage factor complex;nucleoplasm mRNA surveillance pathway Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Processing of Intronless Pre-mRNAs;RNA polymerase II transcribes snRNA genes CF IIAm complex (Cleavage factor IIAm complex) 0.70542186498642 0.348015904426575 0.549564778804779 0.0819422751665115 0.549564778804779 1.57828140258789 1.33707690238953 1.09469819068909 0.100932903587818 -1.54890334606171 -2.19313073158264 -0.923977792263031 0.412997752428055 0.156801581382751 0.0861501544713974 -0.426309138536453 -0.871343791484833 -1.0377836227417 + Cluster -674 2 2 2 23.4 23.4 23.4 11.676 0 86.813 42114000000 30 3.7104024279458 0.000286396181384248 P17096;P17096-3 P17096;P17096-3 High mobility group protein HMG-I/HMG-Y HMGA1 702 HMG-I/Y bind preferentially to the minor groove of A+Trich regions in double-stranded DNA. It is suggested that theseproteins could function in nucleosome phasing and in the 3'-endprocessing of mRNA transcripts. They are also involved in thetranscription regulation of genes containing, or in closeproximity to A+T-rich regions. Nucleus. Chromosome. base-excision repair;DNA unwinding involved in DNA replication;establishment of integrated proviral latency;negative regulation of cell proliferation;negative regulation of chromatin silencing;negative regulation of transcription, DNA-templated;nuclear transport;nucleosome disassembly;oncogene-induced cell senescence;positive regulation of cellular senescence;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;protein-containing complex assembly;regulation of transcription, DNA-templated;response to virus;senescence-associated heterochromatin focus assembly 5'-deoxyribose-5-phosphate lyase activity;AT DNA binding;chromatin binding;DNA binding;DNA-(apurinic or apyrimidinic site) endonuclease activity;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer sequence-specific DNA binding;enzyme binding;nuclear receptor transcription coactivator activity;peroxisome proliferator activated receptor binding;retinoic acid receptor binding;retinoid X receptor binding;structural constituent of chromatin;transcription coactivator activity;transcription factor binding cytosol;focal adhesion;nucleoplasm;nucleus;RNA polymerase II transcription factor complex;senescence-associated heterochromatin focus;transcription factor complex 2-LTR circle formation;APOBEC3G mediated resistance to HIV-1 infection;Autointegration results in viral DNA circles;Formation of Senescence-Associated Heterochromatin Foci (SAHF);Integration of provirus;Integration of viral DNA into host genomic DNA;Vpr-mediated nuclear import of PICs 0.439944684505463 0.451539486646652 0.684053421020508 -0.197113171219826 0.387596428394318 1.75497627258301 1.42987251281738 0.919327139854431 0.420076847076416 -1.38632535934448 -2.40242099761963 -0.558349907398224 0.354360520839691 -0.0224233232438564 -0.0890387371182442 -0.519656896591187 -0.861862421035767 -0.804556548595428 + Cluster -674 2 2 2 3.5 3.5 3.5 125.97 0 66.502 680470000 7 3.07816429790035 0.000939907550077042 O75717;O75717-2 O75717;O75717-2 WD repeat and HMG-box DNA-binding protein 1 WDHD1 353 Acts as a replication initiation factor that bringstogether the MCM2-7 helicase and the DNA polymerase alpha/primasecomplex in order to initiate DNA replication Nucleus, nucleoplasm {ECO:0000250}. cellular response to DNA damage stimulus;DNA repair;DNA-dependent DNA replication;mitotic cell cycle chromatin binding;DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific cytoplasm;nuclear replication fork;nucleoplasm;replication fork protection complex DDX11-Ctf18-RFC complex -0.583683252334595 -0.137646317481995 0.158287718892097 0.186681851744652 0.79303252696991 1.77970016002655 2.24657011032104 1.29036390781403 0.604427397251129 -0.836283683776855 -1.55817544460297 -0.66702675819397 -0.930020868778229 -0.782487869262695 -0.542588233947754 -0.441586911678314 -0.289782226085663 -0.289782226085663 + Cluster -674 1 1 1 1.9 1.9 1.9 57.761 0.0019036 1.5445 5492900000 2 3.20686706662085 0.000733113673805601 Q9BZI7;Q9BZI7-2 Q9BZI7;Q9BZI7-2 Regulator of nonsense transcripts 3B UPF3B 2729 the function isindependent of association with UPF2 and components of the EJCcore.;Involved in nonsense-mediated decay (NMD) of mRNAscontaining premature stop codons by associating with the nuclearexon junction complex (EJC) and serving as link between the EJCcore and NMD machinery. Recruits UPF2 at the cytoplasmic side ofthe nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factorsat the stalled ribosome) is believed to activate NMD. Incooperation with UPF2 stimulates both ATPase and RNA helicaseactivities of UPF1. Binds spliced mRNA upstream of exon-exonjunctions. In vitro, stimulates translation Nucleus. Cytoplasm. Note=Shuttling betweenthe nucleus and the cytoplasm. mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;positive regulation of translation;RNA export from nucleus mRNA binding;RNA binding;structural constituent of nuclear pore cytoplasm;cytosol;exon-exon junction complex;microtubule organizing center;nucleolus;nucleoplasm;nucleus mRNA surveillance pathway;RNA transport Syndromic X-linked mental retardation Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Regulation of expression of SLITs and ROBOs;Transport of Mature mRNA derived from an Intron-Containing Transcript CBP80/20- dependent translation complex;Exon junction complex;mRNA decay complex (UPF1, UPF2, UPF3B, DCP2, XRN1, XRN2, EXOSC2, EXOSC4, EXOSC10, PARN);Postsplicing complex;SMG1-UPF2-Y14-MAGOH-UPF3B-EIF4A3 complex;Upf complex (UPF1, UPF2, UPF3b) -0.659676730632782 0.475444376468658 0.521942853927612 0.618462085723877 0.908864498138428 2.0612199306488 2.06971263885498 0.820521175861359 -0.163617506623268 -1.27835166454315 -1.15039598941803 -0.353480637073517 -0.683766961097717 -0.71147745847702 -0.774003446102142 -0.602038204669952 -0.508716940879822 -0.590641736984253 + Cluster -674 3 3 3 5.6 5.6 5.6 56.05 0 23.844 1462800000 6 4.17309352997504 0.000104430379746835 Q8WUB8;Q8WUB8-2;Q8WUB8-3 Q8WUB8;Q8WUB8-2;Q8WUB8-3 PHD finger protein 10 PHF10 2286 Involved in transcription activity regulation bychromatin remodeling. Belongs to the neural progenitors-specificchromatin remodeling complex (npBAF complex) and is required forthe proliferation of neural progenitors. During neural developmenta switch from a stem/progenitor to a post-mitotic chromatinremodeling mechanism occurs as neurons exit the cell cycle andbecome committed to their adult state. The transition fromproliferating neural stem/progenitor cells to post-mitotic neuronsrequires a switch in subunit composition of the npBAF and nBAFcomplexes. As neural progenitors exit mitosis and differentiateinto neurons, npBAF complexes which contain ACTL6A/BAF53A andPHF10/BAF45A, are exchanged for homologous alternativeACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for theself-renewal/proliferative capacity of the multipotent neural stemcells. The nBAF complex along with CREST plays a role regulatingthe activity of genes essential for dendrite growth (Bysimilarity). Nucleus {ECO:0000250}. negative regulation of transcription, DNA-templated;nervous system development;positive regulation of transcription by RNA polymerase II histone acetyltransferase activity;histone binding;metal ion binding histone acetyltransferase complex;npBAF complex;nuclear chromatin;nucleus Hepatocellular carcinoma BRD7-CBP-SWI\u2013SNF complex;BRD7-SWI\u2013SNF complex -1.08648312091827 0.493770569562912 0.9808070063591 0.438932448625565 0.801297783851624 2.17151308059692 1.32694435119629 1.22707760334015 0.00182390038389713 -1.44674563407898 -1.19358313083649 -0.654416918754578 -0.188199356198311 -0.588195025920868 -0.654416918754578 -0.23473633825779 -0.617810487747192 -0.777579724788666 + Cluster -674 2 2 2 3.7 3.7 3.7 97.667 0 28.683 3090200000 10 4.21600076509289 9.0032154340836E-05 P78316;P78316-2 P78316;P78316-2 Nucleolar protein 14 NOP14 1424 Involved in nucleolar processing of pre-18S ribosomalRNA. Has a role in the nuclear export of 40S pre-ribosomal subunitto the cytoplasm (By similarity). Nucleus, nucleolus {ECO:0000250}. endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);endonucleolytic cleavage to generate mature 5'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA);maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);ribosomal small subunit biogenesis;rRNA processing enzyme binding;RNA binding;snoRNA binding 90S preribosome;membrane;Noc4p-Nop14p complex;nucleolus;nucleoplasm;nucleus;small-subunit processome Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol -0.627925634384155 -0.0208319388329983 0.0925029739737511 0.53686261177063 0.832630336284637 1.91084456443787 1.91084456443787 0.936805963516235 0.182464689016342 -1.82033514976501 -0.637371718883514 -1.61877715587616 -0.165856897830963 -0.350351005792618 -0.165856897830963 -0.0726867392659187 -0.937082767486572 0.0141203105449677 + Cluster -674 3 3 3 1.9 1.9 1.9 202.02 0.0046497 1.1897 434540000 4 3.62056972768298 0.000342857142857143 Q69YN4;Q69YN4-4;Q69YN4-2;Q69YN4-3 Q69YN4;Q69YN4-4;Q69YN4-2;Q69YN4-3 Protein virilizer homolog KIAA1429 1966 Associated component of the WMM complex, a complex thatmediates N6-methyladenosine (m6A) methylation of RNAs, amodification that plays a role in the efficiency of mRNA splicingand RNA processing (PubMed:24981863, PubMed:29507755). Acts as akey regulator of m6A methylation by promoting m6A methylation ofmRNAs in the 3'-UTR near the stop codon: recruits the catalyticcore components METTL3 and METTL14, thereby guiding m6Amethylation at specific sites (PubMed:29507755). Required for mRNApolyadenylation via its role in selective m6A methylation: m6Amethylation of mRNAs in the 3'-UTR near the stop codon correlatingwith alternative polyadenylation (APA) (PubMed:29507755) Nucleus speckle{ECO:0000269|PubMed:24100041}. Nucleus, nucleoplasm{ECO:0000269|PubMed:24100041}. Cytoplasm{ECO:0000250|UniProtKB:A2AIV2}. Note=Mainly nuclear with somefraction located in the cytoplasm. ZC3H13 is required to anchorcomponent of the MACOM subcomplex, such as VIRMA, in the nucleus.{ECO:0000250|UniProtKB:A2AIV2}. mRNA alternative polyadenylation;mRNA methylation;mRNA processing;multicellular organism development;RNA splicing RNA binding cytosol;nuclear body;nuclear speck;nucleoplasm;RNA N6-methyladenosine methyltransferase complex CEN complex;Spliceosome 0.493764489889145 0.455310732126236 0.597956776618958 -0.114933699369431 0.915343344211578 1.57063603401184 2.2935893535614 0.777242004871368 -0.0537357702851295 -1.26876664161682 -1.51708805561066 -0.675090312957764 -0.203905180096626 -0.212820559740067 -0.76379668712616 -0.455023020505905 -0.730819702148438 -1.10786306858063 + Cluster -674 1 1 1 10.8 10.8 10.8 12.939 0 7.1122 683250000 5 3.50424181851968 0.000422535211267606 Q13542 Q13542 Eukaryotic translation initiation factor 4E-binding protein 2 EIF4EBP2 1644 Repressor of translation initiation involved in synapticplasticity, learning and memory formation (By similarity).Regulates EIF4E activity by preventing its assembly into the eIF4Fcomplex: hypophosphorylated form of EIF4EBP2 competes withEIF4G1/EIF4G3 and strongly binds to EIF4E, leading to represstranslation. In contrast, hyperphosphorylated form dissociatesfrom EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E,leading to initiation of translation (PubMed:25533957). EIF4EBP2is enriched in brain and acts as a regulator of synapse activityand neuronal stem cell renewal via its ability to represstranslation initiation (By similarity). Mediates the regulation ofprotein translation by hormones, growth factors and other stimulithat signal through the MAP kinase and mTORC1 pathways (Bysimilarity). cAMP-mediated signaling;insulin receptor signaling pathway;memory;modulation of chemical synaptic transmission;negative regulation of translational initiation;regulation of synaptic plasticity;social behavior;TOR signaling;translation eukaryotic initiation factor 4E binding;translation repressor activity cytoplasm;postsynapse Longevity regulating pathway - multiple species;RNA transport 0.311507821083069 -0.355814069509506 1.06607174873352 -0.0221824999898672 1.15388810634613 2.06497597694397 1.71592307090759 0.654608905315399 0.340112090110779 -1.52069222927094 -1.02901601791382 -0.553798913955688 -0.197736844420433 -0.527889966964722 -0.606367349624634 -1.09424531459808 -0.612443208694458 -0.7869011759758 + Cluster -674 3 3 3 5.7 5.7 5.7 62.888 0 39.608 694800000 8 3.96084217342455 0.000156424581005587 Q99856;Q8IVW6;Q8IVW6-3;Q8IVW6-4 Q99856 AT-rich interactive domain-containing protein 3A ARID3A 2600 Transcription factor which may be involved in thecontrol of cell cycle progression by the RB1/E2F1 pathway and inB-cell differentiation.;Transcription factor which may be involved inneuroblastoma growth and malignant transformation. Favors nucleartargeting of ARID3A. Nucleus {ECO:0000255|PROSITE-ProRule:PRU00355, ECO:0000269|PubMed:10446990,ECO:0000269|PubMed:17400556}.;Nucleus {ECO:0000255|PROSITE-ProRule:PRU00355, ECO:0000269|PubMed:17400556}. Cytoplasm{ECO:0000269|PubMed:17400556}. Note=Shuttles between nucleus andcytoplasm. DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest chromatin binding;DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity, RNA polymerase II-specific;protein homodimerization activity;RNA polymerase II distal enhancer sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding cytosol;intracellular membrane-bounded organelle;membrane raft;nucleoplasm;nucleus TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest -0.147413849830627 0.0227585304528475 0.911971271038055 0.365721613168716 1.24989986419678 1.93346762657166 1.96919047832489 0.176219791173935 0.00782825890928507 -1.27726292610168 -0.797232031822205 -1.23112440109253 -0.471779078245163 0.00811704527586699 -0.309615701436996 -1.14062833786011 -0.0900126770138741 -1.18010544776917 + Cluster -674 4 4 4 13.7 13.7 13.7 48.207 0 94.809 690790000 9 3.67492648032881 0.000323325635103926 Q9UJU6;Q9UJU6-2;Q9UJU6-3;Q9UJU6-6;Q9UJU6-5;Q9UJU6-4 Q9UJU6;Q9UJU6-2;Q9UJU6-3;Q9UJU6-6;Q9UJU6-5 Drebrin-like protein DBNL 3134 Adapter protein that binds F-actin and DNM1, and therebyplays a role in receptor-mediated endocytosis. Plays a role in thereorganization of the actin cytoskeleton, formation of cellprojections, such as neurites, in neuron morphogenesis and synapseformation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for theformation of organized podosome rosettes (By similarity). May actas a common effector of antigen receptor-signaling pathways inleukocytes. Acts as a key component of the immunological synapsethat regulates T-cell activation by bridging TCRs and the actincytoskeleton to gene activation and endocytic processes Cytoplasmic side. Golgi apparatus membrane{ECO:0000250|UniProtKB:Q62418}; Peripheral membrane protein; Peripheralmembrane protein;Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:Q62418}. Cell projection, lamellipodium{ECO:0000250|UniProtKB:Q62418}. Cell projection, ruffle{ECO:0000250|UniProtKB:Q62418}. Cytoplasm, cell cortex{ECO:0000250|UniProtKB:Q62418}. Cytoplasm, cytosol{ECO:0000250|UniProtKB:Q62418}. Cell junction, synapse{ECO:0000250|UniProtKB:Q62418}. Cell projection{ECO:0000250|UniProtKB:Q62418}. Cell membrane{ECO:0000269|PubMed:14729663};Cytoplasmic side {ECO:0000250}. Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000250|UniProtKB:Q62418};Cytoplasmic side. Cell projection, podosome{ECO:0000250|UniProtKB:Q62418}. Early endosome{ECO:0000269|PubMed:14729663}. Note=Detected in neuron cell bodyand cell projections, such as neurites. Colocalizes with cytosolicdynamin in hippocampus neurons (By similarity). Cortical actincytoskeleton. Associates with lamellipodial actin and membraneruffles. Colocalizes with actin and cortactin at podosome dots andpodosome rosettes (By similarity). {ECO:0000250|UniProtKB:Q62418}. activation of JUN kinase activity;adaptive immune response;neuron projection morphogenesis;neutrophil degranulation;podosome assembly;Rac protein signal transduction;receptor-mediated endocytosis;ruffle assembly;synapse assembly actin binding;actin filament binding;cadherin binding;enzyme activator activity;protein C-terminus binding;protein domain specific binding cell cortex;cell junction;clathrin-coated vesicle membrane;cytoplasm;cytosol;dendrite;early endosome;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;Golgi membrane;lamellipodium;plasma membrane;podosome;postsynaptic density;ruffle;secretory granule lumen;tertiary granule lumen Caspase-mediated cleavage of cytoskeletal proteins;Neurexins and neuroligins;Neutrophil degranulation 0.520386099815369 -0.00569467060267925 1.21015858650208 -0.0745048299431801 0.152183413505554 1.94732344150543 1.66128420829773 0.998494505882263 0.818577289581299 -1.47614407539368 -0.929170310497284 -0.312419772148132 -0.75708281993866 -0.272580862045288 -0.859655916690826 -0.621533811092377 -0.770698487758636 -1.22892189025879 + Cluster -674 3 3 3 22.9 22.9 22.9 12.895 0 134.62 27039000000 35 3.431924780584 0.000493358633776091 P58546 P58546 Myotrophin MTPN 1268 Promotes dimerization of NF-kappa-B subunits andregulates NF-kappa-B transcription factor activity (Bysimilarity). Plays a role in the regulation of the growth of actinfilaments. Inhibits the activity of the F-actin-capping proteincomplex formed by the CAPZA1 and CAPZB heterodimer. Promotesgrowth of cardiomyocytes, but not cardiomyocyte proliferation.Promotes cardiac muscle hypertrophy. Cytoplasm {ECO:0000305}. Nucleus{ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. catecholamine metabolic process;cellular response to mechanical stimulus;cerebellar granule cell differentiation;neuron differentiation;positive regulation of cardiac muscle hypertrophy;positive regulation of cell growth;positive regulation of macromolecule biosynthetic process;positive regulation of NF-kappaB transcription factor activity;positive regulation of protein metabolic process;regulation of barbed-end actin filament capping;regulation of cell size;regulation of striated muscle tissue development;regulation of translation;skeletal muscle tissue regeneration;striated muscle cell differentiation sequence-specific DNA binding axon;cytosol;F-actin capping protein complex;nucleus;perinuclear region of cytoplasm 0.535711705684662 1.06628310680389 0.323945373296738 0.786545813083649 0.238826304674149 1.86078572273254 1.3136875629425 1.3136875629425 0.238826304674149 -1.41879618167877 -1.16502952575684 -0.357479393482208 -0.752431869506836 -0.241941124200821 -0.552569806575775 -1.03728878498077 -1.03728878498077 -1.11547410488129 + Cluster -674 20 20 20 33.1 33.1 33.1 105.84 0 282.21 39624000000 115 4.29348204650899 8.27814569536424E-05 Q99460;Q99460-2 Q99460;Q99460-2 26S proteasome non-ATPase regulatory subunit 1 PSMD1 2563 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair neutrophil degranulation;post-translational protein modification;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination;regulation of protein catabolic process enzyme regulator activity;ubiquitin protein ligase binding azurophil granule lumen;cytosol;extracellular region;membrane;nucleoplasm;nucleus;proteasome accessory complex;proteasome complex;proteasome regulatory particle;proteasome regulatory particle, base subcomplex;proteasome storage granule Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;Neutrophil degranulation;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 PA700 complex;PA700-20S-PA28 complex 1.13075315952301 0.249507457017899 0.500598251819611 0.10950718075037 0.0282074473798275 1.59709978103638 1.97751617431641 1.37440645694733 0.136634409427643 -1.07583391666412 -1.45969247817993 -0.168055191636086 -0.551421940326691 -0.482866287231445 -1.21114230155945 -0.957900166511536 -0.788375437259674 -0.408942550420761 + Cluster -674 6 5 5 24.7 21.9 21.9 33.304 0 20.539 2309900000 14 3.07874071072233 0.000939814814814815 Q00535;Q00535-2 Q00535;Q00535-2 Cyclin-dependent-like kinase 5 CDK5 1471 phosphorylates the linkerdomain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAITcomplex. Phosphorylation of SH3GLB1 is required for autophagyinduction in starved neurons. Phosphorylation of TONEBP/NFAT5 inresponse to osmotic stress mediates its rapid nuclearlocalization. MEF2 is inactivated by phosphorylation in nucleus inresponse to neurotoxin, thus leading to neuronal apoptosis. APEX1AP-endodeoxyribonuclease is repressed by phosphorylation,resulting in accumulation of DNA damage and contributing toneuronal death. NOS3 phosphorylation down regulates NOS3-derivednitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletalreorganization. May regulate endothelial cell migration andangiogenesis via the modulation of lamellipodia formation.Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in theregulation of the circadian clock by modulating the function ofCLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' andregulates the transcriptional activity of the CLOCK-ARNTL/BMAL1heterodimer in association with altered stability and subcellulardistribution.;Proline-directed serine/threonine-protein kinaseessential for neuronal cell cycle arrest and differentiation andmay be involved in apoptotic cell death in neuronal diseases bytriggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin,p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5,SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5,MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1,huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates severalneuronal development and physiological processes includingneuronal survival, migration and differentiation, axonal andneurite growth, synaptogenesis, oligodendrocyte differentiation,synaptic plasticity and neurotransmission, by phosphorylating keyproteins. Activated by interaction with CDK5R1 (p35) and CDK5R2(p39), especially in post-mitotic neurons, and promotes CDK5R1(p35) expression in an autostimulation loop. Phosphorylates manydownstream substrates such as Rho and Ras family small GTPases(e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins(e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics toregulate neurite growth and/or spine morphogenesis. Phosphorylatesalso exocytosis associated proteins such as MCAM/MUC18, SEPT5,SYN1, and CDK16/PCTAIRE1 as well as endocytosis associatedproteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. Inthe mature central nervous system (CNS), regulatesneurotransmitter movements by phosphorylating substratesassociated with neurotransmitter release and synapse plasticity;synaptic vesicle exocytosis, vesicles fusion with the presynapticmembrane, and endocytosis. Promotes cell survival by activatinganti-apoptotic proteins BCL2 and STAT3, and negatively regulatingof JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in responseto genotoxic and oxidative stresses enhances its stabilization bypreventing ubiquitin ligase-mediated proteasomal degradation, andinduces transactivation of p53/TP53 target genes, thus regulatingapoptosis. Phosphorylation of p35/CDK5R1 enhances itsstabilization by preventing calpain-mediated proteolysis producingp25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomaldegradation. During aberrant cell-cycle activity and DNA damage,p25/CDK5 activity elicits cell-cycle activity and double-strandDNA breaks that precedes neuronal death by deregulating HDAC1. DNAdamage triggered phosphorylation of huntingtin/HTT in nuclei ofneurons protects neurons against polyglutamine expansion as wellas DNA damage mediated toxicity. Phosphorylation of PXN reducesits interaction with PTK2/FAK1 in matrix-cell focal adhesions(MCFA) during oligodendrocytes (OLs) differentiation. Negativeregulator of Wnt/beta-catenin signaling pathway. Activator of theGAIT (IFN-gamma-activated inhibitor of translation) pathway, whichsuppresses expression of a post-transcriptional regulon ofproinflammatory genes in myeloid cells Isoform 1: Cytoplasm. Cell membrane;Peripheral membrane protein. Perikaryon. Cell projection,lamellipodium {ECO:0000250}. Cell projection, growth cone{ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane,postsynaptic density {ECO:0000250}. Note=In axonal growth conewith extension to the peripheral lamellipodia (By similarity).Under neurotoxic stress and neuronal injury conditions, CDK5R(p35) is cleaved by calpain to generate CDK5R1 (p25) in responseto increased intracellular calcium. The elevated level of p25,when in complex with CDK5, leads to its subcellular misallocationas well as its hyperactivation. Colocalizes with CTNND2 in thecell body of neuronal cells, and with CTNNB1 in the cell-cellcontacts and plasma membrane of undifferentiated anddifferentiated neuroblastoma cells. Reversibly attached to theplasma membrane in an inactive form when complexed todephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation releasesthis attachment and activates CDK5. {ECO:0000250}.Isoform 2: Nucleus. axon extension;axonogenesis;behavioral response to cocaine;calcium ion import;cell cycle;cell division;cell proliferation;cell-matrix adhesion;cellular response to amyloid-beta;central nervous system neuron development;cerebellar cortex formation;chemical synaptic transmission;corpus callosum development;cortical actin cytoskeleton organization;dendrite morphogenesis;excitatory postsynaptic potential;hippocampus development;histone phosphorylation;intracellular protein transport;layer formation in cerebral cortex;microtubule cytoskeleton organization;mitochondrion organization;motor neuron axon guidance;negative regulation of axon extension;negative regulation of cell cycle;negative regulation of neuron death;negative regulation of protein export from nucleus;negative regulation of protein ubiquitination;negative regulation of proteolysis;negative regulation of synaptic plasticity;negative regulation of transcription, DNA-templated;neuron apoptotic process;neuron differentiation;neuron migration;neuron projection development;nucleocytoplasmic transport;oligodendrocyte differentiation;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;phosphorylation;positive regulation of actin cytoskeleton reorganization;positive regulation of glial cell apoptotic process;positive regulation of neuron apoptotic process;positive regulation of protein binding;positive regulation of protein kinase activity;positive regulation of protein targeting to membrane;protein autophosphorylation;protein localization to synapse;protein phosphorylation;receptor catabolic process;receptor clustering;regulation of apoptotic process;regulation of cell cycle arrest;regulation of cell migration;regulation of dendritic spine morphogenesis;regulation of macroautophagy;regulation of protein localization to plasma membrane;regulation of synaptic plasticity;regulation of synaptic transmission, glutamatergic;regulation of synaptic vesicle recycling;response to wounding;rhythmic process;Schwann cell development;sensory perception of pain;serine phosphorylation of STAT protein;skeletal muscle tissue development;synapse assembly;synapse pruning;synaptic transmission, dopaminergic;synaptic transmission, glutamatergic;synaptic vesicle endocytosis;synaptic vesicle exocytosis;synaptic vesicle transport;visual learning acetylcholine receptor activator activity;ATP binding;cyclin-dependent protein serine/threonine kinase activity;ephrin receptor binding;ErbB-2 class receptor binding;ErbB-3 class receptor binding;Hsp90 protein binding;kinase activity;p53 binding;protein kinase activity;protein kinase binding;protein serine/threonine kinase activity;tau protein binding;tau-protein kinase activity;voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels axon;cell junction;cytoplasm;cytosol;dendrite;filopodium;glutamatergic synapse;growth cone;lamellipodium;membrane;microtubule;neuromuscular junction;neuron projection;neuronal cell body;nucleoplasm;nucleus;perikaryon;plasma membrane;postsynaptic density;postsynaptic membrane;presynapse;protein kinase 5 complex;Schaffer collateral - CA1 synapse Alzheimer disease;Axon guidance;Cocaine addiction Lissencephaly Dinaciclib Activated NTRK2 signals through CDK5;CRMPs in Sema3A signaling;DARPP-32 events;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models;Factors involved in megakaryocyte development and platelet production;Regulation of TP53 Activity through Phosphorylation Cell cycle kinase complex CDK5 1.33722460269928 -0.153970539569855 0.764358580112457 -0.153970539569855 0.412385314702988 1.55089223384857 1.86712872982025 1.23150718212128 0.236448854207993 -0.675345063209534 -1.37115085124969 -0.225305959582329 -0.816912055015564 -0.472628027200699 -1.08815479278564 -1.35844421386719 -0.70246434211731 -0.38159915804863 + Cluster -674 2 2 2 2.2 2.2 2.2 143.16 0 5.6147 120060000 2 3.07488282546414 0.000940275650842267 Q15047;Q15047-2;Q15047-3 Q15047;Q15047-2;Q15047-3 Histone-lysine N-methyltransferase SETDB1 SETDB1 1761 Histone methyltransferase that specificallytrimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylationrepresents a specific tag for epigenetic transcriptionalrepression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins tomethylated histones. Mainly functions in euchromatin regions,thereby playing a central role in the silencing of euchromaticgenes. H3 'Lys-9' trimethylation is coordinated with DNAmethylation. Probably forms a complex with MBD1 and ATF7IP thatrepresses transcription and couples DNA methylation and histone'Lys-9' trimethylation. Its activity is dependent on MBD1 and isheritably maintained through DNA replication by being recruited byCAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factorrecruited by KRAB zinc-finger proteins. Probably forms acorepressor complex required for activated KRAS-mediated promoterhypermethylation and transcriptional silencing of tumor suppressorgenes (TSGs) or other tumor-related genes in colorectal cancer(CRC) cells (PubMed:24623306). Also required to maintain atranscriptionally repressive state of genes in undifferentiatedembryonic stem cells (ESCs) (PubMed:24623306). Associates atpromoter regions of tumor suppressor genes (TSGs) leading to theirgene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complexmay play a role in recruiting ATRX to the 3'-exons of zinc-fingercoding genes with atypical chromatin signatures to establish ormaintain/protect H3K9me3 at these transcriptionally active regions(PubMed:27029610). Nucleus. Chromosome. Note=Associated withnon-pericentromeric regions of chromatin. Excluded from nucleoliand islands of condensed chromatin. positive regulation of methylation-dependent chromatin silencing;Ras protein signal transduction;response to ethanol;response to vitamin chromatin binding;DNA binding;histone-lysine N-methyltransferase activity;promoter-specific chromatin binding;zinc ion binding chromosome;cytosol;intracellular membrane-bounded organelle;nucleoplasm;nucleus;plasma membrane Lysine degradation;Signaling pathways regulating pluripotency of stem cells PKMTs methylate histone lysines MBD1-MCAF1-SETDB1 complex;Replication-coupled CAF-1-MBD1-ETDB1 complex;SETDB1-containing HMTase complex;SETDB1-DNMT3A complex;SETDB1-DNMT3B complex;ZNF304-corepressor complex 1.328240275383 0.404642432928085 0.0566411502659321 -0.30866926908493 0.650607824325562 1.12298619747162 1.74365925788879 1.56559658050537 0.836339831352234 -0.565274715423584 -1.13662731647491 -1.34215426445007 -0.264411240816116 -0.629176020622253 -0.494552880525589 -1.06993722915649 -1.06993722915649 -0.827973246574402 + Cluster -674 17 17 17 38.4 38.4 38.4 54.972 0 195.68 28516000000 74 3.49747738114287 0.000424849699398798 O76021;O76021-2 O76021 Ribosomal L1 domain-containing protein 1 RSL1D1 375 Regulates cellular senescence through inhibition of PTENtranslation. Acts as a pro-apoptotic regulator in response to DNAdamage. Nucleus, nucleolus{ECO:0000269|PubMed:11790298, ECO:0000269|PubMed:12429849,ECO:0000269|PubMed:18678645, ECO:0000269|PubMed:22419112}.Note=Colocalizes with ING1 in the nucleolus after UV stress.{ECO:0000269|PubMed:22419112}. maturation of LSU-rRNA;osteoblast differentiation;regulation of apoptotic process;regulation of cellular senescence;regulation of protein localization cadherin binding;mRNA 3'-UTR binding;mRNA 5'-UTR binding;RNA binding 90S preribosome;membrane;nucleolus Nop56p-associated pre-rRNA complex;Parvulin-associated pre-rRNP complex 1.58749854564667 0.24077969789505 0.467611521482468 0.107136018574238 0.406940072774887 1.42518067359924 1.57646679878235 1.45148801803589 0.0948057621717453 -0.355475783348083 -1.56531047821045 -0.202997341752052 -0.974089801311493 -0.645847678184509 -0.709429085254669 -0.719357013702393 -1.06574332714081 -1.11965644359589 + Cluster -674 2 2 2 4.7 4.7 4.7 93.23 0 28.678 1476300000 8 3.42452758124785 0.00049622641509434 Q05682;Q05682-3;Q05682-4;Q05682-6;Q05682-2;Q05682-5 Q05682;Q05682-3;Q05682-4;Q05682-6;Q05682-2;Q05682-5 Caldesmon CALD1 1521 Actin- and myosin-binding protein implicated in theregulation of actomyosin interactions in smooth muscle andnonmuscle cells (could act as a bridge between myosin and actinfilaments). Stimulates actin binding of tropomyosin whichincreases the stabilization of actin filament structure. In muscletissues, inhibits the actomyosin ATPase by binding to F-actin.This inhibition is attenuated by calcium-calmodulin and ispotentiated by tropomyosin. Interacts with actin, myosin, twomolecules of tropomyosin and with calmodulin. Also play anessential role during cellular mitosis and receptor capping.Involved in Schwann cell migration during peripheral nerveregeneration (By similarity). Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:P13505}. Cytoplasm, myofibril{ECO:0000250|UniProtKB:P13505}. Cytoplasm, cytoskeleton, stressfiber {ECO:0000250|UniProtKB:P13505}. Note=On thin filaments insmooth muscle and on stress fibers in fibroblasts (nonmuscle).{ECO:0000250|UniProtKB:P13505}. muscle contraction actin binding;cadherin binding;calmodulin binding;myosin binding;tropomyosin binding actin cap;actin cytoskeleton;cytoskeleton;cytosol;intracellular membrane-bounded organelle;myofibril;plasma membrane Vascular smooth muscle contraction Smooth Muscle Contraction 1.77039957046509 -0.120942369103432 0.352027982473373 0.842355310916901 0.401969730854034 1.50956249237061 1.17426693439484 1.33327305316925 0.0253285709768534 -1.20642018318176 -1.14421439170837 -0.70253998041153 -0.186509355902672 -0.565501093864441 -0.211940139532089 -0.730304300785065 -1.29397714138031 -1.24683463573456 + Cluster -674 4 4 4 29.5 29.5 29.5 18.237 0 10.367 731760000 7 3.46097460653726 0.000463937621832359 Q9Y3C6 Q9Y3C6 Peptidyl-prolyl cis-trans isomerase-like 1 PPIL1 3263 Involved in pre-mRNA splicing as component of thespliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346).PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds inoligopeptides (PubMed:16595688). Nucleus {ECO:0000269|PubMed:11991638,ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}. mRNA splicing, via spliceosome;protein folding;protein peptidyl-prolyl isomerization cyclosporin A binding;disordered domain specific binding;peptidyl-prolyl cis-trans isomerase activity catalytic step 2 spliceosome;nucleoplasm;nucleus;U2-type catalytic step 2 spliceosome Spliceosome mRNA Splicing - Major Pathway C complex spliceosome;Spliceosome 1.02143776416779 0.258214771747589 0.738508820533752 0.679806470870972 1.24133574962616 0.952803432941437 1.50627291202545 1.11212694644928 -0.95441746711731 -1.34937334060669 -1.67792570590973 -0.44052991271019 0.150715589523315 -0.278218895196915 0.0241756606847048 -0.728238940238953 -1.19702088832855 -1.05967259407043 + Cluster -674 11 11 11 44.4 44.4 44.4 32.463 0 212.12 38328000000 64 3.35019123142282 0.000555755395683453 Q9UKM9;Q9UKM9-2 Q9UKM9;Q9UKM9-2 RNA-binding protein Raly RALY 3150 RNA-binding protein that acts as a transcriptionalcofactor for cholesterol biosynthetic genes in the liver. Bindsthe lipid-responsive non-coding RNA LeXis and is required forLeXis-mediated effect on cholesterogenesis (By similarity). May bea heterogeneous nuclear ribonucleoprotein (hnRNP)(PubMed:9376072). Nucleus {ECO:0000250|UniProtKB:Q64012}. cholesterol homeostasis;mRNA splicing, via spliceosome;regulation of nucleic acid-templated transcription RNA binding;transcription coregulator activity catalytic step 2 spliceosome;nucleus C complex spliceosome;Large Drosha complex 0.220999300479889 -0.0481592640280724 1.01670455932617 0.661651134490967 1.53514385223389 1.2130047082901 1.43588936328888 1.29992294311523 -0.589169859886169 -1.3765252828598 -1.57471096515656 -0.588631153106689 0.0165379121899605 -0.246829688549042 -0.178550198674202 -1.02772080898285 -1.12420094013214 -0.645355641841888 + Cluster -674 16 16 16 19.2 19.2 19.2 97.394 0 123.66 12394000000 57 5.35745933844672 1.40845070422535E-05 Q9NTZ6 Q9NTZ6 RNA-binding protein 12 RBM12 2940 Nucleus {ECO:0000269|PubMed:9853615}. RNA binding nucleoplasm 0.607438385486603 0.789557814598083 0.918534159660339 0.425398737192154 1.18131363391876 1.17126905918121 1.40071535110474 1.00228977203369 -0.405208468437195 -1.20963108539581 -1.56495022773743 -0.62505704164505 0.215786293148994 -0.311551839113235 -0.0788662880659103 -0.636936604976654 -1.63853359222412 -1.2415679693222 + Cluster -674 1 1 1 5.4 5.4 5.4 31.608 0.00032723 2.0724 303290000 2 3.70331506215107 0.000297619047619048 P42574 P42574 Caspase-3;Caspase-3 subunit p17;Caspase-3 subunit p12 CASP3 1014 Involved in the activation cascade of caspasesresponsible for apoptosis execution. At the onset of apoptosis itproteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a'216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatoryelement binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain.Cleaves and activates caspase-6, -7 and -9. Involved in thecleavage of huntingtin. Triggers cell adhesion in sympatheticneurons through RET cleavage. Cytoplasm. apoptotic DNA fragmentation;apoptotic process;apoptotic signaling pathway;axonal fasciculation;B cell homeostasis;cell fate commitment;cellular response to DNA damage stimulus;cellular response to staurosporine;cytokine-mediated signaling pathway;erythrocyte differentiation;execution phase of apoptosis;extrinsic apoptotic signaling pathway in absence of ligand;glial cell apoptotic process;heart development;hippo signaling;hippocampus development;intrinsic apoptotic signaling pathway in response to osmotic stress;keratinocyte differentiation;learning or memory;leukocyte apoptotic process;luteolysis;negative regulation of activated T cell proliferation;negative regulation of apoptotic process;negative regulation of B cell proliferation;neuron apoptotic process;neuron differentiation;neurotrophin TRK receptor signaling pathway;platelet formation;positive regulation of amyloid-beta formation;positive regulation of neuron apoptotic process;protein processing;proteolysis;regulation of macroautophagy;regulation of protein stability;response to amino acid;response to cobalt ion;response to estradiol;response to glucocorticoid;response to glucose;response to hydrogen peroxide;response to hypoxia;response to lipopolysaccharide;response to nicotine;response to tumor necrosis factor;response to UV;response to X-ray;sensory perception of sound;striated muscle cell differentiation;T cell homeostasis;wound healing aspartic-type endopeptidase activity;cyclin-dependent protein serine/threonine kinase inhibitor activity;cysteine-type endopeptidase activator activity involved in apoptotic process;cysteine-type endopeptidase activity;cysteine-type endopeptidase activity involved in apoptotic process;cysteine-type endopeptidase activity involved in apoptotic signaling pathway;cysteine-type endopeptidase activity involved in execution phase of apoptosis;death receptor binding;peptidase activity;phospholipase A2 activator activity;protease binding;protein-containing complex binding cytoplasm;cytosol;death-inducing signaling complex;membrane raft;neuronal cell body;nucleoplasm;nucleus AGE-RAGE signaling pathway in diabetic complications;Alzheimer disease;Amoebiasis;Amyotrophic lateral sclerosis (ALS);Apoptosis;Apoptosis - multiple species;Colorectal cancer;Epithelial cell signaling in Helicobacter pylori infection;Epstein-Barr virus infection;Hepatitis B;Hepatitis C;Herpes simplex virus 1 infection;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Human papillomavirus infection;Huntington disease;IL-17 signaling pathway;Influenza A;Kaposi sarcoma-associated herpesvirus infection;Legionellosis;MAPK signaling pathway;Measles;MicroRNAs in cancer;Natural killer cell mediated cytotoxicity;Non-alcoholic fatty liver disease (NAFLD);p53 signaling pathway;Parkinson disease;Pathways in cancer;Pertussis;Platinum drug resistance;Proteoglycans in cancer;Serotonergic synapse;Small cell lung cancer;TNF signaling pathway;Toxoplasmosis;Tuberculosis;Viral carcinogenesis;Viral myocarditis Activation of caspases through apoptosome-mediated cleavage;Activation of DNA fragmentation factor;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Caspase activation via Dependence Receptors in the absence of ligand;Caspase-mediated cleavage of cytoskeletal proteins;Degradation of the extracellular matrix;NADE modulates death signalling;Other interleukin signaling;Signaling by Hippo;SMAC binds to IAPs;SMAC-mediated dissociation of IAP:caspase complexes;Stimulation of the cell death response by PAK-2p34 0.790759325027466 0.393622308969498 1.10584199428558 0.585572421550751 1.04476916790009 1.25138521194458 1.20680212974548 0.856494009494781 -0.199922427535057 -1.20572602748871 -1.74620807170868 -0.680617809295654 0.288544863462448 -0.033009871840477 0.0623424835503101 -1.35197699069977 -1.38296937942505 -0.985703110694885 + Cluster -674 9 9 9 32.6 32.6 32.6 65.536 0 123.81 6559900000 29 3.77332799541468 0.00025609756097561 Q9HCD5 Q9HCD5 Nuclear receptor coactivator 5 NCOA5 2856 Nuclear receptor coregulator that can have bothcoactivator and corepressor functions. Interacts with nuclearreceptors for steroids (ESR1 and ESR2) independently of thesteroid binding domain (AF-2) of the ESR receptors, and with theorphan nuclear receptor NR1D2. Involved in the coactivation ofnuclear steroid receptors (ER) as well as the corepression of MYCin response to 17-beta-estradiol (E2) Nucleus. glucose homeostasis;negative regulation of insulin receptor signaling pathway chromatin binding;RNA binding actin cytoskeleton;extracellular space;nucleus -0.371145874261856 0.410318613052368 1.42886519432068 1.36228621006012 0.911850333213806 1.61337435245514 0.755272746086121 0.715080916881561 -0.229192048311234 -0.846733510494232 -1.43036770820618 -0.846733510494232 0.332916110754013 -0.512307405471802 0.219538375735283 -1.46422123908997 -0.819997131824493 -1.22880434989929 + Cluster -674 3 3 3 15.7 15.7 15.7 22.348 0 5.0781 9017600000 11 3.91572196881855 0.000178861788617886 Q9NY12;Q9NY12-2 Q9NY12;Q9NY12-2 H/ACA ribonucleoprotein complex subunit 1 GAR1 3002 Required for ribosome biogenesis and telomeremaintenance. Part of the H/ACA small nucleolar ribonucleoprotein(H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA.This involves the isomerization of uridine such that the ribose issubsequently attached to C5, instead of the normal N1. Each rRNAcan contain up to 100 pseudouridine ("psi") residues, which mayserve to stabilize the conformation of rRNAs. May also be requiredfor correct processing or intranuclear trafficking of TERC, theRNA component of the telomerase reverse transcriptase (TERT)holoenzyme. Nucleus, nucleolus. Nucleus, Cajal body.Note=Also localized to Cajal bodies (coiled bodies). snoRNA guided rRNA pseudouridine synthesis;telomere maintenance via telomerase box H/ACA snoRNA binding;RNA binding;telomerase RNA binding box H/ACA scaRNP complex;box H/ACA snoRNP complex;box H/ACA telomerase RNP complex;fibrillar center;nuclear chromosome, telomeric region;nucleoplasm;nucleus;telomerase holoenzyme complex Ribosome biogenesis in eukaryotes rRNA modification in the nucleus and cytosol Telomerase holoenzyme 0.403988540172577 0.403988540172577 1.45431792736053 0.705213367938995 0.991042137145996 1.50294613838196 1.25974118709564 0.982790291309357 -0.217742100358009 -0.898263216018677 -1.37682259082794 -0.347764998674393 -0.00110684731043875 -0.380627930164337 -0.740835785865784 -1.10789883136749 -1.24901521205902 -1.38395059108734 + Cluster -674 29 29 29 28.5 28.5 28.5 191.48 0 323.31 53707000000 146 5.10376470894753 1.74418604651163E-05 Q02952;Q02952-3;Q02952-2 Q02952;Q02952-3;Q02952-2 A-kinase anchor protein 12 AKAP12 1501 Anchoring protein that mediates the subcellularcompartmentation of protein kinase A (PKA) and protein kinase C(PKC). Cytoplasm, cell cortex {ECO:0000305}.Cytoplasm, cytoskeleton {ECO:0000305}. Membrane {ECO:0000305};Lipid-anchor {ECO:0000305}. Note=May be part of the corticalcytoskeleton. adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway;modulation of chemical synaptic transmission;positive regulation of protein kinase A signaling;protein targeting;regulation of protein kinase A signaling;regulation of protein kinase C signaling adenylate cyclase binding;protein kinase A binding cell cortex;cytoplasm;cytoskeleton;cytosol;focal adhesion;plasma membrane;Schaffer collateral - CA1 synapse AKAP250-PKA-PDE4D complex 0.409606277942657 0.435172289609909 1.23085522651672 0.435172289609909 1.3665783405304 1.43619334697723 1.41677975654602 0.807081520557404 -0.256402611732483 -0.830616891384125 -1.60446488857269 -0.709094285964966 -0.0423098728060722 -0.186279192566872 -0.287267953157425 -1.14916229248047 -1.13042080402374 -1.34142017364502 + Cluster -674 9 9 7 31.9 31.9 28.4 31.279 0 46.732 14528000000 33 4.55252133147656 4.76190476190476E-05 P09012 P09012 U1 small nuclear ribonucleoprotein A SNRPA 566 Component of the spliceosomal U1 snRNP, which isessential for recognition of the pre-mRNA 5' splice-site and thesubsequent assembly of the spliceosome. U1 snRNP is the firstsnRNP to interact with pre-mRNA. This interaction is required forthe subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP.SNRPA binds stem loop II of U1 snRNA. In a snRNP-free form (SF-A)may be involved in coupled pre-mRNA splicing and polyadenylationprocess. May bind preferentially to the 5'-UGCAC-3' motif on RNAs Nucleus. mRNA splicing, via spliceosome;regulation of mRNA polyadenylation identical protein binding;RNA binding;snRNA stem-loop binding;U1 snRNA binding;U1 snRNP binding nucleoplasm;spliceosomal complex;U1 snRNP Spliceosome mRNA Splicing - Major Pathway CDC5L complex;SMN complex;snRNP-free U1A (SF-A) complex;Spliceosome 0.184255957603455 0.795330822467804 1.53260040283203 0.709841787815094 0.476859509944916 1.7210693359375 0.900939345359802 1.30217289924622 -0.30895209312439 -1.21361315250397 -1.10503220558167 -0.85649973154068 -0.0862383246421814 -0.217321559786797 -0.445513516664505 -0.786143243312836 -1.30187809467316 -1.30187809467316 + Cluster -674 29 29 17 49.3 49.3 29.7 75.491 0 323.31 166110000000 257 4.54645098962036 4.7244094488189E-05 P42166 P42166 Lamina-associated polypeptide 2, isoform alpha;Thymopoietin;Thymopentin TMPO 1006 May be involved in the structural organization of thenucleus and in the post-mitotic nuclear assembly. Plays animportant role, together with LMNA, in the nuclear anchorage ofRB1.TP and TP5 may play a role in T-cell development andfunction. TP5 is an immunomodulating pentapeptide. Nucleus. Chromosome. Note=Expresseddiffusely throughout the nucleus. regulation of transcription, DNA-templated cadherin binding;DNA binding;lamin binding chromatin;nuclear envelope;nucleus 0.83995795249939 0.295415997505188 1.41529357433319 0.540283143520355 0.82783442735672 1.49778020381927 1.16135251522064 1.19674384593964 -0.751878976821899 -0.911051511764526 -1.43945050239563 -0.878206074237823 -0.152361571788788 0.0205757915973663 -0.495354622602463 -0.735540211200714 -0.900914371013641 -1.53047943115234 + Cluster -674 4 4 4 8.5 8.5 8.5 107.19 0 19.741 1359400000 6 4.16008506038767 0.00010377358490566 Q96T37;Q96T37-4;Q96T37-2;Q96T37-3 Q96T37;Q96T37-4;Q96T37-2;Q96T37-3 Putative RNA-binding protein 15 RBM15 2550 probably regulatesalternative splicing via m6A regulation (PubMed:26575292).Required for placental vascular branching morphogenesis andembryonic development of the heart and spleen (By similarity).Acts as a regulator of thrombopoietin response in hematopoieticstem cells by regulating alternative splicing of MPL (Bysimilarity). May also function as an mRNA export factor,stimulating export and expression of RTE-containing mRNAs whichare present in many retrotransposons that require to be exportedprior to splicing (PubMed:17001072, PubMed:19786495). Highaffinity binding of pre-mRNA to RBM15 may allow targeting of themRNP to the export helicase DBP5 in a manner that is independentof splicing-mediated NXF1 deposition, resulting in export prior tosplicing (PubMed:17001072, PubMed:19786495). May be implicated inHOX gene regulation (PubMed:11344311);RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulatingdifferent processes, such as hematopoietic cell homeostasis,alternative splicing of mRNAs and X chromosome inactivationmediated by Xist RNA (PubMed:27602518). Associated component ofthe WMM complex, a complex that mediates N6-methyladenosine (m6A)methylation of RNAs, a modification that plays a role in theefficiency of mRNA splicing and RNA processing (By similarity).Plays a key role in m6A methylation, possibly by binding targetRNAs and recruiting the WMM complex (PubMed:27602518). Involved inrandom X inactivation mediated by Xist RNA: acts by binding XistRNA and recruiting the WMM complex, which mediates m6Amethylation, leading to target YTHDC1 reader on Xist RNA andpromoting transcription repression activity of Xist(PubMed:27602518). Required for the development of multipletissues, such as the maintenance of the homeostasis of long-termhematopoietic stem cells and for megakaryocyte (MK) and B-celldifferentiation (By similarity). Regulates megakaryocytedifferentiation by regulating alternative splicing of genesimportant for megakaryocyte differentiation Peripheral membrane protein{ECO:0000269|PubMed:19786495}. Note=Colocalizes at the nuclearpore with DBP5 and NXF1. {ECO:0000269|PubMed:19786495}.;Nucleus speckle{ECO:0000269|PubMed:19586903, ECO:0000269|PubMed:24100041}.Nucleus, nucleoplasm {ECO:0000269|PubMed:17001072,ECO:0000269|PubMed:19786495, ECO:0000269|PubMed:24100041}. Nucleusenvelope {ECO:0000269|PubMed:19586903}. Nucleus membrane{ECO:0000269|PubMed:19786495} branching involved in blood vessel morphogenesis;dosage compensation by inactivation of X chromosome;negative regulation of myeloid cell differentiation;placenta blood vessel development;positive regulation of transcription of Notch receptor target;regulation of alternative mRNA splicing, via spliceosome;regulation of megakaryocyte differentiation;RNA methylation;spleen development;thrombopoietin-mediated signaling pathway;ventricular septum morphogenesis;viral process mRNA binding;RNA binding nuclear membrane;nuclear speck;nucleoplasm;nucleus;RNA N6-methyladenosine methyltransferase complex Spliceosome 0.44763857126236 0.41211998462677 0.664355874061584 0.226641193032265 0.738083183765411 1.28904390335083 1.76007044315338 1.93655669689178 -0.08758844435215 -1.29672706127167 -1.4057948589325 -0.828626036643982 -0.404991537332535 -0.55750834941864 -0.492029547691345 -0.592658042907715 -0.788477659225464 -1.02010834217072 + Cluster -674 2 2 2 7.8 7.8 7.8 43.603 0 18.856 184180000 3 4.9406816212541 2.11640211640212E-05 Q53HC9 Q53HC9 Protein TSSC1 TSSC1 1909 Acts as a component of endosomal retrieval machinerythat is involved in protein transport from early endosomes toeither recycling endosomes or the trans-Golgi network. Mediatesthe recruitment of Golgi-associated retrograde protein (GARP)complex to the trans-Golgi network and controls early endosome-to-Golgi transport of internalized protein. Promotes the recycling ofinternalized transferrin receptor (TFRC) to the plasma membranethrough interaction with endosome-associated recycling protein(EARP) complex. Golgi apparatus, trans-Golgi network{ECO:0000269|PubMed:27440922}. protein ubiquitination Golgi apparatus 0.807749390602112 0.144265860319138 0.531341671943665 0.389038354158401 1.21502339839935 1.45493268966675 1.39854156970978 1.42319977283478 0.144265860319138 -0.793719172477722 -1.56989920139313 -0.603358209133148 -0.315550118684769 -0.378356158733368 -0.615821659564972 -0.383818089962006 -1.33807897567749 -1.50975692272186 + Cluster -674 4 4 4 8.9 8.9 8.9 58.599 0 38.806 2324300000 11 4.45925042829724 6.36704119850187E-05 P07101;P07101-3;P07101-4;P07101-2;P07101-6;P07101-5 P07101;P07101-3;P07101-4;P07101-2;P07101-6;P07101-5 Tyrosine 3-monooxygenase TH 528 Plays an important role in the physiology of adrenergicneurons. aminergic neurotransmitter loading into synaptic vesicle;anatomical structure morphogenesis;animal organ morphogenesis;catecholamine biosynthetic process;cellular response to alkaloid;cellular response to glucose stimulus;cellular response to growth factor stimulus;cellular response to manganese ion;cellular response to nicotine;cerebral cortex development;circadian sleep/wake cycle;dopamine biosynthetic process;dopamine biosynthetic process from tyrosine;eating behavior;embryonic camera-type eye morphogenesis;epinephrine biosynthetic process;eye photoreceptor cell development;fatty acid metabolic process;glycoside metabolic process;heart development;heart morphogenesis;isoquinoline alkaloid metabolic process;learning;locomotory behavior;mating behavior;memory;multicellular organism aging;neurotransmitter biosynthetic process;norepinephrine biosynthetic process;phthalate metabolic process;phytoalexin metabolic process;pigmentation;regulation of heart contraction;response to activity;response to amphetamine;response to corticosterone;response to electrical stimulus;response to estradiol;response to ethanol;response to ether;response to herbicide;response to hypoxia;response to immobilization stress;response to isolation stress;response to light stimulus;response to lipopolysaccharide;response to nutrient levels;response to peptide hormone;response to pyrethroid;response to salt stress;response to water deprivation;response to zinc ion;sensory perception of sound;social behavior;sphingolipid metabolic process;synaptic transmission, dopaminergic;terpene metabolic process;visual perception amino acid binding;dopamine binding;enzyme binding;ferric iron binding;ferrous iron binding;oxygen binding;protein domain specific binding;tetrahydrobiopterin binding;tyrosine 3-monooxygenase activity axon;cytoplasm;cytoplasmic side of plasma membrane;cytoplasmic vesicle;cytosol;dendrite;melanosome membrane;mitochondrion;neuron projection;nucleus;perikaryon;smooth endoplasmic reticulum;synaptic vesicle;terminal bouton Alcoholism;Amphetamine addiction;Cocaine addiction;Dopaminergic synapse;Folate biosynthesis;Metabolic pathways;Parkinson disease;Prolactin signaling pathway;Tyrosine metabolism Primary dystonia Metirosine Catecholamine biosynthesis 0.210489481687546 0.41101261973381 0.727878034114838 0.259995341300964 0.829612910747528 1.44831740856171 1.75297737121582 1.48808968067169 -0.0913495868444443 -1.29874777793884 -1.73587954044342 -0.967931389808655 0.230068385601044 -0.222829878330231 -0.694036245346069 -0.601029455661774 -0.873318612575531 -0.873318612575531 + Cluster -674 8 8 8 31.7 31.7 31.7 37.551 0 146.31 10235000000 35 4.83770298088354 2.3696682464455E-05 Q9NZL9;Q9NZL9-2;Q9NZL9-3;Q9NZL9-4;Q9NZL9-5 Q9NZL9;Q9NZL9-2;Q9NZL9-3;Q9NZL9-4 Methionine adenosyltransferase 2 subunit beta MAT2B 3027 Regulatory subunit of S-adenosylmethionine synthetase 2,an enzyme that catalyzes the formation of S-adenosylmethioninefrom methionine and ATP. Regulates MAT2A catalytic activity bychanging its kinetic properties, increasing its affinity for L-methionine (PubMed:10644686, PubMed:23189196, PubMed:25075345).Can bind NADP (in vitro) (PubMed:23189196, PubMed:23425511) one-carbon metabolic process;S-adenosylmethionine biosynthetic process enzyme binding;methionine adenosyltransferase regulator activity cytosol;extracellular exosome;intracellular;methionine adenosyltransferase complex;nucleus Biosynthesis of amino acids;Cysteine and methionine metabolism;Metabolic pathways Methylation;Ub-specific processing proteases Methionine adenosyltransferase alpha2 beta-v1 0.544834792613983 -0.150589480996132 0.956198573112488 0.467458516359329 0.718314468860626 1.75408744812012 1.60545551776886 1.40403664112091 -0.39592170715332 -1.19041609764099 -1.80766224861145 -0.708536088466644 -0.281919777393341 -0.456023067235947 -0.319026529788971 -0.794607758522034 -0.934072136878967 -0.411610782146454 + Cluster -674 2 2 2 10.4 10.4 10.4 24.669 0 13.135 912640000 4 5.05327316383847 1.70454545454545E-05 O75608;O75608-2 O75608;O75608-2 Acyl-protein thioesterase 1 LYPLA1 348 Hydrolyzes fatty acids from S-acylated cysteine residuesin proteins such as trimeric G alpha proteins or HRAS. Hasdepalmitoylating activity toward KCNMA1. Has low lysophospholipaseactivity. Cytoplasm {ECO:0000250}. fatty acid metabolic process;negative regulation of Golgi to plasma membrane protein transport;protein depalmitoylation;regulation of nitric-oxide synthase activity carboxylic ester hydrolase activity;lipase activity;lysophospholipase activity;palmitoyl-(protein) hydrolase activity cytoplasm;cytosol;extracellular exosome Choline metabolism in cancer;Glycerophospholipid metabolism eNOS activation 0.556143999099731 0.0777596160769463 0.878572821617126 0.36558410525322 0.711376667022705 2.02018046379089 1.64553940296173 1.06906318664551 -0.256639540195465 -1.16775131225586 -1.51767301559448 -0.939570188522339 0.0501901917159557 -0.348641902208328 -0.811364710330963 -0.484709441661835 -0.906522989273071 -0.941537439823151 + Cluster -674 6 4 4 3.1 2.2 2.2 271.32 0 26.581 832450000 8 4.67852321648249 3.38983050847458E-05 O15020;O15020-2 O15020;O15020-2 Spectrin beta chain, non-erythrocytic 2 SPTBN2 154 Probably plays an important role in neuronal membraneskeleton. Cytoplasm, cytoskeleton. Cytoplasm, cellcortex. actin filament capping;adult behavior;antigen processing and presentation of exogenous peptide antigen via MHC class II;axon guidance;cerebellar Purkinje cell layer morphogenesis;endoplasmic reticulum to Golgi vesicle-mediated transport;MAPK cascade;multicellular organism growth;postsynapse organization;synapse assembly;vesicle-mediated transport actin binding;cadherin binding;phospholipid binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;structural constituent of synapse apical plasma membrane;cell junction;cytosol;extracellular space;glutamatergic synapse;neuronal cell body;parallel fiber to Purkinje cell synapse;postsynaptic spectrin-associated cytoskeleton;presynapse;spectrin Autosomal recessive spinocerebellar ataxias;Spinocerebellar ataxia (SCA) COPI-mediated anterograde transport;Interaction between L1 and Ankyrins;MHC class II antigen presentation;NCAM signaling for neurite out-growth;RAF/MAP kinase cascade 0.472551226615906 0.427128165960312 0.750563681125641 0.300856411457062 0.382194101810455 1.75668299198151 1.71450638771057 1.13810622692108 -0.131083682179451 -1.13637435436249 -1.98910939693451 -0.94881409406662 0.15834566950798 -0.241775214672089 -0.451578378677368 -0.270341217517853 -0.763861894607544 -1.16799664497375 + Cluster -674 3 3 3 12.8 12.8 12.8 38.169 0 15.822 3836000000 11 4.00055402614472 0.000138328530259366 O75436;O75436-2 O75436;O75436-2 Vacuolar protein sorting-associated protein 26A VPS26A 332 Acts as component of the retromer cargo-selectivecomplex (CSC). The CSC is believed to be the core functionalcomponent of retromer or respective retromer complex variantsacting to prevent missorting of selected transmembrane cargoproteins into the lysosomal degradation pathway. The recruitmentof the CSC to the endosomal membrane involves RAB7A and SNX3. TheSNX-BAR retromer mediates retrograde transport of cargo proteinsfrom endosomes to the trans-Golgi network (TGN) and is involved inendosome-to-plasma membrane transport for cargo protein recycling.The SNX3-retromer mediates the retrograde endosome-to-TGNtransport of WLS distinct from the SNX-BAR retromer pathway. TheSNX27-retromer is believed to be involved in endosome-to-plasmamembrane trafficking and recycling of a broad spectrum of cargoproteins (Probable). The CSC seems to act as recruitment hub forother proteins, such as the WASH complex and TBC1D5 (Probable).Required for retrograde transport of lysosomal enzyme receptorIGF2R (PubMed:15078902, PubMed:15078903). Required to regulatetranscytosis of the polymeric immunoglobulin receptor (pIgR-pIgA)(PubMed:15247922). Required for the endosomal localization ofWASHC2A (indicative for the WASH complex) (PubMed:22070227).Required for the endosomal localization of TBC1D5(PubMed:20923837). Mediates retromer cargo recognition of SORL1and is involved in trafficking of SORL1 implicated in sorting andprocessing of APP (PubMed:22279231). Involved in retromer-independent lysosomal sorting of F2R (PubMed:16407403). Involvedin recycling of ADRB2 (PubMed:21602791). Enhances the affinity ofSNX27 for PDZ-binding motifs in cargo proteins (By similarity) Peripheralmembrane protein {ECO:0000250|UniProtKB:P40336}. Early endosome{ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:16190980,ECO:0000269|PubMed:16732284, ECO:0000269|PubMed:20682791}.Note=Localizes to tubular profiles adjacent to endosomes(PubMed:15078903). Predominantly found in early not late endosomes(By similarity). {ECO:0000250|UniProtKB:P40336}.;Cytoplasm {ECO:0000269|PubMed:15078903}.Endosome membrane {ECO:0000269|PubMed:22431521} intracellular protein transport;regulation of macroautophagy;retrograde transport, endosome to Golgi;retrograde transport, endosome to plasma membrane;Wnt signaling pathway protein transporter activity cytosol;early endosome;endosome;endosome membrane;lysosome;retromer complex;retromer, cargo-selective complex;tubular endosome;vesicle Endocytosis WNT ligand biogenesis and trafficking Retromer complex (SNX1, SNX2, VPS35, VPS29, VPS26A);VPS35-VPS29-VPS26A complex 0.31078115105629 0.547426402568817 0.69404536485672 0.297888875007629 1.40384006500244 1.38340842723846 1.50494825839996 0.965652525424957 0.0483748875558376 -0.733804523944855 -1.88521945476532 -0.54140830039978 0.107561677694321 0.0224101338535547 -0.823572218418121 -0.989361047744751 -0.825366914272308 -1.48760533332825 + Cluster -674 3 3 3 7.9 7.9 7.9 87.977 0 146.9 1685400000 9 3.78818244691108 0.000253101736972705 Q9BVJ6;Q9BVJ6-3;Q9BVJ6-2 Q9BVJ6;Q9BVJ6-3;Q9BVJ6-2 U3 small nucleolar RNA-associated protein 14 homolog A UTP14A 2685 May be required for ribosome biogenesis. Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. rRNA processing RNA binding cytosol;nucleolus;nucleoplasm;small-subunit processome Ribosome biogenesis in eukaryotes Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol 0.677130460739136 -0.162921339273453 0.957823038101196 0.905895948410034 1.01110506057739 1.46700251102448 1.75754618644714 0.749202966690063 -0.19465246796608 -0.950602889060974 -1.60144555568695 -0.762659907341003 0.0871797055006027 -0.123618304729462 -0.622566819190979 -1.10291481018066 -1.20429992675781 -0.887203931808472 + Cluster -674 1 1 1 2.9 2.9 2.9 51.4 0 8.0022 391990000 3 4.8009922243994 2.75229357798165E-05 Q6YP21;Q6YP21-3 Q6YP21;Q6YP21-3 Kynurenine--oxoglutarate transaminase 3 CCBL2 2028 Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA).May catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of theC-S or C-Se bond (By similarity). Has transaminase activitytowards L-kynurenine, tryptophan, phenylalanine, serine, cysteine,methionine, histidine, glutamine and asparagine with glyoxylate asan amino group acceptor (in vitro). Has lower activity with 2-oxoglutarate as amino group acceptor (in vitro) (By similarity) 2-oxoglutarate metabolic process;biosynthetic process;cellular amino acid metabolic process;kynurenine metabolic process cysteine-S-conjugate beta-lyase activity;kynurenine-glyoxylate transaminase activity;kynurenine-oxoglutarate transaminase activity;protein homodimerization activity;pyridoxal phosphate binding;RNA binding cytoplasm;mitochondrion Chemical carcinogenesis;Cysteine and methionine metabolism;Metabolic pathways;Selenocompound metabolism;Tryptophan metabolism Tryptophan catabolism 0.181766048073769 0.581059873104095 0.329314589500427 0.438295602798462 0.961001515388489 1.55837690830231 1.38378608226776 1.32130718231201 0.245810389518738 -1.07031738758087 -2.13396596908569 -0.526918888092041 0.184808790683746 -0.0673865675926208 -0.649724304676056 -0.454519212245941 -1.0876247882843 -1.19506978988647 + Cluster -674 3 3 3 13.8 13.8 13.8 35.138 0 53.109 3382900000 8 3.76774463115935 0.000255474452554745 Q5TBB1;Q5TBB1-2 Q5TBB1;Q5TBB1-2 Ribonuclease H2 subunit B RNASEH2B 1942 Non catalytic subunit of RNase H2, an endonuclease thatspecifically degrades the RNA of RNA:DNA hybrids. Participates inDNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication.Mediates the excision of single ribonucleotides from DNA:RNAduplexes. Nucleus {ECO:0000305}. in utero embryonic development;negative regulation of gene expression;positive regulation of fibroblast proliferation;regulation of DNA damage checkpoint;regulation of G2/M transition of mitotic cell cycle;ribonucleotide metabolic process;RNA catabolic process RNA-DNA hybrid ribonuclease activity nucleoplasm;nucleus;ribonuclease H2 complex DNA replication Aicardi-Goutieres syndrome 0.473360389471054 0.0834880471229553 0.921673357486725 0.706111073493958 1.07347178459167 1.39125621318817 1.84140872955322 1.08309495449066 -0.301750898361206 -0.89606761932373 -1.74151921272278 -0.709685444831848 -0.0900402143597603 -0.476474851369858 -0.4019495844841 -0.993208050727844 -0.862507104873657 -1.10066151618958 + Cluster -674 20 20 20 28.8 28.8 28.8 85.104 0 253.43 31403000000 100 5.39689489032314 7.46268656716418E-06 Q1KMD3 Q1KMD3 Heterogeneous nuclear ribonucleoprotein U-like protein 2 HNRNPUL2 1875 Nucleus {ECO:0000250|UniProtKB:Q00PI9}. RNA binding membrane;nucleoplasm;nucleus 0.265073359012604 0.29631370306015 1.0926855802536 0.600080728530884 0.916371047496796 1.53188240528107 1.58309996128082 1.28614699840546 -0.00471023004502058 -0.713874757289886 -1.63346338272095 -0.40340992808342 -0.180646777153015 -0.650744676589966 -0.819004416465759 -0.769967794418335 -1.12446773052216 -1.27136421203613 + Cluster -674 4 4 4 13.6 13.6 13.6 47.535 0 60.6 4775600000 18 5.58786071010712 8.40336134453782E-06 Q13363;Q13363-2 Q13363;Q13363-2 C-terminal-binding protein 1 CTBP1 1624 Corepressor targeting diverse transcription regulatorssuch as GLIS2 or BCL6. Has dehydrogenase activity. Involved incontrolling the equilibrium between tubular and stacked structuresin the Golgi complex. Functions in brown adipose tissue (BAT)differentiation. Cytoplasm {ECO:0000269|PubMed:12679040}.Nucleus {ECO:0000269|PubMed:12679040}. chromatin organization involved in negative regulation of transcription;negative regulation of cell proliferation;negative regulation of histone acetylation;negative regulation of histone H4 acetylation;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;positive regulation of histone deacetylation;protein phosphorylation;regulation of cell cycle;viral genome replication;white fat cell differentiation DNA-binding transcription factor activity;identical protein binding;NAD binding;oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor;protein C-terminus binding;protein domain specific binding;repressing transcription factor binding;transcription corepressor activity;transcription factor binding GABA-ergic synapse;glutamatergic synapse;nucleoplasm;nucleus;presynaptic active zone cytoplasmic component;transcription factor complex;transcriptional repressor complex Chronic myeloid leukemia;Notch signaling pathway;Pathways in cancer;Wnt signaling pathway 4p deletion syndrome Deactivation of the beta-catenin transactivating complex;Repression of WNT target genes;SUMOylation of transcription cofactors;TCF7L2 mutants don't bind CTBP BRCA1-CtIP-CtBP complex;CtBP complex;CtBP core complex;LSD1 complex;SHARP-CtBP complex;SHARP-CtBP1-CtIP complex;SHARP-CtBP1-CtIP-RBP-Jkappa corepressor complex -0.0719453096389771 0.0101902475580573 1.00302493572235 0.464246422052383 1.2095844745636 1.52067363262177 1.50356936454773 1.38883817195892 0.11521390080452 -0.511992514133453 -1.82893705368042 -0.842859923839569 -0.62762463092804 -0.139519676566124 -0.462132811546326 -0.639584541320801 -0.687918424606323 -1.40282618999481 + Cluster -674 3 3 3 7.7 7.7 7.7 48.948 0 23.316 1817600000 8 5.20868394484906 1.24223602484472E-05 Q06265;Q06265-2;Q06265-3;Q06265-4 Q06265;Q06265-2;Q06265-3;Q06265-4 Exosome complex component RRP45 EXOSC9 1526 Non-catalytic component of the RNA exosome complex whichhas 3'->5' exoribonuclease activity and participates in amultitude of cellular RNA processing and degradation events. Inthe nucleus, the RNA exosome complex is involved in propermaturation of stable RNA species such as rRNA, snRNA and snoRNA,in the elimination of RNA processing by-products and non-coding'pervasive' transcripts, such as antisense RNA species andpromoter-upstream transcripts (PROMPTs), and of mRNAs withprocessing defects, thereby limiting or excluding their export tothe cytoplasm. The RNA exosome may be involved in Ig class switchrecombination (CSR) and/or Ig variable region somatichypermutation (SHM) by targeting AICDA deamination activity totranscribed dsDNA substrates. In the cytoplasm, the RNA exosomecomplex is involved in general mRNA turnover and specificallydegrades inherently unstable mRNAs containing AU-rich elements(AREs) within their 3' untranslated regions, and in RNAsurveillance pathways, preventing translation of aberrant mRNAs.It seems to be involved in degradation of histone mRNA. Thecatalytic inactive RNA exosome core complex of 9 subunits (Exo-9)is proposed to play a pivotal role in the binding and presentationof RNA for ribonucleolysis, and to serve as a scaffold for theassociation with catalytic subunits and accessory proteins orcomplexes. EXOSC9 binds to ARE-containing RNAs Cytoplasm {ECO:0000269|PubMed:11782436}.Nucleus {ECO:0000269|PubMed:24105744}. Nucleus, nucleolus{ECO:0000269|PubMed:24105744}. Nucleus, nucleoplasm{ECO:0000269|PubMed:24105744}. Note=Colocalizes with SETX innuclear foci upon induction of transcription-related DNA damage atthe S phase (PubMed:24105744). {ECO:0000269|PubMed:24105744}.Isoform 1: Nucleus, nucleolus.Isoform 2: Nucleus, nucleolus.Isoform 3: Nucleus. Note=Excluded from thenucleolus. exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);immune response;nuclear mRNA surveillance;nuclear polyadenylation-dependent mRNA catabolic process;nuclear polyadenylation-dependent rRNA catabolic process;nuclear polyadenylation-dependent tRNA catabolic process;nuclear-transcribed mRNA catabolic process;nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5';positive regulation of cell growth;positive regulation of transcription by RNA polymerase II;regulation of mRNA stability;rRNA catabolic process;rRNA processing;U1 snRNA 3'-end processing;U4 snRNA 3'-end processing;U5 snRNA 3'-end processing 3'-5'-exoribonuclease activity;AU-rich element binding;RNA binding;RNA polymerase II activating transcription factor binding cytoplasm;cytoplasmic exosome (RNase complex);cytosol;exosome (RNase complex);extracellular exosome;nuclear chromosome;nuclear exosome (RNase complex);nucleolus;nucleoplasm;nucleus RNA degradation ATF4 activates genes;Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;KSRP (KHSRP) binds and destabilizes mRNA;Major pathway of rRNA processing in the nucleolus and cytosol;mRNA decay by 3' to 5' exoribonuclease;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA Exosome 0.383511930704117 0.246171176433563 0.864487886428833 0.509450316429138 1.04202020168304 1.59139668941498 1.8228235244751 1.00149810314178 -0.115255758166313 -1.08060824871063 -1.74908840656281 -0.526023089885712 -0.253864943981171 -0.253864943981171 -0.552248418331146 -0.902725100517273 -0.914174616336823 -1.11350631713867 + Cluster -674 11 11 11 52.6 52.6 52.6 29.841 0 47.111 13648000000 43 5.10045333130577 1.73410404624277E-05 O75937 O75937 DnaJ homolog subfamily C member 8 DNAJC8 368 Suppresses polyglutamine (polyQ) aggregation of ATXN3 inneuronal cells (PubMed:27133716). Nucleus {ECO:0000269|PubMed:27133716}. mRNA splicing, via spliceosome Hsp70 protein binding cytosol;intercellular bridge;nucleoplasm;nucleus mRNA Splicing - Major Pathway 17S U2 snRNP;Spliceosome 0.873503088951111 0.833439826965332 0.332085907459259 0.134854793548584 1.04903602600098 1.20041620731354 1.73466074466705 1.20041620731354 -0.231581151485443 -0.637157022953033 -2.06541609764099 -0.568999946117401 -0.497228354215622 -0.0234277937561274 -0.343258380889893 -1.04089748859406 -0.870634257793427 -1.0798122882843 + Cluster -674 3 3 3 13.8 13.8 13.8 30.518 0 8.1384 1628800000 9 3.34391343465173 0.000557932263814617 P27707 P27707 Deoxycytidine kinase DCK 830 Required for the phosphorylation of thedeoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) anddeoxyadenosine (dA). Has broad substrate specificity, and does notdisplay selectivity based on the chirality of the substrate. It isalso an essential enzyme for the phosphorylation of numerousnucleoside analogs widely employed as antiviral andchemotherapeutic agents. Nucleus {ECO:0000269|PubMed:9342341}. purine-containing compound salvage;pyrimidine nucleoside salvage;pyrimidine nucleotide metabolic process ATP binding;deoxycytidine kinase activity;deoxynucleoside kinase activity;drug binding;nucleoside kinase activity;protein homodimerization activity cytoplasm;cytosol;nucleus Metabolic pathways;Purine metabolism;Pyrimidine metabolism Purine salvage;Pyrimidine salvage 0.692319512367249 0.39732551574707 0.692319512367249 0.644189953804016 0.787570536136627 1.60128223896027 1.68555104732513 1.16872727870941 0.0597312897443771 -1.01167440414429 -1.45311915874481 -0.789875268936157 -0.332285523414612 -0.471679478883743 -0.396972507238388 -0.689767003059387 -1.21839785575867 -1.36524569988251 + Cluster -674 31 22 22 46.1 35.9 35.9 80.272 0 323.31 97222000000 172 5.38834488827381 7.35294117647059E-06 Q92841;Q92841-3;Q92841-1;Q92841-2 Q92841;Q92841-3;Q92841-1;Q92841-2 Probable ATP-dependent RNA helicase DDX17 DDX17 2357 this activity requires acetylation on lysineresidues (PubMed:17226766, PubMed:20663877, PubMed:19995069). Mayalso coactivate MDM2 transcription through a TP53-independentpathway (PubMed:17226766). Coactivates MMP7 transcription(PubMed:17226766). Along with CTNNB1, coactivates MYC, JUN, FOSL1and cyclin D1/CCND1 transcription (PubMed:17699760). Alone or incombination with DDX5 and/or SRA1 non-coding RNA, plays a criticalrole in promoting the assembly of proteins required for theformation of the transcription initiation complex and chromatinremodeling leading to coactivation of MYOD1-dependenttranscription. This helicase-independent activity is required forskeletal muscle cells to properly differentiate into myotubes(PubMed:17011493, PubMed:24910439). During epithelial-to-mesenchymal transition, coregulates SMAD-dependent transcriptionalactivity, directly controlling key effectors of differentiation,including miRNAs which in turn directly repress its expression(PubMed:24910439). Plays a role in estrogen and testosteronesignaling pathway at several levels. Mediates the use ofalternative promoters in estrogen-responsive genes and regulatestranscription and splicing of a large number of steroid hormonetarget genes (PubMed:24275493, PubMed:20406972, PubMed:20663877,PubMed:19995069). Contrary to splicing regulation activity,transcriptional coregulation of the estrogen receptor ESR1 ishelicase-independent (PubMed:19718048, PubMed:24275493). Plays arole in innate immunity. Specifically restricts bunyavirusinfection, including Rift Valley fever virus (RVFV) or La Crossevirus (LACV), but not vesicular stomatitis virus (VSV), in aninterferon- and DROSHA-independent manner (PubMed:25126784). Bindsto RVFV RNA, likely via structured viral RNA elements(PubMed:25126784). Promotes mRNA degradation mediated by theantiviral zinc-finger protein ZC3HAV1, in an ATPase-dependentmanner (PubMed:18334637).;As an RNA helicase, unwinds RNA and alters RNAstructures through ATP binding and hydrolysis. Involved inmultiple cellular processes, including pre-mRNA splicing,alternative splicing, ribosomal RNA processing and miRNAprocessing, as well as transcription regulation. Regulates thealternative splicing of exons exhibiting specific features(PubMed:12138182, PubMed:23022728, PubMed:24910439,PubMed:22266867). For instance, promotes the inclusion of AC-richalternative exons in CD44 transcripts (PubMed:12138182). Thisfunction requires the RNA helicase activity (PubMed:12138182,PubMed:23022728, PubMed:24910439, PubMed:22266867). Affects NFAT5and histone macro-H2A.1/H2AFY alternative splicing in a CDK9-dependent manner (PubMed:26209609, PubMed:22266867). In NFAT5,promotes the introduction of alternative exon 4, which contains 2stop codons and may target NFAT5 exon 4-containing transcripts tononsense-mediated mRNA decay, leading to the down-regulation ofNFAT5 protein (PubMed:22266867). Affects splicing of mediators ofsteroid hormone signaling pathway, including kinases thatphosphorylates ESR1, such as CDK2, MAPK1 and GSK3B, andtranscriptional regulators, such as CREBBP, MED1, NCOR1 and NCOR2.By affecting GSK3B splicing, participates in ESR1 and ARstabilization (PubMed:24275493). In myoblasts and epithelialcells, cooperates with HNRNPH1 to control the splicing of specificsubsets of exons (PubMed:24910439). In addition to binding maturemRNAs, also interacts with certain pri-microRNAs, includingMIR663/miR-663a, MIR99B/miR-99b, and MIR6087/miR-6087(PubMed:25126784). Binds pri-microRNAs on the 3' segment flankingthe stem loop via the 5'-[ACG]CAUC[ACU]-3' consensus sequence(PubMed:24581491). Required for the production of subsets ofmicroRNAs, including MIR21 and MIR125B1 (PubMed:24581491,PubMed:27478153). May be involved not only in microRNA primarytranscript processing, but also stabilization (By similarity).Participates in MYC down-regulation at high cell density throughthe production of MYC-targeting microRNAs (PubMed:24581491). Alongwith DDX5, may be involved in the processing of the 32Sintermediate into the mature 28S ribosomal RNA (PubMed:17485482).Promoter-specific transcription regulator, functioning as acoactivator or corepressor depending on the context of thepromoter and the transcriptional complex in which it exists(PubMed:15298701). Enhances NFAT5 transcriptional activity(PubMed:22266867). Synergizes with TP53 in the activation of theMDM2 promoter Nucleus {ECO:0000269|PubMed:12138182,ECO:0000269|PubMed:12595555, ECO:0000269|PubMed:17226766,ECO:0000269|PubMed:17699760, ECO:0000269|PubMed:19995069,ECO:0000269|PubMed:22002106, ECO:0000269|PubMed:24581491,ECO:0000269|PubMed:25126784}. Nucleus, nucleolus{ECO:0000269|PubMed:17226766, ECO:0000269|PubMed:22002106}.Cytoplasm, cytosol {ECO:0000269|PubMed:25126784}. Note=In thecourse of bunyavirus infection, relocalizes from the nucleus tothe cytosol where it binds viral RNA to antagonize replication.{ECO:0000269|PubMed:25126784}. alternative mRNA splicing, via spliceosome;androgen receptor signaling pathway;defense response to virus;epithelial to mesenchymal transition;gene silencing by RNA;intracellular estrogen receptor signaling pathway;miRNA metabolic process;myoblast differentiation;positive regulation of transcription by RNA polymerase II;regulation of alternative mRNA splicing, via spliceosome;regulation of skeletal muscle cell differentiation;regulation of transcription by RNA polymerase II;RNA processing;rRNA processing ATP binding;RNA binding;RNA helicase activity;RNA-dependent ATPase activity;transcription coactivator activity cytosol;membrane;nuclear speck;nucleolus;nucleoplasm;nucleus SUMOylation of transcription cofactors DGCR8 multiprotein complex;Large Drosha complex;Spliceosome 0.513871133327484 0.417739659547806 0.997408330440521 0.774158358573914 0.807189345359802 1.84523129463196 1.20581436157227 1.26647114753723 -0.257033973932266 -1.31780529022217 -1.25093472003937 -0.55915504693985 -0.203090608119965 -0.442492723464966 -0.544038534164429 -0.811602354049683 -1.22086524963379 -1.22086524963379 + Cluster -674 16 16 15 15.3 15.3 14.3 164.67 0 169.77 9996400000 37 5.52010165346402 8.13008130081301E-06 Q9NTI5;Q9NTI5-2;Q9NTI5-3;Q9NTI5-5 Q9NTI5;Q9NTI5-2 Sister chromatid cohesion protein PDS5 homolog B PDS5B 2936 Regulator of sister chromatid cohesion in mitosis whichmay stabilize cohesin complex association with chromatin. Maycouple sister chromatid cohesion during mitosis to DNAreplication. Cohesion ensures that chromosome partitioning isaccurate in both meiotic and mitotic cells and plays an importantrole in DNA repair. Plays a role in androgen-induced proliferativearrest in prostate cells. Nucleus {ECO:0000250|UniProtKB:Q6TRW4}. cell division;cell proliferation;DNA repair;enteric nervous system development;lens development in camera-type eye;mitotic sister chromatid cohesion;negative regulation of cell proliferation;neuroblast migration;regulation of cell proliferation ATP binding;DNA binding chromatin;chromosome;chromosome, centromeric region;cytosol;nucleoplasm;nucleus Cohesin Loading onto Chromatin;Establishment of Sister Chromatid Cohesion;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids Sororin-cohesin complex 0.576353251934052 0.251712203025818 0.731121838092804 0.251712203025818 1.13907182216644 1.5944629907608 1.81082785129547 1.29990839958191 -0.175247341394424 -1.23145341873169 -1.28341805934906 -0.707658708095551 -0.19094705581665 -0.575110256671906 -0.71659529209137 -0.844432711601257 -1.11671197414398 -0.813595950603485 + Cluster -674 2 2 2 5.3 5.3 5.3 48.379 0 8.9042 2617000000 11 5.23395669675616 1.26582278481013E-05 Q8NFW8;Q8NFW8-2 Q8NFW8;Q8NFW8-2 N-acylneuraminate cytidylyltransferase CMAS 2247 Catalyzes the activation of N-acetylneuraminic acid(NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid(CMP-NeuNAc), a substrate required for the addition of sialicacid. Has some activity toward NeuNAc, N-glycolylneuraminic acid(Neu5Gc) or 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN). Nucleus {ECO:0000269|PubMed:11602804}. N-acetylneuraminate metabolic process N-acylneuraminate cytidylyltransferase activity membrane;nucleoplasm;nucleus Amino sugar and nucleotide sugar metabolism;Metabolic pathways Sialic acid metabolism 0.419142454862595 0.30047670006752 0.832390546798706 0.755063652992249 0.990000247955322 1.98397707939148 1.40528726577759 1.07504045963287 -0.347513884305954 -1.03974521160126 -1.37910771369934 -0.692281067371368 -0.422338038682938 -0.710447728633881 -0.220412060618401 -0.940119922161102 -1.32627987861633 -0.683133006095886 + Cluster -674 4 4 4 18.8 18.8 18.8 32.789 0 12.344 2156200000 10 5.51146204192016 8.06451612903226E-06 Q13868;Q13868-3;Q13868-2 Q13868;Q13868-3;Q13868-2 Exosome complex component RRP4 EXOSC2 1667 Non-catalytic component of the RNA exosome complex whichhas 3'->5' exoribonuclease activity and participates in amultitude of cellular RNA processing and degradation events. Inthe nucleus, the RNA exosome complex is involved in propermaturation of stable RNA species such as rRNA, snRNA and snoRNA,in the elimination of RNA processing by-products and non-coding'pervasive' transcripts, such as antisense RNA species andpromoter-upstream transcripts (PROMPTs), and of mRNAs withprocessing defects, thereby limiting or excluding their export tothe cytoplasm. The RNA exosome may be involved in Ig class switchrecombination (CSR) and/or Ig variable region somatichypermutation (SHM) by targeting AICDA deamination activity totranscribed dsDNA substrates. In the cytoplasm, the RNA exosomecomplex is involved in general mRNA turnover and specificallydegrades inherently unstable mRNAs containing AU-rich elements(AREs) within their 3' untranslated regions, and in RNAsurveillance pathways, preventing translation of aberrant mRNAs.It seems to be involved in degradation of histone mRNA. Thecatalytic inactive RNA exosome core complex of 9 subunits (Exo-9)is proposed to play a pivotal role in the binding and presentationof RNA for ribonucleolysis, and to serve as a scaffold for theassociation with catalytic subunits and accessory proteins orcomplexes. EXOSC2 as peripheral part of the Exo-9 complexstabilizes the hexameric ring of RNase PH-domain subunits throughcontacts with EXOSC4 and EXOSC7. Cytoplasm. Nucleus, nucleolus. Nucleus. CUT catabolic process;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);nuclear polyadenylation-dependent rRNA catabolic process;nuclear polyadenylation-dependent tRNA catabolic process;nuclear retention of pre-mRNA with aberrant 3'-ends at the site of transcription;nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5';polyadenylation-dependent snoRNA 3'-end processing;positive regulation of cell growth;regulation of mRNA stability;rRNA processing;U4 snRNA 3'-end processing 3'-5'-exoribonuclease activity;7S RNA binding;RNA binding cytoplasm;cytoplasmic exosome (RNase complex);cytosol;exosome (RNase complex);nuclear exosome (RNase complex);nucleolus;nucleoplasm;nucleus RNA degradation ATF4 activates genes;Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;KSRP (KHSRP) binds and destabilizes mRNA;Major pathway of rRNA processing in the nucleolus and cytosol;mRNA decay by 3' to 5' exoribonuclease;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA Exosome;mRNA decay complex (UPF1, UPF2, UPF3B, DCP2, XRN1, XRN2, EXOSC2, EXOSC4, EXOSC10, PARN) 0.219453692436218 0.219453692436218 0.960813283920288 0.423859357833862 1.34606516361237 1.36863136291504 1.62362158298492 1.36863136291504 -0.60443776845932 -1.1307487487793 -1.1307487487793 -1.1307487487793 -0.00928405020385981 -0.950057089328766 -0.00928405020385981 -0.401080578565598 -1.08206987380981 -1.08206987380981 + Cluster -674 1 1 1 3.6 3.6 3.6 67.257 0 104.16 108770000 2 5.13792549718424 1.79640718562874E-05 O15240 O15240 Neurosecretory protein VGF;Neuroendocrine regulatory peptide-1;Neuroendocrine regulatory peptide-2;Antimicrobial peptide VGF[554-577] VGF 176 May be involved in the regulation of cell-cellinteractions or in synatogenesis during the maturation of thenervous system. Secreted {ECO:0000269|PubMed:19194657}.Cytoplasmic vesicle, secretory vesicle{ECO:0000269|PubMed:19194657}. Note=Stored in secretory vesiclesand then secreted, NERP peptides colocalize with vasopressin inthe storage granules of hypothalamus. cellular protein metabolic process;defense response to bacterium;generation of precursor metabolites and energy;glucose homeostasis;insulin secretion;ovarian follicle development;post-translational protein modification;response to cAMP;response to cold;response to dietary excess;response to insulin;sexual reproduction growth factor activity;neuropeptide hormone activity cytoplasmic vesicle;endoplasmic reticulum lumen;extracellular space;Golgi apparatus;intracellular membrane-bounded organelle;transport vesicle Post-translational protein phosphorylation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) 0.601766884326935 0.186362594366074 0.756360232830048 0.566493093967438 1.66352200508118 1.42337965965271 1.67432177066803 0.8680060505867 -0.265818804502487 -1.06798946857452 -1.09789168834686 -0.43991082906723 -0.316068857908249 -0.548443138599396 -0.495381504297256 -1.16029381752014 -1.17420709133148 -1.17420709133148 + Cluster -674 2 2 2 4.3 4.3 4.3 79.994 0 18.105 1939700000 7 5.19655555286355 1.23456790123457E-05 P17655;P17655-2 P17655;P17655-2 Calpain-2 catalytic subunit CAPN2 707 Calcium-regulated non-lysosomal thiol-protease whichcatalyzes limited proteolysis of substrates involved incytoskeletal remodeling and signal transduction. Proteolyticallycleaves MYOC at 'Arg-226' (PubMed:17650508). Proteolyticallycleaves CPEB3 following neuronal stimulation which abolishes CPEB3translational repressor activity, leading to translation of CPEB3target mRNAs (By similarity). Cytoplasm. Cell membrane. Note=Translocatesto the plasma membrane upon Ca(2+) binding. behavioral response to pain;blastocyst development;cellular response to amino acid stimulus;cellular response to interferon-beta;cellular response to lipopolysaccharide;female pregnancy;myoblast fusion;positive regulation of cardiac muscle cell apoptotic process;positive regulation of myoblast fusion;positive regulation of neuron death;positive regulation of phosphatidylcholine biosynthetic process;protein autoprocessing;proteolysis;proteolysis involved in cellular protein catabolic process;regulation of cytoskeleton organization;regulation of interleukin-6 production;response to hydrogen peroxide;response to hypoxia calcium ion binding;calcium-dependent cysteine-type endopeptidase activity;cysteine-type peptidase activity;cytoskeletal protein binding;enzyme binding;protein heterodimerization activity chromatin;cortical actin cytoskeleton;cytoplasm;cytosol;dendrite;endoplasmic reticulum;external side of plasma membrane;extracellular exosome;focal adhesion;Golgi apparatus;lysosome;membrane raft;mitochondrial intermembrane space;neuronal cell body;nucleus;perinuclear endoplasmic reticulum;plasma membrane;pseudopodium Alzheimer disease;Apoptosis;Cellular senescence;Focal adhesion;Necroptosis;Protein processing in endoplasmic reticulum Degradation of the extracellular matrix;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models 1.43501770496368 0.217349782586098 0.263527393341064 0.171408995985985 1.23430395126343 1.64763402938843 1.51984488964081 0.918551385402679 0.011538514867425 -0.754885077476501 -1.27997612953186 -0.161107137799263 -0.620976269245148 -0.514175713062286 -0.754885077476501 -0.814087092876434 -1.02180528640747 -1.49727880954742 + Cluster -674 5 5 5 9.3 9.3 9.3 65.699 0 30.305 1479600000 12 3.66609710958526 0.000329519450800915 Q969N2;Q969N2-2;Q969N2-4;Q969N2-5;Q969N2-3;Q969N2-6 Q969N2;Q969N2-2;Q969N2-4;Q969N2-5 GPI transamidase component PIG-T PIGT 2384 Component of the GPI transamidase complex. Essential fortransfer of GPI to proteins, particularly for formation ofcarbonyl intermediates. Single-pass type I membrane protein{ECO:0000269|PubMed:11483512}.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:11483512} attachment of GPI anchor to protein;neuron apoptotic process;neuron differentiation GPI-anchor transamidase activity cytoplasmic vesicle;endoplasmic reticulum membrane;GPI-anchor transamidase complex;integral component of endoplasmic reticulum membrane;membrane Glycosylphosphatidylinositol (GPI)-anchor biosynthesis;Metabolic pathways Inherited glycosylphosphatidylinositol deficiencies;Multiple congenital anomalies-hypotonia-seizures syndrome Attachment of GPI anchor to uPAR GAA1-GPI8-PIGT-PIG-PIGS complex 1.87450516223907 0.229877054691315 0.535057187080383 0.0724517181515694 1.00850462913513 1.63361442089081 1.20383381843567 0.958107769489288 -0.19513912498951 -0.926782071590424 -0.966203272342682 -0.23268911242485 -0.383305758237839 -0.714958012104034 -0.571606040000916 -1.02388060092926 -1.10480642318726 -1.39658141136169 + Cluster -674 6 6 6 7.6 7.6 7.6 145.89 0 30.164 782060000 7 3.34795233550648 0.000553763440860215 Q9C0J8;Q9C0J8-2;Q9C0J8-3 Q9C0J8 pre-mRNA 3 end processing protein WDR33 WDR33 2740 Essential for both cleavage and polyadenylation of pre-mRNA 3' ends. Nucleus {ECO:0000269|PubMed:11162572,ECO:0000269|PubMed:19217410}. mRNA 3'-end processing;mRNA export from nucleus;mRNA polyadenylation;mRNA splicing, via spliceosome;postreplication repair;spermatogenesis;termination of RNA polymerase II transcription RNA binding collagen trimer;fibrillar center;mRNA cleavage and polyadenylation specificity factor complex;nucleoplasm;nucleus mRNA surveillance pathway Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Processing of Intronless Pre-mRNAs;Transport of Mature mRNA Derived from an Intronless Transcript 1.27771854400635 0.5475794672966 0.936584711074829 0.6556795835495 0.83747273683548 1.09044253826141 1.18945980072021 1.10754835605621 -8.55258804222103E-06 -0.680529475212097 -1.00950741767883 -0.323225349187851 -0.391974329948425 -0.474797606468201 -0.507428348064423 -1.071772813797 -0.963086545467377 -2.22015523910522 + Cluster -674 1 1 1 1.4 1.4 1.4 129.59 0.00033979 2.9001 153420000 3 4.25219871217658 8.7378640776699E-05 Q9UNY4;Q9UNY4-2 Q9UNY4;Q9UNY4-2 Transcription termination factor 2 TTF2 3192 DsDNA-dependent ATPase which acts as a transcriptiontermination factor by coupling ATP hydrolysis with removal of RNApolymerase II from the DNA template. May contribute to mitotictranscription repression. May also be involved in pre-mRNAsplicing. Cytoplasm {ECO:0000269|PubMed:15125840}.Nucleus {ECO:0000269|PubMed:15125840}. Note=Cytoplasmic duringinterphase. Relocates to the nucleus as cells enter mitosis. DNA-templated transcription, termination;mRNA processing;RNA splicing;termination of RNA polymerase II transcription ATP binding;DNA binding;DNA-dependent ATPase activity;helicase activity;zinc ion binding cytosol;spliceosomal complex;transcription elongation factor complex Thyroid hormone synthesis 0.743695378303528 0.596727073192596 0.960912525653839 0.366704404354095 0.725144445896149 1.72051537036896 1.12688517570496 1.22038781642914 0.14499968290329 -0.853204250335693 -1.35234594345093 -0.468529999256134 -0.169947057962418 -0.263053089380264 -0.960679590702057 -0.846144258975983 -0.78483659029007 -1.90723097324371 + Cluster -674 5 5 4 11.4 11.4 9.4 58.47 0 48.715 2631600000 15 4.28009549633935 8.16993464052288E-05 O60749;O60749-2 O60749;O60749-2 Sorting nexin-2 SNX2 285 the function isdependent on GEF activity of KALRN (PubMed:20604901);Involved in several stages of intracellular trafficking.Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate(PtdIns(3,5)P2) (PubMed:16179610). Acts in part as component ofthe retromer membrane-deforming SNX-BAR subcomplex(PubMed:17101778). The SNX-BAR retromer mediates retrogradetransport of cargo proteins from endosomes to the trans-Golginetwork (TGN) and is involved in endosome-to-plasma membranetransport for cargo protein recycling. The SNX-BAR subcomplexfunctions to deform the donor membrane into a tubular profilecalled endosome-to-TGN transport carrier (ETC) (Probable). Cansense membrane curvature and has in vitro vesicle-to-membraneremodeling activity (PubMed:23085988). Required for retrogradeendosome-to-TGN transport of TGN38 (PubMed:20138391). PromotesKALRN- and RHOG-dependent but retromer-independent membraneremodeling such as lamellipodium formation Cytoplasmic side{ECO:0000269|PubMed:16179610, ECO:0000269|PubMed:17101778}. Cellprojection, lamellipodium {ECO:0000269|PubMed:20604901}.Note=Colocalized with SORT1 to tubular endosomal membranestructures called endosome-to-TGN transport carriers (ETCs) whichare budding from early endosome vacuoles just before maturing intolate endosome vacuoles (PubMed:18088323). Colocalized with F-actinat the leading edge of lamellipodia in cells in a KALRN-dependentmanner (PubMed:20604901). {ECO:0000269|PubMed:18088323,ECO:0000269|PubMed:20604901}.;Early endosome membrane{ECO:0000269|PubMed:16179610, ECO:0000269|PubMed:17101778};Peripheral membrane protein {ECO:0000269|PubMed:16179610,ECO:0000269|PubMed:17101778} early endosome to Golgi transport;endocytosis;intracellular protein transport;lamellipodium morphogenesis;protein complex oligomerization;retrograde transport, endosome to Golgi cadherin binding;epidermal growth factor receptor binding;insulin receptor binding;leptin receptor binding;phosphatidylinositol binding;protein heterodimerization activity;protein homodimerization activity;transferrin receptor binding cytoplasm;cytosol;early endosome membrane;endosome;endosome membrane;lamellipodium;lysosome;membrane;protein-containing complex;retromer complex;retromer, tubulation complex Endocytosis Golgi Associated Vesicle Biogenesis Retromer complex (SNX1, SNX2, VPS35, VPS29, VPS26A);Retromer complex (SNX1, SNX2, VPS35, VPS29, VPS26B);SNX complex (SNX1, SNX1a, SNX2, SNX4);SNX complex (SNX1, SNX1a, SNX2, SNX4, EGFR);SNX complex (SNX1, SNX1a, SNX2, SNX4, INSR);SNX complex (SNX1, SNX1a, SNX2, SNX4, LEPR);SNX complex (SNX1, SNX1a, SNX2, SNX4, PDGFRA);SNX complex (SNX2), oligomeric 1.04880917072296 0.244582965970039 0.856401324272156 0.344011545181274 0.492697566747665 1.90288782119751 1.20682394504547 0.681482255458832 0.507785022258759 -1.14941477775574 -1.6018477678299 0.0835082307457924 -0.122085183858871 -0.315385490655899 -0.685995519161224 -1.01816439628601 -0.810966551303864 -1.66513013839722 + Cluster -674 2 2 2 6.3 6.3 6.3 47.151 0 12.621 906340000 4 3.30005402919248 0.000592720970537262 Q8NBX0 Q8NBX0 Saccharopine dehydrogenase-like oxidoreductase SCCPDH 2227 glycolipid biosynthetic process;platelet degranulation oxidoreductase activity extracellular region;lipid droplet;membrane;midbody;mitochondrion;nucleus;plasma membrane;platelet alpha granule lumen Platelet degranulation 1.3843412399292 0.00825915113091469 0.886983573436737 0.351253479719162 0.663538932800293 1.55811452865601 1.65158402919769 0.911076903343201 -0.0162490215152502 -0.943662285804749 -1.30656886100769 -0.851611971855164 0.178953930735588 -0.479415267705917 -0.718449115753174 -0.919361531734467 -1.08118093013763 -1.27760660648346 + Cluster -674 11 11 11 13.1 13.1 13.1 108.66 0 150.51 12581000000 61 3.92284368663644 0.000177595628415301 Q9Y2W1 Q9Y2W1 Thyroid hormone receptor-associated protein 3 THRAP3 3243 however, it is not regarded as a stable Mediator complexsubunit. Cooperatively with HELZ2, enhances the transcriptionalactivation mediated by PPARG, maybe through the stabilization ofthe PPARG binding to DNA in presence of ligand. May play a role inthe terminal stage of adipocyte differentiation. Plays a role inthe positive regulation of the circadian clock. Acts as acoactivator of the CLOCK-ARNTL/BMAL1 heterodimer and promotes itstranscriptional activator activity and binding to circadian targetgenes (PubMed:24043798).; the function mayinvolve the SNARP complex. Initially thought to play a role intranscriptional coactivation through its association with the TRAPcomplex;Involved in pre-mRNA splicing. Remains associated withspliced mRNA after splicing which probably involves interactionswith the exon junction complex (EJC). Can trigger mRNA decay whichseems to be independent of nonsense-mediated decay involvingpremature stop codons (PTC) recognition. May be involved innuclear mRNA decay. Involved in regulation of signal-inducedalternative splicing. During splicing of PTPRC/CD45 is proposed tosequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in restingT-cells. Involved in cyclin-D1/CCND1 mRNA stability probably byacting as component of the SNARP complex which associates withboth the 3'end of the CCND1 gene and its mRNA. Involved inresponse to DNA damage. Is excluced from DNA damage sites in amanner that parallels transcription inhibition Nucleus {ECO:0000269|PubMed:20123736,ECO:0000269|PubMed:23525231}. Nucleus, nucleoplasm{ECO:0000269|PubMed:24100041}. Nucleus speckle{ECO:0000269|PubMed:24100041}. androgen receptor signaling pathway;circadian rhythm;intracellular steroid hormone receptor signaling pathway;mRNA processing;mRNA stabilization;nuclear-transcribed mRNA catabolic process;positive regulation of circadian rhythm;positive regulation of mRNA splicing, via spliceosome;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;regulation of alternative mRNA splicing, via spliceosome;RNA splicing;transcription initiation from RNA polymerase II promoter ATP binding;nuclear receptor transcription coactivator activity;phosphoprotein binding;RNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;signaling receptor activity;thyroid hormone receptor binding;transcription coactivator activity;transcription coregulator activity;vitamin D receptor binding extracellular exosome;mediator complex;nuclear speck;nucleoplasm;nucleus PPARA activates gene expression;Transcriptional regulation of white adipocyte differentiation PC2 complex;SMCC complex;TRAP complex 1.14379799365997 0.0616618022322655 0.920833110809326 0.847720682621002 0.116763286292553 1.10505056381226 1.86072516441345 1.17097616195679 0.0989092290401459 -0.538758039474487 -1.06427133083344 -1.6145213842392 -0.289105206727982 -0.066620722413063 -0.563445866107941 -0.725926637649536 -1.0800369977951 -1.38375198841095 + Cluster -674 2 2 2 5 5 5 61.247 0 14.18 318280000 4 3.86059959800026 0.000221932114882507 O14773;O14773-2 O14773;O14773-2 Tripeptidyl-peptidase 1 TPP1 131 Lysosomal serine protease with tripeptidyl-peptidase Iactivity. May act as a non-specific lysosomal peptidase whichgenerates tripeptides from the breakdown products produced bylysosomal proteinases. Requires substrates with an unsubstitutedN-terminus (By similarity). Lysosome {ECO:0000269|PubMed:19941651}.Melanosome {ECO:0000269|PubMed:12643545}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV.{ECO:0000269|PubMed:12643545}. bone resorption;central nervous system development;epithelial cell differentiation;IRE1-mediated unfolded protein response;lipid metabolic process;lysosome organization;nervous system development;neuromuscular process controlling balance;peptide catabolic process;protein catabolic process;proteolysis endopeptidase activity;metal ion binding;peptidase activity;peptide binding;serine-type endopeptidase activity;serine-type peptidase activity;tripeptidyl-peptidase activity extracellular exosome;lysosomal lumen;lysosome;melanosome Lysosome Autosomal recessive spinocerebellar ataxias;Jansky-Bielschowsky disease;Neuronal ceroid lipofuscinosis Cerliponase alfa XBP1(S) activates chaperone genes 1.26308906078339 -0.00407363660633564 0.73627507686615 0.421533495187759 0.709518551826477 1.88523805141449 1.38841271400452 0.905258059501648 0.360581427812576 -0.441859185695648 -1.11110961437225 -1.18675231933594 -0.785929441452026 -0.380434662103653 -0.272853672504425 -1.25444602966309 -1.04744291305542 -1.1850049495697 + Cluster -674 3 3 3 1.9 1.9 1.9 159 0 3.5784 117270000 5 4.36230995385587 6.89655172413793E-05 P54132 P54132 Bloom syndrome protein BLM 1217 ATP-dependent DNA helicase that unwinds single- anddouble-stranded DNA in a 3'-5' direction (PubMed:9388193,PubMed:24816114, PubMed:25901030). Participates in DNA replicationand repair (PubMed:12019152, PubMed:21325134, PubMed:23509288).Involved in 5'-end resection of DNA during double-strand break(DSB) repair: unwinds DNA and recruits DNA2 which mediates thecleavage of 5'-ssDNA (PubMed:21325134). Negatively regulatessister chromatid exchange (SCE) (PubMed:25901030). Stimulates DNA4-way junction branch migration and DNA Holliday junctiondissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA),forked duplex DNA and DNA Holliday junction (PubMed:20639533,PubMed:24257077, PubMed:25901030). Nucleus {ECO:0000269|PubMed:23509288}.Note=Together with SPIDR, is redistributed in discrete nuclear DNAdamage-induced foci following hydroxyurea (HU) or camptothecin(CPT) treatment. Accumulated at sites of DNA damage in a RMIcomplex- and SPIDR-dependent manner. alpha-beta T cell differentiation;cellular response to camptothecin;cellular response to DNA damage stimulus;cellular response to hydroxyurea;cellular response to ionizing radiation;DNA double-strand break processing;DNA duplex unwinding;DNA recombination;DNA repair;DNA replication;DNA synthesis involved in DNA repair;double-strand break repair via homologous recombination;double-strand break repair via nonhomologous end joining;double-strand break repair via synthesis-dependent strand annealing;G-quadruplex DNA unwinding;meiotic chromosome separation;meiotic DNA double-strand break processing involved in reciprocal meiotic recombination;mitotic G2 DNA damage checkpoint;negative regulation of apoptotic process;negative regulation of cell division;negative regulation of DNA recombination;negative regulation of double-strand break repair via single-strand annealing;negative regulation of mitotic recombination;negative regulation of thymocyte apoptotic process;positive regulation of alpha-beta T cell proliferation;positive regulation of double-strand break repair via homologous recombination;positive regulation of transcription, DNA-templated;protein complex oligomerization;protein homooligomerization;regulation of cyclin-dependent protein serine/threonine kinase activity;regulation of DNA-dependent DNA replication;replication fork processing;replication fork protection;resolution of meiotic recombination intermediates;resolution of recombination intermediates;response to X-ray;strand displacement;t-circle formation;telomeric D-loop disassembly 8-hydroxy-2'-deoxyguanosine DNA binding;annealing helicase activity;ATP binding;ATPase activity;ATP-dependent 3'-5' DNA helicase activity;ATP-dependent DNA helicase activity;ATP-dependent helicase activity;bubble DNA binding;DNA binding;DNA helicase activity;DNA-dependent ATPase activity;forked DNA-dependent helicase activity;four-way junction DNA binding;four-way junction helicase activity;G-quadruplex DNA binding;helicase activity;p53 binding;protein homodimerization activity;single-stranded DNA binding;telomeric D-loop binding;telomeric G-quadruplex DNA binding;Y-form DNA binding;zinc ion binding chromosome;cytoplasm;cytosol;lateral element;nuclear chromosome;nuclear matrix;nucleolus;nucleoplasm;nucleus;PML body;pronucleus;replication fork Fanconi anemia pathway;Homologous recombination Bloom syndrome;Defects in RecQ helicases;Immunodeficiency associated with DNA repair defects G2/M DNA damage checkpoint;HDR through Homologous Recombination (HRR);HDR through Single Strand Annealing (SSA);Homologous DNA Pairing and Strand Exchange;Meiotic recombination;Presynaptic phase of homologous DNA pairing and strand exchange;Processing of DNA double-strand break ends;Regulation of TP53 Activity through Phosphorylation;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);SUMOylation of DNA damage response and repair proteins BASC (Ab 80) complex (BRCA1-associated genome surveillance complex);BASC complex (BRCA1-associated genome surveillance complex);BLM complex II;BLM complex III;BLM-RAD51L3-XRCC2 complex;BLM-TOP3A complex;BLM-TRF2 complex;BRAFT complex;FA complex (Fanconi anemia complex);MSH2/6-BLM-p53-RAD51 complex;PTIP-DNA damage response complex 1.45725321769714 0.222162798047066 0.797346234321594 0.38348400592804 0.972366213798523 1.49101662635803 1.43203938007355 0.932399809360504 -0.218336462974548 -1.41726267337799 -0.736182987689972 -0.591797828674316 -0.180043041706085 -0.529344201087952 -0.400862991809845 -0.859688818454742 -1.39802372455597 -1.35652554035187 + Cluster -674 10 10 10 38 38 38 22.487 0 172.8 41190000000 106 3.92278568859094 0.000177111716621253 Q92522 Q92522 Histone H1x H1FX 2325 Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structures. Nucleus. Chromosome. chromosome condensation;negative regulation of chromatin silencing;negative regulation of DNA recombination;nucleosome assembly;nucleosome positioning;regulation of transcription, DNA-templated cadherin binding;double-stranded DNA binding;nucleosomal DNA binding;RNA binding nucleolus;nucleosome;nucleus Nop56p-associated pre-rRNA complex 0.978880643844604 0.615289926528931 0.68995988368988 0.585511326789856 0.946251690387726 1.46794044971466 1.6194965839386 1.04331731796265 -0.402200698852539 -1.41942429542542 -1.10179305076599 -0.598875343799591 -0.352483004331589 -0.504319548606873 -0.153879210352898 -1.31498241424561 -1.04934513568878 -1.04934513568878 + Cluster -674 3 3 3 6.1 6.1 6.1 46.701 0 21.426 2625500000 8 4.53290620597494 4.6875E-05 Q96M27;Q96M27-3;Q96M27-2;Q96M27-5;Q96M27-4 Q96M27;Q96M27-3;Q96M27-2;Q96M27-5 Protein PRRC1 PRRC1 2505 Golgi apparatus{ECO:0000269|PubMed:15541471}. activation of protein kinase A activity protein kinase A regulatory subunit binding cytoplasm;Golgi apparatus 1.18335139751434 0.213533997535706 1.04687058925629 0.318691939115524 0.896020472049713 1.67030358314514 1.30846869945526 0.952278852462769 -0.21803967654705 -1.25454413890839 -1.2920161485672 -0.769855380058289 0.0938418135046959 -0.316058784723282 -0.392450660467148 -0.959597885608673 -1.22094857692719 -1.25985014438629 + Cluster -674 8 8 8 38.1 38.1 38.1 23.671 0 84.862 4765500000 26 4.1534771578095 0.000106583072100313 P82979 P82979 SAP domain-containing ribonucleoprotein SARNP 1445 Binds both single-stranded and double-stranded DNA withhigher affinity for the single-stranded form. Specifically bindsto scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. Mayparticipate in important transcriptional or translational controlof cell growth, metabolism and carcinogenesis. Component of theTREX complex which is thought to couple mRNA transcription,processing and nuclear export, and specifically associates withspliced mRNA and not with unspliced pre-mRNA. TREX is recruited tospliced mRNAs by a transcription-independent mechanism, binds tomRNA upstream of the exon-junction complex (EJC) and is recruitedin a splicing- and cap-dependent manner to a region near the 5'end of the mRNA where it functions in mRNA export to the cytoplasmvia the TAP/NFX1 pathway. The TREX complex is essential for theexport of Kaposi's sarcoma-associated herpesvirus (KSHV)intronless mRNAs and infectious virus production Nucleus. Nucleus speckle. mRNA 3'-end processing;mRNA export from nucleus;regulation of translation;RNA export from nucleus DNA binding;RNA binding cytoplasmic ribonucleoprotein granule;nuclear speck;nucleoplasm;nucleus;transcription export complex Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;Transport of Mature mRNA derived from an Intron-Containing Transcript 1.355024933815 0.166264101862907 1.21494388580322 0.197620570659637 0.668679654598236 1.58378565311432 1.33017599582672 0.817656695842743 -0.276133418083191 -1.22373163700104 -1.37038326263428 -0.711167275905609 0.385822504758835 -0.417269110679626 -0.394862592220306 -0.855809032917023 -1.29416871070862 -1.17644906044006 + Cluster -674 17 17 17 56 56 56 44.172 0 88.551 11574000000 57 3.3703461430231 0.000540983606557377 P62333 P62333 26S protease regulatory subunit 10B PSMC6 1357 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. PSMC6 belongs to theheterohexameric ring of AAA (ATPases associated with diversecellular activities) proteins that unfolds ubiquitinated targetproteins that are concurrently translocated into a proteolyticchamber and degraded into peptides. Cytoplasm {ECO:0000250}. Nucleus{ECO:0000250}. positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;post-translational protein modification;protein deubiquitination;ubiquitin-dependent ERAD pathway;ubiquitin-dependent protein catabolic process ATP binding;ATPase activity;identical protein binding;proteasome-activating ATPase activity;protein binding, bridging cytosol;cytosolic proteasome complex;extracellular exosome;membrane;nucleoplasm;nucleus;proteasome accessory complex;proteasome complex;proteasome regulatory particle, base subcomplex Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 26S proteasome;PA700 complex;PA700-20S-PA28 complex 1.1613517999649 0.1606724858284 1.59759104251862 0.798366606235504 0.798366606235504 1.00424444675446 0.995450854301453 0.671290993690491 0.0364103354513645 -0.937718093395233 -0.937718093395233 -0.670088589191437 0.221180930733681 -0.185903236269951 -0.160687029361725 -1.24168658256531 -1.71245908737183 -1.59866559505463 + Cluster -674 14 14 14 27 27 27 67.314 0 119.89 27361000000 56 3.3820345836442 0.000523897058823529 P61221 P61221 ATP-binding cassette sub-family E member 1 ABCE1 1303 Antagonizes the binding of 2-5A (5'-phosphorylated2',5'-linked oligoadenylates) by RNase L through directinteraction with RNase L and therefore inhibits itsendoribonuclease activity. May play a central role in theregulation of mRNA turnover. Antagonizes the anti-viral effect ofthe interferon-regulated 2-5A/RNase L pathway. May act as achaperone for post-translational events during HIV-1 capsidassembly. Cytoplasm {ECO:0000269|PubMed:11585831}.Mitochondrion {ECO:0000269|PubMed:11585831}. Note=Localized toclusters of virus formation at the plasma membrane. defense response to virus;negative regulation of endoribonuclease activity;regulation of type I interferon-mediated signaling pathway;ribosomal subunit export from nucleus;translational initiation;translational termination;viral process ATP binding;ATPase activity;endoribonuclease inhibitor activity;iron ion binding;ribosomal small subunit binding cytoplasm;cytosol;membrane;mitochondrial matrix;mitochondrion Interferon alpha/beta signaling;OAS antiviral response 1.45544385910034 0.253246665000916 0.922263383865356 0.416830509901047 0.875254034996033 1.50081992149353 1.28029918670654 0.828938126564026 -0.139115527272224 -0.967454969882965 -1.13429629802704 -0.60699200630188 -0.121824614703655 -0.379755675792694 -0.399710953235626 -0.588889002799988 -1.4128669500351 -1.78218972682953 + Cluster -674 20 8 8 57.3 27.3 27.3 50.67 0 164.88 34352000000 49 3.65373838785183 0.000332574031890661 P42167;P42167-2;P42167-3 P42167;P42167-2;P42167-3 Lamina-associated polypeptide 2, isoforms beta/gamma;Thymopoietin;Thymopentin TMPO 1007 May help direct the assembly of the nuclear lamina andthereby help maintain the structural organization of the nuclearenvelope. Possible receptor for attachment of lamin filaments tothe inner nuclear membrane. May be involved in the control ofinitiation of DNA replication through its interaction withNAKAP95.Thymopoietin (TP) and Thymopentin (TP5) may play a rolein T-cell development and function. TP5 is an immunomodulatingpentapeptide. Single-pass type IImembrane protein. Note=Tightly associated with the nuclear lamina.Isoform Zeta: Cytoplasm{ECO:0000269|PubMed:18403046}.;Nucleus inner membrane DNA binding;lamin binding cytoplasm;integral component of membrane;membrane;nuclear envelope;nuclear inner membrane;nuclear membrane;nucleus Dilated cardiomyopathy Clearance of Nuclear Envelope Membranes from Chromatin;Depolymerisation of the Nuclear Lamina;Initiation of Nuclear Envelope Reformation BAFL-BAF-LAP2beta complex 1.38277554512024 0.328695684671402 1.21174120903015 0.0972516164183617 0.744117617607117 1.14007771015167 1.27805650234222 0.967836380004883 0.0510296560823917 -0.668205559253693 -1.81612205505371 -0.430020421743393 0.00477055367082357 -0.238168656826019 -0.238168656826019 -1.21999073028564 -1.59411180019379 -1.00156450271606 + Cluster -674 6 6 1 40.7 40.7 5.7 15.088 0 150.16 17399000000 37 3.20636648119958 0.000735197368421053 P35080-2 P35080-2 Profilin-2 PFN2 921 Binds to actin and affects the structure of thecytoskeleton. At high concentrations, profilin prevents thepolymerization of actin, whereas it enhances it at lowconcentrations. By binding to PIP2, it inhibits the formation ofIP3 and DG. Cytoplasm, cytoskeleton. actin cytoskeleton organization;modification of postsynaptic actin cytoskeleton;negative regulation of actin filament polymerization;negative regulation of epithelial cell migration;negative regulation of ruffle assembly;positive regulation of actin filament bundle assembly;positive regulation of actin filament polymerization;positive regulation of ATPase activity;positive regulation of peptidyl-serine phosphorylation;positive regulation of stress fiber assembly;protein stabilization;regulation of actin filament polymerization;regulation of synaptic vesicle exocytosis actin binding;actin monomer binding;ATPase activity;phosphatidylinositol-4,5-bisphosphate binding cytoplasm;cytoskeleton;extracellular exosome;glutamatergic synapse;postsynapse;presynapse;Schaffer collateral - CA1 synapse Rap1 signaling pathway;Regulation of actin cytoskeleton;Salmonella infection;Shigellosis RHO GTPases Activate Formins;Signaling by ROBO receptors Profilin 2 complex 1.62509167194366 -0.391849130392075 1.16059303283691 0.548236966133118 1.12419879436493 1.09119474887848 1.28485012054443 0.857936382293701 -0.411897748708725 -0.63051563501358 -1.36380922794342 -0.63051563501358 -0.100805953145027 -0.264484316110611 -0.243880733847618 -1.58422315120697 -1.25842022895813 -0.811699986457825 + Cluster -674 6 6 6 16.9 16.9 16.9 48.275 0 80.644 27486000000 39 3.10738110307006 0.000896875 P14324;P14324-2 P14324;P14324-2 Farnesyl pyrophosphate synthase FDPS 667 Key enzyme in isoprenoid biosynthesis which catalyzesthe formation of farnesyl diphosphate (FPP), a precursor forseveral classes of essential metabolites including sterols,dolichols, carotenoids, and ubiquinones. FPP also serves assubstrate for protein farnesylation and geranylgeranylation.Catalyzes the sequential condensation of isopentenyl pyrophosphatewith the allylic pyrophosphates, dimethylallyl pyrophosphate, andthen with the resultant geranylpyrophosphate to the ultimateproduct farnesyl pyrophosphate. Cytoplasm. cholesterol biosynthetic process;farnesyl diphosphate biosynthetic process;geranyl diphosphate biosynthetic process;regulation of cholesterol biosynthetic process;viral process dimethylallyltranstransferase activity;geranyltranstransferase activity;metal ion binding;RNA binding cytoplasm;cytosol;nucleoplasm Human T-cell leukemia virus 1 infection;Influenza A;Metabolic pathways;Terpenoid backbone biosynthesis Porokeratosis Alendronic acid;Ibandronic acid;Incadronic acid;Minodronic acid hydrate;Pamidronic acid;Risedronic acid;Zoledronic acid Activation of gene expression by SREBF (SREBP);Cholesterol biosynthesis 1.48743581771851 0.215350940823555 1.10283207893372 0.215350940823555 0.964086353778839 1.58966553211212 1.19437658786774 1.05970144271851 -0.410607069730759 -0.904942870140076 -1.03685736656189 -0.429000407457352 -0.161631241440773 -0.655663907527924 -0.655663907527924 -1.02686500549316 -1.41606974601746 -1.13149809837341 + Cluster -674 42 42 37 61.1 61.1 57.2 66.408 0 323.31 242100000000 479 3.90048380332199 0.000189333333333333 P20700 P20700 Lamin-B1 LMNB1 748 Lamins are components of the nuclear lamina, a fibrouslayer on the nucleoplasmic side of the inner nuclear membrane,which is thought to provide a framework for the nuclear envelopeand may also interact with chromatin. Lipid-anchor;Nucleoplasmic side.;Nucleus inner membrane interleukin-12-mediated signaling pathway phospholipase binding;sequence-specific double-stranded DNA binding;structural molecule activity lamin filament;membrane;nuclear envelope;nuclear inner membrane;nuclear matrix;nuclear membrane;nucleoplasm;nucleus Apoptosis Adult-onset autosomal dominant leukodystrophy Breakdown of the nuclear lamina;Clearance of Nuclear Envelope Membranes from Chromatin;Depolymerisation of the Nuclear Lamina;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models;Formation of Senescence-Associated Heterochromatin Foci (SAHF);Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Initiation of Nuclear Envelope Reformation;Meiotic synapsis Emerin architectural complex;Emerin complex 24;Emerin complex 25;Emerin complex 32;Emerin complex 52 1.13913071155548 0.080438643693924 1.0036495923996 0.511270403862 0.956266641616821 1.62526273727417 1.46821653842926 1.13481771945953 -0.442251682281494 -0.867520987987518 -1.13250041007996 -0.900186896324158 -0.344085812568665 -0.639953017234802 -0.344085812568665 -0.751862823963165 -1.41945326328278 -1.07715225219727 + Cluster -674 31 26 26 43.1 39.4 39.4 69.948 0 256.05 27056000000 98 4.789138400074 2.72727272727273E-05 Q03252 Q03252 Lamin-B2 LMNB2 1505 Lamins are components of the nuclear lamina, a fibrouslayer on the nucleoplasmic side of the inner nuclear membrane,which is thought to provide a framework for the nuclear envelopeand may also interact with chromatin. Lipid-anchor;Nucleoplasmic side.;Nucleus inner membrane structural molecule activity lamin filament;nuclear inner membrane;nuclear membrane Apoptosis Familial partial lipodystrophy;Progressive myoclonic epilepsy 1.06924068927765 0.0993905365467072 1.03868412971497 0.446040540933609 0.670431733131409 1.81704008579254 1.5865490436554 1.04192161560059 -0.470745444297791 -0.926712334156036 -1.47733354568481 -0.373024851083755 -0.465501815080643 -0.425575256347656 -0.777370989322662 -0.719764530658722 -1.16024518013 -0.973024249076843 + Cluster -674 4 4 4 10.8 10.8 10.8 61.877 0 11.114 1151300000 12 4.26786477693963 8.79478827361564E-05 O14531 O14531 Dihydropyrimidinase-related protein 4 DPYSL4 114 Necessary for signaling by class 3 semaphorins andsubsequent remodeling of the cytoskeleton. Plays a role in axonguidance, neuronal growth cone collapse and cell migration (Bysimilarity). Cytoplasm {ECO:0000250}. nervous system development;neuron death;neuron projection guidance filamin binding;hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds cytosol CRMPs in Sema3A signaling 1.21068060398102 0.220474198460579 1.00646126270294 0.442352265119553 0.522052764892578 1.68976652622223 1.4482524394989 0.906490504741669 -0.488199979066849 -0.411807358264923 -2.04290080070496 -0.308018893003464 -0.571021854877472 -0.0881678462028503 -0.622605204582214 -0.933149933815002 -0.990329325199127 -0.990329325199127 + Cluster -674 32 32 2 75 75 8.9 29.032 0 323.31 174790000000 247 3.17464086262455 0.00077831715210356 P06753-2;P06753-3;P06753-5;P06753-4;P06753-7 P06753-2;P06753-3;P06753-5;P06753-4 Tropomyosin alpha-3 chain TPM3 525 Binds to actin filaments in muscle and non-muscle cells.Plays a central role, in association with the troponin complex, inthe calcium dependent regulation of vertebrate striated musclecontraction. Smooth muscle contraction is regulated by interactionwith caldesmon. In non-muscle cells is implicated in stabilizingcytoskeleton actin filaments. Cytoplasm, cytoskeleton {ECO:0000305}. actin filament organization;muscle contraction;muscle filament sliding actin filament binding actin cytoskeleton;actin filament;cytoskeleton;cytosol;extracellular exosome;muscle thin filament tropomyosin;stress fiber Adrenergic signaling in cardiomyocytes;Cardiac muscle contraction;Dilated cardiomyopathy (DCM);Hypertrophic cardiomyopathy (HCM);Pathways in cancer;Thyroid cancer Cap myopathy;Congenital fiber type disproportion;Nemaline myopathy;Thyroid cancer Smooth Muscle Contraction;Striated Muscle Contraction 1.35073018074036 0.119033843278885 0.637181460857391 0.235385224223137 0.744952321052551 1.87872862815857 1.81032681465149 0.954904496669769 -0.260358273983002 -0.746377885341644 -0.650513589382172 -0.941397845745087 -0.732692897319794 -0.631585597991943 -0.941397845745087 -0.878042638301849 -0.974438190460205 -0.974438190460205 + Cluster -674 12 12 12 21.8 21.8 21.8 95.737 0 206.19 21272000000 46 4.13241548682287 0.000111455108359133 Q9BUJ2;Q9BUJ2-4;Q9BUJ2-2;Q9BUJ2-3;Q9BUJ2-5 Q9BUJ2;Q9BUJ2-4;Q9BUJ2-2;Q9BUJ2-3 Heterogeneous nuclear ribonucleoprotein U-like protein 1 HNRNPUL1 2665 Acts as a basic transcriptional regulator. Repressesbasic transcription driven by several virus and cellularpromoters. When associated with BRD7, activates transcription ofglucocorticoid-responsive promoter in the absence of ligand-stimulation. Plays also a role in mRNA processing and transport.Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro Nucleus {ECO:0000269|PubMed:11513728,ECO:0000269|PubMed:12489984, ECO:0000269|PubMed:9733834}. mRNA splicing, via spliceosome;response to virus;RNA processing enzyme binding;RNA binding nucleoplasm;nucleus Influenza A mRNA Splicing - Major Pathway Large Drosha complex 1.02939772605896 0.427943706512451 0.7426598072052 0.175852313637733 1.07017076015472 1.52161514759064 1.93735134601593 0.934526145458221 -0.436748772859573 -0.764370262622833 -1.24496507644653 -0.482818812131882 -0.336746037006378 -0.687424659729004 -0.877189874649048 -0.695309460163116 -1.07514953613281 -1.23879444599152 + Cluster -674 15 15 11 62.4 62.4 49.7 17.302 0 108.49 230970000000 204 4.12462330184084 0.000115853658536585 P16949;P16949-2;Q9H169;Q9H169-3;Q9H169-4;Q9H169-2 P16949;P16949-2 Stathmin STMN1 698 Exhibits microtubule-destabilizing activity;Involved in the regulation of the microtubule (MT)filament system by destabilizing microtubules. Prevents assemblyand promotes disassembly of microtubules. Phosphorylation at Ser-16 may be required for axon formation during neurogenesis.Involved in the control of the learned and innate fear (Bysimilarity). Cytoplasm, cytoskeleton.;Golgi apparatus {ECO:0000250}. Cellprojection, growth cone {ECO:0000250}. Cell projection, axon{ECO:0000250}. axonogenesis;brain development;establishment of skin barrier;hepatocyte growth factor receptor signaling pathway;intracellular signal transduction;microtubule depolymerization;mitotic cytokinesis;mitotic spindle organization;negative regulation of guanyl-nucleotide exchange factor activity;negative regulation of microtubule polymerization;negative regulation of Rho protein signal transduction;negative regulation of stress fiber assembly;negative regulation of thrombin-activated receptor signaling pathway;neuron projection development;positive regulation of cellular component movement;regulation of cytoskeleton organization;regulation of microtubule polymerization or depolymerization;response to virus;signal transduction tubulin binding cytoplasm;cytosol;extracellular exosome;Golgi apparatus;growth cone;intracellular;membrane;microtubule;neuron projection MAPK signaling pathway;MicroRNAs in cancer 0.999389290809631 0.384108603000641 1.30766904354095 -0.565137267112732 0.861642122268677 1.69250285625458 1.69250285625458 0.941169559955597 -0.233564913272858 -0.723501801490784 -1.34816539287567 -0.415739834308624 -0.579062581062317 -0.53617250919342 -0.723501801490784 -1.08484697341919 -0.532869696617126 -1.13642168045044 + Cluster -674 3 1 1 5.9 2.2 2.2 82.722 0 20.37 212380000 2 3.21781687429992 0.000716417910447761 Q15418;Q15418-2;Q15418-3;Q15418-4 Q15418;Q15418-2;Q15418-3;Q15418-4 Ribosomal protein S6 kinase alpha-1 RPS6KA1 1803 Serine/threonine-protein kinase that acts downstream ofERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenicand stress-induced activation of the transcription factors CREB1,ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 andEIF4B phosphorylation, and mediates cellular proliferation,survival, and differentiation by modulating mTOR signaling andrepressing pro-apoptotic function of BAD and DAPK1. In fibroblast,is required for EGF-stimulated phosphorylation of CREB1, whichresults in the subsequent transcriptional activation of severalimmediate-early genes. In response to mitogenic stimulation (EGFand PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation ofseveral genes by phosphorylating GSK3B at 'Ser-9' and inhibitingits activity. Phosphorylates RPS6 in response to serum or EGF viaan mTOR-independent mechanism and promotes translation initiationby facilitating assembly of the pre-initiation complex. Inresponse to insulin, phosphorylates EIF4B, enhancing EIF4Baffinity for the EIF3 complex and stimulating cap-dependenttranslation. Is involved in the mTOR nutrient-sensing pathway bydirectly phosphorylating TSC2 at 'Ser-1798', which potentlyinhibits TSC2 ability to suppress mTOR signaling, and mediatesphosphorylation of RPTOR, which regulates mTORC1 activity and maypromote rapamycin-sensitive signaling independently of thePI3K/AKT pathway. Mediates cell survival by phosphorylating thepro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellatecells by phosphorylating CEBPB in response to the hepatotoxincarbon tetrachloride (CCl4). Mediates induction of hepatocyteprolifration by TGFA through phosphorylation of CEBPB (Bysimilarity). Is involved in cell cycle regulation byphosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1Bassociation with 14-3-3 proteins and prevents its translocation tothe nucleus and inhibition of G1 progression. Phosphorylates EPHA2at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cellmigration (PubMed:26158630). Nucleus. Cytoplasm. cell cycle;hepatocyte proliferation;intracellular signal transduction;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of cell differentiation;positive regulation of cell growth;positive regulation of hepatic stellate cell activation;positive regulation of transcription by RNA polymerase II;regulation of DNA-templated transcription in response to stress;regulation of translation in response to stress;signal transduction ATP binding;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;kinase activity;magnesium ion binding;protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;ribosomal protein S6 kinase activity cytosol;nucleoplasm;nucleus Insulin resistance;Long-term potentiation;MAPK signaling pathway;mTOR signaling pathway;Neurotrophin signaling pathway;Oocyte meiosis;Progesterone-mediated oocyte maturation;Thermogenesis;Yersinia infection CREB phosphorylation;CREB phosphorylation through the activation of Ras;ERK/MAPK targets;Gastrin-CREB signalling pathway via PKC and MAPK;Recycling pathway of L1;RSK activation;Senescence-Associated Secretory Phenotype (SASP) 1.20396113395691 -0.156113877892494 1.25662195682526 0.106190070509911 0.434971362352371 2.1009578704834 1.30136120319366 0.740540862083435 0.0345282182097435 -0.835493445396423 -1.40531432628632 -0.919340193271637 -0.0228433646261692 -0.398100912570953 -0.561846792697906 -0.4911849796772 -1.16380107402802 -1.22509384155273 + Cluster -674 32 31 31 42.8 41.8 41.8 109.43 0 323.31 82691000000 172 3.3406165342066 0.000562277580071174 Q15029;Q15029-2;Q15029-3 Q15029;Q15029-2;Q15029-3 116 kDa U5 small nuclear ribonucleoprotein component EFTUD2 1757 Component of the U5 snRNP and the U4/U6-U5 tri-snRNPcomplex required for pre-mRNA splicing. Binds GTP. Nucleus {ECO:0000269|PubMed:20858735}. cellular response to drug;mRNA processing;mRNA splicing, via spliceosome;response to cocaine;RNA splicing GTP binding;GTPase activity;RNA binding;U5 snRNA binding Cajal body;catalytic step 2 spliceosome;cytosol;membrane;nuclear speck;nucleoplasm;ribonucleoprotein complex;spliceosomal complex;U2-type catalytic step 2 spliceosome;U4/U6 x U5 tri-snRNP complex Spliceosome Mandibulofacial dysostosis with microcephaly mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway ALL-1 supercomplex;C complex spliceosome;SNW1 complex;Spliceosome 1.67625570297241 0.0719550773501396 0.761990666389465 -0.0514848679304123 0.484812498092651 1.39455580711365 1.12658858299255 1.27533054351807 0.0719550773501396 -1.2363269329071 -1.62586402893066 -1.0757782459259 0.289415925741196 0.05610116943717 -0.203994959592819 -0.931948721408844 -1.15161454677582 -0.931948721408844 + Cluster -674 4 4 4 7.9 7.9 7.9 90.359 0 40.989 2190200000 13 3.17345792142946 0.000778675282714055 Q9Y6A5 Q9Y6A5 Transforming acidic coiled-coil-containing protein 3 TACC3 3335 Plays a role in the microtubule-dependent coupling ofthe nucleus and the centrosome. Involved in the processes thatregulate centrosome-mediated interkinetic nuclear migration (INM)of neural progenitors (By similarity). Acts as component of theTACC3/ch-TOG/clathrin complex proposed to contribute tostabilization of kinetochore fibers of the mitotic spindle byacting as inter-microtubule bridge. The TACC3/ch-TOG/clathrincomplex is required for the maintenance of kinetochore fibertension (PubMed:21297582, PubMed:23532825). May be involved in thecontrol of cell growth and differentiation. May contribute tocancer (PubMed:14767476). Cytoplasm {ECO:0000250}. Cytoplasm,cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:17545617}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:17545617, ECO:0000269|PubMed:21297582,ECO:0000269|PubMed:23918938}. Cytoplasm, cytoskeleton, spindlepole {ECO:0000250|UniProtKB:Q9PTG8}. Note=In complex with CKAP5localized to microtubule plus-ends in mitosis and interphase. Incomplex with CKAP5 and clathrin localized to inter-microtubulebridges in mitotic spindles. {ECO:0000269|PubMed:25596274}. cell division;cell proliferation;cerebral cortex development;metaphase/anaphase transition of mitotic cell cycle;microtubule cytoskeleton organization;microtubule cytoskeleton organization involved in mitosis;mitotic spindle organization;regulation of mitotic spindle organization cytoplasm;cytosol;microtubule organizing center;mitotic spindle;spindle pole RNA transport Negative regulation of NOTCH4 signaling;NOTCH3 Activation and Transmission of Signal to the Nucleus Chromatin remodeling complex (TACC2, TACC3, PCAF) 0.850439786911011 -0.100355833768845 0.736232817173004 0.430308967828751 0.618861138820648 1.71813404560089 1.52974581718445 1.17389225959778 -0.203789800405502 -1.38270425796509 -1.72571861743927 -1.19472587108612 -0.028453815728426 0.0754228830337524 -0.165584176778793 -0.371173113584518 -0.849973380565643 -1.11055874824524 + Cluster -674 29 29 29 28.1 28.1 28.1 141.54 0 323.31 35469000000 139 4.52136471776443 5E-05 Q9UQE7 Q9UQE7 Structural maintenance of chromosomes protein 3 SMC3 3211 Central component of cohesin, a complex required forchromosome cohesion during the cell cycle. The cohesin complex mayform a large proteinaceous ring within which sister chromatids canbe trapped. At anaphase, the complex is cleaved and dissociatesfrom chromatin, allowing sister chromatids to segregate. Cohesionis coupled to DNA replication and is involved in DNA repair. Thecohesin complex plays also an important role in spindle poleassembly during mitosis and in chromosomes movement Nucleus {ECO:0000250|UniProtKB:Q9CW03}.Chromosome {ECO:0000250|UniProtKB:Q9CW03}. Chromosome, centromere{ECO:0000250|UniProtKB:Q9CW03}. Note=Associates with chromatin.Before prophase it is scattered along chromosome arms. Duringprophase, most of cohesin complexes dissociate from chromatinprobably because of phosphorylation by PLK, except at centromeres,where cohesin complexes remain. At anaphase, the RAD21 subunit ofthe cohesin complex is cleaved, leading to the dissociation of thecomplex from chromosomes, allowing chromosome separation. Thephosphorylated form at Ser-1083 is preferentially associated withunsynapsed chromosomal regions (By similarity).{ECO:0000250|UniProtKB:Q9CW03}. cell division;DNA repair;interaction with symbiont;meiotic cell cycle;mitotic cell cycle;negative regulation of DNA endoreduplication;positive regulation by host of viral release from host cell;regulation of DNA replication;regulation of mitotic spindle assembly;sister chromatid cohesion;stem cell population maintenance ATP binding;beta-tubulin binding;chromatin binding;dynein complex binding;mediator complex binding;microtubule motor activity;protein heterodimerization activity basement membrane;chromatin;chromosome;chromosome, centromeric region;cohesin complex;cytosol;intracellular;lateral element;meiotic cohesin complex;mitotic spindle pole;nuclear matrix;nuclear meiotic cohesin complex;nucleoplasm;nucleus Cell cycle;Oocyte meiosis Cornelia de Lange syndrome Cohesin Loading onto Chromatin;Establishment of Sister Chromatid Cohesion;Estrogen-dependent gene expression;Meiotic synapsis;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids;SUMOylation of DNA damage response and repair proteins Cohesin-SA1 complex;Cohesin-SA2 complex;DDX11-RAD21-SMC1A-SMC3 complex;SMC1-SMC3 complex;SNF2h-cohesin-NuRD complex;Sororin-cohesin complex 1.15385830402374 0.0957794040441513 0.763733446598053 0.108635850250721 0.53158563375473 1.64943337440491 1.44314205646515 1.03192031383514 -0.0466262809932232 -1.42279279232025 -1.92211544513702 -0.762860417366028 0.246699064970016 -0.334986835718155 0.0715367868542671 -0.535273909568787 -1.03583431243896 -1.03583431243896 + Cluster -674 3 3 3 23.5 23.5 23.5 21.991 0 86.839 4829000000 14 3.50212607284845 0.00042570281124498 Q13951-2;Q13951 Q13951-2;Q13951 Core-binding factor subunit beta CBFB 1671 Forms the heterodimeric complex core-binding factor(CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNXmembers modulate the transcription of their target genes throughrecognizing the core consensus binding sequence 5'-TGTGGT-3', orvery rarely, 5'-TGCGGT-3', within their regulatory regions viatheir runt domain, while CBFB is a non-DNA-binding regulatorysubunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core siteof a number of enhancers and promoters, including murine leukemiavirus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3and GM-CSF promoters. CBF complexes repress ZBTB7B transcriptionfactor during cytotoxic (CD8+) T cell development. They bind toRUNX-binding sequence within the ZBTB7B locus acting astranscriptional silencer and allowing for cytotoxic T celldifferentiation. Nucleus {ECO:0000305}. cell maturation;definitive hemopoiesis;lymphocyte differentiation;myeloid cell differentiation;negative regulation of CD4-positive, alpha-beta T cell differentiation;negative regulation of transcription by RNA polymerase II;osteoblast differentiation;positive regulation of CD8-positive, alpha-beta T cell differentiation;positive regulation of transcription by RNA polymerase II;protein polyubiquitination;regulation of B cell receptor signaling pathway;regulation of bicellular tight junction assembly;regulation of cytokine-mediated signaling pathway;regulation of hematopoietic stem cell differentiation;regulation of intracellular estrogen receptor signaling pathway;regulation of keratinocyte differentiation;regulation of megakaryocyte differentiation;regulation of myeloid cell differentiation;regulation of regulatory T cell differentiation;regulation of Wnt signaling pathway;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter DNA binding;DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding;transcription coactivator activity;transcription coregulator activity core-binding factor complex;membrane;nucleoplasm;nucleus Estrogen-dependent gene expression;Regulation of RUNX1 Expression and Activity;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;RUNX1 regulates estrogen receptor mediated transcription;RUNX1 regulates expression of components of tight junctions;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RUNX1 regulates transcription of genes involved in BCR signaling;RUNX1 regulates transcription of genes involved in differentiation of HSCs;RUNX1 regulates transcription of genes involved in differentiation of keratinocytes;RUNX1 regulates transcription of genes involved in differentiation of myeloid cells;RUNX1 regulates transcription of genes involved in interleukin signaling;RUNX1 regulates transcription of genes involved in WNT signaling;RUNX2 regulates bone development;RUNX2 regulates chondrocyte maturation;RUNX2 regulates genes involved in cell migration;RUNX2 regulates genes involved in differentiation of myeloid cells;RUNX2 regulates osteoblast differentiation;RUNX3 Regulates Immune Response and Cell Migration;RUNX3 regulates p14-ARF;RUNX3 regulates RUNX1-mediated transcription;Transcriptional regulation by RUNX2 COPRS-PRMT5-RUNX1-CBFB complex;RUNX1-CBF-beta-DNA complex 1.09258592128754 0.0263468697667122 0.59201192855835 -0.146754950284958 0.438954949378967 1.77208602428436 1.57467865943909 0.955610156059265 0.0451174154877663 -1.68472027778625 -1.83506453037262 -0.937009871006012 0.254048228263855 -0.0448811464011669 -0.0547159425914288 -0.365168780088425 -0.877993285655975 -0.805131316184998 + Cluster -674 11 11 11 28.5 28.5 28.5 52.904 0 172 11858000000 76 3.38057314783701 0.000523809523809524 O00232;O00232-2 O00232;O00232-2 26S proteasome non-ATPase regulatory subunit 12 PSMD12 74 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair neutrophil degranulation;post-translational protein modification;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination cytoplasm;cytosol;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;membrane;nuclear proteasome complex;nucleoplasm;proteasome accessory complex;proteasome complex;proteasome regulatory particle;proteasome regulatory particle, lid subcomplex;secretory granule lumen Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;Neutrophil degranulation;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 PA700 complex;PA700-20S-PA28 complex 0.932223618030548 0.264838933944702 0.624054431915283 0.264838933944702 0.54217529296875 1.59569013118744 1.55801296234131 1.11015808582306 -0.014549002982676 -1.4620304107666 -1.96950781345367 -0.477328360080719 0.204661399126053 -0.169310480356216 -0.390320241451263 -0.38863018155098 -1.05144083499908 -1.17353641986847 + Cluster -674 9 9 9 46.1 46.1 46.1 23.207 0 207.35 207620000000 130 3.5569725650171 0.000384615384615385 P52565;P52565-2 P52565;P52565-2 Rho GDP-dissociation inhibitor 1 ARHGDIA 1179 Controls Rho proteins homeostasis. Regulates the GDP/GTPexchange reaction of the Rho proteins by inhibiting thedissociation of GDP from them, and the subsequent binding of GTPto them. Retains Rho proteins such as CDC42, RAC1 and RHOA in aninactive cytosolic pool, regulating their stability and protectingthem from degradation. Actively involved in the recycling anddistribution of activated Rho GTPases in the cell, mediatesextraction from membranes of both inactive and activated moleculesdue its exceptionally high affinity for prenylated forms. Throughthe modulation of Rho proteins, may play a role in cell motilityregulation. In glioma cells, inhibits cell migration and invasionby mediating the signals of SEMA5A and PLXNB3 that lead toinactivation of RAC1. Cytoplasm {ECO:0000269|PubMed:23434736}. negative regulation of apoptotic process;negative regulation of axonogenesis;negative regulation of cell adhesion;positive regulation of axonogenesis;regulation of actin cytoskeleton reorganization;regulation of Rho protein signal transduction;regulation of small GTPase mediated signal transduction;Rho protein signal transduction;semaphorin-plexin signaling pathway GTPase activator activity;Rac GTPase binding;Rho GDP-dissociation inhibitor activity cytoskeleton;cytosol;extracellular exosome;membrane Neurotrophin signaling pathway;Vasopressin-regulated water reabsorption Nephrotic syndrome Axonal growth inhibition (RHOA activation);Axonal growth stimulation;Rho GTPase cycle 1.31650686264038 0.284756481647491 0.800703346729279 0.0424442514777184 0.382685601711273 1.6300482749939 1.1350702047348 1.28111660480499 0.0108353281393647 -1.13989400863647 -1.88742566108704 -0.630450785160065 0.435655772686005 -0.543815910816193 -0.280316859483719 -0.593447029590607 -1.36224663257599 -0.882225811481476 + Cluster -674 1 1 1 3.1 3.1 3.1 62.543 0.00034083 2.9815 258640000 3 3.11162179047745 0.000888888888888889 Q9P270 Q9P270 SLAIN motif-containing protein 2 SLAIN2 3049 Binds to the plus end of microtubules and regulatesmicrotubule dynamics and microtubule organization. Promotescytoplasmic microtubule nucleation and elongation. Required fornormal structure of the microtubule cytoskeleton duringinterphase. Cytoplasm, cytoskeleton. Note=Colocalizeswith microtubules. Detected at the plus end of growingmicrotubules. cytoplasmic microtubule organization;microtubule nucleation;positive regulation of microtubule polymerization centrosome;cytosol;microtubule cytoskeleton 1.38961482048035 0.2838014960289 0.98941957950592 -0.0706923976540565 0.582144975662231 1.83544206619263 1.31228911876678 0.950696885585785 -0.34617891907692 -1.10009956359863 -1.55716955661774 -0.732952177524567 0.214714124798775 -0.491130709648132 -0.431799620389938 -0.551715195178986 -1.2076199054718 -1.06876492500305 + Cluster -674 3 3 3 7.7 7.7 7.7 51.958 0 17.519 5009500000 21 3.13095491339947 0.000856240126382307 P55081 P55081 Microfibrillar-associated protein 1 MFAP1 1236 Involved in pre-mRNA splicing as a component of thespliceosome. Nucleus {ECO:0000269|PubMed:28781166}. mRNA splicing, via spliceosome RNA binding extracellular region;microfibril;nucleus;U2-type precatalytic spliceosome Molecules associated with elastic fibres Spliceosome 1.38903844356537 0.00567331630736589 0.956991195678711 0.0166158154606819 0.654987454414368 1.83910179138184 1.23995172977448 0.833148658275604 -0.136664122343063 -1.29738759994507 -1.41977059841156 -0.845494031906128 0.457219362258911 -0.420226961374283 -0.38656547665596 -0.496670037508011 -1.33872509002686 -1.0512238740921 + Cluster -674 4 4 4 9.4 9.4 9.4 54.29 0 50.757 4552500000 20 3.07131524660178 0.000948170731707317 Q14108;Q14108-2 Q14108;Q14108-2 Lysosome membrane protein 2 SCARB2 1676 Acts as a lysosomal receptor for glucosylceramidase(GBA) targeting. Multi-pass membrane protein{ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:18022370,ECO:0000269|PubMed:7509809}.;Lysosome membrane{ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:18022370,ECO:0000269|PubMed:7509809} aminophospholipid transport;membrane organization;positive regulation of neuron projection development;protein targeting to lysosome;receptor-mediated endocytosis;regulation of cellular carbohydrate catabolic process;regulation of endosome organization;regulation of glucosylceramidase activity;regulation of lysosome organization cholesterol binding;enzyme binding;phosphatidylcholine binding;phosphatidylserine binding;phospholipid transporter activity;protein homodimerization activity;protein transporter activity;scavenger receptor activity;transmembrane signaling receptor activity;virus receptor activity clathrin-coated vesicle membrane;endocytic vesicle membrane;endoplasmic reticulum membrane;endosome membrane;extracellular exosome;focal adhesion;Golgi membrane;integral component of membrane;late endosome membrane;lysosomal lumen;lysosomal membrane;membrane;plasma membrane Lysosome Progressive myoclonic epilepsy Cargo recognition for clathrin-mediated endocytosis;Clathrin-mediated endocytosis 1.4128258228302 0.189050272107124 0.796144962310791 -0.0239376276731491 0.679518163204193 1.70802652835846 1.75787079334259 0.787595689296722 -0.184055596590042 -1.21104633808136 -1.47969424724579 -0.539553880691528 -0.17265023291111 -0.380303084850311 -0.47025454044342 -0.672044456005096 -1.12535548210144 -1.072136759758 + Cluster -674 8 8 8 29.3 29.3 29.3 34.333 0 59.35 7297700000 31 3.34705088422324 0.000554561717352415 O15144 O15144 Actin-related protein 2/3 complex subunit 2 ARPC2 168 Actin-binding component of the Arp2/3 complex, amultiprotein complex that mediates actin polymerization uponstimulation by nucleation-promoting factor (NPF) (PubMed:9230079).The Arp2/3 complex mediates the formation of branched actinnetworks in the cytoplasm, providing the force for cell motility(PubMed:9230079). Seems to contact the mother actin filament(PubMed:9230079). In addition to its role in the cytoplasmiccytoskeleton, the Arp2/3 complex also promotes actinpolymerization in the nucleus, thereby regulating genetranscription and repair of damaged DNA (PubMed:29925947). TheArp2/3 complex promotes homologous recombination (HR) repair inresponse to DNA damage by promoting nuclear actin polymerization,leading to drive motility of double-strand breaks (DSBs)(PubMed:29925947). Cytoplasm, cytoskeleton{ECO:0000269|PubMed:9230079}. Cell projection{ECO:0000269|PubMed:9230079}. Cell junction, synapse, synaptosome{ECO:0000250|UniProtKB:Q9CVB6}. Nucleus{ECO:0000269|PubMed:29925947}. actin filament polymerization;actin polymerization-dependent cell motility;Arp2/3 complex-mediated actin nucleation;ephrin receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;membrane organization;positive regulation of lamellipodium assembly;positive regulation of substrate adhesion-dependent cell spreading actin filament binding;structural constituent of cytoskeleton actin cytoskeleton;Arp2/3 protein complex;cytosol;endosome;extracellular exosome;focal adhesion;glutamatergic synapse;lamellipodium;muscle cell projection membrane;neuron projection;nucleus;site of double-strand break Bacterial invasion of epithelial cells;Endocytosis;Fc gamma R-mediated phagocytosis;Pathogenic Escherichia coli infection;Regulation of actin cytoskeleton;Salmonella infection;Shigellosis Clathrin-mediated endocytosis;EPHB-mediated forward signaling;Regulation of actin dynamics for phagocytic cup formation;RHO GTPases Activate WASPs and WAVEs Arp2/3 protein complex 1.17999279499054 0.107524946331978 0.639071464538574 -0.0242587607353926 0.542649149894714 1.87331330776215 1.7147045135498 1.09050524234772 -0.248453482985497 -1.3466888666153 -1.68798935413361 -0.57042270898819 -0.0636465698480606 -0.416497528553009 -0.593259215354919 -0.589980661869049 -0.669489026069641 -0.937075316905975 + Cluster -674 8 7 7 9.4 8.5 8.5 120.68 0 86.535 3164800000 23 3.37860523631493 0.000530164533820841 Q9Y2J2;Q9Y2J2-2;Q9Y2J2-4;Q9Y2J2-3 Q9Y2J2;Q9Y2J2-2;Q9Y2J2-4;Q9Y2J2-3 Band 4.1-like protein 3;Band 4.1-like protein 3, N-terminally processed EPB41L3 3230 Tumor suppressor that inhibits cell proliferation andpromotes apoptosis. Modulates the activity of protein arginine N-methyltransferases, including PRMT3 and PRMT5 Cytoplasmic side{ECO:0000269|PubMed:9892180}. Cytoplasm{ECO:0000269|PubMed:9892180}. Note=Detected in the cytoplasm ofactively dividing cells.; Peripheral membrane protein{ECO:0000269|PubMed:9892180};Cytoplasm, cytoskeleton {ECO:0000250}. Celljunction {ECO:0000269|PubMed:9892180}. Cell membrane{ECO:0000269|PubMed:9892180} actomyosin structure organization;apoptotic process;cortical actin cytoskeleton organization;cortical cytoskeleton organization;cytoskeletal anchoring at plasma membrane;myelin maintenance;neuron projection morphogenesis;paranodal junction assembly;protein localization to juxtaparanode region of axon;protein localization to paranode region of axon;protein localization to plasma membrane;regulation of cell growth;regulation of cell shape actin binding;structural constituent of cytoskeleton axolemma;cell-cell junction;cytoskeleton;cytosol;juxtaparanode region of axon;paranode region of axon;plasma membrane;postsynaptic density Neurexins and neuroligins CADM1-4.1B-MPP3 complex 1.47025692462921 -0.184971302747726 0.808987259864807 -0.126251459121704 0.692753851413727 1.74792444705963 1.64688301086426 0.907718539237976 -0.114040918648243 -1.49262583255768 -1.27983474731445 -0.832790017127991 -0.130746483802795 -0.40173402428627 -0.16480627655983 -0.57261335849762 -1.04976892471313 -0.924340665340424 + Cluster -674 14 14 14 16.7 16.7 16.7 113.37 0 164.92 7488400000 41 3.23912295977955 0.000693467336683417 Q8WWM7;Q8WWM7-6;Q8WWM7-8;Q8WWM7-5;Q8WWM7-4;Q8WWM7-9;Q8WWM7-2;Q8WWM7-3;Q8WWM7-7 Q8WWM7;Q8WWM7-6;Q8WWM7-8;Q8WWM7-5;Q8WWM7-4;Q8WWM7-9;Q8WWM7-2;Q8WWM7-3;Q8WWM7-7 Ataxin-2-like protein ATXN2L 2304 Involved in the regulation of stress granule and P-bodyformation. Membrane {ECO:0000269|PubMed:11784712};Peripheral membrane protein {ECO:0000269|PubMed:11784712}.Cytoplasm {ECO:0000269|PubMed:23209657}. Nucleus speckle{ECO:0000269|PubMed:23209657}. Cytoplasmic granule{ECO:0000269|PubMed:23209657}. Note=Predominantly cytoplasmic butis also detected in nuclear speckles (PubMed:23209657). Componentof cytoplasmic stress granules (PubMed:23209657). Inhibition ofmethylation alters nuclear localization (PubMed:25748791).Methylation does not seem to be required for localization tostress granules under stress conditions (PubMed:25748791).{ECO:0000269|PubMed:23209657, ECO:0000269|PubMed:25748791}. regulation of cytoplasmic mRNA processing body assembly;stress granule assembly cadherin binding;RNA binding cytoplasmic stress granule;cytosol;membrane;nuclear speck 1.0052170753479 0.661374032497406 0.365589559078217 0.341830909252167 0.535931587219238 1.61655735969543 1.91381096839905 0.499117285013199 -0.0384397991001606 -1.16014337539673 -1.91931521892548 -0.77279257774353 0.0622278898954391 -0.0515838153660297 -0.187917068600655 -0.829753696918488 -0.868655562400818 -1.17305541038513 + Cluster -674 3 3 3 14.4 14.4 14.4 30.188 0 24.146 1498000000 7 3.29566546849387 0.000599309153713299 P29218;P29218-3;P29218-2 P29218;P29218-3 Inositol monophosphatase 1 IMPA1 849 Responsible for the provision of inositol required forsynthesis of phosphatidylinositol and polyphosphoinositides andhas been implicated as the pharmacological target for lithiumaction in brain. Has broad substrate specificity and can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, D-galactose1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates Cytoplasm {ECO:0000269|PubMed:17068342}. inositol biosynthetic process;inositol phosphate dephosphorylation;inositol phosphate metabolic process;phosphate-containing compound metabolic process;phosphatidylinositol biosynthetic process;phosphatidylinositol phosphorylation;signal transduction identical protein binding;inositol monophosphate 1-phosphatase activity;inositol monophosphate 3-phosphatase activity;inositol monophosphate 4-phosphatase activity;inositol monophosphate phosphatase activity;lithium ion binding;magnesium ion binding;manganese ion binding;protein homodimerization activity cytoplasm;cytosol Inositol phosphate metabolism;Metabolic pathways;Phosphatidylinositol signaling system Autosomal recessive mental retardation Synthesis of IP2, IP, and Ins in the cytosol 0.933176100254059 0.442850440740585 0.690086841583252 0.381515234708786 0.690086841583252 1.50235116481781 1.31002461910248 1.03463017940521 -0.0500917062163353 -1.34492135047913 -1.95351231098175 -0.829285562038422 -0.0214353837072849 -0.165117472410202 0.467234998941422 -0.866280734539032 -1.03142833709717 -1.18988358974457 + Cluster -674 4 4 4 21.3 21.3 21.3 31.698 0 71.893 3350800000 12 3.82137462826253 0.000239185750636132 Q96GD0 Q96GD0 Pyridoxal phosphate phosphatase PDXP 2461 Protein serine phosphatase that dephosphorylates 'Ser-3'in cofilin and probably also dephosphorylates phospho-serineresidues in DSTN. Regulates cofilin-dependent actin cytoskeletonreorganization. Required for normal progress through mitosis andnormal cytokinesis. Does not dephosphorylate phospho-threonines inLIMK1. Does not dephosphorylate peptides containing phospho-tyrosine (PubMed:15580268). Pyridoxal phosphate (PLP) phosphatase,which also catalyzes the dephosphorylation of pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), with order ofsubstrate preference PLP > PNP > PMP (PubMed:14522954) Cytoplasmic side{ECO:0000269|PubMed:15580268}. Cell membrane{ECO:0000269|PubMed:15580268}; Cytoplasmic side{ECO:0000269|PubMed:15580268}. Cell projection, lamellipodiummembrane {ECO:0000269|PubMed:15580268}; Cytoplasmic side{ECO:0000269|PubMed:15580268}. Note=Colocalizes with the actincytoskeleton in membrane ruffles and lamellipodia. Diffuselydistributed throughout the cytosol during pro-metaphase andmetaphase. Detected at the dynamic cell poles during telophase.Detected at the cleavage furrow and contractile ring duringcytokinesis. Transiently detected at the plasma membrane in latestages of cytokinesis. Detected at the midbody.{ECO:0000269|PubMed:15580268}.; Peripheral membrane protein{ECO:0000269|PubMed:15580268}; Peripheral membraneprotein {ECO:0000269|PubMed:15580268};Cytoplasm, cytosol{ECO:0000269|PubMed:15580268}. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:15580268}. Cell projection, ruffle membrane{ECO:0000269|PubMed:15580268} actin rod assembly;cellular response to ATP;dephosphorylation;positive regulation of actin filament depolymerization;protein dephosphorylation;pyridoxal phosphate catabolic process;regulation of cytokinesis;regulation of mitotic nuclear division heat shock protein binding;magnesium ion binding;phosphatase activity;phosphoprotein phosphatase activity;phosphoserine phosphatase activity;protein homodimerization activity;pyridoxal phosphatase activity cell-cell junction;cytoplasm;cytoskeleton;cytosol;lamellipodium membrane;ruffle membrane Metabolic pathways;Vitamin B6 metabolism 1.27086770534515 0.20408108830452 0.853510737419128 0.14133295416832 0.709558248519897 1.25300133228302 1.45111644268036 1.0364089012146 0.285048454999924 -1.37646794319153 -1.69037711620331 -0.361500054597855 0.114623002707958 -0.0653202757239342 -0.361500054597855 -0.841562986373901 -1.109494805336 -1.51332557201385 + Cluster -674 3 3 3 38.2 38.2 38.2 10.378 0 5.9597 494840000 4 3.45173839670194 0.000471264367816092 Q9Y5J7 Q9Y5J7 Mitochondrial import inner membrane translocase subunit Tim9 TIMM9 3309 Mitochondrial intermembrane chaperone that participatesin the import and insertion of multi-pass transmembrane proteinsinto the mitochondrial inner membrane. May also be required forthe transfer of beta-barrel precursors from the TOM complex to thesorting and assembly machinery (SAM complex) of the outermembrane. Acts as a chaperone-like protein that protects thehydrophobic precursors from aggregation and guide them through themitochondrial intermembrane space. Intermembrane side{ECO:0000269|PubMed:11489896, ECO:0000269|PubMed:14726512}.;Mitochondrion inner membrane{ECO:0000269|PubMed:11489896, ECO:0000269|PubMed:14726512};Peripheral membrane protein {ECO:0000269|PubMed:11489896,ECO:0000269|PubMed:14726512} chaperone-mediated protein transport;protein import into mitochondrial inner membrane;protein targeting to mitochondrion;sensory perception of sound chaperone binding;protein homodimerization activity;transporter activity;zinc ion binding mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrial intermembrane space protein transporter complex;mitochondrion Mitochondrial protein import TIM (TIM9, TIM10) complex, mitochondrial 1.16308331489563 0.253688812255859 0.535114824771881 0.850417971611023 0.442220240831375 1.53704023361206 1.62200057506561 0.812970876693726 -0.056677408516407 -0.67820405960083 -2.09337282180786 -0.409966915845871 -0.14644929766655 -0.234034895896912 -0.409966915845871 -0.839852035045624 -1.21748340129852 -1.13052904605865 + Cluster -674 4 4 4 11.1 11.1 11.1 51.026 0 10.651 194750000 5 3.43050899614012 0.000492424242424242 P31146 P31146 Coronin-1A CORO1A 883 May be a crucial component of the cytoskeleton of highlymotile cells, functioning both in the invagination of large piecesof plasma membrane, as well as in forming protrusions of theplasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane preventsfusion between phagosomes and lysosomes Cytoplasm, cytoskeleton {ECO:0000250}.Cytoplasm, cell cortex {ECO:0000250}. Cytoplasmic vesicle,phagosome membrane {ECO:0000250}. Note=In non-infectedmacrophages, associated with the cortical microtubule network. Inmycobacteria-infected macrophages, becomes progressivelyrelocalized and retained around the mycobacterial phagosomes.Retention on the phagosomal membrane is strictly dependent onmycobacterial viability and not due to impaired acidification (Bysimilarity). {ECO:0000250}. actin cytoskeleton organization;actin filament organization;calcium ion transport;cell-substrate adhesion;cellular response to interleukin-4;early endosome to recycling endosome transport;homeostasis of number of cells within a tissue;innate immune response;leukocyte chemotaxis;natural killer cell degranulation;negative regulation of actin nucleation;negative regulation of neuron apoptotic process;negative regulation of vesicle fusion;nerve growth factor signaling pathway;phagocytosis;phagolysosome assembly;positive chemotaxis;positive regulation of cell migration;positive regulation of T cell proliferation;regulation of actin cytoskeleton organization;regulation of cell shape;regulation of release of sequestered calcium ion into cytosol;T cell homeostasis;uropod organization actin binding;actin filament binding;actin monomer binding;cytoskeletal protein binding;myosin heavy chain binding;phosphatidylinositol 3-kinase binding;protein C-terminus binding;protein homodimerization activity;RNA binding actin filament;axon;cell-cell junction;cortical actin cytoskeleton;cytoplasm;cytosol;early endosome;extracellular exosome;glutamatergic synapse;immunological synapse;lamellipodium;membrane;phagocytic cup;phagocytic vesicle;phagocytic vesicle membrane;plasma membrane;protein-containing complex Phagosome;Tuberculosis T-B+Severe combined immunodeficiency 1.49841332435608 0.368577092885971 0.49841383099556 0.234813421964645 0.582809269428253 1.57667398452759 1.20668113231659 0.872457385063171 0.274237543344498 -0.775445580482483 -1.95904076099396 -0.659826278686523 0.0801781564950943 -0.0155343012884259 -0.326159179210663 -0.889290034770966 -1.03730201721191 -1.53065693378448 + Cluster -674 1 1 1 5.3 5.3 5.3 33.814 0 4.2525 1082100000 4 3.16794650100239 0.000789389067524116 O75880 O75880 Protein SCO1 homolog, mitochondrial SCO1 363 Copper metallochaperone essential for the maturation ofcytochrome c oxidase subunit II (MT-CO2/COX2). Not required forthe synthesis of MT-CO2/COX2 but plays a crucial role instabilizing MT-CO2/COX2 during its subsequent maturation. Involvedin transporting copper to the Cu(A) site on MT-CO2/COX2(PubMed:15659396, PubMed:16735468, PubMed:17189203,PubMed:19336478, PubMed:15229189). Plays an important role in theregulation of copper homeostasis by controlling the abundance andcell membrane localization of copper transporter CTR1 (Bysimilarity). Mitochondrion {ECO:0000269|PubMed:9878253}.Mitochondrion inner membrane {ECO:0000269|PubMed:15229189};Single-pass membrane protein {ECO:0000255}. cellular copper ion homeostasis;copper ion transport;generation of precursor metabolites and energy;mitochondrial respiratory chain complex IV assembly;negative regulation of proteasomal protein catabolic process;respiratory chain complex IV assembly copper ion binding host cell mitochondrial intermembrane space;integral component of mitochondrial inner membrane;mitochondrion;myofibril Cytochrome c oxidase (COX) deficiency Respiratory electron transport;TP53 Regulates Metabolic Genes 1.52740275859833 0.293552994728088 0.208503782749176 0.155281960964203 1.02059161663055 1.01579606533051 1.3350682258606 1.08960974216461 0.618521273136139 -0.372179746627808 -1.49330258369446 -0.96770042181015 0.312167912721634 -0.342622935771942 -0.576885104179382 -1.1646740436554 -0.915378987789154 -1.74375247955322 + Cluster -674 16 16 1 67.3 67.3 10.6 23.548 0 94.389 24670000000 62 3.1783195883196 0.000773983739837398 P20340-2;P20340-4;Q53S08;Q9H0N0 P20340-2;P20340-4 Ras-related protein Rab-6A RAB6A 743 May be involved in the regulation of centrosomeduplication and cell cycle progression;Protein transport. Regulator of membrane traffic fromthe Golgi apparatus towards the endoplasmic reticulum (ER). Has alow GTPase activity. Involved in COPI-independent retrogradetransport from the Golgi to the ER (PubMed:25962623) Lipid-anchor {ECO:0000269|PubMed:25962623}. Note=BICD2 facilitates itstargeting to Golgi apparatus membrane.{ECO:0000269|PubMed:25962623}.Isoform 1: Golgi apparatus membrane{ECO:0000269|PubMed:11071909}; Lipid-anchor {ECO:0000305}.; Lipid-anchor {ECO:0000305}.Isoform 2: Golgi apparatus membrane{ECO:0000269|PubMed:11071909};Golgi apparatus membrane{ECO:0000269|PubMed:23091056, ECO:0000269|PubMed:25962623};Nucleus {ECO:0000269|PubMed:16103095}.Cytoplasm {ECO:0000269|PubMed:16103095}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome{ECO:0000269|PubMed:20064528}. antigen processing and presentation;early endosome to Golgi transport;intracellular protein transport;intra-Golgi vesicle-mediated transport;minus-end-directed organelle transport along microtubule;mitotic cell cycle;neutrophil degranulation;peptidyl-cysteine methylation;protein localization to Golgi apparatus;Rab protein signal transduction;regulation of centrosome duplication;response to drug;retrograde transport, endosome to Golgi;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;small GTPase mediated signal transduction;viral process GTP binding;GTPase activity;myosin V binding;protein domain specific binding centrosome;cytoplasmic vesicle;cytosol;endoplasmic reticulum membrane;endosome to plasma membrane transport vesicle;extracellular exosome;Golgi apparatus;Golgi membrane;intracellular;membrane;nucleus;plasma membrane;secretory granule membrane;trans-Golgi network;trans-Golgi network membrane COPI-independent Golgi-to-ER retrograde traffic;Neutrophil degranulation;Pre-NOTCH Processing in Golgi;RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation;Retrograde transport at the Trans-Golgi-Network;TBC/RABGAPs 1.41382431983948 0.219542220234871 0.572421371936798 0.193472146987915 0.669154405593872 1.27580213546753 1.64806115627289 1.47065734863281 -0.511622667312622 -1.47201359272003 -1.39863443374634 -0.424842208623886 -0.270204871892929 -0.00915847159922123 -0.819660186767578 -0.5831218957901 -1.12008130550385 -0.853595554828644 + Cluster -674 6 2 2 22.6 11.8 11.8 40.089 0 17.848 554290000 3 3.24722552877925 0.000680203045685279 P16989;P16989-3;P16989-2 P16989;P16989-3;P16989-2 Y-box-binding protein 3 YBX3 699 Binds to the GM-CSF promoter. Seems to act as arepressor. Binds also to full-length mRNA and to short RNAsequences containing the consensus site 5'-UCCAUCA-3'. May have arole in translation repression (By similarity). Cytoplasm. Nucleus. 3'-UTR-mediated mRNA stabilization;cellular hyperosmotic response;cellular response to tumor necrosis factor;fertilization;in utero embryonic development;male gonad development;negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress;negative regulation of necroptotic process;negative regulation of skeletal muscle tissue development;negative regulation of transcription by RNA polymerase II;positive regulation of cytoplasmic translation;positive regulation of organ growth;response to cold;spermatogenesis DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;double-stranded DNA binding;mRNA 3'-UTR binding;polysome binding;Rho GTPase binding;RNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;transcription corepressor activity bicellular tight junction;cytoplasm;cytosol;nucleus;perinuclear region of cytoplasm Tight junction H2AX complex II 1.50010907649994 0.148860737681389 0.608382046222687 0.148860737681389 0.608382046222687 1.47197508811951 1.47197508811951 1.47197508811951 -0.333040475845337 -1.27148854732513 -1.5433201789856 -0.198657289147377 -0.198657289147377 -0.601897716522217 -0.601897716522217 -0.593909561634064 -0.943414866924286 -1.14423620700836 + Cluster -674 55 35 35 61.6 42.3 42.3 84.659 0 323.31 627230000000 536 3.26136249214175 0.000650254668930391 P07900;P07900-2;Q14568;Q58FG0;Q58FF6;Q58FG1 P07900;P07900-2 Heat shock protein HSP 90-alpha HSP90AA1 543 Molecular chaperone that promotes the maturation,structural maintenance and proper regulation of specific targetproteins involved for instance in cell cycle control and signaltransduction. Undergoes a functional cycle that is linked to itsATPase activity which is essential for its chaperone activity.This cycle probably induces conformational changes in the clientproteins, thereby causing their activation. Interacts dynamicallywith various co-chaperones that modulate its substraterecognition, ATPase cycle and chaperone function (PubMed:11274138,PubMed:15577939, PubMed:15937123, PubMed:27353360,PubMed:29127155). Engages with a range of client protein classesvia its interaction with various co-chaperone proteins orcomplexes, that act as adapters, simultaneously able to interactwith the specific client and the central chaperone itself(PubMed:29127155). Recruitment of ATP and co-chaperone followed byclient protein forms a functional chaperone. After the completionof the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformationand finally, ADP is released from HSP90 which acquires an openconformation for the next cycle (PubMed:27295069,PubMed:26991466). Apart from its chaperone activity, it also playsa role in the regulation of the transcription machinery. HSP90 andits co-chaperones modulate transcription at least at threedifferent levels (PubMed:25973397). In the first place, they alterthe steady-state levels of certain transcription factors inresponse to various physiological cues(PubMed:25973397). Second,they modulate the activity of certain epigenetic modifiers, suchas histone deacetylases or DNA methyl transferases, and therebyrespond to the change in the environment (PubMed:25973397). Third,they participate in the eviction of histones from the promoterregion of certain genes and thereby turn on gene expression(PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) andmediates LPS-induced inflammatory response, including TNFsecretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385);Putative molecular chaperone that may promote thematuration, structural maintenance and proper regulation ofspecific target proteins. Cytoplasm {ECO:0000250}.;Nucleus {ECO:0000250|UniProtKB:P07901}.Cytoplasm {ECO:0000250|UniProtKB:P07901}. Melanosome{ECO:0000269|PubMed:17081065}. Cell membrane{ECO:0000269|PubMed:11276205}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV. axon extension;cellular response to heat;central nervous system neuron axonogenesis;chaperone-mediated autophagy;chaperone-mediated protein complex assembly;ciliary basal body-plasma membrane docking;cofactor metabolic process;cytokine-mediated signaling pathway;ERBB2 signaling pathway;establishment of cell polarity;Fc-gamma receptor signaling pathway involved in phagocytosis;G2/M transition of mitotic cell cycle;mitochondrial transport;negative regulation of proteasomal protein catabolic process;neutrophil degranulation;positive regulation of cellular protein catabolic process;positive regulation of nitric oxide biosynthetic process;positive regulation of peptidyl-serine phosphorylation;positive regulation of protein kinase B signaling;positive regulation of protein phosphorylation;positive regulation of protein polymerization;positive regulation of tau-protein kinase activity;positive regulation of telomerase activity;protein folding;protein import into mitochondrial outer membrane;protein refolding;protein stabilization;protein unfolding;receptor-mediated endocytosis;regulation of cellular protein localization;regulation of cellular response to heat;regulation of G2/M transition of mitotic cell cycle;regulation of nitric-oxide synthase activity;regulation of protein complex assembly;regulation of protein ubiquitination;response to antibiotic;response to cold;response to heat;response to unfolded protein;signal transduction;telomerase holoenzyme complex assembly;telomere maintenance via telomerase;vascular endothelial growth factor receptor signaling pathway ATP binding;ATPase activity;ATPase activity, coupled;disordered domain specific binding;DNA polymerase binding;GTPase binding;histone deacetylase binding;identical protein binding;MHC class II protein complex binding;nitric-oxide synthase regulator activity;nucleotide binding;protein homodimerization activity;protein kinase binding;protein tyrosine kinase activity;protein tyrosine kinase binding;RNA binding;scaffold protein binding;tau protein binding;TPR domain binding;ubiquitin protein ligase binding;unfolded protein binding axonal growth cone;cell surface;cytoplasm;cytosol;dendritic growth cone;endocytic vesicle lumen;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;lysosomal lumen;melanosome;membrane;myelin sheath;neuronal cell body;nucleoplasm;nucleus;perinuclear region of cytoplasm;plasma membrane;protein-containing complex;secretory granule lumen Antigen processing and presentation;Estrogen signaling pathway;Fluid shear stress and atherosclerosis;IL-17 signaling pathway;Necroptosis;NOD-like receptor signaling pathway;Pathways in cancer;PI3K-Akt signaling pathway;Progesterone-mediated oocyte maturation;Prostate cancer;Protein processing in endoplasmic reticulum;Th17 cell differentiation Alvespimycin hydrochloride;Ganetespib;Luminespib;Onalespib;Retaspimycin;Tanespimycin Anchoring of the basal body to the plasma membrane;Attenuation phase;AURKA Activation by TPX2;Constitutive Signaling by EGFRvIII;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Downregulation of ERBB2 signaling;eNOS activation;ESR-mediated signaling;Estrogen-dependent gene expression;HSF1 activation;HSF1-dependent transactivation;HSP90 chaperone cycle for steroid hormone receptors (SHR);Interleukin-4 and Interleukin-13 signaling;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Neutrophil degranulation;PIWI-interacting RNA (piRNA) biogenesis;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of actin dynamics for phagocytic cup formation;Regulation of PLK1 Activity at G2/M Transition;Scavenging by Class F Receptors;Sema3A PAK dependent Axon repulsion;Signaling by ERBB2;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation;The role of GTSE1 in G2/M progression after G2 checkpoint;Uptake and function of diphtheria toxin;VEGFA-VEGFR2 Pathway;VEGFR2 mediated vascular permeability;vRNP Assembly CDC37-HSP90AA1-HSP90AB1-MAP3K11 complex;DNAJC7-HSPA8-HSP90AA1 complex;GSK3B-HSP90AA1-PKM2 complex;HCF-1 complex;HSP90-CIP1-FKBPL complex;HSP90-FKBP38-CAM-Ca(2+) complex;Hsp90-p23 complex;IKBKB-CDC37-KIAA1967-HSP90AB1-HSP90AA1 complex;ILK-HSP90-CDC37 complex;Kinase maturation complex 1;Kinase maturation complex 2;NMNAT2-HSP90 complex;NOS3-HSP90 complex, VEGF induced;NOS3-HSP90-AKT complex, VEGF induced;TNF-alpha/NF-kappa B signaling complex 10;TNF-alpha/NF-kappa B signaling complex 6;TNF-alpha/NF-kappa B signaling complex 7;TNF-alpha/NF-kappa B signaling complex 8 1.13609170913696 0.248215764760971 0.741890251636505 0.0914106518030167 0.234954416751862 1.33003890514374 1.59880793094635 1.50449562072754 0.199178546667099 -1.12748098373413 -1.9103798866272 -0.293285071849823 -0.613228142261505 0.124266169965267 -0.613228142261505 -0.52271032333374 -0.850734531879425 -1.27830302715302 + Cluster -674 1 1 1 2 2 2 118.72 0 10.417 538470000 3 3.24542518458994 0.000681281618887015 Q9P2N5 Q9P2N5 RNA-binding protein 27 RBM27 3058 Cytoplasm. Nucleus speckle.Note=Incorporated into the nuclear speckles and to specklesproximal to the nuclear periphery. Also localizes to punctatestructures in the cytoplasm termed cytospeckles (By similarity).{ECO:0000250}. mRNA processing;positive regulation of RNA export from nucleus metal ion binding;mRNA binding;RNA binding cytoplasm;nuclear speck;nucleus 0.729061841964722 0.0811071470379829 0.839717268943787 0.335949122905731 0.729061841964722 1.65780103206635 1.47409462928772 1.47409462928772 -0.0997625291347504 -1.25238239765167 -1.73399043083191 -0.429498136043549 -0.590413987636566 -0.126456573605537 -0.473212361335754 -0.589613854885101 -0.651560544967651 -1.37399673461914 + Cluster -674 14 14 14 26.2 26.2 26.2 73.964 0 84.361 16779000000 54 4.38143330881257 5.94405594405594E-05 Q9BZE4;Q9BZE4-3;Q9BZE4-2 Q9BZE4;Q9BZE4-3;Q9BZE4-2 Nucleolar GTP-binding protein 1 GTPBP4 2725 Involved in the biogenesis of the 60S ribosomal subunit Nucleus, nucleolus{ECO:0000269|PubMed:11316846, ECO:0000269|PubMed:12429849,ECO:0000269|Ref.8}. maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);negative regulation of cell migration;negative regulation of cell proliferation;negative regulation of cell-cell adhesion;negative regulation of collagen binding;negative regulation of DNA replication;negative regulation of protein ubiquitination;osteoblast differentiation;protein stabilization;regulation of cyclin-dependent protein serine/threonine kinase activity GTP binding;GTPase activity;RNA binding cytoplasm;cytosol;Golgi apparatus;membrane;nuclear membrane;nucleolus;nucleus;perinuclear region of cytoplasm Ribosome biogenesis in eukaryotes 0.370941609144211 -0.222205370664597 1.44812703132629 0.87078732252121 0.60864394903183 2.05197954177856 1.13647186756134 1.00643599033356 -0.355663686990738 -1.13806903362274 -1.39981997013092 -0.874465346336365 -0.118253380060196 -0.118253380060196 -0.54605370759964 -0.881611466407776 -1.1763277053833 -0.662664294242859 + Cluster -674 1 1 1 5 5 5 29.717 0 8.3169 1089800000 4 5.23758135085815 1.28205128205128E-05 Q14847;Q14847-3;Q14847-2 Q14847;Q14847-3;Q14847-2 LIM and SH3 domain protein 1 LASP1 1736 Plays an important role in the regulation of dynamicactin-based, cytoskeletal activities. Agonist-dependent changes inLASP1 phosphorylation may also serve to regulate actin-associatedion transport activities, not only in the parietal cell but alsoin certain other F-actin-rich secretory epithelial cell types (Bysimilarity). Cytoplasm, cell cortex {ECO:0000250}.Cytoplasm, cytoskeleton {ECO:0000250}. Note=Associated with the F-actin rich cortical cytoskeleton. {ECO:0000250}. ion transport actin filament binding;cadherin binding;ion transmembrane transporter activity;metal ion binding;SH3/SH2 adaptor activity cortical actin cytoskeleton;cytoplasm;focal adhesion 0.746353566646576 -0.0982756614685059 0.891262829303741 0.548101246356964 0.454433917999268 1.92966389656067 1.45233297348022 1.06354403495789 -0.323599815368652 -1.71133291721344 -1.50988972187042 -0.536205232143402 0.185238972306252 -0.600010216236115 -0.273347437381744 -0.360177338123322 -0.580954313278198 -1.27713894844055 + Cluster -674 5 5 5 20.2 20.2 20.2 48.357 0 27.89 5197400000 15 3.83960432451318 0.000229381443298969 Q05048 Q05048 Cleavage stimulation factor subunit 1 CSTF1 1516 One of the multiple factors required for polyadenylationand 3'-end cleavage of mammalian pre-mRNAs. May be responsible forthe interaction of CSTF with other factors to form a stablecomplex on the pre-mRNA. Nucleus. mRNA 3'-end processing;mRNA splicing, via spliceosome;termination of RNA polymerase II transcription RNA binding mRNA cleavage stimulating factor complex;nucleoplasm mRNA surveillance pathway Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Processing of Intronless Pre-mRNAs BARD1-BRCA1-CSTF complex;Cleavage stimulation factor;Polyadenylation complex (CSTF1, CSTF2, CSTF3, SYMPK CPSF1, CPSF2, CPSF3) 0.754248857498169 0.0891484618186951 0.884243249893188 0.121326237916946 0.212909758090973 1.81777334213257 1.45656442642212 1.22994911670685 0.00528059853240848 -1.73828148841858 -1.82060301303864 -0.574333846569061 0.0991676524281502 -0.110103473067284 -0.360112905502319 -0.688896954059601 -0.241692006587982 -1.13658809661865 + Cluster -674 3 2 2 13.8 11.6 11.6 39.609 0 33.492 2237100000 9 3.52488831457462 0.000401622718052738 P54725;P54725-3;P54725-2 P54725;P54725-3;P54725-2 UV excision repair protein RAD23 homolog A RAD23A 1226 Multiubiquitin chain receptor involved in modulation ofproteasomal degradation. Binds to 'Lys-48'-linked polyubiquitinchains in a length-dependent manner and with a lower affinity to'Lys-63'-linked polyubiquitin chains. Proposed to be capable tobind simultaneously to the 26S proteasome and to polyubiquitinatedsubstrates and to deliver ubiquitinated proteins to theproteasome.Involved in nucleotide excision repair and is thought tobe functional equivalent for RAD23B in global genome nucleotideexcision repair (GG-NER) by association with XPC. In vitro, theXPC:RAD23A dimer has NER activity. Can stabilize XPC.(Microbial infection) Involved in Vpr-dependentreplication of HIV-1 in non-proliferating cells and primarymacrophages. Required for the association of HIV-1 Vpr with thehost proteasome. Nucleus. nucleotide-excision repair;positive regulation of cell cycle;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of viral genome replication;proteasome-mediated ubiquitin-dependent protein catabolic process;protein destabilization;protein deubiquitination;regulation of proteasomal ubiquitin-dependent protein catabolic process;viral process damaged DNA binding;kinase binding;polyubiquitin modification-dependent protein binding;proteasome binding;single-stranded DNA binding;ubiquitin binding;ubiquitin-specific protease binding cytoplasm;cytosol;intracellular membrane-bounded organelle;microtubule organizing center;nucleoplasm;nucleus;proteasome complex;protein-containing complex Nucleotide excision repair;Protein processing in endoplasmic reticulum DNA Damage Recognition in GG-NER;Formation of Incision Complex in GG-NER;Josephin domain DUBs 0.33030754327774 0.0778882801532745 0.80593204498291 0.591547667980194 0.510676383972168 2.16087651252747 1.15423429012299 1.2606508731842 -0.24751204252243 -1.82660591602325 -0.732874572277069 -1.52826166152954 -0.0189927015453577 -0.340144455432892 -0.128916129469872 -0.379190891981125 -1.01713788509369 -0.6724773645401 + Cluster -674 3 3 3 25.6 25.6 25.6 18.048 0 15.469 7514900000 12 4.5041224914678 5.72519083969466E-05 Q9NWV4 Q9NWV4 UPF0587 protein C1orf123 C1orf123 2981 zinc ion binding 0.0547370053827763 -0.0116940252482891 1.27978086471558 0.503129065036774 1.11709439754486 1.36954963207245 1.3218480348587 1.46371829509735 -0.56734961271286 -1.65734016895294 -1.34749686717987 -0.396402716636658 -0.0549263656139374 -0.23481185734272 -0.464103251695633 -0.0856898427009583 -0.873001873493195 -1.41704070568085 + Cluster -674 14 14 14 40 40 40 54.416 0 151.51 31375000000 74 4.69098171747239 2.99145299145299E-05 P26196 P26196 Probable ATP-dependent RNA helicase DDX6 DDX6 810 In the process of mRNA degradation, plays a role in mRNAdecapping (PubMed:16364915). Blocks autophagy in nutrient-richconditions by repressing the expression of ATG-related genesthrough degration of their transcripts (PubMed:26098573) Cytoplasm, P-body{ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16699599,ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:22915799,ECO:0000269|PubMed:26184334}. Cytoplasm{ECO:0000269|PubMed:26184334}. Nucleus{ECO:0000269|PubMed:26184334}. Note=Upon cellular stress,relocalizes to stress granules (PubMed:26184334).{ECO:0000269|PubMed:26184334}. cytoplasmic mRNA processing body assembly;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;negative regulation of neuron differentiation;spermatid differentiation;stem cell population maintenance;viral RNA genome packaging ATP binding;cadherin binding;helicase activity;protein domain specific binding;RNA binding;RNA helicase activity cell-cell adherens junction;chromatoid body;concave side of sperm head;cytoplasm;cytoplasmic ribonucleoprotein granule;cytoplasmic stress granule;cytosol;heterochromatin;membrane;mitochondrion;nucleolus;nucleus;outer dense fiber;P-body;perinuclear region of cytoplasm;RISC complex;sperm annulus RNA degradation mRNA decay by 5' to 3' exoribonuclease 4E-T-DDX6-CNOT1 complex;Decapping complex 0.501680314540863 0.153386652469635 1.01482748985291 0.483343541622162 0.638113856315613 1.65097999572754 1.2625470161438 1.52030944824219 -0.448131591081619 -1.73887014389038 -1.34290897846222 -0.980639159679413 0.462072908878326 -0.381869405508041 -0.451613575220108 -0.625550806522369 -0.901512980461121 -0.816164433956146 + Cluster -674 2 2 2 5.7 5.7 5.7 54.271 0 3.4179 459060000 3 4.75114018837357 2.6431718061674E-05 Q969S3 Q969S3 Zinc finger protein 622 ZNF622 2385 May behave as an activator of the bound transcriptionfactor, MYBL2, and be involved in embryonic development. Cytoplasm {ECO:0000269|PubMed:11802789}.Nucleus {ECO:0000269|PubMed:11802789}. intrinsic apoptotic signaling pathway in response to oxidative stress;positive regulation of apoptotic process;positive regulation of JNK cascade;positive regulation of kinase activity;positive regulation of MAPK cascade;ribosomal large subunit biogenesis DNA-binding transcription factor activity, RNA polymerase II-specific;RNA binding;zinc ion binding cytosol;cytosolic large ribosomal subunit;Golgi apparatus;nucleolus;nucleus;preribosome, large subunit precursor 1.08368396759033 -0.36418828368187 0.355760723352432 0.854961574077606 1.14491057395935 1.86097776889801 1.28628849983215 0.757770359516144 -0.526016533374786 -1.26474153995514 -1.55006468296051 -0.977979719638824 0.442782610654831 -0.277538418769836 -0.277538418769836 -1.04249274730682 -0.866117477416992 -0.640458285808563 + Cluster -674 4 4 3 10.8 10.8 8.4 52.259 0 32.544 1666800000 9 3.61443358958357 0.000346491228070175 Q15797;Q99717;Q15797-2;P84022-4 Q15797;Q99717 Mothers against decapentaplegic homolog 1;Mothers against decapentaplegic homolog 5 SMAD1;SMAD5 1830 Receptor-regulated SMAD (R-SMAD) that is anintracellular signal transducer and transcriptional modulatoractivated by TGF-beta (transforming growth factor) and activintype 1 receptor kinases. Binds the TRE element in the promoterregion of many genes that are regulated by TGF-beta and, onformation of the SMAD3/SMAD4 complex, activates transcription.Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD siteto regulate TGF-beta-mediated transcription. Has an inhibitoryeffect on wound healing probably by modulating both growth andmigration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healingappears to be hormone-sensitive. Regulator of chondrogenesis andosteogenesis and inhibits early healing of bone fractures.Positively regulates PDPK1 kinase activity by stimulating itsdissociation from the 14-3-3 protein YWHAQ which acts as anegative regulator.;Transcriptional modulator activated by BMP (bonemorphogenetic proteins) type 1 receptor kinase. SMAD1 is areceptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complexmediates the degradation of the CREBBP/EP300 repressor SNIP1. Mayact synergistically with SMAD4 and YY1 in bone morphogeneticprotein (BMP)-mediated cardiac-specific gene expression;Transcriptional modulator activated by BMP (bonemorphogenetic proteins) type 1 receptor kinase. SMAD5 is areceptor-regulated SMAD (R-SMAD). Cytoplasm {ECO:0000269|PubMed:15647271}.Nucleus {ECO:0000269|PubMed:15647271,ECO:0000269|PubMed:22781750}. Note=Cytoplasmic in the absence ofligand. Migrates to the nucleus when complexed with SMAD4(PubMed:15647271). Co-localizes with LEMD3 at the nucleus innermembrane (PubMed:15647271). Exported from the nucleus to thecytoplasm when dephosphorylated (By similarity).{ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:15647271}.;Cytoplasm {ECO:0000269|PubMed:15799969,ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19218245,ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:22781750}. Nucleus{ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15799969,ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081,ECO:0000269|PubMed:22781750}. Note=Cytoplasmic and nuclear in theabsence of TGF-beta. On TGF-beta stimulation, migrates to thenucleus when complexed with SMAD4 (PubMed:15799969). Through theaction of the phosphatase PPM1A, released from the SMAD2/SMAD4complex, and exported out of the nucleus by interaction withRANBP1 (PubMed:16751101, PubMed:19289081). Co-localizes with LEMD3at the nucleus inner membrane (PubMed:15601644). MAPK-mediatedphosphorylation appears to have no effect on nuclear import(PubMed:19218245). PDPK1 prevents its nuclear translocation inresponse to TGF-beta (PubMed:17327236).{ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15799969,ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:17327236,ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081}.;Cytoplasm. Nucleus. Note=Cytoplasmic in theabsence of ligand. Migrates to the nucleus when complexed withSMAD4. activation of cysteine-type endopeptidase activity involved in apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway;activin receptor signaling pathway;adrenal gland development;BMP signaling pathway;bone development;cardiac muscle cell proliferation;cardiac muscle contraction;cartilage development;cell cycle arrest;cell-cell junction organization;cellular response to cytokine stimulus;cellular response to organic cyclic compound;cellular response to transforming growth factor beta stimulus;developmental growth;embryonic cranial skeleton morphogenesis;embryonic foregut morphogenesis;embryonic pattern specification;endoderm development;erythrocyte differentiation;evasion or tolerance of host defenses by virus;extrinsic apoptotic signaling pathway;gamete generation;germ cell development;heart looping;hindbrain development;homeostatic process;immune response;immune system development;in utero embryonic development;inflammatory response;lens fiber cell differentiation;liver development;MAPK cascade;mesoderm formation;mesodermal cell fate commitment;midbrain development;Mullerian duct regression;negative regulation of apoptotic process;negative regulation of cardiac muscle hypertrophy in response to stress;negative regulation of cell growth;negative regulation of cell proliferation;negative regulation of cytosolic calcium ion concentration;negative regulation of fat cell differentiation;negative regulation of inflammatory response;negative regulation of lung blood pressure;negative regulation of mitotic cell cycle;negative regulation of osteoblast differentiation;negative regulation of osteoblast proliferation;negative regulation of protein catabolic process;negative regulation of transcription by RNA polymerase II;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of wound healing;nodal signaling pathway;osteoblast development;osteoblast fate commitment;paraxial mesoderm morphogenesis;pericardium development;positive regulation of alkaline phosphatase activity;positive regulation of bone mineralization;positive regulation of canonical Wnt signaling pathway;positive regulation of cartilage development;positive regulation of cell migration;positive regulation of chondrocyte differentiation;positive regulation of DNA-binding transcription factor activity;positive regulation of epithelial to mesenchymal transition;positive regulation of extracellular matrix assembly;positive regulation of focal adhesion assembly;positive regulation of gene expression;positive regulation of interleukin-1 beta production;positive regulation of nitric oxide biosynthetic process;positive regulation of osteoblast differentiation;positive regulation of positive chemotaxis;positive regulation of pri-miRNA transcription by RNA polymerase II;positive regulation of protein import into nucleus;positive regulation of sprouting angiogenesis;positive regulation of stress fiber assembly;positive regulation of transcription by RNA polymerase II;positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus;positive regulation of transcription, DNA-templated;positive regulation of transforming growth factor beta3 production;primary miRNA processing;protein deubiquitination;protein phosphorylation;protein stabilization;regulation of binding;regulation of epithelial cell proliferation;regulation of immune response;regulation of striated muscle tissue development;regulation of transcription by RNA polymerase II;regulation of transforming growth factor beta receptor signaling pathway;regulation of transforming growth factor beta2 production;response to hypoxia;signal transduction;signal transduction involved in regulation of gene expression;SMAD protein complex assembly;SMAD protein signal transduction;somitogenesis;T cell activation;thyroid gland development;transdifferentiation;transforming growth factor beta receptor signaling pathway;ureteric bud development;wound healing beta-catenin binding;bHLH transcription factor binding;chromatin DNA binding;collagen binding;co-SMAD binding;DEAD/H-box RNA helicase binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;enhancer binding;glucocorticoid receptor binding;identical protein binding;I-SMAD binding;metal ion binding;mineralocorticoid receptor binding;phosphatase binding;primary miRNA binding;protein heterodimerization activity;protein homodimerization activity;protein kinase binding;proximal promoter sequence-specific DNA binding;RNA polymerase II activating transcription factor binding;RNA polymerase II general transcription initiation factor activity;RNA polymerase II proximal promoter sequence-specific DNA binding;R-SMAD binding;sequence-specific DNA binding;transcription coregulator activity;transcription factor binding;transcription regulatory region DNA binding;transforming growth factor beta receptor binding;transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity;ubiquitin binding;ubiquitin protein ligase binding;zinc ion binding cytoplasm;cytosol;heteromeric SMAD protein complex;integral component of membrane;intracellular;nuclear chromatin;nuclear inner membrane;nucleoplasm;nucleus;plasma membrane;protein-containing complex;receptor complex;SMAD protein complex;transcription factor complex Adherens junction;AGE-RAGE signaling pathway in diabetic complications;Apelin signaling pathway;Cell cycle;Cellular senescence;Chagas disease (American trypanosomiasis);Chronic myeloid leukemia;Colorectal cancer;Endocytosis;FoxO signaling pathway;Gastric cancer;Hepatitis B;Hepatocellular carcinoma;Hippo signaling pathway;Human T-cell leukemia virus 1 infection;Inflammatory bowel disease (IBD);Pancreatic cancer;Pathways in cancer;Relaxin signaling pathway;Signaling pathways regulating pluripotency of stem cells;TGF-beta signaling pathway;Th17 cell differentiation;Transcriptional misregulation in cancer;Wnt signaling pathway Loeys-Dietz syndrome Downregulation of SMAD2/3:SMAD4 transcriptional activity;Downregulation of TGF-beta receptor signaling;Interleukin-37 signaling;NOTCH4 Intracellular Domain Regulates Transcription;RUNX2 regulates bone development;RUNX3 regulates BCL2L11 (BIM) transcription;RUNX3 regulates CDKN1A transcription;Signaling by Activin;Signaling by BMP;Signaling by NODAL;SMAD2/3 MH2 Domain Mutants in Cancer;SMAD2/3 Phosphorylation Motif Mutants in Cancer;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;SMAD4 MH2 Domain Mutants in Cancer;TGF-beta receptor signaling activates SMADs;TGFBR1 KD Mutants in Cancer;Ub-specific processing proteases Axin-SMAD3 complex;BRCA1-SMAD3 complex;CREBBP-SMAD3 hexameric complex;CREBBP-SMAD3-SMAD4 pentameric complex;JUND-FOSB-SMAD3-SMAD4 complex;p300-SMAD1-STAT3 complex;PIAS3-SMAD3-P300 complex;PML-SMAD2/3-SARA complex;RSmad complex;SKI-SMAD3 complex;SKI-SMAD3-SMAD4 complex;SKI-SMAD3-SMAD4 complex, TGF(beta)-dependent;SMAD1-CBP complex;SMAD1-OAZ-HsN3 complex;SMAD1-P300 complex;SMAD3/4-E2F4/5-p107-DP1 complex;SMAD3-cSKI-SIN3A-HDAC1 complex;SMAD3-E2F4/5-p107-DP1 complex;SMAD3-HEF1-APC10-CDH1 complex;SMAD3-SKI-NCOR complex;SMAD3-SMAD4-cJUN complex;SMAD3-SMAD4-cJun-cFos complex;SMAD3-SMAD4-CTCF protein-DNA complex;SMAD3-SMAD4-FOXO1 complex;SMAD3-SMAD4-FOXO3 complex;SMAD3-SMAD4-FOXO3-FOXG1 complex;SMAD3-SMAD4-FOXO4 complex;SMAD3-SMAD4-SP1 complex;SMAD3-SMAD4-WWTR1 complex;SMAD4-SMAD2-SMAD3 complex;TGF-beta receptor I-Axin-SMAD3 complex;TGF-beta receptor-SMAD3 complex;TIF1gamma-SMAD2-SMAD3 complex;Ubiquitin E3 ligase (SMAD3, BTRC, CUL1, SKP1A, RBX1);Ubiquitin E3 ligase (SMURF2, SMAD3) - SnoN complex, TGF(beta)-dependent 1.05776405334473 0.108079671859741 0.592179775238037 0.28469517827034 0.644115328788757 2.00104379653931 1.66766464710236 0.808154225349426 -0.47877961397171 -1.50275993347168 -1.47323632240295 -0.776411533355713 0.252464950084686 -0.389407306909561 -0.587529718875885 -0.464703142642975 -0.754266679286957 -0.989067316055298 + Cluster -674 8 8 8 5.6 5.6 5.6 242.04 0 94.845 5473100000 22 3.45875632131493 0.000461240310077519 O14497;O14497-3;O14497-2 O14497;O14497-3;O14497-2 AT-rich interactive domain-containing protein 1A ARID1A 112 Involved in transcriptional activation and repression ofselect genes by chromatin remodeling (alteration of DNA-nucleosometopology). Component of SWI/SNF chromatin remodeling complexesthat carry out key enzymatic activities, changing chromatinstructure by altering DNA-histone contacts within a nucleosome inan ATP-dependent manner. Binds DNA non-specifically. Belongs tothe neural progenitors-specific chromatin remodeling complex(npBAF complex) and the neuron-specific chromatin remodelingcomplex (nBAF complex). During neural development a switch from astem/progenitor to a postmitotic chromatin remodeling mechanismoccurs as neurons exit the cell cycle and become committed totheir adult state. The transition from proliferating neuralstem/progenitor cells to postmitotic neurons requires a switch insubunit composition of the npBAF and nBAF complexes. As neuralprogenitors exit mitosis and differentiate into neurons, npBAFcomplexes which contain ACTL6A/BAF53A and PHF10/BAF45A, areexchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45Bor DPF3/BAF45C subunits in neuron-specific complexes (nBAF). ThenpBAF complex is essential for the self-renewal/proliferativecapacity of the multipotent neural stem cells. The nBAF complexalong with CREST plays a role regulating the activity of genesessential for dendrite growth (By similarity) Nucleus {ECO:0000255|PROSITE-ProRule:PRU00355, ECO:0000269|PubMed:11318604,ECO:0000269|PubMed:26614907}. androgen receptor signaling pathway;ATP-dependent chromatin remodeling;cardiac chamber development;cardiac muscle cell differentiation;chromatin remodeling;chromatin-mediated maintenance of transcription;embryo implantation;forebrain development;formation of primary germ layer;glucocorticoid receptor signaling pathway;intracellular estrogen receptor signaling pathway;maintenance of chromatin silencing;negative regulation of transcription by RNA polymerase II;neural tube closure;nucleosome disassembly;nucleosome mobilization;optic cup formation involved in camera-type eye development;placenta blood vessel development;positive regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;stem cell population maintenance;toxin transport DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;nuclear receptor binding;nucleosome binding;transcription coactivator activity nBAF complex;npBAF complex;nuclear chromatin;nucleoplasm;nucleus;SWI/SNF complex Hepatocellular carcinoma;Thermogenesis Autosomal dominant mental retardation;Coffin-Siris syndrome;Hepatocellular carcinoma RMTs methylate histone arginines;RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known BAF complex;BRD7-SWI\u2013SNF complex;BRG1-associated complex;Brg1-associated complex I;Brg1-associated complex II;BRG1-SIN3A complex;BRG1-SIN3A-HDAC containing SWI/SNF remodeling complex I;Brm-associated complex;BRM-associated complex;BRM-SIN3A complex;BRM-SIN3A-HDAC complex;EBAFa complex;LARC complex (LCR-associated remodeling complex);NUMAC complex (nucleosomal methylation activator complex);p300-CBP-p270 complex;p300-CBP-p270-SWI/SNF complex;SIN3-ING1b complex II;SWI-SNF chromatin remodeling-related-BRCA1 complex;WINAC complex 0.562880516052246 -0.78485119342804 0.599256753921509 0.0139727750793099 0.894121110439301 2.12038064002991 1.77529799938202 0.834492981433868 -0.506133615970612 -1.5515022277832 -1.34177827835083 -1.0763566493988 0.343784719705582 -0.601553857326508 -0.502768397331238 -0.205002352595329 -0.252725183963776 -0.321515649557114 + Cluster -674 3 3 3 7.7 7.7 7.7 48.115 0 33.764 912200000 7 3.47714978175504 0.000454365079365079 P37268;P37268-5;P37268-4;P37268-3;P37268-2 P37268;P37268-5;P37268-4;P37268-3;P37268-2 Squalene synthase FDFT1 964 Multi-passmembrane protein.;Endoplasmic reticulum membrane cholesterol biosynthetic process;ergosterol biosynthetic process;farnesyl diphosphate metabolic process;isoprenoid biosynthetic process;regulation of cholesterol biosynthetic process;regulation of lipid metabolic process;steroid biosynthetic process farnesyl-diphosphate farnesyltransferase activity;squalene synthase activity endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane Metabolic pathways;Steroid biosynthesis Lapaquistat acetate Activation of gene expression by SREBF (SREBP);Cholesterol biosynthesis;PPARA activates gene expression 0.594815254211426 0.282408028841019 0.48679855465889 0.396807610988617 0.08158328384161 2.19727635383606 1.47336935997009 1.27766668796539 0.127347052097321 -1.91913878917694 -1.10559558868408 -0.542206704616547 -0.328576773405075 -0.424989998340607 -0.627725660800934 -0.179484963417053 -0.873664081096649 -0.916689515113831 + Cluster -674 45 45 43 26.6 26.6 25.7 274.61 0 323.31 41228000000 128 3.45717862045008 0.0004642166344294 Q01082;Q01082-3;Q01082-2;P11277;P11277-2;P11277-3 Q01082;Q01082-3;Q01082-2 Spectrin beta chain, non-erythrocytic 1 SPTBN1 1476 Fodrin, which seems to be involved in secretion,interacts with calmodulin in a calcium-dependent manner and isthus candidate for the calcium-dependent movement of thecytoskeleton at the membrane.;Spectrin is the major constituent of the cytoskeletalnetwork underlying the erythrocyte plasma membrane. It associateswith band 4.1 and actin to form the cytoskeletal superstructure ofthe erythrocyte plasma membrane. Cytoplasmic side{ECO:0000250}.;Cytoplasm, cytoskeleton {ECO:0000250}.Cytoplasm, myofibril, sarcomere, M line {ECO:0000250}.Note=Colocalizes with ANK2 in a distinct intracellular compartmentof neonatal cardiomyocytes. {ECO:0000250}.Isoform 2: Cell membrane {ECO:0000250};Cytoplasm, cytoskeleton. Cytoplasm, cellcortex.;Peripheral membrane protein {ECO:0000250} actin filament capping;axon guidance;common-partner SMAD protein phosphorylation;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi to plasma membrane protein transport;MAPK cascade;membrane assembly;mitotic cytokinesis;plasma membrane organization;positive regulation of interleukin-2 secretion;positive regulation of protein localization to plasma membrane;protein localization to plasma membrane;regulation of protein localization to plasma membrane;regulation of SMAD protein signal transduction actin binding;actin filament binding;ankyrin binding;cadherin binding;calmodulin binding;GTPase binding;phospholipid binding;protein-containing complex binding;Ras guanyl-nucleotide exchange factor activity;RNA binding;structural constituent of cytoskeleton actin cytoskeleton;axolemma;cell surface;cuticular plate;cytoplasm;cytosol;extracellular exosome;glutamatergic synapse;Golgi apparatus;intrinsic component of the cytoplasmic side of the plasma membrane;M band;nucleolus;postsynaptic density;protein-containing complex;spectrin;spectrin-associated cytoskeleton Hereditary elliptocytosis;Hereditary spherocytosis COPI-mediated anterograde transport;Interaction between L1 and Ankyrins;NCAM signaling for neurite out-growth;Nephrin family interactions;RAF/MAP kinase cascade 0.83786416053772 0.312513381242752 0.552419722080231 0.0255455169826746 0.284096300601959 2.26017165184021 1.50726246833801 1.16378581523895 -0.267072767019272 -1.08183455467224 -1.73822474479675 -1.14693212509155 -0.307333081960678 -0.194471210241318 -0.462422043085098 -0.286113411188126 -0.66669499874115 -0.792560338973999 + Cluster -674 9 9 8 12.3 12.3 11.3 112.59 0 159.79 5978400000 18 3.4860924411441 0.000434262948207171 O43491;O43491-4;O43491-2;O43491-3 O43491;O43491-4;O43491-2;O43491-3 Band 4.1-like protein 2 EPB41L2 220 Required for dynein-dynactin complex and NUMA1recruitment at the mitotic cell cortex during anaphase(PubMed:23870127). Cytoplasm, cytoskeleton {ECO:0000250}.Cytoplasm, cell cortex {ECO:0000269|PubMed:23870127}. Cellmembrane {ECO:0000269|PubMed:22361696}. actomyosin structure organization;cell cycle;cell division;cortical actin cytoskeleton organization;positive regulation of protein localization to cell cortex actin binding;PH domain binding;spectrin binding;structural molecule activity cell cortex region;cell junction;cytosol;extracellular exosome;focal adhesion;nucleoplasm;nucleus;plasma membrane;spectrin Neurexins and neuroligins 0.741143882274628 0.382295459508896 0.12063179910183 0.0934593230485916 0.287328660488129 1.80986499786377 1.91664838790894 1.30617845058441 0.0934593230485916 -1.24936497211456 -1.93317878246307 -0.874565958976746 -0.142966687679291 -0.183069452643394 -0.649569571018219 -0.653174936771393 -0.501003444194794 -0.564116477966309 + Cluster -674 11 11 11 22.2 22.2 22.2 77.86 0 74.921 5193300000 24 3.46782780245003 0.000458823529411765 Q96AC1;Q96AC1-2;Q96AC1-3;Q9BQL6;Q9BQL6-4;Q9BQL6-2 Q96AC1;Q96AC1-2;Q96AC1-3 Fermitin family homolog 2 FERMT2 2396 this requires both its ability tointeract with integrins and with phospholipid membranes. Requiredfor the assembly of focal adhesions. Participates in theconnection between extracellular matrix adhesion sites and theactin cytoskeleton and also in the orchestration of actin assemblyand cell shape modulation. Recruits FBLIM1 to focal adhesions.Plays a role in the TGFB1 and integrin signaling pathways.Stabilizes active CTNNB1 and plays a role in the regulation oftranscription mediated by CTNNB1 and TCF7L2/TCF4 and in Wntsignaling.;Involved in cell adhesion. Contributes to integrinactivation. When coexpressed with talin, potentiates activation ofITGA2B. Required for normal keratinocyte proliferation. Requiredfor normal polarization of basal keratinocytes in skin, and fornormal cell shape. Required for normal adhesion of keratinocytesto fibronectin and laminin, and for normal keratinocyte migrationto wound sites. May mediate TGF-beta 1 signaling in tumorprogression.;Scaffolding protein that enhances integrin activationmediated by TLN1 and/or TLN2, but activates integrins only weaklyby itself. Binds to membranes enriched in phosphoinositides.Enhances integrin-mediated cell adhesion onto the extracellularmatrix and cell spreading Cytoplasmic side. Cell projection, lamellipodiummembrane; Cytoplasmic side. Note=Constituent of focaladhesions. Localized at the basal aspect of skin keratinocytes,close to the cell membrane. Colocalizes with filamentous actin.Upon TGFB1 treatment, it localizes to membrane ruffles.; Cytoplasmic side. Nucleus.Cytoplasm, myofibril, sarcomere, I band {ECO:0000250}. Cellsurface {ECO:0000250}. Note=Colocalizes with actin stress fibersat cell-ECM focal adhesion sites. Colocalizes with ITGB3 atlamellipodia at the leading edge of spreading cells. Binds tomembranes that contain phosphatidylinositides.; Peripheral membrane protein; Peripheral membraneprotein; Peripheralmembrane protein;Cytoplasm, cytoskeleton. Cell junction,focal adhesion. Cell projection, ruffle membrane;Cytoplasm. Cytoplasm, cell cortex.Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, stress fiber.Cell junction, focal adhesion. Membrane basement membrane organization;cell adhesion;cell junction assembly;cell-matrix adhesion;establishment of epithelial cell polarity;focal adhesion assembly;integrin activation;integrin-mediated signaling pathway;keratinocyte migration;keratinocyte proliferation;negative regulation of canonical Wnt signaling pathway;negative regulation of gene expression;negative regulation of protein import into nucleus;negative regulation of stem cell proliferation;negative regulation of timing of anagen;positive regulation of cell adhesion mediated by integrin;positive regulation of cell-matrix adhesion;positive regulation of transforming growth factor beta receptor signaling pathway;positive regulation of transforming growth factor-beta secretion;protein localization to membrane;regulation of cell shape;substrate adhesion-dependent cell spreading;transforming growth factor beta receptor signaling pathway;Wnt signaling pathway actin filament binding;phosphatidylinositol-3,4,5-trisphosphate binding cell cortex;cell junction;cell surface;cytoplasm;cytoskeleton;cytosol;extrinsic component of cytoplasmic side of plasma membrane;focal adhesion;I band;lamellipodium membrane;nucleoplasm;nucleus;ruffle membrane;stress fiber Kindler syndrome Cell-extracellular matrix interactions CTNNB1-FERMT2-TCF7L2 complex;CTNNB1-FERMT2-YBX1 complex -0.140727788209915 0.0413095839321613 0.561420559883118 0.340662777423859 0.48553878068924 1.40960931777954 1.94414675235748 1.6872044801712 -0.639426112174988 -1.42021918296814 -1.97643566131592 0.14021247625351 -0.82215416431427 -0.560623466968536 -0.401735484600067 -0.0285924486815929 -0.337704688310623 -0.282485634088516 + Cluster -674 1 1 1 7.7 7.7 7.7 22.574 0 3.2714 805710000 2 3.05528460175983 0.000974358974358974 Q9NP77;Q9NP77-2 Q9NP77;Q9NP77-2 RNA polymerase II subunit A C-terminal domain phosphatase SSU72 SSU72 2872 Protein phosphatase that catalyzes the dephosphorylationof the C-terminal domain of RNA polymerase II. Plays a role in RNAprocessing and termination. Plays a role in pre-mRNApolyadenylation via its interaction with SYMPK Nucleus. Cytoplasm. Note=Predominantly inthe cytosol. dephosphorylation of RNA polymerase II C-terminal domain;mRNA polyadenylation;termination of RNA polymerase II transcription RNA polymerase II CTD heptapeptide repeat phosphatase activity cytosol;mRNA cleavage and polyadenylation specificity factor complex;nucleoplasm mRNA surveillance pathway RNA polymerase II transcribes snRNA genes POL2R-SYMPK-SSU72 complex 0.152688041329384 0.511838316917419 0.527005612850189 0.152688041329384 0.472185105085373 2.25223255157471 1.38955640792847 1.36314785480499 0.0218164101243019 -1.16442573070526 -1.81752300262451 -0.60694694519043 -0.228837549686432 -0.186000660061836 -1.00119841098785 -0.493540942668915 -0.851144075393677 -0.493540942668915 + Cluster -674 3 3 3 29.1 29.1 29.1 19.053 0 42.7 1971800000 7 3.62273880562775 0.000342163355408389 Q8N9N8 Q8N9N8 Probable RNA-binding protein EIF1AD EIF1AD 2212 Plays a role into cellular response to oxidative stress.Decreases cell proliferation. Nucleus {ECO:0000269|PubMed:20644585,ECO:0000269|PubMed:22095125}. translation initiation factor activity nucleus 0.458895832300186 0.0532888993620872 0.913571834564209 0.00396541832014918 0.381698697805405 2.35422444343567 1.43251776695251 1.34045362472534 -0.0711964443325996 -1.32958126068115 -1.42679715156555 -0.780217528343201 -0.460743814706802 -0.505249440670013 -0.624646604061127 -0.369093090295792 -0.507093906402588 -0.863997459411621 + Cluster -674 8 8 6 55.6 55.6 39.7 16.93 0 164.18 58467000000 87 3.92653726943064 0.000172602739726027 P60660;P60660-2 P60660;P60660-2 Myosin light polypeptide 6 MYL6 1275 Regulatory light chain of myosin. Does not bind calcium. muscle contraction;muscle filament sliding;skeletal muscle tissue development actin-dependent ATPase activity;calcium ion binding;motor activity;structural constituent of muscle brush border;cytosol;extracellular exosome;membrane;myosin complex;unconventional myosin complex;vesicle Oxytocin signaling pathway;Tight junction;Vascular smooth muscle contraction EPHA-mediated growth cone collapse;RHO GTPases activate CIT;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases Activate ROCKs;Sema4D induced cell migration and growth-cone collapse;Smooth Muscle Contraction WIP-WASp-actin-myosin-IIa complex -0.101132608950138 0.390946269035339 0.692016005516052 0.308411180973053 0.455824702978134 2.12333846092224 1.79503166675568 1.20747911930084 -0.40570479631424 -1.19316697120667 -1.7799985408783 -0.269004762172699 -0.571825742721558 -0.676055610179901 -0.635818243026733 -0.044433519244194 -0.709102630615234 -0.586804032325745 + Cluster -674 30 30 30 29.4 29.4 29.4 143.23 0 323.31 36460000000 124 3.57535336700509 0.000379828326180258 Q14683 Q14683 Structural maintenance of chromosomes protein 1A SMC1A 1723 Involved in chromosome cohesion during cell cycle and inDNA repair. Central component of cohesin complex. The cohesincomplex is required for the cohesion of sister chromatids afterDNA replication. The cohesin complex apparently forms a largeproteinaceous ring within which sister chromatids can be trapped.At anaphase, the complex is cleaved and dissociates fromchromatin, allowing sister chromatids to segregate. The cohesincomplex may also play a role in spindle pole assembly duringmitosis. Involved in DNA repair via its interaction with BRCA1 andits related phosphorylation by ATM, or via its phosphorylation byATR. Works as a downstream effector both in the ATM/NBS1 branchand in the ATR/MSH2 branch of S-phase checkpoint Nucleus {ECO:0000269|PubMed:12199140}.Chromosome {ECO:0000269|PubMed:12199140}. Chromosome, centromere,kinetochore {ECO:0000269|PubMed:12199140}. Note=Associates withchromatin. Before prophase it is scattered along chromosome arms.During prophase, most of cohesin complexes dissociate fromchromatin probably because of phosphorylation by PLK, except atcentromeres, where cohesin complexes remain. At anaphase, theRAD21 subunit of the cohesin complex is cleaved, leading to thedissociation of the complex from chromosomes, allowing chromosomeseparation. In germ cells, cohesin complex dissociates fromchromatin at prophase I, and may be replaced by a meiosis-specificcohesin complex. The phosphorylated form on Ser-957 and Ser-966associates with chromatin during G1/S/G2 phases but not during Mphase, suggesting that phosphorylation does not regulate cohesinfunction. Integral component of the functional centromere-kinetochore complex at the kinetochore region during mitosis. cell division;DNA repair;meiotic cell cycle;mitotic sister chromatid cohesion;mitotic sister chromatid segregation;negative regulation of DNA endoreduplication;regulation of mitotic spindle assembly;response to DNA damage checkpoint signaling;response to radiation;sister chromatid cohesion;stem cell population maintenance ATP binding;chromatin binding;mediator complex binding;protein heterodimerization activity;RNA binding chromosome;chromosome, centromeric region;cohesin complex;condensed chromosome kinetochore;condensed nuclear chromosome;cytosol;kinetochore;meiotic cohesin complex;mitotic spindle pole;nuclear matrix;nucleoplasm;nucleus Cell cycle;Oocyte meiosis Cornelia de Lange syndrome Cohesin Loading onto Chromatin;Establishment of Sister Chromatid Cohesion;Estrogen-dependent gene expression;Meiotic synapsis;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids;SUMOylation of DNA damage response and repair proteins Cohesin-SA1 complex;Cohesin-SA2 complex;DDX11-RAD21-SMC1A-SMC3 complex;MDC1-p53BP1-SMC1 complex;SMC1-SMC3 complex;SNF2h-cohesin-NuRD complex;Sororin-cohesin complex 1.30273652076721 1.37304186820984 -0.134556457400322 -1.56373333930969 -0.830115139484406 -1.43903255462646 -1.80443143844604 -0.508267164230347 0.197836741805077 1.47295665740967 0.682042002677917 0.662148833274841 -0.508267164230347 1.04330790042877 0.399565905332565 -0.0333752930164337 -0.231650784611702 -0.0802071318030357 + Cluster -674 4 4 4 21.3 21.3 21.3 28.912 0 93.495 3449100000 11 3.30523237916813 0.000587826086956522 Q9GZU8 Q9GZU8 Protein FAM192A FAM192A 2751 Promotes the association of the proteasome activatorcomplex subunit PSME3 with the 20S proteasome and regulates itsactivity. Inhibits PSME3-mediated degradation of some proteasomesubstrates, probably by affecting their diffusion rate into thecatalytic chamber of the proteasome. Also inhibits the interactionof PSME3 with COIL, inhibits accumulation of PSME3 in Cajal bodiesand positively regulates the number of Cajal bodies in thenucleus. Nucleus {ECO:0000269|PubMed:29934401}. negative regulation of proteasomal protein catabolic process;negative regulation of protein binding nucleus 1.0694100856781 0.485317587852478 0.485317587852478 -0.021978884935379 0.20241279900074 -1.34348154067993 -0.206904590129852 -0.33104407787323 -0.724253714084625 2.11809968948364 1.40920150279999 1.32102036476135 -1.55141270160675 -0.370588451623917 -1.04495882987976 -0.908473968505859 -0.221385896205902 -0.366296947002411 + Cluster -674 5 5 5 51.6 51.6 51.6 13.802 0 124.09 164310000000 101 3.07731125305445 0.000938556067588326 P49773 P49773 Histidine triad nucleotide-binding protein 1 HINT1 1119 Hydrolyzes purine nucleotide phosphoramidates with asingle phosphate group, including adenosine 5'monophosphoramidate(AMP-NH2), adenosine 5'monophosphomorpholidate (AMP-morpholidate)and guanosine 5'monophosphomorpholidate (GMP-morpholidate).Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methylester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysinemethyl ester)) and AMP-N-alanine methyl ester. Can also convertadenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphateswith concomitant release of hydrogen sulfide. In addition,functions as scaffolding protein that modulates transcriptionalactivation by the LEF1/TCF1-CTNNB1 complex and by the complexformed with MITF and CTNNB1. Modulates p53/TP53 levels andp53/TP53-mediated apoptosis. Modulates proteasomal degradation oftarget proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Cytoplasm. Nucleus. Note=Interaction withCDK7 leads to a more nuclear localization. intrinsic apoptotic signaling pathway by p53 class mediator;positive regulation of calcium-mediated signaling;purine ribonucleotide catabolic process;regulation of transcription, DNA-templated;signal transduction hydrolase activity;nucleotide binding;protein kinase C binding cytoskeleton;cytosol;extracellular exosome;histone deacetylase complex;nucleus;plasma membrane HINT1-SP1 complex;HINT1-TIP60 complex;HINT1-UBC3-RBX1 complex 2.21465587615967 0.164430916309357 0.291597485542297 0.164430916309357 -0.196247115731239 -0.53703099489212 -0.386580884456635 -0.0680750012397766 0.488397926092148 1.45221996307373 1.06577920913696 1.15288007259369 -1.52868747711182 -0.50838166475296 -0.642092943191528 -0.52921199798584 -1.29904222488403 -1.29904222488403 + Cluster -674 2 2 2 2.6 2.6 2.6 96.412 0 16.431 380230000 5 3.90797493731959 0.00018230563002681 Q93050;Q93050-1;Q93050-3 Q93050;Q93050-1;Q93050-3 V-type proton ATPase 116 kDa subunit a isoform 1 ATP6V0A1 2379 Required for assembly and activity of the vacuolarATPase. Potential role in differential targeting and regulation ofthe enzyme for a specific organelle (By similarity) Multi-passmembrane protein. Melanosome. Note=Coated vesicle. Identified bymass spectrometry in melanosome fractions from stage I to stageIV.;Cytoplasmic vesicle membrane ATP hydrolysis coupled proton transport;insulin receptor signaling pathway;ion transmembrane transport;neutrophil degranulation;regulation of macroautophagy;toxin transport;transferrin transport;vacuolar acidification ATPase binding;proton-transporting ATPase activity, rotational mechanism cytosol;endosome membrane;extracellular exosome;ficolin-1-rich granule membrane;Golgi apparatus;integral component of membrane;intracellular membrane-bounded organelle;lysosomal membrane;melanosome;nuclear speck;phagocytic vesicle membrane;plasma membrane;secretory granule membrane;vacuolar proton-transporting V-type ATPase complex;vacuolar proton-transporting V-type ATPase, V0 domain Collecting duct acid secretion;Epithelial cell signaling in Helicobacter pylori infection;Human papillomavirus infection;Lysosome;Metabolic pathways;Oxidative phosphorylation;Phagosome;Rheumatoid arthritis;Synaptic vesicle cycle;Tuberculosis;Vibrio cholerae infection Insulin receptor recycling;Ion channel transport;Neutrophil degranulation;ROS, RNS production in phagocytes;Transferrin endocytosis and recycling 1.26089251041412 0.417578876018524 -0.0123388087376952 -0.783698916435242 0.298369914293289 -1.23664581775665 -1.41064608097076 -0.915754318237305 -0.250352144241333 1.57767045497894 2.38686180114746 0.777717769145966 -0.889049887657166 -0.0448932610452175 -0.245328202843666 0.0290833991020918 -0.419834226369858 -0.539633214473724 + Cluster -674 5 5 5 13.4 13.4 13.4 56.878 0 128.01 5696000000 28 3.0964560941401 0.000911353032659409 P53041 P53041 Serine/threonine-protein phosphatase 5 PPP5C 1197 Serine/threonine-protein phosphatase thatdephosphorylates a myriad of proteins involved in differentsignaling pathways including the kinases CSNK1E, ASK1/MAP3K5,PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2,SMAD proteins and TAU/MAPT. Implicated in wide ranging cellularprocesses, including apoptosis, differentiation, DNA damageresponse, cell survival, regulation of ion channels or circadianrhythms, in response to steroid and thyroid hormones, calcium,fatty acids, TGF-beta as well as oxidative and genotoxic stresses.Participates in the control of DNA damage response mechanisms suchas checkpoint activation and DNA damage repair through, forinstance, the regulation ATM/ATR-signaling and dephosphorylationof PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosisinduced by oxidative stress. Plays a positive role inadipogenesis, mainly through the dephosphorylation and activationof PPARG transactivation function. Also dephosphorylates andinhibits the anti-adipogenic effect of NR3C1. Regulates thecircadian rhythms, through the dephosphorylation and activation ofCSNK1E. May modulate TGF-beta signaling pathway by the regulationof SMAD3 phosphorylation and protein expression levels.Dephosphorylates and may play a role in the regulation ofTAU/MAPT. Through their dephosphorylation, may play a role in theregulation of ions channels such as KCNH2 Nucleus {ECO:0000269|PubMed:15383005}.Cytoplasm {ECO:0000269|PubMed:15383005,ECO:0000269|PubMed:19948726}. Cell membrane{ECO:0000269|PubMed:19948726}. Note=Predominantly nuclear(PubMed:15383005). But also present in the cytoplasm(PubMed:15383005). Translocates from the cytoplasm to the plasmamembrane in a RAC1-dependent manner (PubMed:19948726).{ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:19948726}. cellular response to cadmium ion;cellular response to hydrogen peroxide;DNA repair;histone dephosphorylation;MAPK cascade;mitotic cell cycle;negative regulation of neuron death;negative regulation of protein phosphorylation;peptidyl-serine dephosphorylation;peptidyl-threonine dephosphorylation;positive regulation of glucocorticoid receptor signaling pathway;positive regulation of I-kappaB kinase/NF-kappaB signaling;protein dephosphorylation;protein heterooligomerization;response to arachidonic acid;response to lead ion;response to morphine;transcription, DNA-templated ADP binding;ATP binding;G-protein alpha-subunit binding;Hsp90 protein binding;identical protein binding;lipid binding;metal ion binding;microtubule binding;phosphatase activity;phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;RNA binding;tau protein binding chaperone complex;cytosol;intracellular membrane-bounded organelle;nucleoplasm;nucleus;perikaryon;plasma membrane;protein-containing complex;proximal dendrite MAPK signaling pathway ESR-mediated signaling;Negative regulation of MAPK pathway;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks 0.7379070520401 1.39955580234528 -0.448337078094482 0.7379070520401 0.7379070520401 -0.35360911488533 -0.675673842430115 0.630827784538269 0.7379070520401 1.14400219917297 0.630827784538269 0.934391379356384 -0.959599316120148 -0.675673842430115 -0.675673842430115 -0.0920090600848198 -1.90532851219177 -1.90532851219177 + Cluster -674 25 25 25 35.7 35.7 35.7 81.074 0 323.31 178960000000 274 3.1171354959504 0.000877358490566038 Q08945 Q08945 FACT complex subunit SSRP1 SSRP1 1551 Component of the FACT complex, a general chromatinfactor that acts to reorganize nucleosomes. The FACT complex isinvolved in multiple processes that require DNA as a template suchas mRNA elongation, DNA replication and DNA repair. Duringtranscription elongation the FACT complex acts as a histonechaperone that both destabilizes and restores nucleosomalstructure. It facilitates the passage of RNA polymerase II andtranscription by promoting the dissociation of one histone H2A-H2Bdimer from the nucleosome, then subsequently promotes thereestablishment of the nucleosome following the passage of RNApolymerase II. The FACT complex is probably also involved inphosphorylation of 'Ser-392' of p53/TP53 via its association withCK2 (casein kinase II). Binds specifically to double-stranded DNAand at low levels to DNA modified by the antitumor agentcisplatin. May potentiate cisplatin-induced cell death by blockingreplication and repair of modified DNA. Also acts as atranscriptional coactivator for p63/TP63 Nucleus {ECO:0000269|PubMed:10421373,ECO:0000269|PubMed:22002106}. Nucleus, nucleolus{ECO:0000269|PubMed:22002106}. Chromosome{ECO:0000269|PubMed:10421373}. Note=Colocalizes with RNApolymerase II on chromatin. Recruited to actively transcribedloci. {ECO:0000250|UniProtKB:Q05344}. DNA repair;DNA replication;regulation of signal transduction by p53 class mediator;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter chromatin binding;DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA binding chromosome;nucleolus;nucleoplasm Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;HIV elongation arrest and recovery;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;Regulation of TP53 Activity through Phosphorylation;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Elongation;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes CEN complex;CENP-A nucleosomal complex;FACT complex;FACT complex, UV-activated;FACT-NEK9 complex;H2AX complex, isolated from cells without IR exposure;Toposome 3.01882076263428 0.737134277820587 -0.385007560253143 -0.880231261253357 -0.733843863010406 -0.341870218515396 -0.0260716620832682 0.333634555339813 1.07926607131958 0.697334945201874 0.54712450504303 0.174893647432327 -0.341870218515396 -0.341870218515396 -0.701291143894196 -0.537842750549316 -1.05985617637634 -1.23845386505127 + Cluster -674 22 22 21 56.4 56.4 55.2 64.132 0 323.31 258590000000 336 3.36201110934786 0.000548094373865699 P14866;P14866-2 P14866;P14866-2 Heterogeneous nuclear ribonucleoprotein L HNRNPL 677 Splicing factor binding to exonic or intronic sites andacting as either an activator or repressor of exon inclusion.Exhibits a binding preference for CA-rich elements(PubMed:11809897, PubMed:22570490, PubMed:24164894,PubMed:25623890, PubMed:26051023). Component of the heterogeneousnuclear ribonucleoprotein (hnRNP) complexes and associated withmost nascent transcripts (PubMed:2687284). Associates, togetherwith APEX1, to the negative calcium responsive element (nCaRE) B2of the APEX2 promoter (PubMed:11809897) Nucleus, nucleoplasm{ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:2687284,ECO:0000305|PubMed:26051023}. Cytoplasm{ECO:0000269|PubMed:17289661}. Note=Localized in cytoplasmic mRNPgranules containing untranslated mRNAs. These granules are notidentical with P bodies or stress granules.{ECO:0000269|PubMed:17289661}. cellular response to amino acid starvation;circadian rhythm;mRNA splicing, via spliceosome;negative regulation of mRNA splicing, via spliceosome;positive regulation of mRNA binding;positive regulation of translation;regulation of alternative mRNA splicing, via spliceosome;response to peptide;RNA metabolic process;RNA processing mRNA 3'-UTR binding;mRNA CDS binding;pre-mRNA intronic binding;RNA binding;transcription regulatory region DNA binding cytosol;extracellular exosome;membrane;nucleoplasm;nucleus;perinuclear region of cytoplasm;pronucleus;ribonucleoprotein complex;ribonucleoprotein granule mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA Emerin complex 52 -0.868320226669312 -0.272956669330597 1.70248460769653 0.419851571321487 0.588842213153839 -0.00354186026379466 -0.382892280817032 -0.253017008304596 -0.430411338806152 1.50755703449249 1.50755703449249 1.39441275596619 -1.87844431400299 -1.09632778167725 -0.795246303081512 -0.593634009361267 -0.272956669330597 -0.272956669330597 + Cluster -674 20 20 20 56.5 56.5 56.5 49.203 0 249.86 60803000000 125 3.31007956347877 0.000585664335664336 P17980 P17980 26S protease regulatory subunit 6A PSMC3 711 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. PSMC3 belongs to theheterohexameric ring of AAA (ATPases associated with diversecellular activities) proteins that unfolds ubiquitinated targetproteins that are concurrently translocated into a proteolyticchamber and degraded into peptides. Cytoplasm {ECO:0000305}. Nucleus{ECO:0000305}. Note=Colocalizes with TRIM5 in the cytoplasmicbodies. {ECO:0000250|UniProtKB:O88685}. blastocyst development;modulation by host of viral transcription;neutrophil degranulation;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of transcription by RNA polymerase II;post-translational protein modification;protein catabolic process;protein deubiquitination;viral process ATP binding;ATPase activity;identical protein binding;proteasome-activating ATPase activity cytosol;extracellular region;ficolin-1-rich granule lumen;membrane;nucleoplasm;nucleus;P-body;proteasome accessory complex;proteasome complex;proteasome regulatory particle, base subcomplex;secretory granule lumen Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;Neutrophil degranulation;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 26S proteasome;BP-SMAD complex;PA700 complex;PA700-20S-PA28 complex;VHL-TBP1-HIF1A complex -0.161554470658302 -0.405505686998367 0.488708227872849 0.975599467754364 0.446806758642197 -0.04030567035079 -0.815419554710388 -0.411888867616653 -0.848599433898926 0.878714144229889 2.26054620742798 1.77008402347565 -1.33416354656219 -1.49222612380981 -0.815419554710388 -0.405505686998367 -0.105654262006283 0.0157841481268406 + Cluster -674 20 20 20 62.9 62.9 62.9 47.366 0 173.64 26942000000 84 3.07298152908196 0.000941984732824428 P43686;P43686-2 P43686;P43686-2 26S protease regulatory subunit 6B PSMC4 1032 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. PSMC4 belongs to theheterohexameric ring of AAA (ATPases associated with diversecellular activities) proteins that unfolds ubiquitinated targetproteins that are concurrently translocated into a proteolyticchamber and degraded into peptides. Cytoplasm. Nucleus. blastocyst development;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;post-translational protein modification;protein catabolic process;protein deubiquitination;proteolysis ATP binding;ATPase activity;proteasome-activating ATPase activity cytosol;cytosolic proteasome complex;inclusion body;membrane;nucleoplasm;nucleus;proteasome accessory complex;proteasome complex;proteasome regulatory particle, base subcomplex;synapse Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 26S proteasome;PA700 complex;PA700-20S-PA28 complex -1.11934804916382 0.113534770905972 0.713110983371735 1.45833456516266 1.12343287467957 0.196598932147026 0.629585742950439 0.345182597637177 0.251028656959534 1.24017894268036 0.785109639167786 0.954975008964539 -1.03434252738953 -1.47863757610321 -1.63862645626068 -0.947638392448425 -0.947638392448425 -0.644841253757477 + Cluster -674 36 32 18 60.2 54.9 32.6 70.051 0 323.31 287100000000 299 4.75146420881043 2.65486725663717E-05 P0DMV8;P0DMV9;P0DMV8-2 P0DMV8;P0DMV9;P0DMV8-2 Heat shock 70 kDa protein 1A;Heat shock 70 kDa protein 1B HSPA1A;HSPA1B 595 Molecular chaperone implicated in a wide variety ofcellular processes, including protection of the proteome fromstress, folding and transport of newly synthesized polypeptides,activation of proteolysis of misfolded proteins and the formationand dissociation of protein complexes. Plays a pivotal role in theprotein quality control system, ensuring the correct folding ofproteins, the re-folding of misfolded proteins and controlling thetargeting of proteins for subsequent degradation. This is achievedthrough cycles of ATP binding, ATP hydrolysis and ADP release,mediated by co-chaperones. The co-chaperones have been shown tonot only regulate different steps of the ATPase cycle, but theyalso have an individual specificity such that one co-chaperone maypromote folding of a substrate while another may promotedegradation. The affinity for polypeptides is regulated by itsnucleotide bound state. In the ATP-bound form, it has a lowaffinity for substrate proteins. However, upon hydrolysis of theATP to ADP, it undergoes a conformational change that increasesits affinity for substrate proteins. It goes through repeatedcycles of ATP hydrolysis and nucleotide exchange, which permitscycles of substrate binding and release. The co-chaperones are ofthree types: J-domain co-chaperones such as HSP40s (stimulateATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF)such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release),and the TPR domain chaperones such as HOPX and STUB1(PubMed:24012426, PubMed:26865365, PubMed:24318877). Maintainsprotein homeostasis during cellular stress through two opposingmechanisms: protein refolding and degradation. Itsacetylation/deacetylation state determines whether it functions inprotein refolding or protein degradation by controlling thecompetitive binding of co-chaperones HOPX and STUB1. During theearly stress response, the acetylated form binds to HOPX whichassists in chaperone-mediated protein refolding, thereafter, it isdeacetylated and binds to ubiquitin ligase STUB1 that promotesubiquitin-mediated protein degradation (PubMed:27708256).Regulates centrosome integrity during mitosis, and is required forthe maintenance of a functional mitotic centrosome that supportsthe assembly of a bipolar mitotic spindle (PubMed:27137183).Enhances STUB1-mediated SMAD3 ubiquitination and degradation andfacilitates STUB1-mediated inhibition of TGF-beta signaling(PubMed:24613385). Essential for STUB1-mediated ubiquitination anddegradation of FOXP3 in regulatory T-cells (Treg) duringinflammation (PubMed:23973223).;Molecular chaperone implicated in a wide variety ofcellular processes, including protection of the proteome fromstress, folding and transport of newly synthesized polypeptides,activation of proteolysis of misfolded proteins and the formationand dissociation of protein complexes. Plays a pivotal role in theprotein quality control system, ensuring the correct folding ofproteins, the re-folding of misfolded proteins and controlling thetargeting of proteins for subsequent degradation. This is achievedthrough cycles of ATP binding, ATP hydrolysis and ADP release,mediated by co-chaperones. The co-chaperones have been shown tonot only regulate different steps of the ATPase cycle, but theyalso have an individual specificity such that one co-chaperone maypromote folding of a substrate while another may promotedegradation. The affinity for polypeptides is regulated by itsnucleotide bound state. In the ATP-bound form, it has a lowaffinity for substrate proteins. However, upon hydrolysis of theATP to ADP, it undergoes a conformational change that increasesits affinity for substrate proteins. It goes through repeatedcycles of ATP hydrolysis and nucleotide exchange, which permitscycles of substrate binding and release. The co-chaperones are ofthree types: J-domain co-chaperones such as HSP40s (stimulateATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF)such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release),and the TPR domain chaperones such as HOPX and STUB1(PubMed:24012426, PubMed:26865365, PubMed:24318877). Maintainsprotein homeostasis during cellular stress through two opposingmechanisms: protein refolding and degradation. Itsacetylation/deacetylation state determines whether it functions inprotein refolding or protein degradation by controlling thecompetitive binding of co-chaperones HOPX and STUB1. During theearly stress response, the acetylated form binds to HOPX whichassists in chaperone-mediated protein refolding, thereafter, it isdeacetylated and binds to ubiquitin ligase STUB1 that promotesubiquitin-mediated protein degradation (PubMed:27708256).Regulates centrosome integrity during mitosis, and is required forthe maintenance of a functional mitotic centrosome that supportsthe assembly of a bipolar mitotic spindle (PubMed:27137183).Enhances STUB1-mediated SMAD3 ubiquitination and degradation andfacilitates STUB1-mediated inhibition of TGF-beta signaling(PubMed:24613385). Essential for STUB1-mediated ubiquitination anddegradation of FOXP3 in regulatory T-cells (Treg) duringinflammation (PubMed:23973223). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation andrecovery phase period of the heat shock response (PubMed:9499401) Cytoplasm {ECO:0000269|PubMed:17289661}.Cytoplasm, cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:27137183}. Note=Localized in cytoplasmic mRNPgranules containing untranslated mRNAs.;Cytoplasm {ECO:0000269|PubMed:17289661}.Nucleus {ECO:0000269|PubMed:27137183}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome{ECO:0000269|PubMed:27137183}. Note=Localized in cytoplasmic mRNPgranules containing untranslated mRNAs. ATP metabolic process;cellular heat acclimation;cellular response to heat;cellular response to oxidative stress;cellular response to unfolded protein;chaperone cofactor-dependent protein refolding;chaperone-mediated protein complex assembly;mRNA catabolic process;negative regulation of apoptotic process;negative regulation of cell death;negative regulation of cell growth;negative regulation of cell proliferation;negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand;negative regulation of inclusion body assembly;negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;negative regulation of protein ubiquitination;negative regulation of transcription from RNA polymerase II promoter in response to stress;negative regulation of transforming growth factor beta receptor signaling pathway;neutrophil degranulation;positive regulation of endoribonuclease activity;positive regulation of erythrocyte differentiation;positive regulation of gene expression;positive regulation of interleukin-8 production;positive regulation of microtubule nucleation;positive regulation of NF-kappaB transcription factor activity;positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of RNA splicing;positive regulation of tumor necrosis factor-mediated signaling pathway;protein refolding;protein stabilization;regulation of cellular response to heat;regulation of mitotic spindle assembly;regulation of mRNA stability;regulation of protein ubiquitination;response to unfolded protein ATP binding;ATPase activity;ATPase activity, coupled;C3HC4-type RING finger domain binding;cadherin binding;denatured protein binding;disordered domain specific binding;enzyme binding;G protein-coupled receptor binding;heat shock protein binding;histone deacetylase binding;misfolded protein binding;protein binding involved in protein folding;protein N-terminus binding;RNA binding;signaling receptor binding;transcription corepressor activity;ubiquitin protein ligase binding;unfolded protein binding;virus receptor activity aggresome;blood microparticle;centriole;centrosome;cytoplasm;cytosol;endoplasmic reticulum;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;focal adhesion;inclusion body;mitochondrion;nuclear speck;nucleoplasm;nucleus;perinuclear region of cytoplasm;protein-containing complex;ribonucleoprotein complex;vesicle Antigen processing and presentation;Endocytosis;Estrogen signaling pathway;Legionellosis;Longevity regulating pathway - multiple species;MAPK signaling pathway;Measles;Prion diseases;Protein processing in endoplasmic reticulum;Spliceosome;Toxoplasmosis Attenuation phase;AUF1 (hnRNP D0) binds and destabilizes mRNA;HSF1-dependent transactivation;HSP90 chaperone cycle for steroid hormone receptors (SHR);Neutrophil degranulation;Regulation of HSF1-mediated heat shock response;Viral RNP Complexes in the Host Cell Nucleus BAG1-HSP70 complex;BAX-DNAJA1-HSPA1B complex;BAX-DNAJA2-HSPA1B complex;HSP70-BAG5-PARK2 complex;LSD1 complex;N-NOS-CHIP-HSP70-1 complex;P2X7 receptor signalling complex;p532-Clathrin-HSP70 complex;Polycomb repressive complex 1 (PRC1, hPRC-H) -0.225295707583427 -0.505021154880524 1.26648759841919 0.926963210105896 0.999437034130096 0.875835418701172 0.948309242725372 -0.0221763011068106 -0.0115139773115516 1.27263236045837 0.707315027713776 0.707315027713776 -1.24875032901764 -1.73504221439362 -1.50537407398224 -0.58862829208374 -1.04969882965088 -0.812794029712677 + Cluster -674 12 12 11 36.5 36.5 33.8 45.664 0 191.6 27867000000 72 5.7131983547671 9.61538461538462E-06 P63092;Q5JWF2;P63092-4;Q5JWF2-2;P63092-3;P63092-2;P38405;P38405-2;P38405-3;P19087;A8MTJ3;P11488 P63092;Q5JWF2;P63092-4;Q5JWF2-2;P63092-3;P63092-2 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short;Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas GNAS 1393 Activation of phosphodiesterase lowers intracellular levels ofcAMP and cGMP which may open a cyclic nucleotide-suppressiblecation channel leading to influx of calcium, ultimately leading torelease of neurotransmitter. Indeed, denatonium and strychnineinduce transient reduction in cAMP and cGMP in taste tissue,whereas this decrease is inhibited by GNAT3 antibody. Gustducinheterotrimer transduces response to bitter and sweet compounds viaregulation of phosphodiesterase for alpha subunit, as well as viaactivation of phospholipase C for beta and gamma subunits, withultimate increase inositol trisphosphate and increase ofintracellular Calcium. GNAT3 can functionally couple to tastereceptors to transmit intracellular signal: receptor heterodimerTAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umamitaste, whereas the T2R family GPCRs act as bitter sensors.Functions also as lumenal sugar sensors in the gut to control theexpression of the Na+-glucose transporter SGLT1 in response todietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP.Thus, may modulate the gut capacity to absorb sugars, withimplications in malabsorption syndromes and diet-related disordersincluding diabetes and obesity.;Functions as signal transducer for the rod photoreceptorRHO. Required for normal RHO-mediated light perception by theretina (PubMed:22190596). Guanine nucleotide-binding proteins (Gproteins) function as transducers downstream of G protein-coupledreceptors (GPCRs), such as the photoreceptor RHO. The alpha chaincontains the guanine nucleotide binding site and alternatesbetween an active, GTP-bound state and an inactive, GDP-boundstate. Activated RHO promotes GDP release and GTP binding.Signaling is mediated via downstream effector proteins, such ascGMP-phosphodiesterase (By similarity);Guanine nucleotide-binding protein (G protein) alphasubunit playing a prominent role in bitter and sweet tastetransduction as well as in umami (monosodium glutamate,monopotassium glutamate, and inosine monophosphate) tastetransduction. Transduction by this alpha subunit involves couplingof specific cell-surface receptors with a cGMP-phosphodiesterase;Guanine nucleotide-binding proteins (G proteins) areinvolved as modulators or transducers in various transmembranesignaling systems. G(olf) alpha mediates signal transductionwithin the olfactory neuroepithelium and the basal ganglia. May beinvolved in some aspect of visual transduction, and in mediatingthe effect of one or more hormones/neurotransmitters.;Guanine nucleotide-binding proteins (G proteins) areinvolved as modulators or transducers in various transmembranesignaling systems. Transducin is an amplifier and one of thetransducers of a visual impulse that performs the coupling betweenrhodopsin and cGMP-phosphodiesterase.;Guanine nucleotide-binding proteins (G proteins)function as transducers in numerous signaling pathways controlledby G protein-coupled receptors (GPCRs) (PubMed:17110384).Signaling involves the activation of adenylyl cyclases, resultingin increased levels of the signaling molecule cAMP(PubMed:26206488, PubMed:8702665). GNAS functions downstream ofseveral GPCRs, including beta-adrenergic receptors(PubMed:21488135). Stimulates the Ras signaling pathway viaRAPGEF2 (PubMed:12391161).;Guanine nucleotide-binding proteins (G proteins)function as transducers in numerous signaling pathways controlledby G protein-coupled receptors (GPCRs). Signaling involves theactivation of adenylyl cyclases, resulting in increased levels ofthe signaling molecule cAMP. GNAS functions downstream of severalGPCRs, including beta-adrenergic receptors. XLas isoforms interactwith the same set of receptors as GNAS isoforms (By similarity) Lipid-anchor{ECO:0000250|UniProtKB:P63094}.; Peripheral membrane protein{ECO:0000250|UniProtKB:P04695}.; plasmalemmal pattern with apicalregion localization and cytosolic pattern with localizationthroughout the cytoplasm.;Cell membrane {ECO:0000269|PubMed:27120771};Cell membrane{ECO:0000250|UniProtKB:P63094};Cell projection, cilium, photoreceptor outersegment {ECO:0000250|UniProtKB:P04695}. Membrane{ECO:0000250|UniProtKB:P04695};Cytoplasm {ECO:0000269|PubMed:8015379}.Note=Dual ditribution pattern;Peripheral membrane protein {ECO:0000250|UniProtKB:Q63803}. Apicalcell membrane {ECO:0000269|PubMed:27120771}. activation of adenylate cyclase activity;adenylate cyclase-activating adrenergic receptor signaling pathway;adenylate cyclase-activating dopamine receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;bone development;cartilage development;cell proliferation;cellular response to catecholamine stimulus;cellular response to electrical stimulus;cellular response to glucagon stimulus;cellular response to prostaglandin E stimulus;cognition;detection of chemical stimulus involved in sensory perception of bitter taste;detection of light stimulus involved in visual perception;developmental growth;DNA methylation;embryonic cranial skeleton morphogenesis;embryonic hindlimb morphogenesis;endochondral ossification;energy reserve metabolic process;eye photoreceptor cell development;G protein-coupled receptor signaling pathway;genetic imprinting;hair follicle placode formation;intracellular transport;multicellular organism growth;negative regulation of cyclic-nucleotide phosphodiesterase activity;phototransduction;phototransduction, visible light;platelet aggregation;positive regulation of cAMP-mediated signaling;positive regulation of cold-induced thermogenesis;positive regulation of cyclic-nucleotide phosphodiesterase activity;positive regulation of cytosolic calcium ion concentration;positive regulation of GTPase activity;positive regulation of osteoblast differentiation;positive regulation of osteoclast differentiation;post-embryonic body morphogenesis;protein folding;regulation of insulin secretion;regulation of parathyroid hormone secretion;regulation of rhodopsin mediated signaling pathway;renal water homeostasis;response to drug;response to light intensity;response to light stimulus;response to nicotine;retina development in camera-type eye;retinal cone cell development;rhodopsin mediated signaling pathway;sensory perception of smell;sensory perception of sweet taste;sensory perception of umami taste;signal transduction;skin development;tissue homeostasis;visual perception;Wnt signaling pathway, calcium modulating pathway acyl binding;adenylate cyclase activator activity;beta-2 adrenergic receptor binding;corticotropin-releasing hormone receptor 1 binding;D1 dopamine receptor binding;G protein-coupled photoreceptor activity;G protein-coupled receptor binding;GDP binding;G-protein beta/gamma-subunit complex binding;GTP binding;GTPase activity;insulin-like growth factor receptor binding;ionotropic glutamate receptor binding;metal ion binding;mu-type opioid receptor binding;protein kinase binding acrosomal vesicle;apical plasma membrane;axoneme;cytoplasm;cytosol;dendrite;extracellular exosome;heterotrimeric G-protein complex;intrinsic component of membrane;membrane;neuronal cell body;photoreceptor connecting cilium;photoreceptor disc membrane;photoreceptor inner segment;photoreceptor outer segment;photoreceptor outer segment membrane;plasma membrane;protein-containing complex;trans-Golgi network membrane Adrenergic signaling in cardiomyocytes;Alcoholism;Aldosterone synthesis and secretion;Amoebiasis;Amphetamine addiction;Bile secretion;Calcium signaling pathway;cAMP signaling pathway;Carbohydrate digestion and absorption;Chagas disease (American trypanosomiasis);Circadian entrainment;Cocaine addiction;Cortisol synthesis and secretion;Cushing syndrome;Dilated cardiomyopathy (DCM);Dopaminergic synapse;Endocrine and other factor-regulated calcium reabsorption;Endocrine resistance;Estrogen signaling pathway;Gap junction;Gastric acid secretion;Glucagon signaling pathway;Glutamatergic synapse;GnRH signaling pathway;Human cytomegalovirus infection;Human papillomavirus infection;Inflammatory mediator regulation of TRP channels;Insulin secretion;Long-term depression;Melanogenesis;Morphine addiction;Olfactory transduction;Ovarian steroidogenesis;Oxytocin signaling pathway;Pancreatic secretion;Parathyroid hormone synthesis, secretion and action;Parkinson disease;Pathways in cancer;Phospholipase D signaling pathway;Phototransduction;Platelet activation;Rap1 signaling pathway;Regulation of lipolysis in adipocytes;Relaxin signaling pathway;Renin secretion;Salivary secretion;Serotonergic synapse;Taste transduction;Thermogenesis;Thyroid hormone synthesis;Vascular smooth muscle contraction;Vasopressin-regulated water reabsorption;Vibrio cholerae infection Achromatopsia;Acromegaly;Congenital stationary night blindness;Cushing syndrome;Fibrous dysplasia, polyostotic;Pituitary adenomas;Primary dystonia;Progressive osseous heteroplasia;Pseudohypoparathyroidism Activation of the phototransduction cascade;Adenylate cyclase activating pathway;Adenylate cyclase inhibitory pathway;ADP signalling through P2Y purinoceptor 12;Ca2+ pathway;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;G alpha (i) signalling events;G alpha (s) signalling events;G alpha (z) signalling events;Glucagon signaling in metabolic regulation;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Glucagon-type ligand receptors;G-protein activation;Hedgehog 'off' state;Inactivation, recovery and regulation of the phototransduction cascade;Olfactory Signaling Pathway;PKA activation in glucagon signalling;PLC beta mediated events;Prostacyclin signalling through prostacyclin receptor;Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1);Vasopressin regulates renal water homeostasis via Aquaporins GNAS-GNB1-GNG2 complex;GNAS-L-GNB1-GNG1 complex;GNAS-L-GNB1-GNG10 complex;GNAS-L-GNB1-GNG11 complex;GNAS-L-GNB1-GNG12 complex;GNAS-L-GNB1-GNG13 complex;GNAS-L-GNB1-GNG2 complex;GNAS-L-GNB1-GNG3 complex;GNAS-L-GNB1-GNG4 complex;GNAS-L-GNB1-GNG5 complex;GNAS-L-GNB1-GNG7 complex;GNAS-L-GNB1-GNG8 complex;GNAS-L-GNB2-GNG1 complex;GNAS-L-GNB2-GNG10 complex;GNAS-L-GNB2-GNG11 complex;GNAS-L-GNB2-GNG12 complex;GNAS-L-GNB2-GNG13 complex;GNAS-L-GNB2-GNG2 complex;GNAS-L-GNB2-GNG3 complex;GNAS-L-GNB2-GNG4 complex;GNAS-L-GNB2-GNG5 complex;GNAS-L-GNB2-GNG7 complex;GNAS-L-GNB2-GNG8 complex;GNAS-L-GNB3-GNG1 complex;GNAS-L-GNB3-GNG10 complex;GNAS-L-GNB3-GNG11 complex;GNAS-L-GNB3-GNG12 complex;GNAS-L-GNB3-GNG13 complex;GNAS-L-GNB3-GNG2 complex;GNAS-L-GNB3-GNG4 complex;GNAS-L-GNB3-GNG5 complex;GNAS-L-GNB3-GNG7 complex;GNAS-L-GNB3-GNG8 complex;GNAS-L-GNB4-GNG1 complex;GNAS-L-GNB4-GNG10 complex;GNAS-L-GNB4-GNG11 complex;GNAS-L-GNB4-GNG12 complex;GNAS-L-GNB4-GNG13 complex;GNAS-L-GNB4-GNG2 complex;GNAS-L-GNB4-GNG3 complex;GNAS-L-GNB4-GNG4 complex;GNAS-L-GNB4-GNG5 complex;GNAS-L-GNB4-GNG7 complex;GNAS-L-GNB4-GNG8 complex;GNAS-L-GNB5-GNG10 complex;GNAS-L-GNB5-GNG11 complex;GNAS-L-GNB5-GNG12 complex;GNAS-L-GNB5-GNG13 complex;GNAS-L-GNB5-GNG3 complex;GNAS-L-GNB5-GNG4 complex;GNAS-L-GNB5-GNG5 complex;GNAS-L-GNB5-GNG7 complex;GNAS-L-GNB5-GNG8 complex -0.185029998421669 0.201948896050453 0.788512885570526 0.699394643306732 0.823573768138885 1.00298631191254 0.858368098735809 0.196484357118607 0.427022129297256 1.34485340118408 0.213105350732803 0.65534120798111 -2.04507517814636 -0.903425097465515 -1.32266592979431 -1.8368581533432 -0.0441200956702232 -0.874416768550873 + Cluster -674 2 2 2 33 33 33 11.602 0.00033852 2.8218 1766000000 10 4.03421513769573 0.000134110787172012 Q9UK45 Q9UK45 U6 snRNA-associated Sm-like protein LSm7 LSM7 3141 Plays role in pre-mRNA splicing as component of theU4/U6-U5 tri-snRNP complex that is involved in spliceosomeassembly, and as component of the precatalytic spliceosome(spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8complex binds specifically to the 3'-terminal U-tract of U6 snRNA(PubMed:10523320). Nucleus {ECO:0000269|PubMed:10523320,ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28781166}. exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;mRNA splicing, via spliceosome U6 snRNA binding catalytic step 2 spliceosome;cytosol;Lsm1-7-Pat1 complex;Lsm2-8 complex;nucleoplasm;nucleus;U12-type spliceosomal complex;U2-type precatalytic spliceosome;U2-type prespliceosome;U4/U6 x U5 tri-snRNP complex;U6 snRNP RNA degradation;Spliceosome mRNA decay by 5' to 3' exoribonuclease;mRNA Splicing - Major Pathway LSm1-7 complex;LSm2-8 complex;Spliceosome -1.12223017215729 0.0315258130431175 0.383474230766296 1.480064868927 0.847240090370178 0.36379462480545 0.425575226545334 0.703816473484039 -0.0337124392390251 1.47176349163055 1.29262101650238 0.215009346604347 -1.77403390407562 -1.26943123340607 -1.42909216880798 -1.01265180110931 -0.286866724491119 -0.286866724491119 + Cluster -674 20 20 19 40.2 40.2 37.9 70.905 0 289.13 124420000000 148 3.56419546368685 0.000385593220338983 Q16881;Q16881-3;Q16881-4;Q16881-5;Q16881-2;Q16881-6;Q16881-7 Q16881;Q16881-3;Q16881-4;Q16881-5;Q16881-2;Q16881-6;Q16881-7 Thioredoxin reductase 1, cytoplasmic TXNRD1 1871 Isoform 1 may possess glutaredoxin activity as well asthioredoxin reductase activity and induces actin and tubulinpolymerization, leading to formation of cell membrane protrusions.Isoform 4 enhances the transcriptional activity of estrogenreceptors alpha and beta while isoform 5 enhances thetranscriptional activity of the beta receptor only. Isoform 5 alsomediates cell death induced by a combination of interferon-betaand retinoic acid. Cytoplasm {ECO:0000250}.Isoform 4: Cytoplasm. Nucleus.Isoform 5: Cytoplasm. cell proliferation;cell redox homeostasis;cellular response to oxidative stress;mesoderm formation;nucleobase-containing small molecule interconversion;regulation of lipid metabolic process;selenium compound metabolic process;signal transduction electron transfer activity;flavin adenine dinucleotide binding;methylseleninic acid reductase activity;methylselenol reductase activity;protein disulfide oxidoreductase activity;thioredoxin-disulfide reductase activity cytoplasm;cytosol;extracellular exosome;fibrillar center;mitochondrion;nucleoplasm Hepatocellular carcinoma;Pathways in cancer;Selenocompound metabolism Detoxification of Reactive Oxygen Species;Interconversion of nucleotide di- and triphosphates;Metabolism of ingested H2SeO4 and H2SeO3 into H2Se;Metabolism of ingested MeSeO2H into MeSeH;PPARA activates gene expression;TP53 Regulates Metabolic Genes;Uptake and function of diphtheria toxin -0.242774471640587 0.5253546833992 0.104637071490288 0.577088177204132 0.171165227890015 -0.382453799247742 -0.123714700341225 0.0260183103382587 0.463150531053543 1.71783447265625 1.56889963150024 1.08957529067993 -2.68100428581238 -0.625540614128113 -0.58963805437088 -1.0373957157135 -0.00218914868310094 -0.559012472629547 + Cluster -674 3 3 3 6.4 6.4 6.4 55.866 0 7.817 492910000 5 3.07353566369964 0.000941896024464832 P86791;P86790 P86791;P86790 Vacuolar fusion protein CCZ1 homolog;Vacuolar fusion protein CCZ1 homolog B CCZ1;CCZ1B 1460 Acts in concert with MON1A, as a guanine exchange factor(GEF) for RAB7, promotes the exchange of GDP to GTP, converting itfrom an inactive GDP-bound form into an active GTP-bound form(PubMed:23084991). Lysosome membrane{ECO:0000269|PubMed:17897319}. vesicle-mediated transport guanyl-nucleotide exchange factor activity aggresome;cytosol;intracellular membrane-bounded organelle;lysosomal membrane;Mon1-Ccz1 complex RAB GEFs exchange GTP for GDP on RABs -0.881896793842316 0.563361823558807 0.927041947841644 1.28860723972321 1.1881115436554 0.493367254734039 0.116026565432549 -0.0133097870275378 0.310704737901688 0.419346630573273 1.56477856636047 0.679162979125977 -1.52149760723114 -0.657610356807709 -1.08030343055725 -1.77532958984375 -0.532112121582031 -1.0884495973587 + Cluster -674 7 7 7 46.1 46.1 46.1 26.599 0 272.87 57717000000 100 3.54379901874994 0.000386831275720165 P56537;P56537-2 P56537;P56537-2 Eukaryotic translation initiation factor 6 EIF6 1258 Binds to the 60S ribosomal subunit and prevents itsassociation with the 40S ribosomal subunit to form the 80Sinitiation complex in the cytoplasm. Behaves as a stimulatorytranslation initiation factor downstream insulin/growth factors.Is also involved in ribosome biogenesis. Associates with pre-60Ssubunits in the nucleus and is involved in its nuclear export.Cytoplasmic release of TIF6 from 60S subunits and nuclearrelocalization is promoted by a RACK1 (RACK1)-dependent proteinkinase C activity (PubMed:10085284, PubMed:14654845,PubMed:21536732). In tissues responsive to insulin, controls fattyacid synthesis and glycolysis by exerting translational control ofadipogenic transcription factors such as CEBPB, CEBPD and ATF4that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation,controls the expression of mitochondrial respiratory chain genesinvolved in reactive oxygen species (ROS) synthesis (Bysimilarity). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediatedtranslational repression and miRNA-mediated cleavage ofcomplementary mRNAs by RISC (PubMed:17507929). Modulates cellcycle progression and global translation of pre-B cells, itsactivation seems to be rate-limiting in tumorigenesis and tumorgrowth (By similarity). Cytoplasm. Nucleus, nucleolus. Note=Shuttlesbetween cytoplasm and nucleus/nucleolus. assembly of large subunit precursor of preribosome;gene silencing by miRNA;mature ribosome assembly;miRNA mediated inhibition of translation;positive regulation of translation;regulation of fatty acid biosynthetic process;regulation of glycolytic process;regulation of megakaryocyte differentiation;regulation of reactive oxygen species metabolic process;response to insulin;ribosomal large subunit biogenesis;ribosomal subunit export from nucleus ribosomal large subunit binding;ribosome binding;translation initiation factor activity cytoplasm;cytosol;extracellular exosome;nucleolus;nucleoplasm;nucleus;preribosome, large subunit precursor Ribosome biogenesis in eukaryotes TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle);TRBP containing complex (DICER, TRBP, AGO2, RPL7A, EIF6, MOV10) -1.05133068561554 0.368127524852753 1.01199626922607 1.33175694942474 0.994915246963501 0.294344216585159 0.38397353887558 0.38397353887558 -0.201167479157448 1.13321876525879 0.500107526779175 1.24143600463867 -2.02747130393982 -0.835612654685974 -1.07398188114166 -1.29030513763428 -0.290833860635757 -0.873146533966064 + Cluster -674 3 3 3 5.4 5.4 5.4 107.89 0 21.878 3965000000 14 3.99048436994453 0.000143266475644699 O60763;O60763-2 O60763;O60763-2 General vesicular transport factor p115 USO1 287 it is required fortranscytotic fusion and/or subsequent binding of the vesicles tothe target membrane. May well act as a vesicular anchor byinteracting with the target membrane and holding the vesicular andtarget membranes in proximity.;General vesicular transport factor required forintercisternal transport in the Golgi stack Peripheral membrane protein{ECO:0000269|PubMed:19454686, ECO:0000269|PubMed:9478999}.Note=Recycles between the cytosol and the Golgi apparatus duringinterphase. During interphase, the phosphorylated form is foundexclusively in cytosol; the unphosphorylated form is associatedwith Golgi apparatus membranes. {ECO:0000269|PubMed:19454686,ECO:0000269|PubMed:9478999}.;Cytoplasm, cytosol{ECO:0000269|PubMed:19454686, ECO:0000269|PubMed:9478999}. Golgiapparatus membrane {ECO:0000269|PubMed:19454686,ECO:0000269|PubMed:9478999} COPII vesicle coating;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi organization;Golgi vesicle docking;intracellular protein transport;membrane fusion;transcytosis;vesicle fusion with Golgi apparatus cadherin binding;protein transporter activity;RNA binding cytosol;endoplasmic reticulum;ER to Golgi transport vesicle membrane;fibrillar center;Golgi apparatus;Golgi membrane;Golgi stack;membrane;perinuclear region of cytoplasm;transport vesicle COPII-mediated vesicle transport;COPI-mediated anterograde transport;Golgi Cisternae Pericentriolar Stack Reorganization -1.5569531917572 0.203481137752533 0.74242490530014 0.916592180728912 0.478803366422653 0.488835424184799 0.103567458689213 0.103567458689213 -0.45171657204628 1.34933435916901 1.14651572704315 1.40903842449188 -1.82297587394714 -1.28728795051575 -1.49063575267792 -0.352718591690063 0.0408314354717731 -0.0207039956003428 + Cluster -674 19 19 19 42.5 42.5 42.5 68.569 0 323.31 53715000000 108 3.04031310825563 0.00099554234769688 P04843 P04843 Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1 RPN1 493 Subunit of the oligosaccharyl transferase (OST) complexthat catalyzes the initial transfer of a defined glycan(Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrierdolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the firststep in protein N-glycosylation. N-glycosylation occurscotranslationally and the complex associates with the Sec61complex at the channel-forming translocon complex that mediatesprotein translocation across the endoplasmic reticulum (ER). Allsubunits are required for a maximal enzyme activity Single-pass type I membraneprotein {ECO:0000305}. Melanosome. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV.;Endoplasmic reticulum{ECO:0000250|UniProtKB:E2RQ08, ECO:0000250|UniProtKB:Q9GMB0}.Endoplasmic reticulum membrane cellular protein modification process;protein N-linked glycosylation via asparagine dolichyl-diphosphooligosaccharide-protein glycotransferase activity;RNA binding cytosol;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;melanosome;membrane;oligosaccharyltransferase complex;rough endoplasmic reticulum Metabolic pathways;N-Glycan biosynthesis;Protein processing in endoplasmic reticulum Asparagine N-linked glycosylation;SRP-dependent cotranslational protein targeting to membrane Oligosaccharyltransferase complex (Stt3A variant);Oligosaccharyltransferase complex (Stt3B variant);SELK multiprotein complex -0.477926522493362 0.569679796695709 -1.47479152679443 -0.185474008321762 -1.63470482826233 -0.836548745632172 -0.761666238307953 -0.361464768648148 0.283468574285507 -0.892732501029968 -0.958140790462494 0.283830553293228 1.76310670375824 0.861907660961151 0.901676893234253 1.62704741954803 0.389906853437424 0.90282529592514 + Cluster -671 3 3 3 20.9 20.9 20.9 26.559 0 9.3619 3597400000 6 3.53119091246646 0.000393877551020408 P21266 P21266 Glutathione S-transferase Mu 3 GSTM3 752 Conjugation of reduced glutathione to a wide number ofexogenous and endogenous hydrophobic electrophiles. May governuptake and detoxification of both endogenous compounds andxenobiotics at the testis and brain blood barriers Cytoplasm. cellular detoxification of nitrogen compound;establishment of blood-nerve barrier;glutathione derivative biosynthetic process;glutathione metabolic process;nitrobenzene metabolic process;response to estrogen;xenobiotic catabolic process enzyme binding;glutathione binding;glutathione transferase activity;identical protein binding;protein homodimerization activity cytoplasm;cytosol;extracellular exosome;intercellular bridge;nucleus;sperm fibrous sheath Chemical carcinogenesis;Drug metabolism - cytochrome P450;Drug metabolism - other enzymes;Fluid shear stress and atherosclerosis;Glutathione metabolism;Hepatocellular carcinoma;Metabolic pathways;Metabolism of xenobiotics by cytochrome P450;Pathways in cancer;Platinum drug resistance Glutathione conjugation -0.50016838312149 0.407481163740158 -1.52206790447235 0.0981813594698906 -0.993515431880951 -1.30889451503754 -1.05890309810638 -0.271882444620132 0.407481163740158 -1.05890309810638 -0.958566844463348 0.455316036939621 1.85344421863556 1.32072472572327 1.02769339084625 1.01510679721832 0.757095277309418 0.330377399921417 + Cluster -671 1 1 1 7.2 7.2 7.2 39.038 0 22.454 889740000 4 3.13384578773077 0.000844936708860759 P50613 P50613 Cyclin-dependent kinase 7 CDK7 1142 thisfeedback loop may lead to an arrest of the cell cycle and of thetranscription, helping in cell recovery, or to apoptosis. Requiredfor DNA-bound peptides-mediated transcription and cellular growthinhibition.;Serine/threonine kinase involved in cell cycle controland in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclinand mediate the progression through the cell cycle. Each differentcomplex controls a specific transition between 2 subsequent phasesin the cell cycle. Required for both activation and complexformation of CDK1/cyclin-B during G2-M transition, and foractivation of CDK2/cyclins during G1-S transition (but not complexformation). CDK7 is the catalytic subunit of the CDK-activatingkinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1,POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAKactivates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6by threonine phosphorylation, thus regulating cell cycleprogression. CAK complexed to the core-TFIIH basal transcriptionfactor activates RNA polymerase II by serine phosphorylation ofthe repetitive C-terminal domain (CTD) of its large subunit(POLR2A), allowing its escape from the promoter and elongation ofthe transcripts. Phosphorylation of POLR2A in complex with DNApromotes transcription initiation by triggering dissociation fromDNA. Its expression and activity are constant throughout the cellcycle. Upon DNA damage, triggers p53/TP53 activation byphosphorylation, but is inactivated in turn by p53/TP53 Nucleus. Cytoplasm. Cytoplasm, perinuclearregion. Note=Colocalizes with PRKCI in the cytoplasm and nucleus.Translocates from the nucleus to cytoplasm and perinuclear regionin response to DNA-bound peptides. 7-methylguanosine mRNA capping;androgen receptor signaling pathway;cell cycle arrest;cell division;cell proliferation;nucleotide-excision repair, preincision complex assembly;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;protein phosphorylation;protein stabilization;regulation of cyclin-dependent protein serine/threonine kinase activity;snRNA transcription by RNA polymerase II;termination of RNA polymerase I transcription;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;transcription initiation from RNA polymerase I promoter;transcription initiation from RNA polymerase II promoter;transcription-coupled nucleotide-excision repair androgen receptor binding;ATP binding;cyclin-dependent protein serine/threonine kinase activity;DNA-dependent ATPase activity;kinase activity;protein C-terminus binding;protein kinase activity;protein serine/threonine kinase activity;RNA polymerase II CTD heptapeptide repeat kinase activity;transcription coactivator activity cyclin-dependent protein kinase activating kinase holoenzyme complex;cytoplasm;nucleoplasm;nucleus;perinuclear region of cytoplasm;transcription factor TFIIH holo complex;transcription factor TFIIK complex Basal transcription factors;Cell cycle;Nucleotide excision repair Alvocidib;Zotiraciclib;Zotiraciclib citrate Cyclin A/B1/B2 associated events during G2/M transition;Cyclin A:Cdk2-associated events at S phase entry;Cyclin D associated events in G1;Cyclin E associated events during G1/S transition;Dual incision in TC-NER;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of Incision Complex in GG-NER;Formation of RNA Pol II elongation complex;Formation of TC-NER Pre-Incision Complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;Gap-filling DNA repair synthesis and ligation in TC-NER;HIV Transcription Initiation;mRNA Capping;NoRC negatively regulates rRNA expression;RNA Pol II CTD phosphorylation and interaction with CE;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;RNA Polymerase I Chain Elongation;RNA Polymerase I Promoter Escape;RNA Polymerase I Transcription Initiation;RNA Polymerase I Transcription Termination;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Promoter Escape;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription Elongation;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Tat-mediated elongation of the HIV-1 transcript;TP53 Regulates Transcription of DNA Repair Genes;Transcription of the HIV genome;Transcription-Coupled Nucleotide Excision Repair (TC-NER) CAK complex (Cdk-activating kinase complex);CAK core complex (Cdk-activating kinase core complex);CAK-ERCC2 complex;ESR1-CDK7-CCNH-MNAT1-MTA1-HDAC2 complex;HES1 promoter corepressor complex;HES1 promoter-Notch enhancer complex;TFIIH transcription factor complex -0.995473980903625 -0.209796100854874 -0.491799741983414 -0.116019636392593 -0.291759461164474 -1.01230359077454 -1.27353990077972 -0.539402663707733 -0.291759461164474 -0.126214489340782 -1.06149780750275 -0.919498085975647 1.80622243881226 1.49269032478333 1.63347637653351 0.720254957675934 0.323006302118301 1.35341465473175 + Cluster -671 5 5 5 16.9 16.9 16.9 51.169 0 88.528 10690000000 30 4.34384310854224 7.11864406779661E-05 P23258;Q9NRH3 P23258;Q9NRH3 Tubulin gamma-1 chain;Tubulin gamma-2 chain TUBG1;TUBG2 778 Tubulin is the major constituent of microtubules. Thegamma chain is found at microtubule organizing centers (MTOC) suchas the spindle poles or the centrosome. Pericentriolar matrixcomponent that regulates alpha/beta chain minus-end nucleation,centrosome duplication and spindle formation (By similarity);Tubulin is the major constituent of microtubules. Thegamma chain is found at microtubule organizing centers (MTOC) suchas the spindle poles or the centrosome. Pericentriolar matrixcomponent that regulates alpha/beta chain minus-end nucleation,centrosome duplication and spindle formation. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:14654843,ECO:0000269|PubMed:24107630, ECO:0000269|PubMed:9566967,ECO:0000269|PubMed:9566969}.;Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000305}. ciliary basal body-plasma membrane docking;cytoplasmic microtubule organization;G2/M transition of mitotic cell cycle;meiotic spindle organization;microtubule cytoskeleton organization;microtubule nucleation;microtubule-based process;mitotic cell cycle;mitotic sister chromatid segregation;mitotic spindle organization;regulation of G2/M transition of mitotic cell cycle GTP binding;GTPase activity;identical protein binding;structural constituent of cytoskeleton;structural molecule activity apical part of cell;cell leading edge;centriole;centrosome;ciliary basal body;condensed nuclear chromosome;cytoplasm;cytoplasmic microtubule;cytosol;gamma-tubulin complex;microtubule;microtubule cytoskeleton;non-motile cilium;nucleus;pericentriolar material;polar microtubule;recycling endosome;spindle;spindle microtubule Human papillomavirus infection Complex cortical dysplasia with other brain malformations Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition 60S APC containing complex;Gamma-tubulin complex -1.01474475860596 -0.532531797885895 -0.582946062088013 -0.624930322170258 -0.258505880832672 -1.06244575977325 -0.955228388309479 -1.01109397411346 -0.342631995677948 -0.745356976985931 0.396896183490753 -0.33618500828743 1.3799661397934 0.840352535247803 1.49311602115631 0.905386626720428 0.1720150411129 2.27886843681335 + Cluster -671 2 2 2 9.7 9.7 9.7 39.548 0 12.629 2888800000 6 3.98513863025882 0.000142450142450142 Q6IBS0;Q9NR96-4 Q6IBS0;Q9NR96-4 Twinfilin-2 TWF2 1977 Actin-binding protein involved in motile andmorphological processes. Inhibits actin polymerization, likely bysequestering G-actin. By capping the barbed ends of filaments, italso regulates motility. Seems to play an important role inclathrin-mediated endocytosis and distribution of endocyticorganelles. May play a role in regulating the mature length of themiddle and short rows of stereocilia (By similarity);Key component of innate and adaptive immunity. TLRs(Toll-like receptors) control host immune response againstpathogens through recognition of molecular patterns specific tomicroorganisms. TLR9 is a nucleotide-sensing TLR which isactivated by unmethylated cytidine-phosphate-guanosine (CpG)dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-Bactivation, cytokine secretion and the inflammatory response(PubMed:11564765, PubMed:17932028). Controls lymphocyte responseto Helicobacter infection (By similarity). Upon CpG stimulation,induces B-cell proliferation, activation, survival and antibodyproduction (PubMed:23857366). Single-pass type I membraneprotein {ECO:0000250|UniProtKB:Q9EQU3}. Endosome{ECO:0000250|UniProtKB:Q9EQU3}. Lysosome{ECO:0000250|UniProtKB:Q9EQU3}. Cytoplasmic vesicle, phagosome{ECO:0000250|UniProtKB:Q9EQU3}. Note=Relocalizes from endoplasmicreticulum to endosome and lysosome upon stimulation with agonist.Exit from the ER requires UNC93B1. Endolysosomal localization isrequired for proteolytic cleavage and subsequent activation.Intracellular localization of the active receptor may prevent fromresponding to self nucleic acid. {ECO:0000250|UniProtKB:Q9EQU3}.;Cytoplasm, cytoskeleton{ECO:0000269|PubMed:10406962}. Cytoplasm, perinuclear region{ECO:0000269|PubMed:10406962}. Cell projection, stereocilium{ECO:0000250}. Note=Perinuclear and G-actin-rich cortical actinstructure sublocalization.;Endoplasmic reticulum membrane{ECO:0000250|UniProtKB:Q9EQU3} actin filament depolymerization;barbed-end actin filament capping;cell projection organization;cellular response to growth factor stimulus;cellular response to retinoic acid;defense response to bacterium;defense response to Gram-negative bacterium;defense response to virus;I-kappaB kinase/NF-kappaB signaling;I-kappaB phosphorylation;immune response;inflammatory response;innate immune response;maintenance of gastrointestinal epithelium;MyD88-dependent toll-like receptor signaling pathway;negative regulation of actin filament polymerization;negative regulation of calcium-transporting ATPase activity;negative regulation of interleukin-6 production;negative regulation of interleukin-8 production;negative regulation of NF-kappaB transcription factor activity;negative regulation of toll-like receptor signaling pathway;positive regulation of axon extension;positive regulation of B cell activation;positive regulation of B cell proliferation;positive regulation of chemokine production;positive regulation of gene expression;positive regulation of granulocyte macrophage colony-stimulating factor production;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of immunoglobulin production;positive regulation of inflammatory response;positive regulation of interferon-alpha biosynthetic process;positive regulation of interferon-beta biosynthetic process;positive regulation of interferon-beta production;positive regulation of interferon-gamma biosynthetic process;positive regulation of interleukin-10 production;positive regulation of interleukin-12 production;positive regulation of interleukin-18 production;positive regulation of interleukin-6 production;positive regulation of interleukin-8 biosynthetic process;positive regulation of interleukin-8 production;positive regulation of JNK cascade;positive regulation of JUN kinase activity;positive regulation of lamellipodium assembly;positive regulation of MAPK cascade;positive regulation of neuron projection development;positive regulation of NF-kappaB transcription factor activity;positive regulation of NIK/NF-kappaB signaling;positive regulation of nitric-oxide synthase biosynthetic process;positive regulation of toll-like receptor signaling pathway;positive regulation of transcription by RNA polymerase II;positive regulation of tumor necrosis factor production;regulation of actin cytoskeleton organization;regulation of B cell differentiation;regulation of cytokine secretion;regulation of lamellipodium assembly;regulation of microvillus length;regulation of toll-like receptor 9 signaling pathway;response to molecule of bacterial origin;sequestering of actin monomers;toll-like receptor 9 signaling pathway;toll-like receptor signaling pathway;tumor necrosis factor production 1-phosphatidylinositol-3-kinase activity;actin filament binding;actin monomer binding;ATP binding;cadherin binding;interleukin-1 receptor binding;phosphatidylinositol-4,5-bisphosphate binding;protein homodimerization activity;protein kinase C binding;RNA binding;signaling pattern recognition receptor activity;siRNA binding;transmembrane signaling receptor activity;unmethylated CpG binding actin filament;apical plasma membrane;basolateral plasma membrane;cytoplasm;early phagosome;endolysosome membrane;endoplasmic reticulum;endoplasmic reticulum membrane;endosome;endosome membrane;extracellular exosome;extracellular region;filopodium;Golgi membrane;growth cone;integral component of membrane;lamellipodium;lysosome;myofibril;perinuclear region of cytoplasm;plasma membrane;stereocilium African trypanosomiasis;Chagas disease (American trypanosomiasis);Herpes simplex virus 1 infection;Malaria;Measles;PD-L1 expression and PD-1 checkpoint pathway in cancer;Toll-like receptor signaling pathway;Tuberculosis Atopic dermatitis Agatolimod;Tilsotolimod MyD88 dependent cascade initiated on endosome;PI3K Cascade;Toll Like Receptor 9 (TLR9) Cascade;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling;Trafficking and processing of endosomal TLR -1.91304874420166 0.373848408460617 -1.40956056118011 -0.605436980724335 -0.571994185447693 -0.993459045886993 -0.600093126296997 -0.639754235744476 -0.212071090936661 0.338637292385101 -0.370870977640152 0.0367387197911739 1.31360876560211 0.537195444107056 0.378026336431503 1.47054314613342 1.56348729133606 1.30420351028442 + Cluster -671 7 7 5 34.5 34.5 27.8 29.653 0 83.258 22122000000 43 3.3372359259075 0.000570921985815603 O14813 O14813 Paired mesoderm homeobox protein 2A PHOX2A 136 May be involved in regulating the specificity ofexpression of the catecholamine biosynthetic genes. Acts as atranscription activator/factor. Could maintain the noradrenergicphenotype. Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}. dopaminergic neuron differentiation;locus ceruleus development;midbrain development;noradrenergic neuron differentiation;oculomotor nerve formation;positive regulation of transcription by RNA polymerase II;regulation of respiratory gaseous exchange;somatic motor neuron differentiation;sympathetic nervous system development;trochlear nerve formation DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II regulatory region sequence-specific DNA binding nuclear chromatin Congenital fibrosis of the extraocular muscles -1.97259891033173 0.233436077833176 0.0558449737727642 -0.498951017856598 -0.858986020088196 0.276256680488586 -0.731240630149841 0.397069454193115 -0.694543838500977 -0.313433587551117 -1.72193777561188 -0.655004680156708 0.731915891170502 0.987175703048706 1.02914130687714 1.27950191497803 1.44918978214264 1.00716483592987 + Cluster -671 3 2 2 8.9 6.3 6.3 54.099 0 54.067 788140000 8 3.11669035170409 0.000875981161695447 O43237;O43237-2 O43237;O43237-2 Cytoplasmic dynein 1 light intermediate chain 2 DYNC1LI2 202 Acts as one of several non-catalytic accessorycomponents of the cytoplasmic dynein 1 complex that are thought tobe involved in linking dynein to cargos and to adapter proteinsthat regulate dynein function. Cytoplasmic dynein 1 acts as amotor for the intracellular retrograde motility of vesicles andorganelles along microtubules. May play a role in binding dyneinto membranous organelles or chromosomes. Cytoplasm, cytoskeleton {ECO:0000250}. antigen processing and presentation of exogenous peptide antigen via MHC class II;cellular response to nerve growth factor stimulus;centrosome localization;endoplasmic reticulum to Golgi vesicle-mediated transport;microtubule cytoskeleton organization;microtubule-based movement;protein homooligomerization ATP binding;dynein heavy chain binding;microtubule motor activity centrosome;cytoplasmic dynein complex;cytosol;kinetochore;late endosome;lysosome;membrane;microtubule Phagosome;Salmonella infection;Vasopressin-regulated water reabsorption Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;HSP90 chaperone cycle for steroid hormone receptors (SHR);MHC class II antigen presentation;Mitotic Prometaphase;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Separation of Sister Chromatids -1.14299952983856 -0.92221200466156 -0.869810521602631 -0.389859676361084 -0.192214533686638 -1.06094932556152 -0.0272569954395294 -1.06094932556152 -0.192214533686638 -1.06094932556152 -0.894472301006317 1.11345899105072 1.42977690696716 0.280528664588928 1.28094899654388 1.48404848575592 1.1389000415802 1.08622586727142 + Cluster -671 20 20 17 23.9 23.9 20.9 112.89 0 323.31 39388000000 142 3.04844010235682 0.000982035928143713 P05023;P05023-3;P05023-4;P05023-2;P13637;P13637-2;P13637-3;P50993;Q13733;P20648 P05023;P05023-3;P05023-4;P05023-2 Sodium/potassium-transporting ATPase subunit alpha-1 ATP1A1 496 Catalyzes the hydrolysis of ATP coupled with theexchange of H(+) and K(+) ions across the plasma membrane.Responsible for acid production in the stomach.;This is the catalytic component of the active enzyme,which catalyzes the hydrolysis of ATP coupled with the exchange ofsodium and potassium ions across the plasma membrane. This actioncreates the electrochemical gradient of sodium and potassium ions,providing the energy for active transport of various nutrients;This is the catalytic component of the active enzyme,which catalyzes the hydrolysis of ATP coupled with the exchange ofsodium and potassium ions across the plasma membrane. This actioncreates the electrochemical gradient of sodium and potassium ions,providing the energy for active transport of various nutrients.;This is the catalytic component of the active enzyme,which catalyzes the hydrolysis of ATP coupled with the exchange ofsodium and potassium ions across the plasma membrane. This actioncreates the electrochemical gradient of sodium and potassium ions,providing the energy for active transport of various nutrients.Plays a role in sperm motility.;This is the catalytic component of the active enzyme,which catalyzes the hydrolysis of ATP coupled with the exchange ofsodium and potassium ions across the plasma membrane. This actioncreates the electrochemical gradient of sodium and potassium,providing the energy for active transport of various nutrients. Multi-pass membrane protein.; Multi-pass membrane protein{ECO:0000255}. Melanosome {ECO:0000269|PubMed:17081065}.Note=Identified by mass spectrometry in melanosome fractions fromstage I to stage IV. {ECO:0000269|PubMed:17081065}.; Multi-pass membrane protein{ECO:0000269|PubMed:7711835}.;Cell membrane;Cell membrane {ECO:0000269|PubMed:16175638};Cell membrane {ECO:0000269|PubMed:7711835};Cell membrane, sarcolemma{ECO:0000269|PubMed:7711835};Membrane {ECO:0000269|PubMed:7711835};Multi-pass membrane protein {ECO:0000269|PubMed:16175638}. Note=Inmature sperm, located in the principle piece of the spermflagellum.;Multi-pass membrane protein {ECO:0000269|PubMed:7711835}.;Multi-pass membrane protein {ECO:0000269|PubMed:7711835}. Cellmembrane {ECO:0000269|PubMed:7711835} adult locomotory behavior;ATP hydrolysis coupled proton transport;ATP metabolic process;cardiac muscle cell action potential involved in contraction;cardiac muscle contraction;cell communication by electrical coupling involved in cardiac conduction;cellular potassium ion homeostasis;cellular response to amyloid-beta;cellular response to mechanical stimulus;cellular response to steroid hormone stimulus;cellular sodium ion homeostasis;fertilization;flagellated sperm motility;locomotion;membrane depolarization during cardiac muscle cell action potential;membrane hyperpolarization;membrane repolarization;membrane repolarization during cardiac muscle cell action potential;negative regulation of calcium ion transmembrane transport;negative regulation of calcium:sodium antiporter activity;negative regulation of cytosolic calcium ion concentration;negative regulation of glucocorticoid biosynthetic process;negative regulation of heart contraction;negative regulation of striated muscle contraction;neuron projection maintenance;neurotransmitter uptake;positive regulation of heart contraction;positive regulation of striated muscle contraction;potassium ion import across plasma membrane;potassium ion transport;regulation of blood pressure;regulation of cardiac muscle cell contraction;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;regulation of cellular pH;regulation of glutamate uptake involved in transmission of nerve impulse;regulation of membrane potential;regulation of respiratory gaseous exchange by neurological system process;regulation of resting membrane potential;regulation of smooth muscle contraction;regulation of sodium ion transport;regulation of striated muscle contraction;regulation of synaptic transmission, glutamatergic;regulation of the force of heart contraction;regulation of vasoconstriction;relaxation of cardiac muscle;response to drug;response to glycoside;response to nicotine;sodium ion export across plasma membrane;sodium ion transport;spermatogenesis;visual learning ADP binding;amyloid-beta binding;ankyrin binding;ATP binding;chaperone binding;ion antiporter activity involved in regulation of presynaptic membrane potential;magnesium ion binding;metal ion binding;phosphatase activity;phosphatidylinositol 3-kinase binding;potassium ion binding;potassium:proton exchanging ATPase activity;protein domain specific binding;protein kinase binding;sodium ion binding;sodium:potassium-exchanging ATPase activity;steroid hormone binding apical plasma membrane;axon;basolateral plasma membrane;caveola;cytoplasm;dendritic spine;endoplasmic reticulum;endosome;extracellular exosome;extracellular space;extracellular vesicle;Golgi apparatus;integral component of membrane;integral component of plasma membrane;intercalated disc;melanosome;membrane;myelin sheath;neuronal cell body;neuronal cell body membrane;plasma membrane;postsynaptic density;protein-containing complex;sarcolemma;sodium:potassium-exchanging ATPase complex;synapse;T-tubule Adrenergic signaling in cardiomyocytes;Aldosterone synthesis and secretion;Aldosterone-regulated sodium reabsorption;Bile secretion;cAMP signaling pathway;Carbohydrate digestion and absorption;Cardiac muscle contraction;cGMP-PKG signaling pathway;Collecting duct acid secretion;Endocrine and other factor-regulated calcium reabsorption;Gastric acid secretion;Insulin secretion;Metabolic pathways;Mineral absorption;Oxidative phosphorylation;Pancreatic secretion;Protein digestion and absorption;Proximal tubule bicarbonate reclamation;Salivary secretion;Thyroid hormone signaling pathway;Thyroid hormone synthesis Alternating hemiplegia of childhood;CAPOS syndrome;Hemiplegic migraine;Primary aldosteronism;Primary dystonia Acetyldigitoxin;Acetyldigoxin;Bepridil;beta-Acetyldigoxin;Bretylium tosilate;Deslanoside;Dexlansoprazole;Digitoxin;Digoxin;Esomeprazole;Gitoformate;G-strophanthin;Lanatoside C;Lansoprazole;Leminoprazole;Metildigoxin;Omeprazole;Pantoprazole;Penaprazole sodium hydrate;Picoprazole;Proscillaridin;Rabeprazole;Revaprazan hydrochloride;Tenatoprazole;Timoprazole;Vonoprazan fumarate Ion homeostasis;Ion transport by P-type ATPases ATP4A-ATP4B complex -2.07869410514832 -0.450584173202515 -0.246068939566612 0.89403373003006 -0.333424001932144 -0.758478760719299 0.453183680772781 -0.211502328515053 -1.43021547794342 -0.35736882686615 -1.27276575565338 -0.211502328515053 0.453183680772781 0.680956959724426 1.22445380687714 1.38368916511536 1.44870185852051 0.812401652336121 + Cluster -671 16 16 16 10.1 10.1 10.1 265.55 0 130.07 7042100000 27 3.51604936763797 0.000412955465587045 Q13085;Q13085-4;Q13085-3;Q13085-2;O00763;O00763-3;O00763-2 Q13085;Q13085-4;Q13085-3;Q13085-2 Acetyl-CoA carboxylase 1;Biotin carboxylase ACACA 1591 Catalyzes the ATP-dependent carboxylation of acetyl-CoAto malonyl-CoA. Carries out three functions: biotin carboxylcarrier protein, biotin carboxylase and carboxyltransferase.Involved in inhibition of fatty acid and glucose oxidation andenhancement of fat storage (By similarity). May play a role inregulation of mitochondrial fatty acid oxidation through malonyl-CoA-dependent inhibition of carnitine palmitoyltransferase 1 (Bysimilarity).;Catalyzes the rate-limiting reaction in the biogenesisof long-chain fatty acids. Carries out three functions: biotincarboxyl carrier protein, biotin carboxylase andcarboxyltransferase. Cytoplasm.;Mitochondrion {ECO:0000269|PubMed:10677481}.Nucleus {ECO:0000269|PubMed:10677481}. Endomembrane system.Note=May associate with membranes. acetyl-CoA metabolic process;carnitine shuttle;cellular response to prostaglandin E stimulus;energy homeostasis;fatty acid biosynthetic process;fatty-acyl-CoA biosynthetic process;lipid homeostasis;malonyl-CoA biosynthetic process;negative regulation of catalytic activity;negative regulation of fatty acid beta-oxidation;negative regulation of gene expression;positive regulation of cellular metabolic process;positive regulation of heart growth;positive regulation of lipid storage;protein homotetramerization;protein metabolic process;regulation of cholesterol biosynthetic process;regulation of glucose metabolic process;response to drug;response to nutrient levels;response to organic cyclic compound;tissue homeostasis acetyl-CoA carboxylase activity;ATP binding;biotin binding;biotin carboxylase activity;identical protein binding;metal ion binding actin cytoskeleton;cytosol;endomembrane system;fibrillar center;mitochondrial outer membrane;mitochondrion;nucleus Adipocytokine signaling pathway;AMPK signaling pathway;Fatty acid biosynthesis;Fatty acid metabolism;Glucagon signaling pathway;Insulin resistance;Insulin signaling pathway;Metabolic pathways;Propanoate metabolism;Pyruvate metabolism Activation of gene expression by SREBF (SREBP);Biotin transport and metabolism;ChREBP activates metabolic gene expression;Defective HLCS causes multiple carboxylase deficiency;Fatty acyl-CoA biosynthesis;Import of palmitoyl-CoA into the mitochondrial matrix -0.193216681480408 -1.56445419788361 0.211133643984795 -0.721081376075745 -1.03505635261536 0.00854571908712387 -0.692168354988098 -0.846915066242218 -1.47745943069458 0.374430477619171 -0.651422739028931 -0.0513245463371277 0.678518772125244 0.501738369464874 0.678518772125244 1.28484773635864 1.7299633026123 1.76540195941925 + Cluster -671 10 10 10 29 29 29 46.588 0 123.25 12858000000 41 3.56599519700939 0.000385106382978723 P11310;P11310-2 P11310;P11310-2 Medium-chain specific acyl-CoA dehydrogenase, mitochondrial ACADM 623 Acyl-CoA dehydrogenase specific for acyl chain lengthsof 4 to 16 that catalyzes the initial step of fatty acid beta-oxidation. Utilizes the electron transfer flavoprotein (ETF) as anelectron acceptor to transfer electrons to the main mitochondrialrespiratory chain via ETF-ubiquinone oxidoreductase (ETFdehydrogenase). Mitochondrion matrix. carnitine biosynthetic process;carnitine metabolic process, CoA-linked;fatty acid beta-oxidation;fatty acid beta-oxidation using acyl-CoA dehydrogenase;medium-chain fatty acid catabolic process;medium-chain fatty acid metabolic process;oxidation-reduction process;regulation of lipid metabolic process acyl-CoA dehydrogenase activity;flavin adenine dinucleotide binding;identical protein binding;medium-chain-acyl-CoA dehydrogenase activity axon;mitochondrial matrix;mitochondrial membrane;mitochondrion;nuclear speck;nucleus Fatty acid degradation;Fatty acid metabolism;Metabolic pathways;PPAR signaling pathway;Valine, leucine and isoleucine degradation Disorders of mitochondrial fatty-acid oxidation;MCAD deficiency;Secondary hyperammonemia Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA;Beta oxidation of octanoyl-CoA to hexanoyl-CoA;mitochondrial fatty acid beta-oxidation of unsaturated fatty acids;PPARA activates gene expression 1.75583517551422 -0.284563332796097 -0.284563332796097 -0.710996448993683 -0.765174090862274 -1.77709102630615 -1.92010200023651 -1.1577684879303 0.0807454437017441 1.20915699005127 1.13281571865082 0.832661986351013 0.372372329235077 0.759588301181793 0.548375248908997 0.0998620688915253 0.0807454437017441 0.0281001925468445 + Cluster -671 3 3 3 51.4 51.4 51.4 8.0061 0.00032712 2.0685 2288800000 8 3.31864553152449 0.000584507042253521 Q9UBI6 Q9UBI6 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 GNG12 3069 Guanine nucleotide-binding proteins (G proteins) areinvolved as a modulator or transducer in various transmembranesignaling systems. The beta and gamma chains are required for theGTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Cytoplasmic side {ECO:0000305}.; Lipid-anchor{ECO:0000305};Cell membrane {ECO:0000305} cerebral cortex development;G protein-coupled receptor signaling pathway;response to lipopolysaccharide;signal transduction GTPase activity;PDZ domain binding;phosphate ion binding actin filament;extracellular exosome;heterotrimeric G-protein complex;plasma membrane Alcoholism;Apelin signaling pathway;Chemokine signaling pathway;Cholinergic synapse;Circadian entrainment;Dopaminergic synapse;GABAergic synapse;Glutamatergic synapse;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Kaposi sarcoma-associated herpesvirus infection;MAPK signaling pathway;Morphine addiction;Pathways in cancer;PI3K-Akt signaling pathway;Ras signaling pathway;Regulation of actin cytoskeleton;Relaxin signaling pathway;Retrograde endocannabinoid signaling;Serotonergic synapse Activation of G protein gated Potassium channels;ADP signalling through P2Y purinoceptor 1;ADP signalling through P2Y purinoceptor 12;Adrenaline,noradrenaline inhibits insulin secretion;Ca2+ pathway;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;G alpha (12/13) signalling events;G alpha (i) signalling events;G alpha (q) signalling events;G alpha (s) signalling events;G alpha (z) signalling events;G beta:gamma signalling through PI3Kgamma;G beta:gamma signalling through PLC beta;Glucagon signaling in metabolic regulation;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Glucagon-type ligand receptors;G-protein activation;Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits;Presynaptic function of Kainate receptors;Prostacyclin signalling through prostacyclin receptor;Thrombin signalling through proteinase activated receptors (PARs);Thromboxane signalling through TP receptor;Vasopressin regulates renal water homeostasis via Aquaporins GNAI1-GNB2-GNG12 complex;GNAI1-GNB3-GNG12 complex;GNAI1-GNB4-GNG12 complex;GNAI1-GNB5-GNG12 complex;GNAS-L-GNB1-GNG12 complex;GNAS-L-GNB2-GNG12 complex;GNAS-L-GNB3-GNG12 complex;GNAS-L-GNB4-GNG12 complex;GNAS-L-GNB5-GNG12 complex 1.7343670129776 0.0458399839699268 -0.756533682346344 -0.953693568706512 -0.682998538017273 -1.53195536136627 -1.98270285129547 -0.872312664985657 0.664146721363068 0.822977364063263 1.17379558086395 0.133900612592697 0.879604995250702 0.688333630561829 0.688333630561829 0.664146721363068 -0.545081555843353 -0.170167997479439 + Cluster -671 3 3 3 5.2 5.2 5.2 98.636 0 10.709 513170000 6 3.27434762607397 0.000627986348122867 Q86UK7;Q86UK7-2;Q86UK7-3 Q86UK7;Q86UK7-2;Q86UK7-3 Zinc finger protein 598 ZNF598 2106 E3 ubiquitin-protein ligase that plays a key role in theribosome quality control (RQC), a pathway that takes place when aribosome has stalled during translation (PubMed:28065601,PubMed:28132843). Required for ribosomes to terminally stallduring translation of poly(A) sequences by mediatingmonoubiquitination of 40S ribosomal protein RPS10/eS10, RPS20/uS10and RPS3/uS3 (PubMed:28065601, PubMed:28132843). Stallingprecludes synthesis of a long poly-lysine tail and initiates theRQC pathway to degrade the potentially detrimental aberrantnascent polypeptide (PubMed:28065601, PubMed:28132843). Also actsas a component of the 4EHP-GYF2 complex, a multiprotein complexthat acts as a repressor of translation initiation(PubMed:22751931). protein monoubiquitination;protein ubiquitination;rescue of stalled ribosome metal ion binding;ribosome binding;RNA binding;ubiquitin protein ligase activity 2.03228878974915 0.0010750318178907 -0.947781145572662 -0.395898163318634 -1.19244015216827 -1.10466694831848 -0.973211646080017 -0.973211646080017 1.40911853313446 1.54207038879395 0.867021918296814 0.792671263217926 0.139966532588005 -0.460836559534073 0.170190840959549 0.487563610076904 -0.876528918743134 -0.517391681671143 + Cluster -671 3 3 3 20.7 20.7 20.7 30.062 0 5.5903 792730000 3 3.77533714914845 0.000257352941176471 Q9NQ88 Q9NQ88 Fructose-2,6-bisphosphatase TIGAR TIGAR 2892 contributes to the growth, proliferationand survival of intestinal crypts following tissue ablation(PubMed:23726973). Plays a neuroprotective role against ischemicbrain damage by enhancing PPP flux and preserving mitochondriafunctions (By similarity). Protects glioma cells from hypoxia- andROS-induced cell death by inhibiting glycolysis and activatingmitochondrial energy metabolism and oxygen consumption in a TKTL1-dependent and p53/TP53-independent manner (PubMed:22887998). Playsa role in cancer cell survival by promoting DNA repair throughactivating PPP flux in a CDK5-ATM-dependent signaling pathwayduring hypoxia and/or genome stress-induced DNA damage responses(PubMed:25928429). Involved in intestinal tumor progression(PubMed:23726973).;Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate(PubMed:19015259). Acts as a negative regulator of glycolysis bylowering intracellular levels of fructose-2,6-bisphosphate in ap53/TP53-dependent manner, resulting in the pentose phosphatepathway (PPP) activation and NADPH production (PubMed:16839880,PubMed:22887998). Contributes to the generation of reducedglutathione to cause a decrease in intracellular reactive oxygenspecies (ROS) content, correlating with its ability to protectcells from oxidative or metabolic stress-induced cell death(PubMed:16839880, PubMed:19713938, PubMed:23726973,PubMed:22887998, PubMed:23817040). Plays a role in promotingprotection against cell death during hypoxia by decreasingmitochondria ROS levels in a HK2-dependent manner through amechanism that is independent of its fructose-bisphosphataseactivity (PubMed:23185017). In response to cardiac damage stress,mediates p53-induced inhibition of myocyte mitophagy through ROSlevels reduction and the subsequent inactivation of BNIP3. Reducedmitophagy results in an enhanced apoptotic myocyte cell death, andexacerbates cardiac damage (By similarity). Plays a role in adultintestinal regeneration Cytoplasm {ECO:0000269|PubMed:23185017,ECO:0000269|PubMed:25928429}. Nucleus{ECO:0000269|PubMed:25928429}. Mitochondrion{ECO:0000269|PubMed:23185017}. Note=Translocated to themitochondria during hypoxia in a HIF1A-dependent manner(PubMed:23185017). Colocalizes with HK2 in the mitochondria duringhypoxia (PubMed:23185017). Translocated to the nucleus duringhypoxia and/or genome stress-induced DNA damage responses incancer cells (PubMed:25928429). Translocation to the mitochondriais enhanced in ischemic cortex after reperfusion and/or duringoxygen and glucose deprivation (OGD)/reoxygenation insult inprimary neurons (By similarity). {ECO:0000250|UniProtKB:Q8BZA9,ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:25928429}. apoptotic process;autophagy;cellular response to cobalt ion;cellular response to DNA damage stimulus;cellular response to hypoxia;fructose 1,6-bisphosphate metabolic process;fructose 2,6-bisphosphate metabolic process;intestinal epithelial cell development;negative regulation of glucose catabolic process to lactate via pyruvate;negative regulation of glycolytic process;negative regulation of mitophagy;negative regulation of neuron death;negative regulation of programmed cell death;negative regulation of reactive oxygen species metabolic process;positive regulation of cardiac muscle cell apoptotic process;positive regulation of DNA repair;positive regulation of hexokinase activity;regulation of pentose-phosphate shunt;regulation of response to DNA damage checkpoint signaling;response to gamma radiation;response to ischemia;response to xenobiotic stimulus bisphosphoglycerate 2-phosphatase activity;fructose-2,6-bisphosphate 2-phosphatase activity cytoplasm;cytosol;intracellular;mitochondrial outer membrane;nucleus Central carbon metabolism in cancer;Fructose and mannose metabolism;Metabolic pathways TP53 Regulates Metabolic Genes 1.20775973796844 0.186082616448402 -0.697449862957001 -0.908757150173187 -0.908757150173187 -1.74440002441406 -1.4816187620163 -1.30722320079803 0.530249416828156 1.06646645069122 1.82599484920502 0.440542548894882 0.490118891000748 -0.275734812021255 0.985797762870789 0.406821668148041 0.0458436124026775 0.138263329863548 + Cluster -671 7 7 7 8.8 8.8 8.8 134.55 0 77.638 5840200000 13 4.57365845898841 4.8582995951417E-05 Q92896;Q92896-2;Q92896-3 Q92896;Q92896-2;Q92896-3 Golgi apparatus protein 1 GLG1 2364 Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding ofneutrophils). Single-pass type I membrane protein{ECO:0000269|PubMed:2355176}.;Golgi apparatus membrane{ECO:0000269|PubMed:2355176} bone morphogenesis;leukocyte migration;negative regulation of protein processing;negative regulation of transforming growth factor beta receptor signaling pathway;regulation of chondrocyte differentiation fibroblast growth factor binding;signaling receptor binding extracellular exosome;extracellular matrix;Golgi apparatus;Golgi membrane;integral component of membrane;membrane;plasma membrane Cell adhesion molecules (CAMs) Cell surface interactions at the vascular wall TNF-alpha/Nf-kappa B signaling complex (RPL6, RPL30, RPS13, CHUK, DDX3X, NFKB2, NFKBIB, REL, IKBKG, NFKB1, MAP3K8, RELB, GLG1, NFKBIA, RELA, TNIP2, GTF2I) 1.00038540363312 0.321597248315811 -1.48899853229523 -1.17045783996582 -0.378436625003815 -1.89048767089844 -0.667332112789154 -1.55622339248657 0.724423348903656 1.20371663570404 1.20371663570404 1.31959450244904 0.191274583339691 0.191274583339691 0.00439349748194218 0.617264628410339 0.321597248315811 0.0526977516710758 + Cluster -671 31 31 31 54.1 54.1 54.1 57.116 0 323.31 84819000000 187 5.83954557820043 1.06382978723404E-05 P07237 P07237 Protein disulfide-isomerase P4HB 532 theinteraction retains P4HB at the cell surface of Th2 T helpercells, increasing disulfide reductase activity at the plasmamembrane, altering the plasma membrane redox state and enhancingcell migration (PubMed:21670307).;This multifunctional protein catalyzes the formation,breakage and rearrangement of disulfide bonds. At the cellsurface, seems to act as a reductase that cleaves disulfide bondsof proteins attached to the cell. May therefore cause structuralmodifications of exofacial proteins. Inside the cell, seems toform/rearrange disulfide bonds of nascent proteins. At highconcentrations, functions as a chaperone that inhibits aggregationof misfolded proteins. At low concentrations, facilitatesaggregation (anti-chaperone activity). May be involved with otherchaperones in the structural modification of the TG precursor inhormone biogenesis. Also acts a structural subunit of variousenzymes such as prolyl 4-hydroxylase and microsomaltriacylglycerol transfer protein MTTP. Receptor for LGALS9 Peripheral membrane protein{ECO:0000305}. Note=Highly abundant. In some cell types, seems tobe also secreted or associated with the plasma membrane, where itundergoes constant shedding and replacement from intracellularsources (Probable). Localizes near CD4-enriched regions onlymphoid cell surfaces (PubMed:11181151). Identified by massspectrometry in melanosome fractions from stage I to stage IV(PubMed:10636893). Colocalizes with MTTP in the endoplasmicreticulum (PubMed:23475612). {ECO:0000269|PubMed:10636893,ECO:0000269|PubMed:11181151, ECO:0000269|PubMed:23475612,ECO:0000305}.;Endoplasmic reticulum{ECO:0000269|PubMed:23475612}. Endoplasmic reticulum lumen{ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:23475612}.Melanosome {ECO:0000269|PubMed:12643545,ECO:0000269|PubMed:17081065}. Cell membrane{ECO:0000269|PubMed:21670307} cell redox homeostasis;cellular protein metabolic process;cellular response to hypoxia;cellular response to interleukin-7;chylomicron assembly;interleukin-12-mediated signaling pathway;interleukin-23-mediated signaling pathway;peptidyl-proline hydroxylation to 4-hydroxy-L-proline;positive regulation of viral entry into host cell;post-translational protein modification;protein folding;regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;response to endoplasmic reticulum stress;very-low-density lipoprotein particle assembly enzyme binding;integrin binding;peptide disulfide oxidoreductase activity;procollagen-proline 4-dioxygenase activity;protein disulfide isomerase activity;protein heterodimerization activity;RNA binding endoplasmic reticulum;endoplasmic reticulum chaperone complex;endoplasmic reticulum lumen;endoplasmic reticulum-Golgi intermediate compartment;external side of plasma membrane;extracellular exosome;extracellular region;focal adhesion;melanosome;procollagen-proline 4-dioxygenase complex Protein processing in endoplasmic reticulum Cole-Carpenter syndrome Chylomicron assembly;Collagen biosynthesis and modifying enzymes;Detoxification of Reactive Oxygen Species;Hedgehog ligand biogenesis;Interleukin-12 signaling;Interleukin-23 signaling;Post-translational protein phosphorylation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);VLDL assembly Prolyl 4-hydroxylase (alpha(I)-type);Prolyl 4-hydroxylase (alpha(II)-type);Prolyl 4-hydroxylase (alpha(III)-type) 2.11157178878784 0.17451947927475 -0.467545717954636 -1.21698307991028 -0.87817394733429 -0.921276569366455 -1.3267914056778 -1.05676317214966 -0.243723288178444 1.35586309432983 1.49203515052795 1.20472133159637 -0.326640039682388 -0.66347599029541 0.242364659905434 0.319408416748047 0.0263698287308216 0.17451947927475 + Cluster -671 4 4 4 14.2 14.2 14.2 53.846 0 56.289 2601900000 8 3.67545446205704 0.000324074074074074 Q6UX04;Q6UX04-2 Q6UX04;Q6UX04-2 Peptidyl-prolyl cis-trans isomerase CWC27 homolog CWC27 2023 As part of the spliceosome, plays a role in pre-mRNAsplicing (PubMed:29360106). Probable inactive PPIase with nopeptidyl-prolyl cis-trans isomerase activity (PubMed:20676357) Nucleus {ECO:0000305|PubMed:29360106}. mRNA splicing, via spliceosome;protein folding;protein peptidyl-prolyl isomerization peptidyl-prolyl cis-trans isomerase activity catalytic step 1 spliceosome;catalytic step 2 spliceosome;nucleoplasm;nucleus mRNA Splicing - Major Pathway C complex spliceosome 1.24624121189117 0.0437186099588871 -0.130230009555817 -0.448298960924149 -0.953181505203247 -2.06402087211609 -1.09352922439575 -1.29619336128235 -0.614485144615173 0.969807028770447 1.78369331359863 1.28676319122314 0.237778931856155 0.0479797944426537 0.127693802118301 0.904315114021301 -0.281759917736053 0.233707740902901 + Cluster -671 36 36 36 40.9 40.9 40.9 94.622 0 323.31 376880000000 373 3.19048473283652 0.000757774140752864 P43243;P43243-2 P43243 Matrin-3 MATR3 1026 May play a role in transcription or may interact withother nuclear matrix proteins to form the internal fibrogranularnetwork. In association with the SFPQ-NONO heteromer may play arole in nuclear retention of defective RNAs. Plays a role in theregulation of DNA virus-mediated innate immune response byassembling into the HDP-RNP complex, a complex that serves as aplatform for IRF3 phosphorylation and subsequent innate immuneresponse activation through the cGAS-STING pathway(PubMed:28712728). May bind to specific miRNA hairpins(PubMed:28431233). Nucleus matrix. activation of innate immune response;innate immune response;posttranscriptional regulation of gene expression identical protein binding;miRNA binding;RNA binding;structural molecule activity;zinc ion binding membrane;nuclear inner membrane;nuclear matrix Amyotrophic lateral sclerosis (ALS) HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex;p54(nrb)-PSF-matrin3 complex;SNW1 complex 0.735989511013031 -0.259397357702255 -0.126824423670769 -0.202039584517479 -0.773342192173004 -1.53992891311646 -1.22706127166748 -1.62466537952423 -0.126824423670769 0.903321266174316 2.51614546775818 1.27325975894928 0.227111309766769 -0.152903094887733 -0.375298321247101 0.388057231903076 0.217054575681686 0.147345751523972 + Cluster -671 6 6 6 8.4 8.4 8.4 119.7 0 39.8 5953000000 25 3.56506351944918 0.000386411889596603 Q8IZL8 Q8IZL8 Proline-, glutamic acid- and leucine-rich protein 1 PELP1 2173 the 5FMC complex is recruited to ZNF148 bymethylated CHTOP, leading to desumoylation of ZNF148 andsubsequent transactivation of ZNF148 target genes. Component ofthe PELP1 complex involved in the nucleolar steps of 28S rRNAmaturation and the subsequent nucleoplasmic transit of the pre-60Sribosomal subunit. Regulates pre-60S association of the criticalremodeling factor MDN1 (PubMed:21326211);Coactivator of estrogen receptor-mediated transcriptionand a corepressor of other nuclear hormone receptors and sequence-specific transcription factors. Plays a role in estrogen receptor(ER) genomic activity when present in the nuclear compartment byactivating the ER target genes in a hormonal stimulation dependentmanner. Can facilitate ER non-genomic signaling via SRC and PI3Kinteraction in the cytosol. Plays a role in E2-mediated cell cycleprogression by interacting with RB1. May have important functionalimplications in ER/growth factor cross-talk. Interacts withseveral growth factor signaling components including EGFR and HRS.Involved in nuclear receptor signaling via its interaction with ARand NR3C1. May promote tumorigenesis via its interaction with andmodulation of several oncogenes including SRC, PI3K, STAT3 andEGFR. Plays a role in cancer cell metastasis via its ability tomodulate E2-mediated cytoskeleton changes and cell migration viaits interaction with SRC and PI3K. Functions as the keystabilizing component of the Five Friends of Methylated CHTOP(5FMC) complex Nucleus, nucleolus{ECO:0000269|PubMed:21326211}. Nucleus, nucleoplasm{ECO:0000269|PubMed:21326211}. Nucleus. Cytoplasm. Note=Mainlyfound in the nucleoplasm, with low levels detected in thecytoplasm (By similarity). Also found associated with the plasmamembrane. Mainly in cytoplasm in a subset of breast tumors.Localization is widely deregulated in endometrial cancers withpredominantly cytoplasm localization in high-grade endometrialtumors (PubMed:16140940). {ECO:0000250|UniProtKB:Q9DBD5,ECO:0000269|PubMed:16140940}. cellular response to estrogen stimulus;positive regulation of transcription by RNA polymerase II;rRNA processing chromatin binding;RNA binding;transcription factor binding cytoplasm;membrane;MLL1 complex;nucleolus;nucleoplasm;nucleus;transcriptionally active chromatin Major pathway of rRNA processing in the nucleolus and cytosol;PTK6 Expression 5FMC (Friends of Methylated Chtop) complex;LAS1L-PELP1-TEX10-WDR18-NOL9-SENP3 complex;MLL1-WDR5 complex;PELP1-TEX10-WDR18 complex 0.552583575248718 -0.685001313686371 -0.710859656333923 -0.787511587142944 -1.52726829051971 -1.387859582901 -1.77216613292694 -0.720177054405212 0.0841351225972176 0.30287954211235 1.70083963871002 0.566650092601776 0.412632465362549 0.48457333445549 0.412632465362549 0.918026924133301 0.825766682624817 1.3301237821579 + Cluster -671 3 3 3 10.2 10.2 10.2 35.092 0 25.698 221010000 7 4.22868874748873 9.03225806451613E-05 Q96GY0 Q96GY0 Zinc finger C2HC domain-containing protein 1A ZC2HC1A 2469 metal ion binding 0.517901539802551 -0.0723242983222008 -0.469224572181702 -1.17082011699677 -1.47638273239136 -1.00539755821228 -1.62546622753143 -1.19963705539703 0.397261917591095 0.594793438911438 2.05896639823914 -0.110616378486156 0.106070525944233 0.45940026640892 0.721867918968201 0.107758514583111 1.09085583686829 1.07499253749847 + Cluster -671 6 1 1 16.9 3.2 3.2 27.774 0 2.996 1061900000 6 3.63352457402885 0.00033630289532294 P31947;P31947-2 P31947;P31947-2 14-3-3 protein sigma SFN 896 Adapter protein implicated in the regulation of a largespectrum of both general and specialized signaling pathways. Bindsto a large number of partners, usually by recognition of aphosphoserine or phosphothreonine motif. Binding generally resultsin the modulation of the activity of the binding partner. Whenbound to KRT17, regulates protein synthesis and epithelial cellgrowth by stimulating Akt/mTOR pathway. May also regulate MDM2autoubiquitination and degradation and thereby activate p53/TP53 Cytoplasm. Nucleus {ECO:0000250}. Secreted.Note=May be secreted by a non-classical secretory pathway. DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;establishment of skin barrier;intrinsic apoptotic signaling pathway in response to DNA damage;keratinization;keratinocyte development;membrane organization;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of keratinocyte proliferation;negative regulation of protein kinase activity;positive regulation of cell growth;positive regulation of epidermal cell differentiation;positive regulation of protein export from nucleus;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;regulation of cyclin-dependent protein serine/threonine kinase activity;regulation of epidermal cell division;release of cytochrome c from mitochondria;signal transduction cadherin binding;identical protein binding;phosphoprotein binding;protein domain specific binding;protein kinase binding;protein kinase C inhibitor activity cytosol;extracellular exosome;extracellular space;mitochondrion;nucleus Aldosterone-regulated sodium reabsorption;Cell cycle;p53 signaling pathway Activation of BAD and translocation to mitochondria;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;RHO GTPases activate PKNs;TP53 Regulates Metabolic Genes;TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest;Translocation of SLC2A4 (GLUT4) to the plasma membrane 0.468468606472015 -0.133902609348297 -0.918066680431366 -1.10615110397339 -1.04019677639008 -1.34352684020996 -1.59781968593597 -1.39329648017883 0.482416659593582 0.653603971004486 1.80894541740417 0.0899136886000633 0.103742182254791 0.823316812515259 0.855103433132172 0.335070490837097 0.873006761074066 1.03937208652496 + + Cluster -671 2 2 2 8.9 8.9 8.9 26.261 1 -2 3949800000 4 5.0463711231732 2.25988700564972E-05 Q8N9Z2;Q8N9Z2-2 Q8N9Z2;Q8N9Z2-2 Coiled-coil domain-containing protein 71L CCDC71L 2214 cellular lipid metabolic process;positive regulation of fat cell differentiation 0.990570187568665 -0.15765517950058 -0.307205826044083 -0.758459150791168 -0.856215417385101 -1.75328660011292 -1.9073828458786 -1.29414701461792 -0.426525980234146 1.42642080783844 1.34477925300598 0.447913408279419 0.310739725828171 0.807845413684845 0.617097437381744 0.476966440677643 0.317024052143097 0.721521437168121 + Cluster -671 6 6 6 78 78 78 13.133 0 244.86 34844000000 34 4.06763535634598 0.000128358208955224 Q15370;Q15370-2 Q15370;Q15370-2 Transcription elongation factor B polypeptide 2 TCEB2 1794 SIII, also known as elongin, is a general transcriptionelongation factor that increases the RNA polymerase IItranscription elongation past template-encoded arresting sites.Subunit A is transcriptionally active and its transcriptionactivity is strongly enhanced by binding to the dimeric complex ofthe SIII regulatory subunits B and C (elongin BC complex)(PubMed:7638163). In embryonic stem cells, the elongin BC complexis recruited by EPOP to Polycomb group (PcG) target genes in ordergenerate genomic region that display both active and repressivechromatin properties, an important feature of pluripotent stemcells (By similarity). Nucleus {ECO:0000305}. post-translational protein modification;protein ubiquitination;protein-containing complex assembly;regulation of transcription from RNA polymerase II promoter in response to hypoxia;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter ubiquitin protein ligase binding Cul2-RING ubiquitin ligase complex;Cul5-RING ubiquitin ligase complex;cytosol;elongin complex;nucleoplasm;VCB complex HIF-1 signaling pathway;Human immunodeficiency virus 1 infection;Pathways in cancer;Renal cell carcinoma;Ubiquitin mediated proteolysis Antigen processing: Ubiquitination & Proteasome degradation;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;HIV elongation arrest and recovery;Neddylation;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;Regulation of expression of SLITs and ROBOs;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Elongation;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes;Vif-mediated degradation of APOBEC3G Cullin-RING E3 ubiquitin ligase complex;HIF1alpha-VHL-ElonginB-ElonginC complex;PRAME complex;PRAME-ElonginBC ubiquitin ligase;Ubiquitin E3 ligase (ASB1, TCEB1, TCEB2, CUL5, RNF7);Ubiquitin E3 ligase (ASB12, TCEB1, TCEB2, CUL5, RNF7);Ubiquitin E3 ligase (ASB2, TCEB1, TCEB2, CUL5, RNF7);Ubiquitin E3 ligase (ASB6, TCEB1, TCEB2, CUL5, RNF7);Ubiquitin E3 ligase (ASB7, TCEB1, TCEB2, CUL5, RNF7);Ubiquitin E3 ligase (VHL, TCEB1, TCEB2, CUL2);Ubiquitin E3 ligase (VHL, TCEB1, TCEB2, CUL2, RBX1);Ubiquitin E3 ligase (WSB1, TCEB1, TCEB2, CUL5, RBX1);VHL-ElonginB-ElonginC complex;VHL-TCEB1-TCEB2 complex;VHL-VDU1-TCEB1-TCEB2 complex -0.0248059406876564 -0.225011840462685 -0.793402910232544 -0.368921041488647 -0.699179351329803 -1.97716748714447 -1.87716150283813 -1.2804399728775 0.415313243865967 1.14256322383881 1.67762291431427 0.472902774810791 0.522329866886139 0.631285727024078 0.688081979751587 0.540353059768677 0.552029609680176 0.603607535362244 + Cluster -671 6 6 6 57.1 57.1 57.1 18.491 0 33.817 10603000000 14 4.68316887381334 2.97872340425532E-05 O75947;O75947-2 O75947;O75947-2 ATP synthase subunit d, mitochondrial ATP5H 370 Mitochondrial membrane ATP synthase (F(1)F(0) ATPsynthase or Complex V) produces ATP from ADP in the presence of aproton gradient across the membrane which is generated by electrontransport complexes of the respiratory chain. F-type ATPasesconsist of two structural domains, F(1) - containing theextramembraneous catalytic core, and F(0) - containing themembrane proton channel, linked together by a central stalk and aperipheral stalk. During catalysis, ATP synthesis in the catalyticdomain of F(1) is coupled via a rotary mechanism of the centralstalk subunits to proton translocation. Part of the complex F(0)domain and the peripheric stalk, which acts as a stator to holdthe catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 staticrelative to the rotary elements. Mitochondrion. Mitochondrion inner membrane. ATP biosynthetic process;ATP hydrolysis coupled cation transmembrane transport;ATP synthesis coupled proton transport;cristae formation;mitochondrial ATP synthesis coupled proton transport proton transmembrane transporter activity;transmembrane transporter activity mitochondrial inner membrane;mitochondrial proton-transporting ATP synthase complex;mitochondrial proton-transporting ATP synthase, stator stalk;mitochondrion;myelin sheath;nucleoplasm Alzheimer disease;Huntington disease;Metabolic pathways;Oxidative phosphorylation;Parkinson disease;Thermogenesis Cristae formation;Formation of ATP by chemiosmotic coupling F1F0-ATP synthase, mitochondrial 0.814791798591614 -0.253036618232727 -0.599557161331177 -0.221401080489159 -0.745742797851563 -1.93143892288208 -1.93143892288208 -1.21941912174225 0.16666305065155 1.25536239147186 1.67811119556427 0.245211720466614 0.378651112318039 0.685238897800446 0.839747369289398 -0.0568055883049965 0.16666305065155 0.728399753570557 + Cluster -671 5 5 2 18.2 18.2 8.3 40.589 0 20.893 1113200000 8 3.38803791460895 0.000520295202952029 P17612;P17612-2;P22694-10;P22612 P17612;P17612-2;P22694-10 cAMP-dependent protein kinase catalytic subunit alpha;cAMP-dependent protein kinase catalytic subunit beta PRKACA;PRKACB 706 this phosphorylation promotes HSF1 nuclear localization andtranscriptional activity upon heat shock (PubMed:21085490);maintains circulating platelets in a resting state byphosphorylating proteins in numerous platelet inhibitory pathwayswhen in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexesand free active PRKACA stimulates platelets and leads to plateletaggregation by phosphorylating VASP. Prevents theantiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated.RYR2 channel activity is potentiated by phosphorylation inpresence of luminal Ca(2+), leading to reduced amplitude andincreased frequency of store overload-induced Ca(2+) release(SOICR) characterized by an increased rate of Ca(2+) release andpropagation velocity of spontaneous Ca(2+) waves, despite reducedwave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activationby phosphorylation stimulates proteasome. Negatively regulatestight junctions (TJs) in ovarian cancer cells via CLDN3phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50DNA binding. Involved in embryonic development by down-regulatingthe Hedgehog (Hh) signaling pathway that determines embryo patternformation and morphogenesis. Prevents meiosis resumption inprophase-arrested oocytes via CDC25B inactivation byphosphorylation. May also regulate rapid eye movement (REM) sleepin the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3Gand AICDA. Isoform 2 phosphorylates and activates ABL1 in spermflagellum to promote spermatozoa capacitation. PhosphorylatesHSF1;Mediates cAMP-dependent signaling triggered by receptorbinding to GPCRs. PKA activation regulates diverse cellularprocesses such as cell proliferation, the cell cycle,differentiation and regulation of microtubule dynamics, chromatincondensation and decondensation, nuclear envelope disassembly andreassembly, as well as regulation of intracellular transportmechanisms and ion flux. Regulates the abundance ofcompartmentalized pools of its regulatory subunits throughphosphorylation of PJA2 which binds and ubiquitinates thesesubunits, leading to their subsequent proteolysis(PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW whichregulates its ability to bind RNA (PubMed:21880142);Phosphorylates a large number of substrates in thecytoplasm and the nucleus.;Phosphorylates a large number of substrates in thecytoplasm and the nucleus. Regulates the abundance ofcompartmentalized pools of its regulatory subunits throughphosphorylation of PJA2 which binds and ubiquitinates thesesubunits, leading to their subsequent proteolysis. PhosphorylatesCDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP.RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenicdifferentiation inhibition from osteoblasts. Involved in theregulation of platelets in response to thrombin and collagen Lipid-anchor {ECO:0000305}. Note=Translocates intothe nucleus (monomeric catalytic subunit). The inactive holoenzymeis found in the cytoplasm. Distributed throughout the cytoplasm inmeiotically incompetent oocytes. Associated to mitochondrion asmeiotic competence is acquired. Aggregates around the germinalvesicles (GV) at the immature GV stage oocytes (By similarity).Colocalizes with HSF1 in nuclear stress bodies (nSBs) upon heatshock (PubMed:21085490). {ECO:0000250,ECO:0000269|PubMed:21085490}.Isoform 2: Cell projection, cilium,flagellum {ECO:0000269|PubMed:10906071}. Cytoplasmic vesicle,secretory vesicle, acrosome {ECO:0000250|UniProtKB:P05132}.Note=Expressed in the midpiece region of the sperm flagellum(PubMed:10906071). Colocalizes with MROH2B and TCP11 on theacrosome and tail regions in round spermatids and spermatozoaregardless of the capacitation status of the sperm (Bysimilarity). {ECO:0000250|UniProtKB:P05132,ECO:0000269|PubMed:10906071}.; Lipid-anchor {ECO:0000305}. Nucleus {ECO:0000250}.Note=Translocates into the nucleus (monomeric catalytic subunit).The inactive holoenzyme is found in the cytoplasm. {ECO:0000250}.;Cytoplasm {ECO:0000269|PubMed:21423175}.Cell membrane {ECO:0000269|PubMed:21423175}. Membrane{ECO:0000305};Cytoplasm. Cell membrane. Nucleus{ECO:0000250}. Mitochondrion {ECO:0000250}. Membrane{ECO:0000305} activation of protein kinase A activity;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;blood coagulation;calcium-mediated signaling using intracellular calcium source;cell communication by electrical coupling involved in cardiac conduction;cellular response to epinephrine stimulus;cellular response to glucagon stimulus;cellular response to glucose stimulus;cellular response to heat;cellular response to parathyroid hormone stimulus;ciliary basal body-plasma membrane docking;cytokine-mediated signaling pathway;G2/M transition of mitotic cell cycle;high-density lipoprotein particle assembly;male gonad development;mesoderm formation;modulation of chemical synaptic transmission;mRNA processing;negative regulation of meiotic cell cycle;negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning;neural tube closure;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;positive regulation of cell cycle arrest;positive regulation of protein export from nucleus;protein autophosphorylation;protein kinase A signaling;protein phosphorylation;regulation of bicellular tight junction assembly;regulation of cardiac conduction;regulation of cardiac muscle contraction;regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion;regulation of cytosolic calcium ion concentration;regulation of G2/M transition of mitotic cell cycle;regulation of heart rate;regulation of macroautophagy;regulation of osteoblast differentiation;regulation of proteasomal protein catabolic process;regulation of protein binding;regulation of protein processing;regulation of ryanodine-sensitive calcium-release channel activity;renal water homeostasis;response to clozapine;signal transduction;sperm capacitation;spermatogenesis;stimulatory C-type lectin receptor signaling pathway ATP binding;cAMP-dependent protein kinase activity;magnesium ion binding;manganese ion binding;protein domain specific binding;protein kinase A regulatory subunit binding;protein kinase activity;protein kinase binding;protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;ubiquitin protein ligase binding acrosomal vesicle;calcium channel complex;cAMP-dependent protein kinase complex;centrosome;ciliary base;cytoplasm;cytosol;dendritic spine;extracellular exosome;intercellular bridge;membrane;mitochondrion;neuromuscular junction;nuclear speck;nucleoplasm;nucleotide-activated protein kinase complex;nucleus;perinuclear region of cytoplasm;plasma membrane;plasma membrane raft;sperm flagellum;sperm midpiece Adrenergic signaling in cardiomyocytes;Alcoholism;Aldosterone synthesis and secretion;Amoebiasis;Amphetamine addiction;Apelin signaling pathway;Autophagy - animal;Bile secretion;Calcium signaling pathway;cAMP signaling pathway;Chemokine signaling pathway;Cholinergic synapse;Circadian entrainment;Cocaine addiction;Cortisol synthesis and secretion;Cushing syndrome;Dilated cardiomyopathy (DCM);Dopaminergic synapse;Endocrine and other factor-regulated calcium reabsorption;Endocrine resistance;Estrogen signaling pathway;GABAergic synapse;Gap junction;Gastric acid secretion;Glucagon signaling pathway;Glutamatergic synapse;GnRH signaling pathway;Hedgehog signaling pathway;Human cytomegalovirus infection;Human papillomavirus infection;Human T-cell leukemia virus 1 infection;Inflammatory mediator regulation of TRP channels;Insulin secretion;Insulin signaling pathway;Longevity regulating pathway;Longevity regulating pathway - multiple species;Long-term potentiation;MAPK signaling pathway;Melanogenesis;Morphine addiction;Olfactory transduction;Oocyte meiosis;Ovarian steroidogenesis;Oxytocin signaling pathway;Parathyroid hormone synthesis, secretion and action;Parkinson disease;Pathways in cancer;Platelet activation;Prion diseases;Progesterone-mediated oocyte maturation;Proteoglycans in cancer;Ras signaling pathway;Regulation of lipolysis in adipocytes;Relaxin signaling pathway;Renin secretion;Retrograde endocannabinoid signaling;Salivary secretion;Serotonergic synapse;Taste transduction;Thermogenesis;Thyroid hormone signaling pathway;Thyroid hormone synthesis;Tight junction;Vascular smooth muscle contraction;Vasopressin-regulated water reabsorption;Vibrio cholerae infection;Viral carcinogenesis;Wnt signaling pathway Bilateral macronodular adrenal hyperplasia;Cushing syndrome;Macrothrombocytopenia Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;CD209 (DC-SIGN) signaling;CREB phosphorylation through the activation of Adenylate Cyclase;DARPP-32 events;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Factors involved in megakaryocyte development and platelet production;GLI3 is processed to GLI3R by the proteasome;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Glycolysis;HDL assembly;Hedgehog 'off' state;Interleukin-3, Interleukin-5 and GM-CSF signaling;Ion homeostasis;Loss of Nlp from mitotic centrosomes;Loss of phosphorylation of MECP2 at T308;Loss of proteins required for interphase microtubule organization from the centrosome;MAPK6/MAPK4 signaling;PKA activation;PKA activation in glucagon signalling;PKA-mediated phosphorylation of CREB;PKA-mediated phosphorylation of key metabolic factors;Rap1 signalling;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of insulin secretion;Regulation of MECP2 expression and activity;Regulation of PLK1 Activity at G2/M Transition;RET signaling;ROBO receptors bind AKAP5;Triglyceride catabolism;Vasopressin regulates renal water homeostasis via Aquaporins;VEGFA-VEGFR2 Pathway AKAP250-PKA-PDE4D complex;KCNQ1 macromolecular complex 0.452053725719452 -0.0477539077401161 -0.989104986190796 -0.667709589004517 -1.3234030008316 -1.76703298091888 -1.91330575942993 -1.00008070468903 0.407927066087723 0.769520878791809 1.17091917991638 0.654237985610962 0.756533026695251 0.521975100040436 0.807270705699921 0.952106237411499 0.348385363817215 0.867461800575256 + Cluster -671 9 9 7 19.8 19.8 14 79.541 0 100.61 4319700000 21 6.4535403970388 0 Q15059;Q15059-2;Q58F21;Q58F21-5;Q58F21-4;Q58F21-3;Q58F21-2 Q15059;Q15059-2 Bromodomain-containing protein 3 BRD3 1766 Chromatin reader that recognizes and bindshyperacetylated chromatin and plays a role in the regulation oftranscription, probably by chromatin remodeling and interactionwith transcription factors (PubMed:18406326, PubMed:27105114).Regulates transcription by promoting the binding of thetranscription factor GATA1 to its targets (By similarity);Testis-specific chromatin protein that specificallybinds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac andH4K8ac, respectively) and plays a key role in spermatogenesis(PubMed:22464331, PubMed:22901802). Required in late pachytenespermatocytes: plays a role in meiotic and post-meiotic cells bybinding to acetylated histones at the promoter of specific meioticand post-meiotic genes, facilitating their activation at theappropriate time (PubMed:22901802). In the post-meiotic phase ofspermatogenesis, binds to hyperacetylated histones andparticipates in their general removal from DNA (PubMed:22901802).Also recognizes and binds a subset of butyrylated histones: ableto bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it isnot able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (Bysimilarity). Also acts as a component of the splicing machinery inpachytene spermatocytes and round spermatids and participates in3'-UTR truncation of specific mRNAs in post-meiotic spermatids (Bysimilarity). Required for chromocenter organization, a structurecomprised of peri-centromeric heterochromatin Nucleus {ECO:0000250|UniProtKB:Q8K2F0}.Note=Detected on chromatin. {ECO:0000250|UniProtKB:Q8K2F0}.;Nucleus {ECO:0000269|PubMed:20538714,ECO:0000269|PubMed:22901802, ECO:0000269|PubMed:22971749}.Note=Detected on chromatin. {ECO:0000250|UniProtKB:Q91Y44}. cell differentiation;chromatin organization;chromatin remodeling;histone displacement;male meiosis I;male meiotic nuclear division;mRNA processing;positive regulation of transcription involved in meiotic cell cycle;regulation of RNA splicing;regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;RNA splicing;spermatogenesis chromatin binding;histone binding;lysine-acetylated histone binding;transcription coactivator activity nucleus Spermatogenic failure Apabetalone;Birabresib 0.541403353214264 -0.338925570249557 -0.615313112735748 -0.670412480831146 -1.5760463476181 -1.44432723522186 -1.88950073719025 -0.644798398017883 0.658726155757904 0.996780455112457 1.69168841838837 -0.0959440097212791 0.783754169940948 0.0181383471935987 0.584184229373932 1.18639409542084 0.0795330628752708 0.73466557264328 + Cluster -671 3 3 3 7 7 7 102.33 0 41.69 13491000000 15 3.40753277737632 0.000510280373831776 Q8IYB3;Q8IYB3-2 Q8IYB3;Q8IYB3-2 Serine/arginine repetitive matrix protein 1 SRRM1 2165 Part of pre- and post-splicing multiprotein mRNPcomplexes. Involved in numerous pre-mRNA processing events.Promotes constitutive and exonic splicing enhancer (ESE)-dependentsplicing activation by bridging together sequence-specific (SRfamily proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP(SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA3'-end cleavage independently of the formation of an exon junctioncomplex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream ofexon-exon junctions. Binds RNA and DNA with low sequencespecificity and has similar preference for either double- orsingle-stranded nucleic acid substrates Nucleus matrix {ECO:0000269|PubMed:12624182,ECO:0000269|PubMed:9531537}. Nucleus speckle{ECO:0000269|PubMed:11546874, ECO:0000269|PubMed:9531537}. mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;RNA export from nucleus;RNA splicing;RNA splicing, via transesterification reactions DNA binding;RNA binding catalytic step 2 spliceosome;cytosol;nuclear matrix;nuclear speck;nucleoplasm;nucleus mRNA surveillance pathway;RNA transport Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Transport of Mature mRNA derived from an Intron-Containing Transcript C complex spliceosome;CDC5L complex;Exon junction complex;Exon junction complex (mRNA splicing-dependent);Spliceosome;Splicing-associated factors complex;SRm160/300 complex;SRm160-SRm300 complex 1.29718625545502 -0.00268174638040364 -1.02496671676636 -0.986379325389862 -0.662440836429596 -1.60600626468658 -1.99688613414764 -0.897396504878998 -0.306182831525803 0.445960402488708 0.383757084608078 0.486241042613983 1.17870593070984 0.959078311920166 1.04656100273132 1.05501222610474 0.527665376663208 0.102772772312164 + Cluster -671 4 4 4 9 9 9 72.691 0 65.357 3503700000 12 4.29407748126225 8.30564784053156E-05 P31040;P31040-3;P31040-2 P31040;P31040-3;P31040-2 Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial SDHA 882 Flavoprotein (FP) subunit of succinate dehydrogenase(SDH) that is involved in complex II of the mitochondrial electrontransport chain and is responsible for transferring electrons fromsuccinate to ubiquinone (coenzyme Q) (PubMed:24781757). Can act asa tumor suppressor (PubMed:20484225) Matrix side{ECO:0000250|UniProtKB:Q0QF01}.; Peripheral membrane protein{ECO:0000250|UniProtKB:Q0QF01};Mitochondrion inner membrane{ECO:0000250|UniProtKB:Q0QF01} mitochondrial electron transport, succinate to ubiquinone;nervous system development;oxidation-reduction process;respiratory electron transport chain;succinate metabolic process;tricarboxylic acid cycle electron transfer activity;flavin adenine dinucleotide binding;succinate dehydrogenase (ubiquinone) activity;succinate dehydrogenase activity mitochondrial inner membrane;mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone);mitochondrion;myelin sheath;nucleolus;plasma membrane succinate dehydrogenase complex Alzheimer disease;Carbon metabolism;Citrate cycle (TCA cycle);Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Thermogenesis Dilated cardiomyopathy;Diseases of the tricarboxylic acid cycle;Leigh syndrome;Mitochondrial complex II deficiency Citric acid cycle (TCA cycle);Respiratory electron transport Frataxin complex 0.796689987182617 -0.206031247973442 -0.543880522251129 -0.669798254966736 -0.633796811103821 -1.60742211341858 -1.77479207515717 -1.47217631340027 0.126392230391502 0.304826110601425 0.81242424249649 -0.374063044786453 1.63590610027313 1.04977416992188 1.42553544044495 0.670634925365448 0.207067713141441 0.252709537744522 + Cluster -671 3 3 3 20.5 20.5 20.5 23.51 0 18.164 5745900000 17 3.54861023339525 0.000385567010309278 Q13257;Q13257-2 Q13257 Mitotic spindle assembly checkpoint protein MAD2A MAD2L1 1614 Component of the spindle-assembly checkpoint thatprevents the onset of anaphase until all chromosomes are properlyaligned at the metaphase plate. Required for the execution of themitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphasepromoting complex by sequestering CDC20 until all chromosomes arealigned at the metaphase plate. Nucleus. Chromosome, centromere,kinetochore. Cytoplasm. Cytoplasm, cytoskeleton, spindle pole.Note=Recruited by MAD1L1 to unattached kinetochores (Probable).Recruited to the nuclear pore complex by TPR during interphase.Recruited to kinetochores in late prometaphase after BUB1, CENPF,BUB1B and CENPE. Kinetochore association requires the presence ofNEK2. Kinetochore association is repressed by UBD. {ECO:0000305}. anaphase-promoting complex-dependent catabolic process;cell division;mitotic cell cycle checkpoint;mitotic sister chromatid segregation;mitotic spindle assembly checkpoint;negative regulation of apoptotic process;negative regulation of mitotic cell cycle;negative regulation of protein catabolic process;negative regulation of ubiquitin protein ligase activity;positive regulation of mitotic cell cycle spindle assembly checkpoint;regulation of mitotic cell cycle phase transition identical protein binding;protein C-terminus binding;protein homodimerization activity chromosome;condensed chromosome kinetochore;cytosol;kinetochore;mitotic spindle;nuclear pore nuclear basket;nucleoplasm;nucleus;perinuclear region of cytoplasm;spindle pole Cell cycle;Human T-cell leukemia virus 1 infection;Oocyte meiosis;Progesterone-mediated oocyte maturation Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;APC/C:Cdc20 mediated degradation of mitotic proteins;APC-Cdc20 mediated degradation of Nek2A;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;Inactivation of APC/C via direct inhibition of the APC/C complex;Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components;Mitotic Prometaphase;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Separation of Sister Chromatids MAD1L1-MAD2L1 complex;MAD2-CDC20 complex;Mitotic checkpoint complex (MCC) 1.30511796474457 -0.379280239343643 -0.511865139007568 -1.04302871227264 -0.619479596614838 -1.6855320930481 -1.7828061580658 -1.40671443939209 0.249315544962883 0.795933306217194 1.20208668708801 0.229955554008484 0.890227198600769 0.47846332192421 1.27836394309998 0.133561983704567 0.133561983704567 0.732118725776672 + Cluster -671 1 1 1 6.2 6.2 6.2 21.188 0 4.978 173170000 4 3.67657841969669 0.000320185614849188 Q9Y3C1;Q9Y3C1-3;Q9Y3C1-2 Q9Y3C1;Q9Y3C1-3;Q9Y3C1-2 Nucleolar protein 16 NOP16 3261 Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. ribosomal large subunit biogenesis RNA binding intracellular membrane-bounded organelle;nucleolus;nucleus 1.45158040523529 0.0810336843132973 -0.883812725543976 -1.11056780815125 -1.23169422149658 -1.65000188350677 -1.49072587490082 -1.15356540679932 0.329871296882629 0.321599245071411 1.21562790870667 0.274835854768753 0.939503908157349 0.569660902023315 0.973076164722443 0.917065441608429 -0.107671439647675 0.554184675216675 + Cluster -671 2 2 2 6.3 6.3 6.3 27.6 0 4.1445 85566000 4 4.9579096813684 2.1505376344086E-05 Q96FF9 Q96FF9 Sororin CDCA5 2448 Regulator of sister chromatid cohesion in mitosisstabilizing cohesin complex association with chromatin. Mayantagonize the action of WAPL which stimulates cohesindissociation from chromatin. Cohesion ensures that chromosomepartitioning is accurate in both meiotic and mitotic cells andplays an important role in DNA repair. Required for efficient DNAdouble-stranded break repair. Nucleus {ECO:0000269|PubMed:15837422}.Chromosome {ECO:0000269|PubMed:15837422}. Cytoplasm{ECO:0000269|PubMed:15837422}. Note=Associates with nuclearchromatin from S phase until metaphase and is released in thecytoplasm upon nuclear envelope breakdown. cell division;double-strand break repair;mitotic cell cycle;mitotic chromosome condensation;mitotic metaphase plate congression;mitotic sister chromatid cohesion;positive regulation of exit from mitosis;regulation of cohesin loading chromatin binding;protein-containing complex binding chromosome;chromosome, centromeric region;cohesin complex;cytoplasm;cytosol;nuclear chromatin;nucleoplasm;nucleus MicroRNAs in cancer Establishment of Sister Chromatid Cohesion;Resolution of Sister Chromatid Cohesion;Separation of Sister Chromatids Sororin-cohesin complex 0.905415415763855 -0.100912861526012 -1.03040981292725 -0.743567764759064 -1.07176685333252 -1.46979403495789 -1.71922636032104 -1.62516283988953 0.59825986623764 0.871927440166473 1.48582255840302 0.35992231965065 0.828193604946136 0.647647202014923 0.620661556720734 0.552743375301361 0.4153111577034 0.474935859441757 + Cluster -671 4 4 4 18.5 18.5 18.5 20.497 0 34.366 2202200000 11 6.00965428682995 1.19047619047619E-05 Q15382 Q15382 GTP-binding protein Rheb RHEB 1795 Activates the protein kinase activity of mTORC1, andthereby plays a role in the regulation of apoptosis. Stimulatesthe phosphorylation of S6K1 and EIF4EBP1 through activation ofmTORC1 signaling. Has low intrinsic GTPase activity Cytoplasmic side{ECO:0000269|PubMed:15489334, ECO:0000305}. Golgi apparatusmembrane {ECO:0000269|PubMed:22002721}; Cytoplasmic side{ECO:0000269|PubMed:22002721}.; Cytoplasmic side{ECO:0000305|PubMed:22002721}. Cytoplasm, cytosol{ECO:0000269|PubMed:22002721}. Endoplasmic reticulum membrane{ECO:0000269|PubMed:22002721}; Lipid-anchor{ECO:0000269|PubMed:22002721, ECO:0000305}; Lipid-anchor{ECO:0000269|PubMed:22002721}; Lipid-anchor{ECO:0000305|PubMed:22002721};Endomembrane system{ECO:0000269|PubMed:22002721, ECO:0000305} cell cycle arrest;negative regulation of cold-induced thermogenesis;positive regulation of oligodendrocyte differentiation;positive regulation of TOR signaling;regulation of macroautophagy;regulation of type B pancreatic cell development;signal transduction GDP binding;GTP binding;GTPase activity;magnesium ion binding;protein kinase binding cytosol;endoplasmic reticulum membrane;extracellular exosome;Golgi membrane;lysosomal membrane;membrane;postsynaptic density;spliceosomal complex AMPK signaling pathway;Autophagy - animal;Cellular senescence;Choline metabolism in cancer;Herpes simplex virus 1 infection;Human cytomegalovirus infection;Human papillomavirus infection;Insulin signaling pathway;Longevity regulating pathway;mTOR signaling pathway;Phospholipase D signaling pathway;PI3K-Akt signaling pathway;Thermogenesis;Thyroid hormone signaling pathway Energy dependent regulation of mTOR by LKB1-AMPK;Macroautophagy;mTOR signalling;mTORC1-mediated signalling;Regulation of PTEN gene transcription;TP53 Regulates Metabolic Genes 1.19448840618134 0.14791339635849 -1.32589817047119 -0.719427406787872 -0.719427406787872 -1.72390532493591 -1.65964901447296 -1.32045125961304 -0.116024009883404 0.632116138935089 1.19605648517609 0.187575876712799 1.11812078952789 0.761708676815033 0.808399975299835 0.323248118162155 0.404079228639603 0.811075329780579 + Cluster -671 9 9 9 28.9 28.9 28.9 47.628 0 86.435 11231000000 22 4.94570526424698 2.13903743315508E-05 Q8NBS9;Q8NBS9-2 Q8NBS9;Q8NBS9-2 Thioredoxin domain-containing protein 5 TXNDC5 2224 Possesses thioredoxin activity. Has been shown to reduceinsulin disulfide bonds. Also complements protein disulfide-isomerase deficiency in yeast (By similarity). Endoplasmic reticulum lumen{ECO:0000255|PROSITE-ProRule:PRU10138}. apoptotic cell clearance;cell redox homeostasis;negative regulation of apoptotic process;neutrophil degranulation isomerase activity azurophil granule lumen;endoplasmic reticulum;endoplasmic reticulum lumen;extracellular exosome;extracellular region;lysosomal lumen Protein processing in endoplasmic reticulum Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Neutrophil degranulation 0.184099048376083 -0.15282230079174 -0.959438264369965 -0.402319997549057 -1.13433051109314 -0.727604806423187 -1.82493996620178 -1.64246463775635 0.391418009996414 0.594713509082794 0.766045928001404 -0.443631231784821 1.99787449836731 0.247277408838272 1.03268432617188 0.354354560375214 0.900494396686554 0.818589866161346 + Cluster -671 6 6 6 30.4 30.4 30.4 26.182 0 63.161 5430700000 13 3.65033826596718 0.000329571106094808 P15374 P15374 Ubiquitin carboxyl-terminal hydrolase isozyme L3 UCHL3 683 Deubiquitinating enzyme (DUB) that controls levels ofcellular ubiquitin through processing of ubiquitin precursors andubiquitinated proteins. Thiol protease that recognizes andhydrolyzes a peptide bond at the C-terminal glycine of eitherubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys atposition P3", and exhibits a preference towards 'Lys-48'-linkedubiquitin chains. Deubiquitinates ENAC in apical compartments,thereby regulating apical membrane recycling. Indirectly increasesthe phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. Maybe involved in working memory. Can hydrolyze UBB(+1), a mutatedform of ubiquitin which is not effectively degraded by theproteasome and is associated with neurogenerative disorders Cytoplasm. post-translational protein modification;protein catabolic process;protein deubiquitination;ubiquitin-dependent protein catabolic process NEDD8-specific protease activity;peptidase activity;thiol-dependent ubiquitin-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity;ubiquitin binding cytoplasm;cytosol;nucleus Neddylation;Synthesis of active ubiquitin: roles of E1 and E2 enzymes;UCH proteinases 0.09459488093853 -0.476612985134125 -0.746789693832397 -0.592326521873474 -0.814826130867004 -1.35701477527618 -1.65502548217773 -1.60186183452606 0.254315167665482 0.798912525177002 1.5315420627594 0.0850556343793869 1.23423862457275 0.00436392426490784 0.959818005561829 1.49420702457428 0.363911360502243 0.423498213291168 + Cluster -671 8 8 1 42.4 42.4 3.9 33.83 0 78.158 8159600000 33 3.8994335624479 0.000188328912466843 P46108 P46108 Adapter molecule crk CRK 1044 Isoform Crk-II: Regulates cell adhesion, spreading andmigration. Mediates attachment-induced MAPK8 activation, membraneruffling and cell motility in a Rac-dependent manner. Involved inphagocytosis of apoptotic cells and cell motility via itsinteraction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3signaling. Cytoplasm {ECO:0000250}. Cell membrane{ECO:0000250}. Note=Translocated to the plasma membrane upon celladhesion. {ECO:0000250}. activation of GTPase activity;activation of MAPKK activity;cell chemotaxis;cellular response to endothelin;cellular response to insulin-like growth factor stimulus;cellular response to nerve growth factor stimulus;cellular response to nitric oxide;cellular response to transforming growth factor beta stimulus;cerebellar neuron development;cerebral cortex development;cytokine-mediated signaling pathway;dendrite development;ephrin receptor signaling pathway;establishment of cell polarity;Fc-gamma receptor signaling pathway involved in phagocytosis;helper T cell diapedesis;hippocampus development;lipid metabolic process;negative regulation of cell motility;negative regulation of natural killer cell mediated cytotoxicity;negative regulation of wound healing;neuron migration;positive regulation of cell growth;positive regulation of smooth muscle cell migration;positive regulation of substrate adhesion-dependent cell spreading;reelin-mediated signaling pathway;regulation of actin cytoskeleton organization;regulation of cell adhesion mediated by integrin;regulation of cell shape;regulation of dendrite development;regulation of GTPase activity;regulation of protein binding;regulation of Rac protein signal transduction;regulation of signal transduction;regulation of T cell migration;regulation of transcription by RNA polymerase II;response to cholecystokinin;response to hepatocyte growth factor;response to hydrogen peroxide;response to yeast;SH2 domain-mediated complex assembly;vascular endothelial growth factor receptor signaling pathway cytoskeletal protein binding;ephrin receptor binding;insulin-like growth factor receptor binding;phosphotyrosine residue binding;protein phosphorylated amino acid binding;protein self-association;protein tyrosine kinase binding;scaffold protein binding;SH2 domain binding;SH3 domain binding;SH3/SH2 adaptor activity actin cytoskeleton;cytoplasm;cytosol;extracellular exosome;membrane raft;nucleus;plasma membrane;protein-containing complex Bacterial invasion of epithelial cells;Chemokine signaling pathway;Chronic myeloid leukemia;ErbB signaling pathway;Fc gamma R-mediated phagocytosis;Focal adhesion;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Insulin signaling pathway;MAPK signaling pathway;MicroRNAs in cancer;Neurotrophin signaling pathway;Pathways in cancer;Rap1 signaling pathway;Regulation of actin cytoskeleton;Renal cell carcinoma;Shigellosis;Yersinia infection ARMS-mediated activation;Downstream signal transduction;MET activates RAP1 and RAC1;MET receptor recycling;p130Cas linkage to MAPK signaling for integrins;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Regulation of actin dynamics for phagocytic cup formation;Regulation of signaling by CBL;VEGFA-VEGFR2 Pathway ACK1 signaling complex;CIN85 complex (CIN85, CRK, BCAR1, CBL, PIK3R1, GRB2, SOS1);CRK-BCAR1-DOCK1 complex;CRKII-C3G complex;CRKL-PDGFRA-CRK-RAPGEF1 complex;ELMO1-DOCK1-CRKII complex 0.290277361869812 -0.643440902233124 -0.723938643932343 -1.07196795940399 -1.30239713191986 -0.74388325214386 -1.44734573364258 -1.21865022182465 -0.0726558566093445 0.195415154099464 1.22565877437592 -0.369860410690308 1.3135153055191 0.276323825120926 0.768813729286194 1.77897143363953 0.528919458389282 1.21624517440796 + Cluster -671 14 8 8 53.8 37.2 37.2 28.302 0 312.85 36713000000 69 4.14915794105541 0.00010625 P61981 P61981 14-3-3 protein gamma;14-3-3 protein gamma, N-terminally processed YWHAG 1331 Adapter protein implicated in the regulation of a largespectrum of both general and specialized signaling pathways. Bindsto a large number of partners, usually by recognition of aphosphoserine or phosphothreonine motif. Binding generally resultsin the modulation of the activity of the binding partner Cytoplasm {ECO:0000250}. cellular response to insulin stimulus;ciliary basal body-plasma membrane docking;G2/M transition of mitotic cell cycle;membrane organization;negative regulation of protein kinase activity;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;protein targeting;regulation of G2/M transition of mitotic cell cycle;regulation of neuron differentiation;regulation of signal transduction;regulation of synaptic plasticity identical protein binding;insulin-like growth factor receptor binding;protein domain specific binding;protein kinase C binding;protein kinase C inhibitor activity;receptor tyrosine kinase binding;RNA binding cytosol;extracellular exosome;focal adhesion;membrane;mitochondrion;myelin sheath;presynapse Cell cycle;Hepatitis C;Hippo signaling pathway;Oocyte meiosis;PI3K-Akt signaling pathway;Viral carcinogenesis Early infantile epileptic encephalopathy Activation of BAD and translocation to mitochondria;Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition;RHO GTPases activate PKNs;TP53 Regulates Metabolic Genes;Translocation of SLC2A4 (GLUT4) to the plasma membrane 14-3-3 gamma-CXCR2 complex, unstimulated;Kinase maturation complex 1 1.69520199298859 0.0930407494306564 -0.492882251739502 -0.878500998020172 -1.568932056427 -0.346293449401855 -1.75694191455841 -1.840784907341 -0.268455475568771 0.363779067993164 0.424409449100494 0.325280904769897 1.16945445537567 0.586158692836761 1.07496619224548 0.369499772787094 0.535809636116028 0.515190124511719 + Cluster -671 5 5 5 20.1 20.1 20.1 46.321 0 44.583 1834400000 14 3.34421448466694 0.000558928571428571 Q9BXW7;Q9BXW7-2 Q9BXW7;Q9BXW7-2 Cat eye syndrome critical region protein 5 CECR5 2709 glycerophospholipid biosynthetic process mitochondrion 1.60936176776886 0.0705064460635185 -1.2460526227951 -0.509291589260101 -1.22150671482086 -1.45638120174408 -1.6090292930603 -0.673052430152893 0.703751683235168 -0.002174386754632 0.712320327758789 0.366216272115707 1.16094279289246 0.244199588894844 1.25702965259552 1.23913931846619 -0.136687859892845 -0.509291589260101 + Cluster -671 3 3 3 4.6 4.6 4.6 97.668 0 96.066 874200000 7 3.03937132532399 0.000995555555555556 Q5H9R7;Q5H9R7-4;Q5H9R7-6;Q5H9R7-2;Q5H9R7-5;Q5H9R7-3 Q5H9R7;Q5H9R7-4;Q5H9R7-6;Q5H9R7-2;Q5H9R7-5;Q5H9R7-3 Serine/threonine-protein phosphatase 6 regulatory subunit 3 PPP6R3 1917 Regulatory subunit of protein phosphatase 6 (PP6). Mayfunction as a scaffolding PP6 subunit. May have an important rolein maintaining immune self-tolerance Cytoplasm. Nucleus. COPII vesicle coating;regulation of phosphoprotein phosphatase activity protein phosphatase binding cytosol;Golgi membrane;nucleoplasm;plasma membrane COPII-mediated vesicle transport UTX-MLL2/3 complex 1.21978724002838 0.789217352867126 -1.19113743305206 -1.07892000675201 -0.643174648284912 -1.5540874004364 -1.12909722328186 -1.33972835540771 0.299453675746918 0.493070632219315 -0.356408357620239 0.210210174322128 1.81098091602325 0.88980633020401 0.975249111652374 0.905033349990845 -0.0576658472418785 -0.242589741945267 + Cluster -671 1 1 1 9.5 9.5 9.5 15.345 0 7.74 288790000 2 3.86998681701212 0.000221052631578947 Q9Y3D3;Q9Y3D3-2 Q9Y3D3;Q9Y3D3-2 28S ribosomal protein S16, mitochondrial MRPS16 3267 Mitochondrion {ECO:0000269|PubMed:25838379}. mitochondrial translation;mitochondrial translational elongation;mitochondrial translational termination;translation structural constituent of ribosome cytosol;mitochondrial inner membrane;mitochondrial small ribosomal subunit;mitochondrion Ribosome Combined oxidative phosphorylation deficiency Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial 0.193438470363617 0.0770544335246086 -1.39965498447418 -0.501106023788452 -0.250379770994186 -0.893571615219116 -1.35180222988129 -1.27105939388275 0.585476160049438 1.09903311729431 2.10436797142029 1.12924861907959 -0.64866840839386 -0.893571615219116 0.726038694381714 1.07670390605927 0.468832284212112 -0.250379770994186 + Cluster -671 7 7 7 8.1 8.1 8.1 139.44 0 69.862 3181500000 13 3.22527494970814 0.000703333333333333 Q5JPE7;Q15155;P69849;Q5JPE7-2;Q5JPE7-3 Q5JPE7;Q15155;P69849;Q5JPE7-2;Q5JPE7-3 Nodal modulator 2;Nodal modulator 1;Nodal modulator 3 NOMO2;NOMO1;NOMO3 1422 May antagonize Nodal signaling and subsequentorganization of axial structures during mesodermal patterning, viaits interaction with NCLN.;May antagonize Nodal signaling. Single-pass type Imembrane protein {ECO:0000305}.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:15257293, ECO:0000269|PubMed:17261586};Membrane {ECO:0000305};Single-pass membrane protein {ECO:0000269|PubMed:15257293,ECO:0000269|PubMed:17261586}. carbohydrate binding endoplasmic reticulum membrane;integral component of membrane;membrane;protein-containing complex -0.276790946722031 -0.305107116699219 -0.844442784786224 -0.335212528705597 -0.598950147628784 -0.868258774280548 -1.80232656002045 -0.810894429683685 0.115989230573177 1.2202250957489 2.47795677185059 0.837136745452881 -0.634979009628296 -0.551508009433746 0.132621079683304 0.60220330953598 0.499768942594528 1.14256918430328 + Cluster -671 5 5 5 10.9 10.9 10.9 68.119 0 48.917 6169800000 15 3.15826450840826 0.000799357945425361 Q8TAT6;Q8TAT6-2 Q8TAT6;Q8TAT6-2 Nuclear protein localization protein 4 homolog NPLOC4 2256 The ternary complex containing UFD1, VCP and NPLOC4binds ubiquitinated proteins and is necessary for the export ofmisfolded proteins from the ER to the cytoplasm, where they aredegraded by the proteasome. The NPLOC4-UFD1-VCP complex regulatesspindle disassembly at the end of mitosis and is necessary for theformation of a closed nuclear envelope (By similarity). Acts as anegative regulator of type I interferon production via the complexformed with VCP and UFD1, which binds to DDX58/RIG-I and recruitsRNF125 to promote ubiquitination and degradation of DDX58/RIG-I(PubMed:26471729). Cytoplasm, cytosol{ECO:0000250|UniProtKB:Q9ES54}. Endoplasmic reticulum{ECO:0000250|UniProtKB:Q9ES54}. Nucleus{ECO:0000250|UniProtKB:Q9ES54}. Note=Associated with theendoplasmic reticulum and nuclear. {ECO:0000250|UniProtKB:Q9ES54}. error-free translesion synthesis;Golgi organization;negative regulation of RIG-I signaling pathway;negative regulation of type I interferon production;retrograde protein transport, ER to cytosol;ubiquitin-dependent ERAD pathway;ubiquitin-dependent protein catabolic process metal ion binding;ubiquitin binding;ubiquitin protein ligase binding cytosol;endoplasmic reticulum;nuclear outer membrane-endoplasmic reticulum membrane network;nucleoplasm;nucleus;UFD1-NPL4 complex;VCP-NPL4-UFD1 AAA ATPase complex Protein processing in endoplasmic reticulum Translesion Synthesis by POLH NUB1L-UFD1-NPL4-NEDD8 complex -0.157033756375313 -0.129415035247803 -0.91357159614563 -0.228260979056358 -0.794295370578766 -1.18519878387451 -1.74880385398865 -1.21403217315674 0.842477142810822 1.54363811016083 2.32861113548279 0.382855445146561 -0.231944799423218 -0.0461606308817863 0.171025648713112 0.197369962930679 0.49410691857338 0.688632726669312 + Cluster -671 7 7 7 28.7 28.7 28.7 29.73 0 110.72 22772000000 44 3.65272434221463 0.000330316742081448 Q7Z7K6-3;Q7Z7K6;Q7Z7K6-2 Q7Z7K6-3;Q7Z7K6 Centromere protein V CENPV 2096 Required for distribution of pericentromericheterochromatin in interphase nuclei and for centromere formationand organization, chromosome alignment and cytokinesis Chromosome, centromere, kinetochore{ECO:0000269|PubMed:18772885}. Nucleus{ECO:0000269|PubMed:12196509}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:18772885}. Note=Enriched at the nuclearperiphery and around the nucleolus (PubMed:12196509). In mitoticcells, localizes to kinetochores from prometaphase to metaphase(PubMed:18772885). At anaphase onset, transfers to the spindlemidzone and then to the mid-body in telophase and cytokinesis(PubMed:18772885). ameboidal-type cell migration;cell cycle;cell division;centromere complex assembly;pericentric heterochromatin assembly;positive regulation of cytokinesis;regulation of chromosome organization carbon-sulfur lyase activity condensed chromosome kinetochore;cytoplasm;kinetochore;microtubule cytoskeleton;nucleus;spindle midzone 0.122280038893223 0.0869953036308289 -1.32714927196503 -0.36635148525238 -0.144800066947937 -1.24347734451294 -1.32998180389404 -0.783262372016907 0.122280038893223 2.05745649337769 1.85409069061279 0.688517332077026 -1.42458319664001 0.0202285088598728 0.161044105887413 0.184649184346199 0.727346062660217 0.594717860221863 + Cluster -671 1 1 1 1.1 1.1 1.1 108.19 0 4.2546 56531000 2 3.05988485407921 0.000968181818181818 O94829 O94829 Importin-13 IPO13 385 Functions in nuclear protein import as nuclear transportreceptor. Serves as receptor for nuclear localization signals(NLS) in cargo substrates. Is thought to mediate docking of theimportin/substrate complex to the nuclear pore complex (NPC)through binding to nucleoporin and the complex is subsequentlytranslocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ranbinds to the importin, the importin/substrate complex dissociatesand importin is re-exported from the nucleus to the cytoplasmwhere GTP hydrolysis releases Ran. The directionality of nuclearimport is thought to be conferred by an asymmetric distribution ofthe GTP- and GDP-bound forms of Ran between the cytoplasm andnucleus (By similarity). Mediates the nuclear import of UBC9, theRBM8A/MAGOH complex, PAX6 and probably other members of the pairedhomeobox family. Also mediates nuclear export of eIF-1A, and thecytoplasmic release of eIF-1A is triggered by the loading ofimport substrates onto IPO13. Cytoplasm. Nucleus. protein import into nucleus nuclear localization sequence binding;protein transporter activity;Ran GTPase binding cytoplasm;nucleus IPO13-RAN-EIF1AX complex;IPO13-RBM8A-MAGOH complex 0.0920776501297951 0.385994702577591 -0.419807344675064 0.0560082830488682 -0.2488744109869 -1.84396111965179 -1.90151345729828 -0.95312362909317 0.824292659759521 1.61343932151794 2.10723805427551 0.840913534164429 0.023594131693244 -0.109252169728279 0.222613587975502 -0.099355511367321 -0.280064404010773 -0.310219913721085 + Cluster -671 6 6 6 37.2 37.2 37.2 20.9 0 76.023 19063000000 37 3.44249482296359 0.000480988593155894 P61081 P61081 NEDD8-conjugating enzyme Ubc12 UBE2M 1292 Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to otherproteins. The specific interaction with the E3 ubiquitin ligaseRBX1, but not RBX2, suggests that the RBX1-UBE2M complexneddylates specific target proteins, such as CUL1, CUL2, CUL3 andCUL4. Involved in cell proliferation cellular protein modification process;positive regulation of neuron apoptotic process;post-translational protein modification;protein neddylation ATP binding;NEDD8 transferase activity;ubiquitin-protein transferase activity cytosol;nucleoplasm Ubiquitin mediated proteolysis Antigen processing: Ubiquitination & Proteasome degradation;Dectin-1 mediated noncanonical NF-kB signaling;Neddylation;NIK-->noncanonical NF-kB signaling;TGF-beta receptor signaling activates SMADs -0.103380054235458 -0.110252737998962 -0.775887548923492 -0.422069430351257 -0.607100784778595 -1.09284317493439 -1.9059751033783 -0.436611384153366 0.505508303642273 0.991922318935394 2.21644687652588 1.53119349479675 -0.843708455562592 -0.0693290457129478 -0.391111135482788 -0.162500739097595 0.753830790519714 0.921867847442627 + Cluster -671 6 6 6 17.4 17.4 17.4 48.162 0 30.116 7365500000 19 3.34812922360029 0.00055475763016158 Q9Y6E2;Q9Y6E2-2 Q9Y6E2;Q9Y6E2-2 Basic leucine zipper and W2 domain-containing protein 2 BZW2 3340 May be involved in neuronal differentiation cell differentiation;nervous system development cadherin binding cytoplasm;membrane -0.866625130176544 0.0541832521557808 -0.51937860250473 0.167662248015404 -0.301554709672928 -1.41289401054382 -1.31008064746857 -0.999220132827759 1.0027768611908 1.15570473670959 2.2525908946991 1.66404259204865 -0.696208357810974 -0.567168593406677 -0.0867117419838905 -0.0714791119098663 0.267180263996124 0.267180263996124 + Cluster -671 4 4 4 4.6 4.6 4.6 163.82 0 61.585 4884700000 20 3.23512023527876 0.000697324414715719 Q96T23;Q96T23-2;Q96T23-3 Q96T23;Q96T23-2;Q96T23-3 Remodeling and spacing factor 1 RSF1 2549 Required for assembly of regular nucleosome arrays bythe RSF chromatin-remodeling complex (PubMed:12972596).Facilitates transcription of hepatitis B virus (HBV) genes by thepX transcription activator. In case of infection by HBV, togetherwith pX, it represses TNF-alpha induced NF-kappa-B transcriptionactivation. Represses transcription when artificially recruited tochromatin by fusion to a heterogeneous DNA binding domain(PubMed:11944984, PubMed:11788598). Nucleus {ECO:0000269|PubMed:11788598,ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596}. CENP-A containing nucleosome assembly;chromatin remodeling;DNA-templated transcription, initiation;negative regulation of DNA binding;negative regulation of transcription, DNA-templated;nucleosome assembly;nucleosome positioning;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;positive regulation of viral transcription histone acetyltransferase activity;histone binding;metal ion binding histone acetyltransferase complex;nuclear chromatin;nucleoplasm;nucleus;RSF complex Deposition of new CENPA-containing nucleosomes at the centromere CEN complex;CENP-A nucleosomal complex;Remodeling and spacing factor (RSF) complex;RSF complex;SNF2L-RSF1 complex -0.0440741516649723 0.0987157076597214 -0.653814971446991 -0.567737638950348 -0.233369469642639 -1.08092832565308 -0.901344776153564 -0.505227029323578 -0.144731283187866 1.48881804943085 2.45624017715454 1.27881872653961 -1.20597362518311 -0.584008514881134 -0.946412801742554 0.00132000329904258 0.489639341831207 1.05407059192657 + Cluster -671 3 3 3 2.3 2.3 2.3 243.87 0 15.141 2283500000 6 3.24430632278267 0.000684033613445378 Q9BTC0;Q9BTC0-1 Q9BTC0;Q9BTC0-1 Death-inducer obliterator 1 DIDO1 2650 Putative transcription factor, weakly pro-apoptotic whenoverexpressed (By similarity). Tumor suppressor. Required forearly embryonic stem cell development. Cytoplasm {ECO:0000250}. Nucleus{ECO:0000255|PROSITE-ProRule:PRU00651}. Cytoplasm, cytoskeleton,spindle {ECO:0000269|PubMed:23831028}. Note=Translocates to thenucleus after pro-apoptotic stimuli (By similarity). Translocatesto the mitotic spindle upon loss of interaction with H3K4me3during early mitosis. {ECO:0000250}. apoptotic signaling pathway;transcription, DNA-templated metal ion binding;RNA binding cytoplasm;nucleus;spindle Meiotic synapsis -0.197903245687485 -0.0380145087838173 -0.563858151435852 -0.436507165431976 -0.492508560419083 -1.85417771339417 -1.85417771339417 -1.02817618846893 -0.0380145087838173 1.41022908687592 1.87113952636719 0.682941794395447 -0.397809237241745 0.35029348731041 0.819765508174896 0.154943525791168 0.661860585212708 0.949973523616791 + Cluster -671 4 4 4 11.1 11.1 11.1 58.687 0 84.363 1840300000 12 3.81012689866478 0.000243718592964824 Q08209;Q08209-2;Q08209-3;P16298;Q08209-4;Q08209-5;P16298-2;P16298-3;P16298-4 Q08209;Q08209-2;Q08209-3;P16298;Q08209-4;Q08209-5;P16298-2;P16298-3;P16298-4 Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform;Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform PPP3CA;PPP3CB 1545 Calcium-dependent, calmodulin-stimulated proteinphosphatase which plays an essential role in the transduction ofintracellular Ca(2+)-mediated signals (PubMed:15671020,PubMed:18838687, PubMed:19154138, PubMed:23468591). Many of thesubstrates contain a PxIxIT motif and/or a LxVP motif(PubMed:17498738, PubMed:17502104, PubMed:23468591,PubMed:27974827, PubMed:22343722). In response to increased Ca(2+)levels, dephosphorylates and activates phosphatase SSH1 whichresults in cofilin dephosphorylation (PubMed:15671020). Inresponse to increased Ca(2+) levels following mitochondrialdepolarization, dephosphorylates DNM1L inducing DNM1Ltranslocation to the mitochondrion (PubMed:18838687).Dephosphorylates heat shock protein HSPB1 (By similarity).Dephosphorylates and activates transcription factor NFATC1(PubMed:19154138). In response to increased Ca(2+) levels,regulates NFAT-mediated transcription probably bydephosphorylating NFAT and promoting its nuclear translocation(PubMed:26248042). Dephosphorylates and inactivates transcriptionfactor ELK1 (PubMed:19154138). Dephosphorylates DARPP32(PubMed:19154138).;Calcium-dependent, calmodulin-stimulated proteinphosphatase which plays an essential role in the transduction ofintracellular Ca(2+)-mediated signals (PubMed:19154138,PubMed:26794871). Dephosphorylates and activates transcriptionfactor NFATC1 (PubMed:19154138). Dephosphorylates and inactivatestranscription factor ELK1 (PubMed:19154138). DephosphorylatesDARPP32 (PubMed:19154138). Peripheral membrane protein{ECO:0000269|PubMed:22343722}. Cell membrane, sarcolemma{ECO:0000250|UniProtKB:P63329}. Cytoplasm, myofibril, sarcomere, Zline {ECO:0000250|UniProtKB:P63329}. Cell projection, dendriticspine {ECO:0000269|PubMed:22343722}. Note=Colocalizes with ACTN1and MYOZ2 at the Z line in heart and skeletal muscle (Bysimilarity). Recruited to the cell membrane by scaffold proteinAKAP5 following L-type Ca(2+)-channel activation(PubMed:22343722). {ECO:0000250|UniProtKB:P63329,ECO:0000269|PubMed:22343722}.;Cytoplasm {ECO:0000269|PubMed:19154138,ECO:0000269|PubMed:22343722}. Cell membrane{ECO:0000269|PubMed:22343722};Cytoplasm {ECO:0000269|PubMed:19154138}. axon extension;brain development;calcineurin-mediated signaling;calcineurin-NFAT signaling cascade;calcium ion regulated exocytosis;calcium ion transport;cardiac muscle hypertrophy in response to stress;cellular response to drug;cellular response to glucose stimulus;dephosphorylation;excitatory postsynaptic potential;Fc-epsilon receptor signaling pathway;G1/S transition of mitotic cell cycle;heart development;learning;locomotion involved in locomotory behavior;lymphangiogenesis;memory;multicellular organismal response to stress;negative regulation of chromatin binding;negative regulation of dendrite morphogenesis;negative regulation of insulin secretion;negative regulation of production of miRNAs involved in gene silencing by miRNA;negative regulation of T cell mediated cytotoxicity;positive regulation of calcineurin-NFAT signaling cascade;positive regulation of cardiac muscle hypertrophy in response to stress;positive regulation of cell adhesion;positive regulation of cell migration;positive regulation of connective tissue replacement;positive regulation of DNA-binding transcription factor activity;positive regulation of endocytosis;positive regulation of insulin secretion involved in cellular response to glucose stimulus;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;postsynaptic modulation of chemical synaptic transmission;protein dephosphorylation;protein import into nucleus;protein phosphorylation;regulation of insulin secretion;regulation of synaptic plasticity;regulation of synaptic vesicle endocytosis;response to amphetamine;response to calcium ion;response to cytokine;signal transduction;skeletal muscle fiber development;skeletal muscle tissue regeneration;social behavior;T cell activation;T cell differentiation;T cell homeostasis;T cell proliferation;transition between fast and slow fiber;Wnt signaling pathway, calcium modulating pathway calcium ion binding;calmodulin binding;calmodulin-dependent protein phosphatase activity;cyclosporin A binding;drug binding;enzyme binding;protein dimerization activity;protein heterodimerization activity;protein phosphatase 2B binding;protein serine/threonine phosphatase activity calcineurin complex;cytoplasm;cytosol;dendritic spine;glutamatergic synapse;mitochondrion;nucleoplasm;plasma membrane;sarcolemma;Schaffer collateral - CA1 synapse;slit diaphragm;T-tubule;Z disc Alzheimer disease;Amphetamine addiction;Amyotrophic lateral sclerosis (ALS);Axon guidance;B cell receptor signaling pathway;Calcium signaling pathway;Cellular senescence;cGMP-PKG signaling pathway;C-type lectin receptor signaling pathway;Dopaminergic synapse;Glucagon signaling pathway;Glutamatergic synapse;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Human T-cell leukemia virus 1 infection;Kaposi sarcoma-associated herpesvirus infection;Long-term potentiation;MAPK signaling pathway;Natural killer cell mediated cytotoxicity;Oocyte meiosis;Osteoclast differentiation;Oxytocin signaling pathway;PD-L1 expression and PD-1 checkpoint pathway in cancer;Renin secretion;T cell receptor signaling pathway;Th1 and Th2 cell differentiation;Th17 cell differentiation;Tuberculosis;VEGF signaling pathway;Wnt signaling pathway Infantile or early childhood epileptic encephalopathy Ciclosporin;Pimecrolimus;Ruclosporin;Tacrolimus;Voclosporin Ca2+ pathway;Calcineurin activates NFAT;CLEC7A (Dectin-1) induces NFAT activation;DARPP-32 events;FCERI mediated Ca+2 mobilization;ROBO receptors bind AKAP5 AKAP5-PRKAR2A-PPP3CA complex;Calcineurin;Calcineurin (subunit CnA) -Cacng8 complex;Calcineurin-FKBP12 complex;MR-UBC9-SRC1 complex;PPP3CA-PPP3CA-RCAN1 complex -0.403641402721405 -0.403641402721405 -0.642204403877258 -0.0940163061022758 -1.28267598152161 -1.69027078151703 -1.49114143848419 -0.800753712654114 0.38037970662117 1.34533286094666 1.72552990913391 0.669122815132141 -0.733462274074554 0.16570770740509 0.809957504272461 0.38037970662117 1.09199631214142 0.973401129245758 + Cluster -671 1 1 1 2.3 2.3 2.3 54.226 0 3.2318 90515000 2 3.24639061267962 0.000679054054054054 Q9Y6V7;Q9Y6V7-2 Q9Y6V7;Q9Y6V7-2 Probable ATP-dependent RNA helicase DDX49 DDX49 3346 rRNA processing ATP binding;helicase activity;RNA binding nucleoplasm Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol -0.243453979492188 0.115795776247978 0.17645475268364 -0.299976289272308 -0.786227345466614 -1.35849738121033 -1.63343954086304 -1.63343954086304 -0.564229011535645 1.06456696987152 2.08144664764404 1.21488738059998 -0.141336768865585 -0.197904840111732 0.603721618652344 0.000362518010661006 0.658157289028168 0.943111717700958 + Cluster -671 2 2 2 5.7 5.7 5.7 38.036 0 6.9821 114740000 3 3.39992089820167 0.000512962962962963 Q9H0U3 Q9H0U3 Magnesium transporter protein 1 MAGT1 2770 in this function seems to act redundantly with TUSC3. Inits oxidized form proposed to form transient mixed disulfides witha glycoprotein substrate to facilitate access of STT3B to theunmodified acceptor site. Has also oxidoreductase-independentfunctions in the STT3B-containing OST complex possibly involvingsubstrate recognition.;Acts as accessory component of the N-oligosaccharyltransferase (OST) complex which catalyzes the transfer of a highmannose oligosaccharide from a lipid-linked oligosaccharide donorto an asparagine residue within an Asn-X-Ser/Thr consensus motifin nascent polypeptide chains. Involved in N-glycosylation ofSTT3B-dependent substrates. Specifically required for theglycosylation of a subset of acceptor sites that are near cysteineresidues Multi-pass membrane protein{ECO:0000250}.;Cell membrane {ECO:0000269|PubMed:19717468};Multi-pass membrane protein {ECO:0000269|PubMed:19717468}.Endoplasmic reticulum {ECO:0000269|PubMed:25135935}. Endoplasmicreticulum membrane {ECO:0000250} cognition;magnesium ion transport;neutrophil degranulation;protein N-linked glycosylation;protein N-linked glycosylation via asparagine;transmembrane transport magnesium ion transmembrane transporter activity azurophil granule membrane;endoplasmic reticulum;integral component of plasma membrane;membrane;oligosaccharyltransferase complex;plasma membrane Asparagine N-linked glycosylation;Miscellaneous transport and binding events;Neutrophil degranulation Oligosaccharyltransferase complex (Stt3A variant);Oligosaccharyltransferase complex (Stt3B variant) -1.03286302089691 0.0655253157019615 -0.368144512176514 -0.638091862201691 -1.36728239059448 -1.60101509094238 -1.69355547428131 -0.923084616661072 1.53483128547668 0.89827573299408 0.335623890161514 1.40936493873596 0.55236428976059 0.494961261749268 0.527131140232086 0.741660118103027 0.649062991142273 0.415235877037048 + Cluster -671 3 3 3 17.8 17.8 17.8 37.92 0 37.76 5709500000 9 3.04985727776943 0.000980509745127436 O15126;O15126-2 O15126;O15126-2 Secretory carrier-associated membrane protein 1 SCAMP1 165 Functions in post-Golgi recycling pathways. Acts as arecycling carrier to the cell surface. Multi-pass membrane protein{ECO:0000269|PubMed:15840657}.; Multi-pass membraneprotein {ECO:0000269|PubMed:15840657}. Recycling endosome membrane{ECO:0000269|PubMed:15840657};Golgi apparatus, trans-Golgi networkmembrane {ECO:0000269|PubMed:15840657} neutrophil degranulation;post-Golgi vesicle-mediated transport;protein transport clathrin-coated vesicle;Golgi apparatus;Golgi membrane;integral component of membrane;plasma membrane;recycling endosome membrane;specific granule membrane;synaptic vesicle membrane;trans-Golgi network;trans-Golgi network membrane;zymogen granule membrane Neutrophil degranulation SCAMP1-SCAMP2 complex;SCAMP1-SCAMP2-SCAMP3 complex -0.141157731413841 -0.0471608228981495 -1.06558454036713 -1.06558454036713 -1.22632873058319 -1.13108170032501 -1.60640466213226 -0.985001266002655 2.10121917724609 0.949284136295319 1.18621921539307 0.144549623131752 0.144549623131752 0.479924649000168 0.81795197725296 0.510367214679718 0.391283065080643 0.542955279350281 + Cluster -671 5 5 5 24.6 24.6 24.6 44.739 0 167.32 47605000000 39 3.73335802404699 0.000274698795180723 Q13148;Q13148-4 Q13148 TAR DNA-binding protein 43 TARDBP 1600 DNA and RNA-binding protein which regulatestranscription and splicing. Involved in the regulation of CFTRsplicing. It promotes CFTR exon 9 skipping by binding to the UGrepeated motifs in the polymorphic region near the 3'-splice siteof this exon. The resulting aberrant splicing is associated withpathological features typical of cystic fibrosis. May also beinvolved in microRNA biogenesis, apoptosis and cell division. Canrepress HIV-1 transcription by binding to the HIV-1 long terminalrepeat. Stabilizes the low molecular weight neurofilament (NFL)mRNA through a direct interaction with the 3' UTR Nucleus {ECO:0000269|PubMed:17023659,ECO:0000269|PubMed:17481916}. Note=In patients with frontotemporallobar degeneration and amyotrophic lateral sclerosis, it is absentfrom the nucleus of affected neurons but it is the primarycomponent of cytoplasmic ubiquitin-positive inclusion bodies. 3'-UTR-mediated mRNA stabilization;mRNA processing;negative regulation by host of viral transcription;negative regulation of gene expression;negative regulation of protein phosphorylation;nuclear inner membrane organization;positive regulation of insulin secretion;positive regulation of protein import into nucleus;regulation of apoptotic process;regulation of cell cycle;response to endoplasmic reticulum stress;RNA splicing;transcription by RNA polymerase II DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;double-stranded DNA binding;identical protein binding;mRNA 3'-UTR binding;RNA binding;sequence-specific double-stranded DNA binding;single-stranded RNA binding cytoplasm;interchromatin granule;nuclear speck;nucleoplasm;nucleus;perichromatin fibrils;ribonucleoprotein complex Amyotrophic lateral sclerosis (ALS) Large Drosha complex -0.0725201591849327 0.256203383207321 -0.488747328519821 -0.769510507583618 -1.05048632621765 -1.73314428329468 -1.20501291751862 -1.41776049137115 -0.821502149105072 1.05367243289948 1.47466015815735 0.338632434606552 0.0825939178466797 0.774408400058746 0.631965577602386 1.55776786804199 0.525014460086823 0.863765597343445 + Cluster -671 8 8 8 39.6 39.6 39.6 31.441 0 137.28 3420600000 25 4.40006778692729 6.00706713780919E-05 P19387 P19387 DNA-directed RNA polymerase II subunit RPB3 POLR2C 731 DNA-dependent RNA polymerase catalyzes the transcriptionof DNA into RNA using the four ribonucleoside triphosphates assubstrates. Component of RNA polymerase II which synthesizes mRNAprecursors and many functional non-coding RNAs. Pol II is thecentral component of the basal RNA polymerase II transcriptionmachinery. It is composed of mobile elements that move relative toeach other. RPB3 is part of the core element with the centrallarge cleft and the clamp element that moves to open and close thecleft (By similarity). Nucleus {ECO:0000269|PubMed:9852112}. 7-methylguanosine mRNA capping;fibroblast growth factor receptor signaling pathway;mRNA splicing, via spliceosome;regulation of gene silencing by miRNA;RNA metabolic process;snRNA transcription by RNA polymerase II;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;transcription initiation from RNA polymerase II promoter;transcription-coupled nucleotide-excision repair DNA binding;DNA-directed 5'-3' RNA polymerase activity;protein dimerization activity cytosol;microtubule cytoskeleton;nucleoplasm;nucleus;RNA polymerase II, core complex Huntington disease;RNA polymerase Abortive elongation of HIV-1 transcript in the absence of Tat;Activation of anterior HOX genes in hindbrain development during early embryogenesis;Dual incision in TC-NER;Estrogen-dependent gene expression;FGFR2 alternative splicing;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;Formation of TC-NER Pre-Incision Complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;Gap-filling DNA repair synthesis and ligation in TC-NER;HIV elongation arrest and recovery;HIV Transcription Initiation;MicroRNA (miRNA) biogenesis;mRNA Capping;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;PIWI-interacting RNA (piRNA) biogenesis;Processing of Capped Intron-Containing Pre-mRNA;RNA Pol II CTD phosphorylation and interaction with CE;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Promoter Escape;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription Elongation;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;Signaling by FGFR2 IIIa TM;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes;Transcription of the HIV genome;Transcriptional regulation by small RNAs;Transcriptional regulation of pluripotent stem cells;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Viral Messenger RNA Synthesis BRCA1-core RNA polymerase II complex;BRCA1-RNA polymerase II complex;RNA polymerase II (RNAPII);RNA polymerase II core complex;RNA polymerase II holoenzyme complex;RPAP1-RPB2-RPB3 complex 0.130141869187355 0.298798263072968 -1.08100163936615 -1.24516427516937 -1.44521772861481 -1.33898556232452 -0.856989681720734 -0.591305613517761 -0.340015411376953 0.880973875522614 1.09171175956726 1.05071544647217 -0.52154141664505 0.171187460422516 0.114243544638157 2.02957963943481 1.1596508026123 0.493218541145325 + Cluster -671 2 2 2 6.3 6.3 6.3 74.138 0.00032982 2.2678 275990000 2 3.40802320855988 0.00051123595505618 Q9NPI1;Q9NPI1-2 Q9NPI1;Q9NPI1-2 Bromodomain-containing protein 7 BRD7 2885 Acts both as coactivator and as corepressor. May play arole in chromatin remodeling. Activator of the Wnt signalingpathway in a DVL1-dependent manner by negatively regulating theGSK3B phosphotransferase activity. Induces dephosphorylation ofGSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation oftranscriptional activation by AR (By similarity). Transcriptionalcorepressor that down-regulates the expression of target genes.Binds to target promoters, leading to increased histone H3acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter.Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator forTP53-mediated activation of transcription of a set of targetgenes. Required for TP53-mediated cell-cycle arrest in response tooncogene activation. Promotes acetylation of TP53 at 'Lys-382',and thereby promotes efficient recruitment of TP53 to targetpromoters. Inhibits cell cycle progression from G1 to S phase Isoform 2: Nucleus. cell cycle;negative regulation of cell proliferation;negative regulation of G1/S transition of mitotic cell cycle;negative regulation of transcription, DNA-templated;positive regulation of histone acetylation;positive regulation of transcription, DNA-templated;regulation of signal transduction by p53 class mediator;regulation of transcription by RNA polymerase II;Wnt signaling pathway histone binding;lysine-acetylated histone binding;p53 binding;transcription coactivator activity;transcription corepressor activity;transcription factor binding;transcription regulatory region DNA binding cytoplasm;cytosol;nucleoplasm;nucleus Hepatocellular carcinoma Regulation of TP53 Activity through Acetylation BRD7-BAF60A-MEP50 complex;BRD7-CBP-SWI\u2013SNF complex;BRD7-EZH2-SUZ12 complex;BRD7-SWI\u2013SNF complex;BRD7-SWI\u2013SNF-SUZ12 complex -0.968378007411957 -0.163212403655052 -1.21887898445129 0.184075444936752 -1.72579073905945 -1.12442719936371 -1.68541467189789 -0.52796071767807 0.74894767999649 0.572193920612335 0.176430016756058 0.176430016756058 0.70518285036087 0.980169832706451 0.727375209331512 0.338574826717377 1.11202228069305 1.69266057014465 + Cluster -671 3 3 3 5.7 5.7 5.7 89.677 0 64.16 3280100000 11 3.10263044693046 0.000904836193447738 Q13616 Q13616 Cullin-1 CUL1 1655 the degradation frees theassociated NFKB1-RELA dimer to translocate into the nucleus and toactivate transcription. SCF(CCNF) directs ubiquitination ofCCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2.SCF(FBXO10) directs ubiquitination of BCL2;Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, whichmediate the ubiquitination of proteins involved in cell cycleprogression, signal transduction and transcription. SCF complexesand ARIH1 collaborate in tandem to mediate ubiquitination oftarget proteins (PubMed:27565346). In the SCF complex, serves as arigid scaffold that organizes the SKP1-F-box protein and RBX1subunits. May contribute to catalysis through positioning of thesubstrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on theneddylation of the cullin subunit and exchange of the substraterecognition component is mediated by TIP120A/CAND1. The functionalspecificity of the SCF complex depends on the F-box protein assubstrate recognition component. SCF(BTRC) and SCF(FBXW11) directubiquitination of CTNNB1 and participate in Wnt signaling.SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA.SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3,SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/orSCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25704143,PubMed:25503564). SCF(SKP2) directs ubiquitination ofphosphorylated CDKN1B/p27kip and is involved in regulation of G1/Stransition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2,ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7)directs ubiquitination of CCNE1, NOTCH1 released notchintracellular domain (NICD), and probably PSEN1. SCF(FBXW2)directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitinationof MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5.SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directsubiquitination of BCL6 and DTL but does not seem to directubiquitination of TP53. SCF(BTRC) mediates the ubiquitination ofNFKBIA at 'Lys-21' and 'Lys-22' animal organ morphogenesis;cell cycle arrest;cell proliferation;cellular iron ion homeostasis;G1/S transition of mitotic cell cycle;G2/M transition of mitotic cell cycle;interleukin-1-mediated signaling pathway;intrinsic apoptotic signaling pathway;negative regulation of cell proliferation;negative regulation of G2/M transition of mitotic cell cycle;NIK/NF-kappaB signaling;post-translational protein modification;proteasome-mediated ubiquitin-dependent protein catabolic process;protein monoubiquitination;protein polyubiquitination;protein ubiquitination;regulation of mitotic cell cycle phase transition;SCF complex assembly;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;stress-activated MAPK cascade;ubiquitin-dependent protein catabolic process;viral process;Wnt signaling pathway ubiquitin protein ligase binding;ubiquitin-protein transferase activity cullin-RING ubiquitin ligase complex;cytosol;nucleoplasm;Parkin-FBXW7-Cul1 ubiquitin ligase complex;SCF ubiquitin ligase complex Cell cycle;Circadian rhythm;Hedgehog signaling pathway;Human immunodeficiency virus 1 infection;Oocyte meiosis;Pathways in cancer;Protein processing in endoplasmic reticulum;TGF-beta signaling pathway;Ubiquitin mediated proteolysis;Wnt signaling pathway Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;Circadian Clock;CLEC7A (Dectin-1) signaling;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Cyclin D associated events in G1;Dectin-1 mediated noncanonical NF-kB signaling;Degradation of beta-catenin by the destruction complex;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;GLI3 is processed to GLI3R by the proteasome;Interleukin-1 signaling;Iron uptake and transport;Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling;MAP3K8 (TPL2)-dependent MAPK1/3 activation;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;NOTCH1 Intracellular Domain Regulates Transcription;Orc1 removal from chromatin;Prolactin receptor signaling;Regulation of PLK1 Activity at G2/M Transition;Regulation of RUNX2 expression and activity;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1 CAND1-CUL1-RBX1 complex;CCDC22-COMMD8-CUL1 complex;Neddylin ligase (FBXO11, SKP1, CUL1, RBX1);p27-cyclinE-Cdk2 - Ubiquitin E3 ligase (SKP1A, SKP2, CUL1, CKS1B, RBX1) complex;TNF-alpha/NF-kappa B signaling complex (CHUK, BTRC, NFKB2, PPP6C, REL, CUL1, IKBKE, SAPS2, SAPS1, ANKRD28, RELA, SKP1);TNF-alpha/NF-kappa B signaling complex 5;Ubiquitin E3 ligase (BTRC, CUL1, RBX1, SKP1);Ubiquitin E3 ligase (CDC34, CUL1, RBX1);Ubiquitin E3 ligase (CDC34, NEDD8, BTRC, CUL1, SKP1A, RBX1);Ubiquitin E3 ligase (CHEK1, CUL1);Ubiquitin E3 ligase (CRY1, SKP1A, CUL1, FBXL3);Ubiquitin E3 ligase (CRY2, SKP1A, CUL1, FBXL3);Ubiquitin E3 ligase (CSN1, CSN8, HRT1, SKP1, SKP2, CUL1, CUL2, CUL3);Ubiquitin E3 ligase (CUL1, FBXO10, SKP1);Ubiquitin E3 ligase (CUL1, FBXO17, RBX1, SKP1);Ubiquitin E3 ligase (CUL1, FBXO27, RBX1, SKP1);Ubiquitin E3 ligase (CUL1, FBXO44, RBX1, SKP1);Ubiquitin E3 ligase (CUL1, FBXO6, RBX1, SKP1);Ubiquitin E3 ligase (CUL1, RBX1, SKP1);Ubiquitin E3 ligase (FBXO18, SKP1A, CUL1, RBX1);Ubiquitin E3 ligase (FBXO31, SKP1A, CUL1, RBX1);Ubiquitin E3 ligase (FBXW11, SKP1, CUL1);Ubiquitin E3 ligase (FBXW11, SKP1A, CUL1, RBX1);Ubiquitin E3 ligase (FBXW7, CUL1, SKP1A, RBX1);Ubiquitin E3 ligase (NFKBIA, BTRC, CUL1, SKP1A);Ubiquitin E3 ligase (NFKBIA, FBXW11, CUL1, SKP1A);Ubiquitin E3 ligase (NIPA, SKP1A, CUL1, RBX1);Ubiquitin E3 ligase (SKP1A, BTRC, CUL1);Ubiquitin E3 ligase (SKP1A, FBXW2, CUL1);Ubiquitin E3 ligase (SKP1A, SKP2, CUL1);Ubiquitin E3 ligase (SKP1A, SKP2, CUL1, CKS1B, RBX1);Ubiquitin E3 ligase (SKP1A, SKP2, CUL1, RBX1);Ubiquitin E3 ligase (SMAD3, BTRC, CUL1, SKP1A, RBX1);URI complex (Unconventional prefoldin RPB5 Interactor) -0.981795072555542 0.0364150665700436 -1.3474280834198 -0.255883008241653 -0.981795072555542 -1.88721001148224 -1.4954582452774 -0.685720324516296 1.10887396335602 0.382672518491745 0.491575241088867 0.234381884336472 0.79202002286911 1.21933948993683 0.948385000228882 0.456485003232956 1.20190298557281 0.763238787651062 + Cluster -671 17 17 17 65.4 65.4 65.4 28.804 0 314.53 222870000000 258 3.68338499658726 0.000312354312354312 P18669;P15259;Q8N0Y7 P18669 Phosphoglycerate mutase 1 PGAM1 722 Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can alsocatalyze the reaction of EC 5.4.2.4 (synthase), but with a reducedactivity. canonical glycolysis;gluconeogenesis;glycolytic process;neutrophil degranulation;Notch signaling pathway;positive regulation of flagellated sperm motility;regulation of glycolytic process;regulation of pentose-phosphate shunt;respiratory burst;response to mercury ion;spermatogenesis;striated muscle contraction 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase activity;bisphosphoglycerate mutase activity;cofactor binding;hydrolase activity;phosphoglycerate mutase activity;protein kinase binding cytoplasm;cytosol;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;membrane;nucleus;secretory granule lumen;sperm principal piece Biosynthesis of amino acids;Carbon metabolism;Central carbon metabolism in cancer;Glucagon signaling pathway;Glycine, serine and threonine metabolism;Glycolysis / Gluconeogenesis;Metabolic pathways Glycogen storage disease;Glycogen storage disease type X;Muscle glycogen storage disease Gluconeogenesis;Glycolysis;Neutrophil degranulation -0.541466414928436 0.410000711679459 -1.69558846950531 -0.941338121891022 -0.678185880184174 -2.10430550575256 -0.686113893985748 -0.686113893985748 0.834158718585968 0.551808953285217 -0.134256392717361 -0.134256392717361 1.24431717395782 1.24431717395782 0.704690158367157 0.956092357635498 0.956092357635498 0.700147390365601 + Cluster -671 25 25 25 50.4 50.4 50.4 47.697 0 323.31 268050000000 246 4.34779607687001 6.84931506849315E-05 P36578 P36578 60S ribosomal protein L4 RPL4 953 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytoplasm;cytosol;cytosolic large ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleolus;nucleus;ribonucleoprotein complex;rough endoplasmic reticulum Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TNF-alpha/NF-kappa B signaling complex 6 -1.04664719104767 -0.32210385799408 -1.19146752357483 -0.183120131492615 -0.746087491512299 -1.28798604011536 -1.65663528442383 -1.12437438964844 0.357425957918167 0.16727888584137 0.273933202028275 0.400816529989243 1.7372270822525 0.400816529989243 1.08888781070709 1.23422062397003 0.801311194896698 1.0965039730072 + Cluster -671 17 7 7 45.2 21.1 21.1 49.129 0 26.993 9947300000 33 4.52861084160281 4.66926070038911E-05 O00148;O00148-2;O00148-3 O00148;O00148-2;O00148-3 ATP-dependent RNA helicase DDX39A DDX39A 63 Isoform 1: Involved in pre-mRNA splicing. Required forthe export of mRNA out of the nucleus Nucleus {ECO:0000269|PubMed:21859714}.Cytoplasm {ECO:0000269|PubMed:21859714}. Note=Can translocate tothe cytoplasm in the presence of MX1. mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;RNA export from nucleus ATP binding;ATPase activity;helicase activity;identical protein binding;RNA binding cytoplasm;membrane;nuclear speck;nucleoplasm;nucleus Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;Transport of Mature mRNA derived from an Intron-Containing Transcript Emerin complex 52 -1.27655673027039 -0.482098251581192 -0.351835638284683 -0.0556527674198151 -0.792292654514313 -0.810463070869446 -1.94231712818146 -0.648959219455719 -0.647860050201416 0.695236265659332 0.0813532173633575 0.111297287046909 1.62537384033203 0.852828800678253 0.0356647521257401 1.97789990901947 0.779800534248352 0.848580777645111 + Cluster -671 5 2 2 3.9 1.9 1.9 176.65 0 3.7506 744740000 3 3.26711962868037 0.000639455782312925 O43432;O43432-4;O43432-3 O43432;O43432-4;O43432-3 Eukaryotic translation initiation factor 4 gamma 3 EIF4G3 216 Probable component of the protein complex eIF4F, whichis involved in the recognition of the mRNA cap, ATP-dependentunwinding of 5'-terminal secondary structure and recruitment ofmRNA to the ribosome. Thought to be a functional homolog ofEIF4G1. regulation of translational initiation mRNA binding;RNA binding;RNA cap binding;translation factor activity, RNA binding;translation initiation factor activity cytosol;eukaryotic translation initiation factor 4F complex RNA transport;Viral myocarditis ISG15 antiviral mechanism -1.07597184181213 -0.166036918759346 -0.778035283088684 -0.817204236984253 -1.07597184181213 -1.9399641752243 -0.830633223056793 -1.06373977661133 0.22719144821167 0.845647871494293 -0.134785935282707 0.892971515655518 0.684079229831696 0.862391352653503 0.684079229831696 1.18063580989838 1.20444226264954 1.30090463161469 + Cluster -671 4 4 4 44 44 44 14.199 0 140.12 18569000000 27 4.90252261564389 2.04081632653061E-05 Q9UI30;Q9UI30-2 Q9UI30;Q9UI30-2 Multifunctional methyltransferase subunit TRM112-like protein TRMT112 3123 Acts as an activator of both rRNA/tRNA and proteinmethyltransferases (PubMed:25851604). Together withmethyltransferase BUD23, methylates the N(7) position of a guaninein 18S rRNA (PubMed:25851604). The heterodimer with HEMK2/N6AMT1catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:18539146). The heterodimer withALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of theanticodon loop in target tRNA species (PubMed:20308323). Involvedin the pre-rRNA processing steps leading to small-subunit rRNAproduction (PubMed:25851604). Nucleus, nucleoplasm{ECO:0000269|PubMed:25851604}. Cytoplasm, perinuclear region{ECO:0000269|PubMed:25851604}. Note=Localizes to a polarizedperinuclear structure, overlapping partially with the Golgi andlysosomes (PubMed:25851604). {ECO:0000269|PubMed:25851604}. peptidyl-glutamine methylation;positive regulation of rRNA processing;rRNA (guanine-N7)-methylation;tRNA methylation protein heterodimerization activity;protein methyltransferase activity cytosol;nucleoplasm;perinuclear region of cytoplasm;protein-containing complex Eukaryotic Translation Termination;Methylation;rRNA modification in the nucleus and cytosol;tRNA modification in the nucleus and cytosol -0.94817191362381 -0.244630083441734 -0.977419316768646 -0.487038373947144 -0.977419316768646 -1.62807178497314 -1.30070340633392 -1.21259117126465 0.0259840078651905 0.51213002204895 0.33648094534874 0.191888466477394 0.909601747989655 0.999029755592346 1.19229030609131 0.989737510681152 1.23359858989716 1.38530421257019 + Cluster -671 33 33 33 69.8 69.8 69.8 54.529 0 323.31 390850000000 369 6.98432917133676 0 Q16658 Q16658 Fascin FSCN1 1859 Organizes filamentous actin into bundles with a minimumof 4.1:1 actin/fascin ratio. Plays a role in the organization ofactin filament bundles and the formation of microspikes, membraneruffles, and stress fibers. Important for the formation of adiverse set of cell protrusions, such as filopodia, and for cellmotility and migration. Cytoplasm, cytosol{ECO:0000269|PubMed:21706053, ECO:0000269|PubMed:9571235}.Cytoplasm, cytoskeleton {ECO:0000269|PubMed:3525578,ECO:0000269|PubMed:9571235}. Cytoplasm, cytoskeleton, stress fiber{ECO:0000269|PubMed:21706053}. Cell projection, filopodium{ECO:0000269|PubMed:20137952, ECO:0000269|PubMed:3525578}. Cellprojection, invadopodium {ECO:0000269|PubMed:20137952}. Cellprojection, microvillus {ECO:0000269|PubMed:9571235}. Celljunction {ECO:0000269|PubMed:9571235}. Note=Colocalized with RUFY3and F-actin at filipodia of the axonal growth cone. Colocalizedwith DBN1 and F-actin at the transitional domain of the axonalgrowth cone (By similarity). {ECO:0000250|UniProtKB:Q61553,ECO:0000269|PubMed:21706053}. actin cytoskeleton organization;actin filament bundle assembly;cell migration;cell motility;cell proliferation;cell-cell junction assembly;cytokine-mediated signaling pathway;establishment of apical/basal cell polarity;establishment or maintenance of cell polarity;microspike assembly;positive regulation of extracellular matrix disassembly;positive regulation of filopodium assembly;positive regulation of lamellipodium assembly;positive regulation of podosome assembly;regulation of actin cytoskeleton organization;regulation of microvillus assembly actin binding;actin filament binding;cadherin binding;drug binding;protein binding, bridging;RNA binding actin cytoskeleton;cell projection membrane;cell-cell junction;cytoplasm;cytoskeleton;cytosol;extracellular exosome;filopodium;growth cone;invadopodium;lamellipodium;microspike;microvillus;myelin sheath;podosome;ruffle;stress fiber MicroRNAs in cancer Interleukin-4 and Interleukin-13 signaling -0.852443218231201 0.317262917757034 -1.1667845249176 -0.7533358335495 -1.17729020118713 -1.00677442550659 -1.33848905563354 -0.926907360553741 -0.415737956762314 0.136337444186211 -0.198901146650314 0.14540833234787 1.17421853542328 1.00164365768433 1.01345801353455 1.54888641834259 1.18084609508514 1.3186023235321 + Cluster -671 1 1 1 3.3 3.3 3.3 46.45 0.0070379 0.96893 1307000000 2 7.56603586442404 0 Q9BPX7;Q9BPX7-2 Q9BPX7;Q9BPX7-2 UPF0415 protein C7orf25 C7orf25 2610 -0.694635152816772 -0.118979245424271 -0.962930500507355 -0.840948522090912 -1.73514974117279 -1.47846400737762 -0.29127362370491 -1.16456758975983 0.286331802606583 1.00412714481354 -0.128439381718636 0.188706234097481 0.265811949968338 0.792605102062225 0.811487853527069 1.00917589664459 1.38716876506805 1.66997301578522 + Cluster -671 4 4 4 7.2 7.2 7.2 72.832 0 9.8362 786530000 6 4.20669461981884 9.2948717948718E-05 Q8N0X7 Q8N0X7 Spartin SPG20 2176 May be implicated in endosomal trafficking, ormicrotubule dynamics, or both. Participates in cytokinesis(PubMed:20719964). Cytoplasm {ECO:0000269|PubMed:19580544}.Midbody {ECO:0000269|PubMed:20719964}. Note=Transiently associatedwith endosomes (PubMed:19580544). Colocalized with IST1 to theends of Flemming bodies during cytokinesis (PubMed:20719964).{ECO:0000269|PubMed:19580544, ECO:0000269|PubMed:20719964}. abscission;adipose tissue development;cell division;lipid droplet organization;negative regulation of BMP signaling pathway;negative regulation of collateral sprouting in absence of injury;neuromuscular process;regulation of mitochondrial membrane potential ubiquitin protein ligase binding cytoplasm;cytosol;lipid droplet;midbody;mitochondrial outer membrane;plasma membrane;synapse Endocytosis Hereditary spastic paraplegia -0.362374931573868 -0.831571578979492 -1.05129170417786 -0.859903335571289 -1.14970171451569 -1.32308924198151 -0.909491837024689 -1.52260148525238 0.52336186170578 0.697547674179077 0.469046175479889 -0.0137215340510011 0.885883748531342 0.697547674179077 1.01883971691132 1.0691169500351 1.0691169500351 1.59328663349152 + Cluster -671 9 9 9 18.5 18.5 18.5 87.133 0 154.76 13489000000 33 6.06603615254356 1.23456790123457E-05 Q14694;Q14694-3;Q14694-2 Q14694;Q14694-3;Q14694-2 Ubiquitin carboxyl-terminal hydrolase 10 USP10 1729 Hydrolase that can remove conjugated ubiquitin fromtarget proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as anessential regulator of p53/TP53 stability: in unstressed cells,specifically deubiquitinates p53/TP53 in the cytoplasm, leading tocounteract MDM2 action and stabilize p53/TP53. Following DNAdamage, translocates to the nucleus and deubiquitinates p53/TP53,leading to regulate the p53/TP53-dependent DNA damage response.Component of a regulatory loop that controls autophagy andp53/TP53 levels: mediates deubiquitination of BECN1, a keyregulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing complexesregulate USP10 stability, suggesting the existence of a regulatorysystem by which PIK3C3/VPS34-containing complexes regulatep53/TP53 protein levels via USP10 and USP13. Does notdeubiquitinate MDM2. Deubiquitinates CFTR in early endosomes,enhancing its endocytic recycling. Involved in a TANK-dependentnegative feedback response to attenuate NF-kappaB activation viadeubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta(IL1B) stimulation or upon DNA damage (PubMed:25861989).Deubiquitinates TBX21 leading to its stabilization(PubMed:24845384). Cytoplasm {ECO:0000269|PubMed:20096447}.Nucleus {ECO:0000269|PubMed:20096447,ECO:0000269|PubMed:24845384}. Early endosome{ECO:0000269|PubMed:19398555}. Note=Cytoplasmic in normalconditions (PubMed:20096447). After DNA damage, translocates tothe nucleus following phosphorylation by ATM (PubMed:20096447).{ECO:0000269|PubMed:20096447}. autophagy;cellular response to DNA damage stimulus;cellular response to interleukin-1;DNA damage response, signal transduction by p53 class mediator;negative regulation of I-kappaB kinase/NF-kappaB signaling;protein deubiquitination;regulation of autophagy;translesion synthesis;ubiquitin-dependent protein catabolic process cysteine-type endopeptidase activity;ion channel binding;p53 binding;RNA binding;thiol-dependent ubiquitin-specific protease activity;thiol-dependent ubiquitinyl hydrolase activity cytoplasm;cytosol;early endosome;nucleoplasm;nucleus;protein-containing complex Termination of translesion DNA synthesis;Ub-specific processing proteases -0.516409993171692 -0.447141081094742 -1.25058174133301 -0.872712552547455 -1.00832152366638 -1.31169259548187 -1.19309198856354 -1.21131443977356 -0.0839904621243477 0.728162050247192 0.255942732095718 0.255942732095718 0.728162050247192 0.953158259391785 0.794704556465149 1.28690361976624 1.41103172302246 1.48124861717224 + Cluster -671 13 13 13 17.9 17.9 17.9 88.884 0 213.83 12171000000 58 8.36523313176166 0 O75534;O75534-2;O75534-3;O75534-4 O75534;O75534-2;O75534-3;O75534-4 Cold shock domain-containing protein E1 CSDE1 344 RNA-binding protein. Required for internal initiation oftranslation of human rhinovirus RNA. May be involved intranslationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translationaland decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain Cytoplasm. male gonad development;nuclear-transcribed mRNA catabolic process, no-go decay;regulation of transcription, DNA-templated DNA binding;RNA binding CRD-mediated mRNA stability complex;cytosol;Golgi apparatus;plasma membrane Multiprotein complex (mRNA turnover) -0.0951013192534447 -0.136296078562737 -1.47676837444305 -1.30261433124542 -1.21683692932129 -1.23979270458221 -0.980299293994904 -1.10703778266907 0.428353875875473 0.98476779460907 0.104257330298424 0.149613916873932 0.98476779460907 0.457661867141724 0.646053791046143 1.60633981227875 0.848960936069489 1.34396970272064 + Cluster -671 14 14 10 32.6 32.6 23.1 63.146 0 242.65 96717000000 152 6.41885790281406 0 P06744;P06744-2 P06744;P06744-2 Glucose-6-phosphate isomerase GPI 521 Besides it's role as a glycolytic enzyme, mammalian GPIcan function as a tumor-secreted cytokine and an angiogenic factor(AMF) that stimulates endothelial cell motility. GPI is also aneurotrophic factor (Neuroleukin) for spinal and sensory neurons Cytoplasm {ECO:0000269|PubMed:11437381}.Secreted {ECO:0000269|PubMed:11437381}. aldehyde catabolic process;canonical glycolysis;carbohydrate metabolic process;erythrocyte homeostasis;gluconeogenesis;glucose 6-phosphate metabolic process;glucose homeostasis;glycolytic process;hemostasis;humoral immune response;in utero embryonic development;learning or memory;mesoderm formation;methylglyoxal biosynthetic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of neuron apoptotic process;neutrophil degranulation;positive regulation of endothelial cell migration;positive regulation of immunoglobulin secretion;response to cadmium ion;response to estradiol;response to immobilization stress;response to morphine;response to muscle stretch;response to progesterone;response to testosterone cytokine activity;glucose-6-phosphate isomerase activity;growth factor activity;intramolecular transferase activity;monosaccharide binding;ubiquitin protein ligase binding ciliary membrane;cytosol;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;membrane;myelin sheath;neuron projection;nucleoplasm;plasma membrane;secretory granule lumen Amino sugar and nucleotide sugar metabolism;Carbon metabolism;Glycolysis / Gluconeogenesis;Metabolic pathways;Pentose phosphate pathway;Starch and sucrose metabolism Anemia due to disorders of glycolytic enzymes Gluconeogenesis;Glycolysis;Neutrophil degranulation;TP53 Regulates Metabolic Genes -0.568991184234619 -0.603641629219055 -0.855733931064606 -0.685792028903961 -1.40614521503448 -0.644677639007568 -1.7175487279892 -0.711765170097351 -0.3463194668293 0.131049692630768 0.237116485834122 0.0417498610913754 0.800220549106598 0.951613008975983 0.912202775478363 1.54934787750244 1.33439373970032 1.58292102813721 + Cluster -671 13 13 13 66.7 66.7 66.7 25.2 0 323.31 61539000000 104 6.59996643282532 0 Q15056-2;Q15056 Q15056-2;Q15056 Eukaryotic translation initiation factor 4H EIF4H 1765 Stimulates the RNA helicase activity of EIF4A in thetranslation initiation complex. Binds weakly mRNA Cytoplasm, perinuclear region {ECO:0000250}. cytoplasmic translation;developmental growth;eukaryotic translation initiation factor 4F complex assembly;formation of translation preinitiation complex;regulation of translational initiation;sexual reproduction;translational initiation;viral process cadherin binding;ribosomal small subunit binding;RNA binding;RNA strand annealing activity;RNA strand-exchange activity;translation factor activity, RNA binding;translation initiation factor activity cytosol;eukaryotic translation initiation factor 4F complex;membrane;perinuclear region of cytoplasm;polysome Williams-Beuren syndrome Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Ribosomal scanning and start codon recognition;Translation initiation complex formation -0.63544625043869 -0.440243899822235 -0.902547478675842 -0.881780803203583 -0.939651072025299 -1.4730406999588 -1.36441612243652 -1.33426189422607 0.0226001441478729 0.21038581430912 0.692834198474884 0.522303938865662 0.988451957702637 0.744929611682892 1.01279890537262 1.20827353000641 1.26255941390991 1.30625057220459 + Cluster -671 5 5 4 35.8 35.8 35.2 19.652 0 158.77 23652000000 39 8.32872122487845 0 O00762;O00762-2;O00762-3;O00762-4 O00762;O00762-2;O00762-3;O00762-4 Ubiquitin-conjugating enzyme E2 C UBE2C 109 Accepts ubiquitin from the E1 complex and catalyzes itscovalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. Acts as an essentialfactor of the anaphase promoting complex/cyclosome (APC/C), a cellcycle-regulated ubiquitin ligase that controls progression throughmitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chainson APC/C substrates, leading to the degradation of APC/Csubstrates by the proteasome and promoting mitotic exit anaphase-promoting complex-dependent catabolic process;cell division;exit from mitosis;free ubiquitin chain polymerization;positive regulation of exit from mitosis;positive regulation of ubiquitin protein ligase activity;protein K11-linked ubiquitination;protein K48-linked ubiquitination;protein ubiquitination;regulation of mitotic cell cycle phase transition;ubiquitin-dependent protein catabolic process ATP binding;ubiquitin conjugating enzyme activity;ubiquitin-like protein ligase binding;ubiquitin-protein transferase activity anaphase-promoting complex;cytosol;nucleoplasm;nucleus;plasma membrane;ubiquitin ligase complex Ubiquitin mediated proteolysis Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Cyclin B;APC/C:Cdc20 mediated degradation of mitotic proteins;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;APC-Cdc20 mediated degradation of Nek2A;Autodegradation of Cdh1 by Cdh1:APC/C;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase;Inactivation of APC/C via direct inhibition of the APC/C complex;Phosphorylation of the APC/C;Regulation of APC/C activators between G1/S and early anaphase;Senescence-Associated Secretory Phenotype (SASP);Separation of Sister Chromatids;Synthesis of active ubiquitin: roles of E1 and E2 enzymes -0.230632185935974 -1.25996291637421 -0.494801908731461 -0.908612310886383 -1.3056526184082 -0.707160294055939 -1.29636454582214 -1.09419727325439 -0.166342988610268 -0.293854206800461 0.376444518566132 0.510265052318573 1.01896119117737 0.70071679353714 0.785141825675964 1.60461211204529 1.10065376758575 1.6607860326767 + Cluster -671 12 12 12 30.3 30.3 30.3 51.712 0 127.22 59650000000 110 5.38474128379276 7.2992700729927E-06 O75390 O75390 Citrate synthase, mitochondrial CS 328 Mitochondrion matrix. carbohydrate metabolic process;tricarboxylic acid cycle citrate (Si)-synthase activity;RNA binding extracellular exosome;mitochondrial matrix;mitochondrion;nucleus 2-Oxocarboxylic acid metabolism;Biosynthesis of amino acids;Carbon metabolism;Citrate cycle (TCA cycle);Glyoxylate and dicarboxylate metabolism;Metabolic pathways Citric acid cycle (TCA cycle);Mitochondrial protein import CS-MAP3K7IP1-MAP3K7IP2 complex -1.14702665805817 -0.578168392181396 -1.20048141479492 -0.85492467880249 -0.31020650267601 -1.31278729438782 -1.31278729438782 -0.997877657413483 -0.159702777862549 0.414241164922714 0.550576210021973 0.362518697977066 0.67238712310791 1.11232793331146 0.511356830596924 1.55806505680084 1.29958593845367 1.39290404319763 + Cluster -671 13 13 13 39 39 39 52.645 0 149.73 22397000000 65 5.87486443433169 1.12359550561798E-05 P31930 P31930 Cytochrome b-c1 complex subunit 1, mitochondrial UQCRC1 891 This is a component of the ubiquinol-cytochrome creductase complex (complex III or cytochrome b-c1 complex), whichis part of the mitochondrial respiratory chain. This protein maymediate formation of the complex between cytochromes c and c1. Mitochondrion inner membrane. aerobic respiration;mitochondrial electron transport, ubiquinol to cytochrome c;oxidation-reduction process;oxidative phosphorylation;response to activity;response to alkaloid metal ion binding;metalloendopeptidase activity;protein-containing complex binding;ubiquinol-cytochrome-c reductase activity;ubiquitin protein ligase binding cytosol;mitochondrial inner membrane;mitochondrial respirasome;mitochondrial respiratory chain complex III;mitochondrion;myelin sheath Alzheimer disease;Cardiac muscle contraction;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Thermogenesis Respiratory electron transport -1.87850522994995 -0.163427725434303 -0.354055255651474 0.00224528252147138 -0.63534140586853 -1.01771759986877 -1.18681979179382 -1.18681979179382 0.129306271672249 -0.147744253277779 -0.493855804204941 0.109616704285145 1.81905543804169 0.839710891246796 1.26455450057983 0.569918572902679 0.924055397510529 1.40582370758057 + Cluster -671 2 2 2 6 6 6 55.63 0 12.597 763990000 6 3.4513707291813 0.000470363288718929 Q13043;Q13043-2 Q13043;Q13043-2 Serine/threonine-protein kinase 4;Serine/threonine-protein kinase 4 37kDa subunit;Serine/threonine-protein kinase 4 18kDa subunit STK4 1588 Stress-activated, pro-apoptotic kinase which, followingcaspase-cleavage, enters the nucleus and induces chromatincondensation followed by internucleosomal DNA fragmentation. Keycomponent of the Hippo signaling pathway which plays a pivotalrole in organ size control and tumor suppression by restrictingproliferation and promoting apoptosis. The core of this pathway iscomposed of a kinase cascade wherein STK3/MST2 and STK4/MST1, incomplex with its regulatory protein SAV1, phosphorylates andactivates LATS1/2 in complex with its regulatory protein MOB1,which in turn phosphorylates and inactivates YAP1 oncoprotein andWWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits itstranslocation into the nucleus to regulate cellular genesimportant for cell proliferation, cell death, and cell migration.STK3/MST2 and STK4/MST1 are required to repress proliferation ofmature hepatocytes, to prevent activation of facultative adultliver stem cells (oval cells), and to inhibit tumor formation (Bysimilarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph)during apoptosis. Phosphorylates FOXO3 upon oxidative stress,which results in its nuclear translocation and cell deathinitiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2.Phosphorylates TNNI3 (cardiac Tn-I) and alters its bindingaffinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T).Phosphorylates FOXO1 on 'Ser-212' and regulates its activation andstimulates transcription of PMAIP1 in a FOXO1-dependent manner.Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53deacetylation, thereby promoting p53/TP53 dependent transcriptionand apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1.Phosphorylates AR on 'Ser-650' and suppresses its activity byintersecting with PKB/AKT1 signaling and antagonizing formation ofAR-chromatin complexes. Cytoplasm. Nucleus. Note=The caspase-cleavedform cycles between the nucleus and cytoplasm. activation of protein kinase activity;apoptotic process;branching involved in blood vessel morphogenesis;cell differentiation involved in embryonic placenta development;cell morphogenesis;central nervous system development;endocardium development;hepatocyte apoptotic process;hippo signaling;intracellular signal transduction;keratinocyte differentiation;negative regulation of canonical Wnt signaling pathway;negative regulation of cell proliferation;negative regulation of organ growth;neural tube formation;peptidyl-serine phosphorylation;positive regulation of apoptotic process;positive regulation of extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of fat cell differentiation;positive regulation of peptidyl-serine phosphorylation;positive regulation of protein binding;positive regulation of protein phosphorylation;positive regulation of vascular associated smooth muscle cell apoptotic process;primitive hemopoiesis;protein autophosphorylation;protein phosphorylation;protein stabilization;regulation of cell differentiation involved in embryonic placenta development;signal transduction;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade ATP binding;identical protein binding;magnesium ion binding;protein dimerization activity;protein homodimerization activity;protein kinase activity;protein serine/threonine kinase activator activity;protein serine/threonine kinase activity;transcription factor binding cytoplasm;cytosol;nuclear body;nucleoplasm;nucleus;protein-containing complex FoxO signaling pathway;MAPK signaling pathway;Non-small cell lung cancer;Pathways in cancer;Ras signaling pathway Signaling by Hippo DLG5-MST1-MST2 complex;MST1-SAV1 complex -1.99293279647827 0.00762305548414588 -0.415538996458054 0.0294720437377691 -1.0633260011673 -1.24877047538757 -1.27887380123138 -0.87599915266037 0.3006811439991 -0.00809092726558447 0.364485234022141 -0.344386875629425 1.52819836139679 0.837619721889496 1.02578318119049 0.924346387386322 0.973217308521271 1.23649275302887 + Cluster -671 11 11 11 34.6 34.6 34.6 49.03 0 103.67 10024000000 35 3.26936515799206 0.000637137989778535 P62495;P62495-2 P62495;P62495-2 Eukaryotic peptide chain release factor subunit 1 ETF1 1360 Directs the termination of nascent peptide synthesis(translation) in response to the termination codons UAA, UAG andUGA (PubMed:7990965, PubMed:24486019). Component of the transientSURF complex which recruits UPF1 to stalled ribosomes in thecontext of nonsense-mediated decay (NMD) of mRNAs containingpremature stop codons. Cytoplasm {ECO:0000269|PubMed:24486019}. cytoplasmic translational termination;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;protein methylation;regulation of translational termination ribosome binding;RNA binding;sequence-specific mRNA binding;translation release factor activity;translation release factor activity, codon specific;translation termination factor activity cytoplasm;cytosol;translation release factor complex mRNA surveillance pathway Eukaryotic Translation Termination;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Regulation of expression of SLITs and ROBOs eRF1-eRF3-GTP-Mg(2+) complex;SMG-1-UPF-ERF1-ERF3 complex (SURF) -1.33528387546539 0.0214562192559242 -0.902085244655609 -0.443091332912445 -0.797092139720917 -1.61284911632538 -1.36154675483704 -1.17636203765869 0.608023107051849 0.456627935171127 0.101516358554363 0.0490636676549911 0.970953643321991 1.22785341739655 1.34468448162079 0.608023107051849 1.0753767490387 1.16473186016083 + Cluster -671 12 12 12 20 20 20 92.48 0 202.06 52670000000 103 4.52508387162162 4.65116279069767E-05 P55884;P55884-2 P55884;P55884-2 Eukaryotic translation initiation factor 3 subunit B EIF3B 1249 RNA-binding component of the eukaryotic translationinitiation factor 3 (eIF-3) complex, which is required for severalsteps in the initiation of protein synthesis (PubMed:9388245,PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3complex associates with the 40S ribosome and facilitates therecruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5to form the 43S pre-initiation complex (43S PIC). The eIF-3complex stimulates mRNA recruitment to the 43S PIC and scanning ofthe mRNA for AUG recognition. The eIF-3 complex is also requiredfor disassembly and recycling of post-termination ribosomalcomplexes and subsequently prevents premature joining of the 40Sand 60S ribosomal subunits prior to initiation (PubMed:9388245,PubMed:17581632). The eIF-3 complex specifically targets andinitiates translation of a subset of mRNAs involved in cellproliferation, including cell cycling, differentiation andapoptosis, and uses different modes of RNA stem-loop binding toexert either translational activation or repression(PubMed:25849773). Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03001}. formation of cytoplasmic translation initiation complex;IRES-dependent viral translational initiation;regulation of translational initiation;translational initiation;viral translational termination-reinitiation protein-containing complex scaffold activity;RNA binding;translation initiation factor activity;translation initiation factor binding cytosol;eukaryotic 43S preinitiation complex;eukaryotic 48S preinitiation complex;eukaryotic translation initiation factor 3 complex;eukaryotic translation initiation factor 3 complex, eIF3m;extracellular exosome;synapse RNA transport Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Ribosomal scanning and start codon recognition;Translation initiation complex formation CBP80/20- dependent translation complex;EIF3 complex (EIF3A, EIF3B, EIF3G, EIF3I, EIF3C);EIF3 complex (EIF3A, EIF3B, EIF3G, EIF3I, EIF3J);EIF3 complex (EIF3B, EIF3G, EIF3I);EIF3 complex (EIF3B, EIF3J, EIF3I);eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7);eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7, PCID1);EIF3 core complex (EIF3A, EIF3B, EIF3G, EIF3I);PRT1-RGP1 complex -1.27071690559387 0.351269394159317 -0.750942826271057 -0.442040503025055 -0.839367806911469 -1.29211139678955 -1.63983833789825 -1.167027592659 -0.228496700525284 0.44385102391243 0.223653092980385 0.030333686619997 1.00014424324036 1.48018550872803 0.920835971832275 0.667891263961792 1.51698410511017 0.995393753051758 + Cluster -671 21 21 20 48.8 48.8 45.2 36.688 0 323.31 266680000000 295 4.90015026505764 2.03045685279188E-05 P00338;P00338-3;P00338-4;P00338-2;P00338-5 P00338;P00338-3;P00338-4;P00338-2;P00338-5 L-lactate dehydrogenase A chain LDHA 461 Cytoplasm. glycolytic process;lactate metabolic process;NAD metabolic process;positive regulation of apoptotic process;post-embryonic animal organ development;pyruvate metabolic process;response to cAMP;response to estrogen;response to glucose;response to hydrogen peroxide;response to hypoxia;response to nutrient;substantia nigra development cadherin binding;identical protein binding;kinase binding;L-lactate dehydrogenase activity;NAD binding cytosol;extracellular exosome;membrane;nucleus Central carbon metabolism in cancer;Cysteine and methionine metabolism;Glucagon signaling pathway;Glycolysis / Gluconeogenesis;HIF-1 signaling pathway;Metabolic pathways;Propanoate metabolism;Pyruvate metabolism Glycogen storage disease;Glycogen storage disease type XI;Muscle glycogen storage disease Pyruvate metabolism -1.5075591802597 0.283833533525467 -0.687288045883179 -0.965589463710785 -0.687288045883179 -1.22004973888397 -1.1997309923172 -1.47347939014435 0.225267007946968 -0.0375744923949242 0.0437345579266548 0.828929245471954 0.999203681945801 1.15466380119324 0.904348790645599 1.29911506175995 1.09875881671906 0.940705120563507 + Cluster -671 11 11 11 40.6 40.6 40.6 35.716 0 185.64 34414000000 59 4.67623178487809 3.37552742616034E-05 P04818;P04818-2;P04818-3 P04818;P04818-2 Thymidylate synthase TYMS 492 Contributes to the de novo mitochondrial thymidylatebiosynthesis pathway. Nucleus {ECO:0000269|PubMed:21876188}.Cytoplasm {ECO:0000269|PubMed:21876188}. Mitochondrion{ECO:0000269|PubMed:21876188}. Mitochondrion matrix{ECO:0000269|PubMed:21876188}. Mitochondrion inner membrane{ECO:0000269|PubMed:21876188}. aging;cartilage development;circadian rhythm;developmental growth;DNA biosynthetic process;dTMP biosynthetic process;dTTP biosynthetic process;dUMP metabolic process;immortalization of host cell by virus;intestinal epithelial cell maturation;liver regeneration;negative regulation of translation;nucleobase-containing small molecule interconversion;regulation of transcription involved in G1/S transition of mitotic cell cycle;response to cytokine;response to ethanol;response to folic acid;response to glucocorticoid;response to organophosphorus;response to progesterone;response to vitamin A;tetrahydrofolate interconversion;uracil metabolic process cofactor binding;folic acid binding;nucleotide binding;protein homodimerization activity;sequence-specific mRNA binding;thymidylate synthase activity;translation repressor activity, mRNA regulatory element binding cytoplasm;cytosol;mitochondrial inner membrane;mitochondrial matrix;mitochondrion;nucleolus;nucleus Antifolate resistance;Metabolic pathways;One carbon pool by folate;Pyrimidine metabolism Capecitabine;Carmofur;Doxifluridine;Floxuridine;Fluorouracil;Metesind glucuronate;Pemetrexed;Plevitrexed;Raltitrexed;Tegafur Activation of E2F1 target genes at G1/S;Interconversion of nucleotide di- and triphosphates -0.861499726772308 -0.259103536605835 -0.510561883449554 -0.978054702281952 -1.07718122005463 -1.13028573989868 -1.51750433444977 -1.41382849216461 0.343091011047363 0.484081119298935 -0.138856172561646 0.2815181016922 1.03783392906189 1.12556838989258 1.27149844169617 1.06473898887634 1.35488522052765 0.923660695552826 + Cluster -671 4 4 3 42.2 42.2 37.7 16.014 0 86.173 59379000000 37 6.54081751059443 0 Q9UK76;Q9UK76-2;Q9UK76-3 Q9UK76;Q9UK76-2;Q9UK76-3 Hematological and neurological expressed 1 protein;Hematological and neurological expressed 1 protein, N-terminally processed HN1 3143 Modulates negatively AKT-mediated GSK3B signaling(PubMed:21323578, PubMed:22155408). Induces CTNNB1 'Ser-33'phosphorylation and degradation through the suppression of theinhibitory 'Ser-9' phosphorylation of GSK3B, which represses thefunction of the APC:CTNNB1:GSK3B complex and the interaction withCDH1/E-cadherin in adherent junctions (PubMed:25169422). Plays arole in the regulation of cell cycle and cell adhesion(PubMed:25169422, PubMed:25450365). Has an inhibitory role on AR-signaling pathway through the induction of receptor proteosomaldegradation (PubMed:22155408). Nucleus {ECO:0000269|PubMed:21323578}.Cytoplasm {ECO:0000269|PubMed:25169422}. cytoplasm;nuclear membrane;nucleolus;nucleus -1.15738320350647 0.0519241914153099 -0.273192584514618 -1.08678805828094 -1.26660919189453 -0.376505315303802 -1.26465058326721 -1.31474387645721 -0.389963954687119 -0.0139754852280021 -0.39798641204834 0.322829723358154 0.941538393497467 1.11547136306763 0.988078713417053 1.37471354007721 1.64066004753113 1.10658264160156 + Cluster -671 2 2 2 32.9 32.9 32.9 9.6601 0 36.845 9644000000 16 5.36412324594013 7.14285714285714E-06 P61024 P61024 Cyclin-dependent kinases regulatory subunit 1 CKS1B 1289 Binds to the catalytic subunit of the cyclin dependentkinases and is essential for their biological function. cell division;cell proliferation;mitotic cell cycle phase transition;positive regulation of cyclin-dependent protein serine/threonine kinase activity;regulation of mitotic cell cycle;regulation of transcription, DNA-templated cyclin-dependent protein serine/threonine kinase activator activity;histone binding;protein kinase binding;ubiquitin binding cyclin-dependent protein kinase holoenzyme complex;nucleoplasm;SCF ubiquitin ligase complex Pathways in cancer;Small cell lung cancer Cyclin D associated events in G1;SCF(Skp2)-mediated degradation of p27/p21 CDH1-CKS1B complex;p27-cyclinE-Cdk2 - Ubiquitin E3 ligase (SKP1A, SKP2, CUL1, CKS1B, RBX1) complex;Ubiquitin E3 ligase (SKP1A, SKP2, CUL1, CKS1B, RBX1) -0.653452277183533 -0.00562019180506468 -0.540816128253937 -0.887087881565094 -0.774183630943298 -1.5235276222229 -1.96444916725159 -0.823693156242371 0.585116446018219 -0.434157580137253 0.082810714840889 0.759619414806366 1.34663009643555 1.27835690975189 1.27835690975189 0.487920224666595 0.861372590065002 0.926804482936859 + Cluster -671 5 5 5 26.9 26.9 26.9 34.234 0 93.253 25857000000 38 4.34476177192597 7.14285714285714E-05 P00387;P00387-2;P00387-3 P00387;P00387-2;P00387-3 NADH-cytochrome b5 reductase 3;NADH-cytochrome b5 reductase 3 membrane-bound form;NADH-cytochrome b5 reductase 3 soluble form CYB5R3 464 Desaturation and elongation of fatty acids, cholesterolbiosynthesis, drug metabolism, and, in erythrocyte, methemoglobinreduction. Cytoplasmic side. Mitochondrion outer membrane; Cytoplasmic side.Isoform 2: Cytoplasm. Note=Produces thesoluble form found in erythrocytes.;Isoform 1: Endoplasmic reticulum membrane;Lipid-anchor blood circulation;cholesterol biosynthetic process;L-ascorbic acid metabolic process;neutrophil degranulation ADP binding;AMP binding;cytochrome-b5 reductase activity, acting on NAD(P)H;FAD binding;NAD binding azurophil granule lumen;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;extracellular region;hemoglobin complex;lipid droplet;membrane;mitochondrial outer membrane;mitochondrion Amino sugar and nucleotide sugar metabolism Methemoglobinemia Neutrophil degranulation;Phase I - Functionalization of compounds;Vitamin C (ascorbate) metabolism -0.859634757041931 -0.362974286079407 -0.734053611755371 -0.773587763309479 -1.10150682926178 -1.14926362037659 -1.61388039588928 -1.30654442310333 0.343126326799393 0.165474086999893 0.605158090591431 0.111453197896481 1.11222922801971 1.03766930103302 1.03766930103302 0.821365177631378 1.33365046977997 1.33365046977997 + Cluster -671 14 14 11 39.1 39.1 36.1 45.374 0 232.66 230990000000 200 6.66888075874038 0 P55209;P55209-2;P55209-3 P55209;P55209-2;P55209-3 Nucleosome assembly protein 1-like 1 NAP1L1 1240 regulates RASSF10 expression by promotingSETD1A-mediated H3K4 methylation at the RASSF10 promoter (Bysimilarity).;Plays a key role in the regulation of embryonicneurogenesis (By similarity). Promotes the proliferation of neuralprogenitors and inhibits neuronal differentiation during corticaldevelopment (By similarity). Regulates neurogenesis via themodulation of RASSF10 Nucleus {ECO:0000269|PubMed:17081065}.Melanosome {ECO:0000269|PubMed:17081065}. Cytoplasm{ECO:0000250|UniProtKB:P28656}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV. DNA replication;nucleosome assembly;positive regulation of cell proliferation;positive regulation of neural precursor cell proliferation;positive regulation of neurogenesis RNA binding cytoplasm;melanosome;membrane;nucleus Nop56p-associated pre-rRNA complex -0.505537331104279 -0.640994787216187 -0.940117001533508 -1.45625805854797 -0.813307464122772 -0.729554235935211 -1.16833436489105 -1.16833436489105 -0.264025330543518 0.563839256763458 0.142729580402374 0.72116756439209 0.183004155755043 0.43859988451004 1.01688647270203 1.80013251304626 1.42338633537292 1.39671719074249 + Cluster -671 2 2 2 11.1 11.1 11.1 21.77 0 10.847 818360000 3 5.28402607229952 1.32450331125828E-05 Q9Y3D9 Q9Y3D9 28S ribosomal protein S23, mitochondrial MRPS23 3271 Mitochondrion {ECO:0000269|PubMed:25838379}. mitochondrial translational elongation;mitochondrial translational termination RNA binding;structural constituent of ribosome intermediate filament cytoskeleton;mitochondrial inner membrane;mitochondrion;nuclear membrane;ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial 0.47075691819191 -0.312114387750626 -1.43046963214874 -0.793349742889404 -1.43046963214874 -1.04753053188324 -0.762094795703888 -1.04753053188324 -0.793349742889404 0.519495964050293 0.519495964050293 -0.264659255743027 1.04379343986511 0.519495964050293 0.519495964050293 1.77920961380005 1.25491213798523 1.25491213798523 + Cluster -671 22 22 19 77.6 77.6 70.6 29.174 0 323.31 645280000000 609 4.98477979213552 2.17391304347826E-05 P62258;P62258-2 P62258;P62258-2 14-3-3 protein epsilon YWHAE 1342 Adapter protein implicated in the regulation of a largespectrum of both general and specialized signaling pathways. Bindsto a large number of partners, usually by recognition of aphosphoserine or phosphothreonine motif. Binding generally resultsin the modulation of the activity of the binding partner (Bysimilarity). Positively regulates phosphorylated protein HSF1nuclear export to the cytoplasm (PubMed:12917326) Nucleus {ECO:0000269|PubMed:12917326}.Cytoplasm {ECO:0000269|PubMed:12917326}. Melanosome{ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:17081065}.Note=Identified by mass spectrometry in melanosome fractions fromstage I to stage IV. {ECO:0000269|PubMed:12042314,ECO:0000269|PubMed:17081065}. cellular response to heat;ciliary basal body-plasma membrane docking;G2/M transition of mitotic cell cycle;hippo signaling;intracellular signal transduction;MAPK cascade;membrane organization;membrane repolarization during cardiac muscle cell action potential;negative regulation of calcium ion export across plasma membrane;negative regulation of calcium ion transmembrane transporter activity;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of peptidyl-serine dephosphorylation;positive regulation of protein export from nucleus;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;protein localization to nucleus;regulation of cellular response to heat;regulation of cytosolic calcium ion concentration;regulation of G2/M transition of mitotic cell cycle;regulation of heart rate by cardiac conduction;regulation of heart rate by hormone;regulation of membrane repolarization;regulation of postsynaptic membrane neurotransmitter receptor levels;regulation of potassium ion transmembrane transporter activity;substantia nigra development;viral process cadherin binding;calcium channel regulator activity;enzyme binding;histone deacetylase binding;identical protein binding;ion channel binding;MHC class II protein complex binding;phosphoprotein binding;phosphoserine residue binding;potassium channel regulator activity;protein domain specific binding;protein heterodimerization activity;Rab guanyl-nucleotide exchange factor activity;RNA binding;scaffold protein binding;ubiquitin protein ligase binding central region of growth cone;cytoplasm;cytosol;extracellular exosome;focal adhesion;glutamatergic synapse;kinesin complex;melanosome;membrane;mitochondrion;nucleus Cell cycle;Hepatitis C;Hippo signaling pathway;Neurotrophin signaling pathway;Oocyte meiosis;PI3K-Akt signaling pathway;Viral carcinogenesis Lissencephaly Activation of BAD and translocation to mitochondria;Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models;HSF1 activation;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;NADE modulates death signalling;RAB GEFs exchange GTP for GDP on RABs;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of HSF1-mediated heat shock response;Regulation of PLK1 Activity at G2/M Transition;RHO GTPases activate PKNs;Signaling by Hippo;TP53 Regulates Metabolic Genes;Translocation of SLC2A4 (GLUT4) to the plasma membrane BRAF-MAP2K1-MAP2K2-YWHAE complex;Emerin complex 25;Emerin complex 52;HSF1-YWHAE complex;Kinase maturation complex 1;MAP2K1-BRAF-RAF1-YWHAE-KSR1 complex;RAF1-MAP2K1-YWHAE complex 0.969826638698578 -1.31005394458771 -0.87291556596756 -1.12428534030914 -0.48590213060379 -1.32423067092896 -0.515320897102356 -1.32423067092896 -0.668485999107361 0.371257901191711 -0.174278259277344 -0.261746376752853 1.25438570976257 0.951549112796783 1.02261424064636 1.10343599319458 1.07099235057831 1.31738781929016 + Cluster -671 1 1 1 4.5 4.5 4.5 30.243 0 3.6008 403020000 3 4.09089704624406 0.000126506024096386 Q9BYD2 Q9BYD2 39S ribosomal protein L9, mitochondrial MRPL9 2717 Mitochondrion {ECO:0000269|PubMed:25278503,ECO:0000269|PubMed:25838379, ECO:0000269|PubMed:28892042}. mitochondrial translational elongation;mitochondrial translational termination;translation RNA binding;structural constituent of ribosome mitochondrial inner membrane;mitochondrial large ribosomal subunit;mitochondrial ribosome;mitochondrion Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 39S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial 0.312771677970886 -0.710900247097015 -0.836312890052795 -0.95042896270752 -1.29043126106262 -1.02026200294495 -1.51014673709869 -1.40391874313354 -0.236853629350662 0.487708389759064 0.510035812854767 0.446488469839096 0.542013108730316 0.612899661064148 1.3352130651474 1.12390792369843 1.19893765449524 1.3892787694931 + Cluster -671 6 6 6 24.6 24.6 24.6 27.887 0 82.984 5113200000 28 6.77162369955778 0 O14818;O14818-2;O14818-4;Q8TAA3;Q8TAA3-2;Q8TAA3-5 O14818;O14818-2;O14818-4 Proteasome subunit alpha type-7 PSMA7 137 Component of the 20S core proteasome complex involved inthe proteolytic degradation of most intracellular proteins. Thiscomplex plays numerous essential roles within the cell byassociating with different regulatory particles. Associated withtwo 19S regulatory particles, forms the 26S proteasome and thusparticipates in the ATP-dependent degradation of ubiquitinatedproteins. The 26S proteasome plays a key role in the maintenanceof protein homeostasis by removing misfolded or damaged proteinsthat could impair cellular functions, and by removing proteinswhose functions are no longer required. Associated with the PA200or PA28, the 20S proteasome mediates ubiquitin-independent proteindegradation. This type of proteolysis is required in severalpathways including spermatogenesis (20S-PA200 complex) orgeneration of a subset of MHC class I-presented antigenic peptides(20S-PA28 complex). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. Theinteraction with EMAP2 increases the proteasome-mediated HIF-1Adegradation under the hypoxic conditions. Plays a role inhepatitis C virus internal ribosome entry site-mediatedtranslation. Mediates nuclear translocation of the androgenreceptor (AR) and thereby enhances androgen-mediatedtransactivation. Promotes MAVS degradation and thereby negativelyregulates MAVS-mediated innate immune response;Component of the spermatoproteasome, a form of theproteasome specifically found in testis that promotes degradationof histones, thereby participating actively to the exchange ofhistones during spermatogenesis. The proteasome is amulticatalytic proteinase complex which is characterized by itsability to cleave peptides with Arg, Phe, Tyr, Leu, and Gluadjacent to the leaving group at neutral or slightly basic pH (Bysimilarity). Cytoplasm {ECO:0000250}. Nucleus{ECO:0000250}.;Cytoplasm {ECO:0000269|PubMed:12181345}.Nucleus {ECO:0000269|PubMed:12181345}. post-translational protein modification;proteasomal protein catabolic process;proteasomal ubiquitin-independent protein catabolic process;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination;viral process endopeptidase activity;identical protein binding;threonine-type endopeptidase activity cytoplasm;cytosol;extracellular exosome;nucleoplasm;nucleus;postsynapse;proteasome complex;proteasome core complex;proteasome core complex, alpha-subunit complex;spermatoproteasome complex Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 20S proteasome;26S proteasome;PA28-20S proteasome;PA28gamma-20S proteasome;PA700-20S-PA28 complex 0.281108021736145 -0.401823401451111 -0.980483055114746 -1.21115052700043 -0.980483055114746 -1.20719516277313 -1.29316663742065 -1.29316663742065 -0.590571224689484 0.339094161987305 0.454215079545975 0.083183690905571 0.996277868747711 1.07236087322235 0.848406255245209 1.31192982196808 1.2595340013504 1.31192982196808 + Cluster -671 2 2 2 18.9 18.9 18.9 11.986 0 8.9848 61717000 3 8.87661038039706 0 Q15004 Q15004 PCNA-associated factor KIAA0101 1747 PCNA-binding protein that acts as a regulator of DNArepair during DNA replication. Following DNA damage, theinteraction with PCNA is disrupted, facilitating the interactionbetween monoubiquitinated PCNA and the translesion DNA synthesisDNA polymerase eta (POLH) at stalled replisomes, facilitating thebypass of replication-fork-blocking lesions. Also acts as aregulator of centrosome number. Nucleus {ECO:0000269|PubMed:11313979,ECO:0000269|PubMed:16288740, ECO:0000269|PubMed:21673012,ECO:0000269|PubMed:23000965}. Cytoplasm, perinuclear region{ECO:0000269|PubMed:21673012}. Note=Following DNA damage,localizes to DNA damage sites (PubMed:21628590). Colocalizes withcentrosomes in perinuclear region (PubMed:21673012). cellular response to DNA damage stimulus;centrosome cycle;DNA replication;regulation of cell cycle;response to UV;translesion synthesis chromatin binding centrosome;nucleoplasm;nucleus;perinuclear region of cytoplasm Termination of translesion DNA synthesis p33ING1b-PCNA complex;PCNA-PAF complex -1.57189428806305 -1.64186978340149 -0.365853428840637 -0.316205948591232 -0.154718562960625 -1.16051518917084 -0.688813745975494 -1.02042031288147 -0.316205948591232 0.361062735319138 1.1089254617691 0.744834423065186 -0.122493028640747 0.416349679231644 0.361062735319138 1.33270597457886 1.53605782985687 1.49799132347107 + Cluster -671 38 38 38 33.1 33.1 33.1 157.9 0 323.31 75437000000 172 3.45967137391352 0.000462135922330097 P42704 P42704 Leucine-rich PPR motif-containing protein, mitochondrial LRPPRC 1018 May play a role in RNA metabolism in both nuclei andmitochondria. In the nucleus binds to HNRPA1-associated poly(A)mRNAs and is part of nmRNP complexes at late stages of mRNAmaturation which are possibly associated with nuclear mRNA export.May bind mature mRNA in the nucleus outer membrane. Inmitochondria binds to poly(A) mRNA. Plays a role in translation orstability of mitochondrially encoded cytochrome c oxidase (COX)subunits. May be involved in transcription regulation. Cooperateswith PPARGC1A to regulate certain mitochondrially encoded genesand gluconeogenic genes and may regulate docking of PPARGC1A totranscription factors. Seems to be involved in the transcriptionregulation of the multidrug-related genes MDR1 and MVP. Part of anuclear factor that binds to the invMED1 element of MDR1 and MVPgene promoters. Binds single-stranded DNA (By similarity) Mitochondrion. Nucleus, nucleoplasm. Nucleusinner membrane. Nucleus outer membrane. Note=Seems to bepredominantly mitochondrial. mitochondrion transport along microtubule;mRNA transport;negative regulation of mitochondrial RNA catabolic process;regulation of mitochondrial translation beta-tubulin binding;microtubule binding;RNA binding;single-stranded DNA binding;ubiquitin protein ligase binding condensed nuclear chromosome;cytoskeleton;membrane;microtubule;mitochondrial nucleoid;mitochondrion;nuclear inner membrane;nuclear outer membrane;nucleoplasm;nucleus;perinuclear region of cytoplasm;ribonucleoprotein complex Cytochrome c oxidase (COX) deficiency;Leigh syndrome Respiratory electron transport;TP53 Regulates Metabolic Genes TNF-alpha/NF-kappa B signaling complex 5 -1.57315504550934 -0.0506114698946476 -0.707442879676819 -0.493580967187881 -1.09676587581635 -0.962557911872864 -1.10504245758057 -1.15073645114899 -0.349508106708527 0.694993197917938 1.10963213443756 0.777348339557648 -0.19284750521183 0.275103002786636 0.554096937179565 1.1293511390686 1.69839251041412 1.44333148002625 + Cluster -671 5 5 5 32.5 32.5 32.5 29.668 0 38.876 9900300000 14 3.67111972981536 0.000324137931034483 P47985;P0C7P4 P47985;P0C7P4 Cytochrome b-c1 complex subunit Rieske, mitochondrial;Cytochrome b-c1 complex subunit 11;Putative cytochrome b-c1 complex subunit Rieske-like protein 1 UQCRFS1;UQCRFS1P1 1068 Cytochrome b-c1 complex subunit Rieske, mitochondrial:Component of the mitochondrial ubiquinol-cytochrome c reductasecomplex dimer (complex III dimer), which is a respiratory chainthat generates an electrochemical potential coupled to ATPsynthesis (PubMed:28673544). Incorporation of UQCRFS1 is thepenultimate step in complex III assembly (PubMed:28673544) Single-pass membrane protein{ECO:0000250|UniProtKB:Q5ZLR5}.;Mitochondrion inner membrane{ECO:0000250|UniProtKB:Q5ZLR5} mitochondrial electron transport, ubiquinol to cytochrome c;response to antibiotic;response to drug;response to hormone 2 iron, 2 sulfur cluster binding;metal ion binding;protein-containing complex binding;ubiquinol-cytochrome-c reductase activity integral component of membrane;mitochondrial inner membrane;mitochondrial respiratory chain complex III;mitochondrial respiratory chain complex IV;mitochondrion Alzheimer disease;Cardiac muscle contraction;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Thermogenesis Respiratory electron transport -1.81299448013306 -0.433089822530746 -0.640750646591187 -0.4930320084095 -0.885124683380127 -0.903812885284424 -1.09656190872192 -0.946743190288544 -0.413922697305679 0.344279736280441 0.29436782002449 0.698296070098877 0.344279736280441 0.723726391792297 0.542131364345551 1.34544706344604 1.72175288200378 1.61175131797791 + Cluster -671 9 9 9 54.9 54.9 54.9 22.168 0 202.54 79428000000 92 4.48773256198723 6.08365019011407E-05 P20290;P20290-2 P20290;P20290-2 Transcription factor BTF3 BTF3 740 When associated with NACA, prevents inappropriatetargeting of non-secretory polypeptides to the endoplasmicreticulum (ER). Binds to nascent polypeptide chains as they emergefrom the ribosome and blocks their interaction with the signalrecognition particle (SRP), which normally targets nascentsecretory peptides to the ER. BTF3 is also a general transcriptionfactor that can form a stable complex with RNA polymerase II.Required for the initiation of transcription Cytoplasm {ECO:0000269|PubMed:10982809}.Nucleus {ECO:0000269|PubMed:10982809}. Note=The heterodimer withNACA is cytoplasmic. in utero embryonic development;protein transport;transcription by RNA polymerase II RNA binding cytosol;nucleus -1.27787029743195 -0.582294464111328 -0.725939750671387 -0.908248484134674 -0.959916651248932 -1.20819318294525 -1.02281653881073 -0.977092921733856 -0.112304709851742 0.668905198574066 0.971618950366974 0.857182443141937 0.205660834908485 0.205660834908485 0.299068331718445 1.54498088359833 1.63154339790344 1.39005613327026 + Cluster -671 1 1 1 9.2 9.2 9.2 38.632 0 19.488 1884400000 3 4.46249398662485 6.39097744360902E-05 P09001 P09001 39S ribosomal protein L3, mitochondrial MRPL3 565 Mitochondrion {ECO:0000269|PubMed:25278503,ECO:0000269|PubMed:25838379, ECO:0000269|PubMed:28892042}. mitochondrial translational elongation;mitochondrial translational termination;translation RNA binding;structural constituent of ribosome mitochondrial inner membrane;mitochondrial large ribosomal subunit;mitochondrion Ribosome Combined oxidative phosphorylation deficiency Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 39S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -1.43799304962158 -0.880114614963531 -0.399174600839615 -0.268456786870956 -1.07568514347076 -0.981449365615845 -0.729374825954437 -0.776642739772797 -0.918421387672424 0.707558691501617 0.707558691501617 0.624371230602264 -0.0291803274303675 0.238591834902763 0.238591834902763 1.48989081382751 1.66827642917633 1.82165336608887 + Cluster -671 9 9 9 22 22 22 54.177 0 61.828 10709000000 26 3.78610821849978 0.000251851851851852 P09622;P09622-3;P09622-2 P09622;P09622-3;P09622-2 Dihydrolipoyl dehydrogenase, mitochondrial DLD 581 Lipoamide dehydrogenase is a component of the glycinecleavage system as well as an E3 component of three alpha-ketoaciddehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, andbranched-chain amino acid-dehydrogenase complex) (PubMed:15712224,PubMed:16442803, PubMed:16770810, PubMed:17404228,PubMed:20160912, PubMed:20385101). The 2-oxoglutaratedehydrogenase complex is mainly active in the mitochondrion(PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenasecomplex also localizes in the nucleus and is required for lysinesuccinylation of histones: associates with KAT2A on chromatin andprovides succinyl-CoA to histone succinyltransferase KAT2A(PubMed:29211711). In monomeric form may have additionalmoonlighting function as serine protease (PubMed:17404228).Involved in the hyperactivation of spermatazoa during capacitationand in the spermatazoal acrosome reaction (By similarity) Mitochondrion matrix{ECO:0000305|PubMed:29211711, ECO:0000305|PubMed:3693355}. Nucleus{ECO:0000269|PubMed:29211711}. Cell projection, cilium, flagellum{ECO:0000250|UniProtKB:Q811C4}. Cytoplasmic vesicle, secretoryvesicle, acrosome {ECO:0000269|PubMed:15888450}. Note=Mainlylocalizes in the mitochondrion. A small fraction localizes to thenucleus, where the 2-oxoglutarate dehydrogenase complex isrequired for histone succinylation. {ECO:0000269|PubMed:29211711}. 2-oxoglutarate metabolic process;aging;cell redox homeostasis;dihydrolipoamide metabolic process;gastrulation;histone succinylation;lipoate metabolic process;mitochondrial acetyl-CoA biosynthetic process from pyruvate;mitochondrial electron transport, NADH to ubiquinone;proteolysis;regulation of membrane potential;sperm capacitation dihydrolipoyl dehydrogenase activity;electron transfer activity;flavin adenine dinucleotide binding;lipoamide binding;NAD binding acrosomal matrix;mitochondrial matrix;mitochondrion;motile cilium;myelin sheath;nucleoplasm;nucleus;oxoglutarate dehydrogenase complex;pyruvate dehydrogenase complex Carbon metabolism;Citrate cycle (TCA cycle);Glycine, serine and threonine metabolism;Glycolysis / Gluconeogenesis;Glyoxylate and dicarboxylate metabolism;Lysine degradation;Metabolic pathways;Propanoate metabolism;Pyruvate metabolism;Tryptophan metabolism;Valine, leucine and isoleucine degradation Alpha-ketoglutarate dehydrogenase complex deficiency;Dihydrolipoamide dehydrogenase deficiency;Maple syrup urine disease;Pyruvate dehydrogenase complex deficiency Branched-chain amino acid catabolism;Citric acid cycle (TCA cycle);Glycine degradation;Glyoxylate metabolism and glycine degradation;Lysine catabolism;Pyruvate metabolism;Regulation of pyruvate dehydrogenase (PDH) complex;Signaling by Retinoic Acid KAT2A-Oxoglutarate dehydrogenase complex 0.487784206867218 0.0300089679658413 -2.2526683807373 -0.818369150161743 -1.25726878643036 -1.52318453788757 -0.80052524805069 -0.65472149848938 0.453686386346817 0.212963461875916 1.16288244724274 0.521526873111725 0.379951506853104 0.321168273687363 0.379951506853104 1.14390528202057 1.00095999240875 1.21194875240326 + Cluster -671 3 3 3 46.9 46.9 46.9 9.0564 0 67.064 15019000000 20 4.52237497672312 5.01930501930502E-05 Q9P1F3 Q9P1F3 Costars family protein ABRACL ABRACL 3046 regulation of actin filament-based process -0.867822527885437 0.572926223278046 -1.74339759349823 -1.20036840438843 -1.10539579391479 -1.00613927841187 -0.536946177482605 -0.784095466136932 -0.0135730160400271 -0.174884706735611 0.590062201023102 0.292827844619751 0.663236796855927 0.663236796855927 0.292827844619751 1.75291764736176 1.75291764736176 0.851670026779175 + Cluster -671 16 16 16 25 25 25 84.87 0 323.31 47763000000 90 3.89898994393253 0.000187830687830688 P02786 P02786 Transferrin receptor protein 1;Transferrin receptor protein 1, serum form TFRC 479 Cellular uptake of iron occurs via receptor-mediatedendocytosis of ligand-occupied transferrin receptor intospecialized endosomes. Endosomal acidification leads to ironrelease. The apotransferrin-receptor complex is then recycled tothe cell surface with a return to neutral pH and the concomitantloss of affinity of apotransferrin for its receptor. Transferrinreceptor is necessary for development of erythrocytes and thenervous system (By similarity). A second ligand, the heditaryhemochromatosis protein HFE, competes for binding with transferrinfor an overlapping C-terminal binding site. Positively regulates Tand B cell proliferation through iron uptake (PubMed:26642240) Cell membrane {ECO:0000269|PubMed:17081065};Single-pass type II membrane protein{ECO:0000269|PubMed:17081065}. Melanosome{ECO:0000269|PubMed:17081065}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV.{ECO:0000269|PubMed:17081065}.Transferrin receptor protein 1, serum form:Secreted {ECO:0000269|PubMed:17081065}. cellular iron ion homeostasis;cellular response to drug;cellular response to leukemia inhibitory factor;iron ion transport;membrane organization;osteoclast differentiation;positive regulation of B cell proliferation;positive regulation of bone resorption;positive regulation of isotype switching;positive regulation of T cell proliferation;receptor internalization;transferrin transport double-stranded RNA binding;identical protein binding;protein homodimerization activity;RNA binding;transferrin receptor activity;transferrin transmembrane transporter activity;virus receptor activity basolateral plasma membrane;blood microparticle;cell surface;clathrin-coated pit;clathrin-coated vesicle membrane;cytoplasmic vesicle;early endosome;endosome;endosome membrane;external side of plasma membrane;extracellular exosome;extracellular region;extracellular space;extracellular vesicle;HFE-transferrin receptor complex;integral component of plasma membrane;melanosome;membrane;perinuclear region of cytoplasm;plasma membrane;recycling endosome Endocytosis;Ferroptosis;Hematopoietic cell lineage;HIF-1 signaling pathway;Phagosome Cargo recognition for clathrin-mediated endocytosis;Clathrin-mediated endocytosis;Golgi Associated Vesicle Biogenesis;Transferrin endocytosis and recycling SNX complex (SNX1, SNX1a, TFRC);TF-TFRC complex -0.463163793087006 -0.0352085866034031 -1.92485082149506 -0.80834835767746 -0.661098837852478 -1.63727927207947 -1.07134914398193 -0.857232511043549 0.0717724934220314 0.0480458103120327 0.744210302829742 0.630178093910217 0.825179517269135 0.688038289546967 0.630178093910217 1.3640273809433 1.3640273809433 1.09287405014038 + Cluster -671 14 14 14 26.9 26.9 26.9 82.588 0 253.64 22087000000 74 5.66127898604326 9.00900900900901E-06 Q9NY33;Q9NY33-4;Q9NY33-2 Q9NY33;Q9NY33-4;Q9NY33-2 Dipeptidyl peptidase 3 DPP3 3004 Cleaves and degrades bioactive peptides, includingangiotensin, Leu-enkephalin and Met-enkephalin (PubMed:3233187,PubMed:1515063). Also cleaves Arg-Arg-beta-naphthylamide (invitro) (PubMed:9425109, PubMed:3233187, PubMed:11209758) Cytoplasm, cytosol{ECO:0000269|PubMed:1515063, ECO:0000269|PubMed:3233187}. proteolysis dipeptidyl-peptidase activity;metallopeptidase activity;zinc ion binding cytosol;extracellular exosome;nuclear speck;plasma membrane -0.663537979125977 0.0948678031563759 -1.5666207075119 -0.497299432754517 -0.989575684070587 -1.60841131210327 -1.44941711425781 -0.862105906009674 -0.0861234962940216 0.44622790813446 0.68786633014679 0.939968943595886 0.880034327507019 0.44622790813446 0.519648432731628 1.38331580162048 1.07371985912323 1.25121426582336 + Cluster -671 19 19 19 73.2 73.2 73.2 42.644 0 323.31 373310000000 331 5.77683003323522 1.01010101010101E-05 P12277;P06732 P12277 Creatine kinase B-type CKB 642 Reversibly catalyzes the transfer of phosphate betweenATP and various phosphogens (e.g. creatine phosphate). Creatinekinase isoenzymes play a central role in energy transduction intissues with large, fluctuating energy demands, such as skeletalmuscle, heart, brain and spermatozoa. Cytoplasm. cellular chloride ion homeostasis;cerebellum development;creatine metabolic process;phosphocreatine biosynthetic process;substantia nigra development ATP binding;creatine kinase activity;ubiquitin protein ligase binding cytosol;dendrite;extracellular exosome;extracellular space;myelin sheath;neuronal cell body;nucleus Arginine and proline metabolism;Metabolic pathways Creatine metabolism Emerin complex 52 0.209715217351913 0.681080996990204 -1.61011040210724 -0.570411682128906 -1.07595407962799 -1.8631865978241 -1.23892951011658 -0.948028266429901 -0.610976159572601 0.188314512372017 0.767281949520111 0.505413413047791 0.862418830394745 0.702768802642822 1.02395880222321 1.04840993881226 1.04840993881226 0.879824101924896 + Cluster -671 5 5 5 28.7 28.7 28.7 27.547 0 30.16 3406900000 15 5.74289072470904 9.9009900990099E-06 O95336 O95336 6-phosphogluconolactonase PGLS 421 Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate. Cytoplasm {ECO:0000250}. carbohydrate metabolic process;pentose-phosphate shunt;pentose-phosphate shunt, oxidative branch 6-phosphogluconolactonase activity cytosol;extracellular exosome Carbon metabolism;Metabolic pathways;Pentose phosphate pathway Pentose phosphate pathway 0.095078781247139 -0.302235454320908 -1.72359538078308 -0.867686569690704 -0.938693284988403 -1.30221843719482 -0.953393816947937 -1.39105236530304 0.358409374952316 0.422034740447998 1.00096940994263 -0.0763978958129883 0.747303009033203 0.606950640678406 0.945826888084412 0.410762846469879 1.33196699619293 1.63597059249878 + Cluster -671 1 1 1 0.7 0.7 0.7 191.89 0 4.2209 36937000 2 5.44677753626851 7.8125E-06 Q8N1W1;Q8N1W1-5;Q8N1W1-4;Q8N1W1-3;Q8N1W1-6 Q8N1W1;Q8N1W1-5;Q8N1W1-4;Q8N1W1-3;Q8N1W1-6 Rho guanine nucleotide exchange factor 28 ARHGEF28 2188 Functions as a RHOA-specific guanine nucleotide exchangefactor regulating signaling pathways downstream of integrins andgrowth factor receptors. Functions in axonal branching, synapseformation and dendritic morphogenesis. Functions also in focaladhesion formation, cell motility and B-lymphocytes activation.May regulate NEFL expression and aggregation and play a role inapoptosis (By similarity). Cytoplasm {ECO:0000250}. Cell membrane{ECO:0000250}. Note=Colocalizes with the microtubule radial andcortical systems. {ECO:0000250}. cell differentiation;ephrin receptor signaling pathway;intracellular signal transduction;regulation of Rho protein signal transduction guanyl-nucleotide exchange factor activity;metal ion binding;Rho guanyl-nucleotide exchange factor activity;RNA binding cytosol;plasma membrane Yersinia infection EPHB-mediated forward signaling -0.0672162175178528 0.259923338890076 -1.17328381538391 -1.22959744930267 -0.91671758890152 -1.73899984359741 -1.58755826950073 -0.696855425834656 0.696066737174988 -0.237095177173615 0.210920602083206 0.860339939594269 0.826492011547089 1.10661113262177 1.25607049465179 1.27764105796814 0.751016318798065 0.402242243289948 + Cluster -671 6 6 6 32.6 32.6 32.6 25.059 0 118.33 21536000000 41 5.67216240862908 9.17431192660551E-06 Q9UBQ5;Q9UBQ5-2 Q9UBQ5;Q9UBQ5-2 Eukaryotic translation initiation factor 3 subunit K EIF3K 3075 Component of the eukaryotic translation initiationfactor 3 (eIF-3) complex, which is required for several steps inthe initiation of protein synthesis (PubMed:17581632,PubMed:25849773, PubMed:27462815). The eIF-3 complex associateswith the 40S ribosome and facilitates the recruitment of eIF-1,eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNArecruitment to the 43S PIC and scanning of the mRNA for AUGrecognition. The eIF-3 complex is also required for disassemblyand recycling of post-termination ribosomal complexes andsubsequently prevents premature joining of the 40S and 60Sribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of asubset of mRNAs involved in cell proliferation, including cellcycling, differentiation and apoptosis, and uses different modesof RNA stem-loop binding to exert either translational activationor repression (PubMed:25849773). Nucleus {ECO:0000255|HAMAP-Rule:MF_03010,ECO:0000269|PubMed:15327989}. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03010, ECO:0000269|PubMed:15327989}. formation of cytoplasmic translation initiation complex;regulation of translational initiation;translational initiation ribosome binding;translation initiation factor activity cytosol;eukaryotic 43S preinitiation complex;eukaryotic 48S preinitiation complex;eukaryotic translation initiation factor 3 complex;membrane;nucleus Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Ribosomal scanning and start codon recognition;Translation initiation complex formation eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7);eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7, PCID1) -0.584982693195343 0.153534337878227 -1.58433294296265 -0.801585972309113 -1.22098779678345 -1.95303511619568 -0.600806593894958 -0.974316358566284 0.830610156059265 0.503074824810028 0.175718009471893 0.633979082107544 0.322830766439438 0.900814950466156 0.991692423820496 0.830610156059265 1.38326513767242 0.99391770362854 + Cluster -671 2 2 2 1.6 1.6 1.6 202.79 0 20.704 1332400000 7 4.82670986135373 2.34741784037559E-05 Q9NQT8 Q9NQT8 Kinesin-like protein KIF13B KIF13B 2901 Involved in reorganization of the cortical cytoskeleton.Regulates axon formation by promoting the formation of extraaxons. May be functionally important for the intracellulartrafficking of MAGUKs and associated protein complexes Cytoplasm, cytoskeleton{ECO:0000269|PubMed:20194617}. Cell projection, axon{ECO:0000269|PubMed:20194617}. Note=accumulates at the distal partof the microtubules in the tips of axons, but not of dendrites. microtubule-based movement;protein targeting;regulation of axonogenesis;signal transduction;T cell activation 14-3-3 protein binding;ATP binding;ATPase activity;microtubule binding;microtubule motor activity;protein kinase binding axon;cytoplasm;cytosol;kinesin complex;microtubule;microvillus;paranode region of axon COPI-dependent Golgi-to-ER retrograde traffic;Kinesins -0.313778012990952 0.157335013151169 -1.5482474565506 -0.796634256839752 -1.16306960582733 -1.67992520332336 -1.49618792533875 -0.86059957742691 0.587396383285522 0.70105642080307 0.848832428455353 0.0574967414140701 0.81493204832077 0.81493204832077 0.799452424049377 1.04169714450836 0.958773672580719 1.07653784751892 + Cluster -671 4 3 3 89.5 74.6 74.6 11.514 0 128.24 284580000000 163 6.82789249486895 0 P05386 P05386 60S acidic ribosomal protein P1 RPLP1 505 Plays an important role in the elongation step ofprotein synthesis. cytoplasmic translation;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational elongation;translational initiation protein kinase activator activity;ribonucleoprotein complex binding;structural constituent of ribosome cytosol;cytosolic large ribosomal subunit;focal adhesion Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle) 0.0143022052943707 -0.0513427071273327 -1.71862125396729 -1.13783442974091 -1.43030035495758 -1.29808485507965 -1.02427184581757 -0.818010628223419 0.995120942592621 0.670848071575165 1.17913675308228 -0.0792393758893013 0.457926958799362 0.287686794996262 0.62399435043335 1.01943898200989 1.34882414340973 0.960426270961761 + Cluster -671 7 7 7 37.7 37.7 37.7 26.72 0 60.55 11848000000 27 5.04532410021969 2.24719101123595E-05 Q92979 Q92979 Ribosomal RNA small subunit methyltransferase NEP1 EMG1 2372 S-adenosyl-L-methionine-dependent pseudouridine N(1)-methyltransferase that methylates pseudouridine at position 1248(Psi1248) in 18S rRNA. Involved the biosynthesis of thehypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine(m1acp3-Psi) conserved in eukaryotic 18S rRNA. Is not able tomethylate uridine at this position (PubMed:20047967). Has also anessential role in 40S ribosomal subunit biogenesis independent onits methyltransferase activity, facilitating the incorporation ofribosomal protein S19 during the formation of pre-ribosomes (Bysimilarity). Nucleus, nucleolus{ECO:0000269|PubMed:11935223}. blastocyst development;nucleologenesis;ribosomal small subunit biogenesis;rRNA base methylation;rRNA processing RNA binding;rRNA (pseudouridine) methyltransferase activity;rRNA binding cytoplasm;nucleolus;nucleoplasm;nucleus;small-subunit processome Ribosome biogenesis in eukaryotes Bowen-Conradi syndrome Major pathway of rRNA processing in the nucleolus and cytosol;rRNA modification in the nucleus and cytosol 0.0955405160784721 0.0404100939631462 -1.30914056301117 -1.04161882400513 -1.56622350215912 -1.02743828296661 -1.80717885494232 -0.574960350990295 0.619308054447174 0.658222198486328 1.25035583972931 0.349408090114594 -0.139009535312653 0.555115044116974 0.735473275184631 0.549825847148895 1.3308539390564 1.28105711936951 + Cluster -671 3 3 3 6.1 6.1 6.1 69.666 0.00033933 2.8657 63636000 3 4.75001835175923 2.63157894736842E-05 Q14145 Q14145 Kelch-like ECH-associated protein 1 KEAP1 1682 Acts as a substrate adapter protein for the E3 ubiquitinligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 forubiquitination and degradation by the proteasome, thus resultingin the suppression of its transcriptional activity and therepression of antioxidant response element-mediated detoxifyingenzyme gene expression. Retains NFE2L2/NRF2 and may also retainBPTF in the cytosol. Targets PGAM5 for ubiquitination anddegradation by the proteasome. Cytoplasm. Nucleus. Note=Shuttles betweencytoplasm and nucleus. cellular response to interleukin-4;cytoplasmic sequestering of transcription factor;in utero embryonic development;negative regulation of DNA-binding transcription factor activity;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;post-translational protein modification;proteasomal ubiquitin-independent protein catabolic process;protein deubiquitination;protein ubiquitination;regulation of epidermal cell differentiation;viral process disordered domain specific binding;protein homodimerization activity;transcription factor binding actin filament;Cul3-RING ubiquitin ligase complex;cytoplasm;cytosol;endoplasmic reticulum;microtubule organizing center;midbody;nucleoplasm Fluid shear stress and atherosclerosis;Hepatocellular carcinoma;Pathways in cancer;Ubiquitin mediated proteolysis Hepatocellular carcinoma Dimethyl fumarate Antigen processing: Ubiquitination & Proteasome degradation;Neddylation;Ub-specific processing proteases PGAM5-KEAP1-NRF2 complex;Ubiquitin E3 ligase (CUL3, KEAP1, RBX1) -0.313281148672104 -0.397671967744827 -1.1488471031189 -0.88158255815506 -0.88158255815506 -1.55789315700531 -1.41891026496887 -1.2058789730072 0.02184222266078 0.812602400779724 1.27706587314606 0.637766003608704 0.211380690336227 0.54524827003479 0.69858330488205 0.936111867427826 1.23499596118927 1.43005108833313 + Cluster -671 12 12 12 31.3 31.3 31.3 39.958 0 115.59 24041000000 65 6.50176657376197 0 Q00325-2;Q00325 Q00325-2;Q00325 Phosphate carrier protein, mitochondrial SLC25A3 1467 Transport of phosphate groups from the cytosol to themitochondrial matrix. Phosphate is cotransported with H(+). Mayplay a role regulation of the mitochondrial permeabilitytransition pore (mPTP). Multi-passmembrane protein.;Mitochondrion inner membrane phosphate ion transmembrane transport inorganic phosphate transmembrane transporter activity;phosphate:proton symporter activity;protein-containing complex binding extracellular exosome;integral component of mitochondrial inner membrane;integral component of plasma membrane;membrane;mitochondrial inner membrane;mitochondrion;myelin sheath Mitochondrial phosphate carrier deficiency ACTB-ANP32A-C1QBP-PSMA1-PTMA-PSMA1 complex;ProTalpha C5 complex -0.583808541297913 -0.256414294242859 -1.16897332668304 -0.73808890581131 -1.0538854598999 -1.70496773719788 -1.49479806423187 -0.95967972278595 0.298609167337418 0.693805575370789 1.11465549468994 0.489617526531219 0.478101789951324 0.610214233398438 0.773047804832458 1.05703282356262 0.948670387268066 1.49686133861542 + Cluster -671 2 2 2 17 17 17 20.7 0 31.897 5881900000 20 6.19250134967157 0 P55145 P55145 Mesencephalic astrocyte-derived neurotrophic factor MANF 1238 Selectively promotes the survival of dopaminergicneurons of the ventral mid-brain (PubMed:12794311). ModulatesGABAergic transmission to the dopaminergic neurons of thesubstantia nigra (By similarity). Enhances spontaneous, as well asevoked, GABAergic inhibitory postsynaptic currents in dopaminergicneurons (By similarity). Inhibits cell proliferation andendoplasmic reticulum (ER) stress-induced cell death(PubMed:18561914, PubMed:22637475, PubMed:29497057). Retained inthe ER/sarcoplasmic reticulum (SR) through association with theendoplasmic reticulum chaperone protein HSPA5 under normalconditions (PubMed:22637475). Up-regulated and secreted by theER/SR in response to ER stress and hypoxia (PubMed:22637475).Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cellmembrane of target cells (PubMed:29497057). Sulfatide bindingpromotes its cellular uptake by endocytosis, and is required forits role in alleviating ER stress and cell toxicity under hypoxicand ER stress conditions (PubMed:29497057) Secreted {ECO:0000269|PubMed:12794311,ECO:0000269|PubMed:18561914, ECO:0000269|PubMed:22637475,ECO:0000269|PubMed:29497057}. Endoplasmic reticulum lumen{ECO:0000305|PubMed:29497057}. Sarcoplasmic reticulum lumen{ECO:0000269|PubMed:22637475}. Note=Retained in the endoplasmicreticulum (ER), and sarcoplasmic reticulum (SR) under normalconditions (PubMed:22637475). Up-regulated and secreted by theER/SR in response to ER stress and hypoxia (PubMed:22637475,PubMed:29497057). {ECO:0000269|PubMed:22637475,ECO:0000269|PubMed:29497057}. dopaminergic neuron differentiation;neuron projection development;platelet degranulation;regulation of response to endoplasmic reticulum stress;response to unfolded protein growth factor activity;lipid binding;RNA binding cytosol;endoplasmic reticulum;endoplasmic reticulum lumen;extracellular region;extracellular space;nucleus;sarcoplasmic reticulum lumen Platelet degranulation -0.658088207244873 -0.186245322227478 -1.16604471206665 -0.722626924514771 -0.994972050189972 -1.61887860298157 -1.56627154350281 -1.03423917293549 0.596412599086761 1.02763307094574 1.24911618232727 0.541431546211243 0.228623509407043 0.586287975311279 0.586287975311279 0.641951084136963 1.26303195953369 1.22659051418304 + Cluster -671 11 11 10 51.6 51.6 48.4 24.763 0 220.39 207060000000 181 5.36154124536402 7.09219858156028E-06 P24534 P24534 Elongation factor 1-beta EEF1B2 792 EF-1-beta and EF-1-delta stimulate the exchange of GDPbound to EF-1-alpha to GTP. response to ethanol;translational elongation translation elongation factor activity cytoplasm;cytosol;eukaryotic translation elongation factor 1 complex Eukaryotic Translation Elongation -0.539524912834167 -0.236915022134781 -0.539524912834167 -0.659118950366974 -1.05392873287201 -1.95249879360199 -1.16821753978729 -1.36638021469116 0.265087842941284 1.31226074695587 1.42262828350067 0.72743833065033 -0.047836035490036 0.345183342695236 0.72743833065033 0.725439250469208 0.725439250469208 1.31302964687347 + Cluster -671 10 10 10 16.6 16.6 16.6 100.07 0 77.346 6927600000 22 4.85884422809811 1.93236714975845E-05 P35221;P35221-2;P35221-3;P26232;P26232-3;P26232-2;P26232-5;REV__Q9P2T0-2;REV__Q9P2T0;P26232-4;P26232-6 P35221;P35221-2;P35221-3 Catenin alpha-1 CTNNA1 922 Associates with the cytoplasmic domain of a variety ofcadherins. The association of catenins to cadherins produces acomplex which is linked to the actin filament network, and whichseems to be of primary importance for cadherins cell-adhesionproperties. Can associate with both E- and N-cadherins. Originallybelieved to be a stable component of E-cadherin/catenin adhesioncomplexes and to mediate the linkage of cadherins to the actincytoskeleton at adherens junctions. In contrast, cortical actinwas found to be much more dynamic than E-cadherin/catenincomplexes and CTNNA1 was shown not to bind to F-actin whenassembled in the complex suggesting a different linkage betweenactin and adherens junctions components. The homodimeric form mayregulate actin filament assembly and inhibit actin branching bycompeting with the Arp2/3 complex for binding to actin filaments.May play a crucial role in cell differentiation;May function as a linker between cadherin adhesionreceptors and the cytoskeleton to regulate cell-cell adhesion anddifferentiation in the nervous system. Regulates morphologicalplasticity of synapses and cerebellar and hippocampal laminationduring development. Functions in the control of startlemodulation. Cytoplasmic side. Cell junction. Note=Found at cell-cellboundaries and probably at cell-matrix boundaries.Isoform 3: Cell membrane{ECO:0000269|PubMed:21708131}; Cytoplasmic side{ECO:0000250|UniProtKB:Q61301}. Cytoplasm{ECO:0000269|PubMed:16182284}. Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:Q61301}. Cell junction, adherens junction{ECO:0000250|UniProtKB:Q61301}. Cell projection, axon{ECO:0000250|UniProtKB:Q61301}. Nucleus{ECO:0000269|PubMed:16182284}.; Cytoplasmic side{ECO:0000269|PubMed:21708131}.; Peripheral membrane protein{ECO:0000250|UniProtKB:Q61301}; Peripheral membrane protein{ECO:0000269|PubMed:21708131}; Peripheral membraneprotein;Cell membrane{ECO:0000250|UniProtKB:Q61301};Isoform 1: Cytoplasm, cytoskeleton. Celljunction, adherens junction. Cell membrane actin filament organization;adherens junction organization;aging;apical junction assembly;axon regeneration;axonogenesis;brain morphogenesis;cell adhesion;cell-cell adhesion;cellular protein localization;cellular response to indole-3-methanol;dendrite morphogenesis;epithelial cell-cell adhesion;establishment or maintenance of cell polarity;gap junction assembly;male gonad development;modification of postsynaptic actin cytoskeleton;negative regulation of cell motility;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand;negative regulation of integrin-mediated signaling pathway;negative regulation of neuroblast proliferation;odontogenesis of dentin-containing tooth;ovarian follicle development;positive regulation of extrinsic apoptotic signaling pathway in absence of ligand;positive regulation of muscle cell differentiation;positive regulation of smoothened signaling pathway;prepulse inhibition;protein heterooligomerization;radial glia guided migration of Purkinje cell;regulation of synapse structural plasticity;response to estrogen actin filament binding;beta-catenin binding;cadherin binding;gamma-catenin binding;identical protein binding;protein heterodimerization activity;RNA binding;structural constituent of cytoskeleton;structural molecule activity;vinculin binding acrosomal vesicle;actin cytoskeleton;adherens junction;axon;basolateral plasma membrane;catenin complex;cell junction;cell-cell adherens junction;cell-cell junction;cytoplasm;cytosol;extrinsic component of postsynaptic membrane;extrinsic component of presynaptic membrane;flotillin complex;focal adhesion;Golgi apparatus;hippocampal mossy fiber to CA3 synapse;intercalated disc;intracellular membrane-bounded organelle;lamellipodium;nucleus;parallel fiber to Purkinje cell synapse;plasma membrane;postsynaptic density, intracellular component;presynaptic active zone cytoplasmic component;zonula adherens Adherens junction;Arrhythmogenic right ventricular cardiomyopathy (ARVC);Bacterial invasion of epithelial cells;Endometrial cancer;Gastric cancer;Hippo signaling pathway;Leukocyte transendothelial migration;Pathways in cancer Pattern dystrophies of the retinal pigment epithelium Adherens junctions interactions;CDO in myogenesis;RHO GTPases activate IQGAPs;VEGFR2 mediated vascular permeability Cell-cell junction complex (ARHGAP10-CTNNA1);CTNNA1-CTNNB1 complex 0.168309554457664 -0.145161032676697 -1.51886343955994 -0.750085592269897 -1.23725807666779 -1.70641601085663 -1.44849157333374 -1.02395987510681 0.770939648151398 0.959274709224701 1.15197837352753 0.232738673686981 0.555542528629303 0.565325915813446 0.71401184797287 0.872217297554016 0.872217297554016 0.967679619789124 + Cluster -671 28 2 0 62.7 3.1 0 50.135 0 26.211 119760000000 153 6.57802277776723 0 Q71U36;Q71U36-2;P0DPH8;P0DPH7;P0DPH7-2;Q9NY65;Q9NY65-2;Q6PEY2 Q71U36;Q71U36-2;P0DPH8;P0DPH7;P0DPH7-2;Q9NY65;Q9NY65-2 Tubulin alpha-1A chain;Tubulin alpha-8 chain TUBA1A;TUBA8 2043 Tubulin is the major constituent of microtubules. Itbinds two moles of GTP, one at an exchangeable site on the betachain and one at a non-exchangeable site on the alpha chain (Bysimilarity).;Tubulin is the major constituent of microtubules. Itbinds two moles of GTP, one at an exchangeable site on the betachain and one at a non-exchangeable site on the alpha chain. Cytoplasm, cytoskeleton {ECO:0000250}.;Cytoplasm, cytoskeleton. cell division;ciliary basal body-plasma membrane docking;cytoskeleton-dependent intracellular transport;G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;microtubule-based process;mitotic cell cycle;regulation of G2/M transition of mitotic cell cycle;regulation of synapse organization GTP binding;GTPase activity;protein domain specific binding;structural constituent of cytoskeleton;structural molecule activity cytoplasm;cytoplasmic microtubule;cytoplasmic ribonucleoprotein granule;cytosol;extracellular exosome;membrane raft;microtubule;microtubule cytoskeleton;myelin sheath;neuromuscular junction;nucleus;recycling endosome Apoptosis;Gap junction;Pathogenic Escherichia coli infection;Phagosome;Tight junction Lissencephaly;Polymicrogyria Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;Carboxyterminal post-translational modifications of tubulin;Cilium Assembly;COPI-dependent Golgi-to-ER retrograde traffic;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;Formation of tubulin folding intermediates by CCT/TriC;Gap junction assembly;Hedgehog 'off' state;HSP90 chaperone cycle for steroid hormone receptors (SHR);Intraflagellar transport;Kinesins;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;MHC class II antigen presentation;Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane;Mitotic Prometaphase;Post-chaperonin tubulin folding pathway;Prefoldin mediated transfer of substrate to CCT/TriC;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Recycling pathway of L1;Regulation of PLK1 Activity at G2/M Transition;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;RHO GTPases activate IQGAPs;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;Translocation of SLC2A4 (GLUT4) to the plasma membrane 60S APC containing complex;FIB-associated protein complex;Nop56p-associated pre-rRNA complex;TBCD-tubulin(alpha)-tubulin(beta) complex;TBCE-TBCB-tubulin(alpha) complex -0.0788187459111214 -0.212602779269218 -1.49950969219208 -0.762448847293854 -1.21828210353851 -1.51218926906586 -1.5597163438797 -1.04287469387054 0.732903718948364 0.801072001457214 0.813189506530762 0.127255663275719 0.726751267910004 0.813189506530762 0.833317756652832 1.0259108543396 0.939266860485077 1.07358539104462 + Cluster -671 32 1 1 83.2 4.5 4.5 41.736 0 95.933 113490000000 179 7.04866864631269 0 P60709;Q6S8J3;A5A3E0;P0CG38;Q9BYX7 P60709 Actin, cytoplasmic 1;Actin, cytoplasmic 1, N-terminally processed ACTB 1276 Actin is a highly conserved protein that polymerizes toproduce filaments that form cross-linked networks in the cytoplasmof cells (PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing keyfunctions, such as cell motility and contraction(PubMed:29581253). In addition to their role in the cytoplasmiccytoskeleton, G- and F-actin also localize in the nucleus, andregulate gene transcription and motility and repair of damaged DNA(PubMed:29925947). Cytoplasm, cell cortex{ECO:0000269|PubMed:17101985}. Note=Colocalizes with actinfilaments.;Cytoplasm, cytoskeleton {ECO:0000250}.;Cytoplasm, cytoskeleton{ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:17289661}.Nucleus {ECO:0000269|PubMed:11687588,ECO:0000269|PubMed:29925947}. Note=Localized in cytoplasmic mRNPgranules containing untranslated mRNAs.{ECO:0000269|PubMed:17289661}. ATP-dependent chromatin remodeling;cell junction assembly;cell motility;cellular response to cytochalasin B;ephrin receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;membrane organization;negative regulation of protein binding;platelet aggregation;platelet degranulation;positive regulation of gene expression, epigenetic;positive regulation of norepinephrine uptake;postsynaptic actin cytoskeleton organization;protein deubiquitination;regulation of cyclin-dependent protein serine/threonine kinase activity;regulation of norepinephrine uptake;regulation of protein localization to plasma membrane;regulation of transmembrane transporter activity;retina homeostasis;substantia nigra development ATP binding;identical protein binding;kinesin binding;nitric-oxide synthase binding;protein kinase binding;structural constituent of cytoskeleton;structural constituent of postsynaptic actin cytoskeleton;Tat protein binding;tau protein binding actin cytoskeleton;blood microparticle;cell cortex;cytoplasm;cytoplasmic ribonucleoprotein granule;cytoskeleton;cytosol;dense body;extracellular exosome;extracellular region;extracellular space;focal adhesion;glutamatergic synapse;membrane;NuA4 histone acetyltransferase complex;nuclear chromatin;nucleoplasm;nucleus;plasma membrane;postsynaptic actin cytoskeleton;presynapse;protein-containing complex;ribonucleoprotein complex;vesicle Adherens junction;Apoptosis;Arrhythmogenic right ventricular cardiomyopathy (ARVC);Bacterial invasion of epithelial cells;Dilated cardiomyopathy (DCM);Fluid shear stress and atherosclerosis;Focal adhesion;Gastric acid secretion;Hepatocellular carcinoma;Hippo signaling pathway;Hypertrophic cardiomyopathy (HCM);Influenza A;Leukocyte transendothelial migration;Oxytocin signaling pathway;Pathogenic Escherichia coli infection;Phagosome;Platelet activation;Proteoglycans in cancer;Rap1 signaling pathway;Regulation of actin cytoskeleton;Salmonella infection;Shigellosis;Thermogenesis;Thyroid hormone signaling pathway;Tight junction;Vibrio cholerae infection;Viral myocarditis;Yersinia infection Baraitser-Winter syndrome;Juvenile-onset dystonia;Other phagocyte defects Adherens junctions interactions;B-WICH complex positively regulates rRNA expression;Cell-extracellular matrix interactions;Clathrin-mediated endocytosis;DNA Damage Recognition in GG-NER;EPHB-mediated forward signaling;EPH-ephrin mediated repulsion of cells;Factors involved in megakaryocyte development and platelet production;Folding of actin by CCT/TriC;Formation of annular gap junctions;Gap junction degradation;HATs acetylate histones;Interaction between L1 and Ankyrins;MAP2K and MAPK activation;Paradoxical activation of RAF signaling by kinase inactive BRAF;Platelet degranulation;Prefoldin mediated transfer of substrate to CCT/TriC;Recycling pathway of L1;Regulation of actin dynamics for phagocytic cup formation;RHO GTPases Activate Formins;RHO GTPases activate IQGAPs;RHO GTPases Activate WASPs and WAVEs;Signaling by BRAF and RAF fusions;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Signaling by RAS mutants;Translocation of SLC2A4 (GLUT4) to the plasma membrane;UCH proteinases;VEGFA-VEGFR2 Pathway ACTB-ANP32A-C1QBP-PSMA1-PTMA-PSMA1 complex;Alpha-dystrobrevin-ZO-1-actin complex;BAF complex;Cofilin-actin-CAP1 complex;CTGF/Hcs24-actin(beta/gamma) complex;Emerin architectural complex;Emerin complex 1;Emerin complex 25;Emerin complex 32;Emerin complex 52;Emerin regulatory complex;Emerin-actin-NMI complex;Emerin-actin-NMI-(alphaII)spectrin complex;LARC complex (LCR-associated remodeling complex);NUMAC complex (nucleosomal methylation activator complex);P2X7 receptor signalling complex;p400-associated complex;PBAF complex (Polybromo- and BAF containing complex);Pre-initiation complex (PIC);Profilin 2 complex;ProTalpha C2 complex;TLE1 corepressor complex (MASH1 promoter-corepressor complex) 0.0357855930924416 -0.0705235525965691 -1.38098037242889 -0.581798255443573 -1.32751619815826 -1.85754311084747 -1.35914373397827 -1.11904561519623 0.905291378498077 0.909894704818726 0.805957317352295 0.129020780324936 0.827256560325623 0.75369656085968 0.909894704818726 0.561840057373047 0.940575897693634 0.91733717918396 + Cluster -671 10 10 10 15.8 15.8 15.8 88.367 0 78.257 7809000000 25 6.18518884034693 0 P50416;P50416-2 P50416;P50416-2 Carnitine O-palmitoyltransferase 1, liver isoform CPT1A 1134 Catalyzes the transfer of the acyl group of long-chainfatty acid-CoA conjugates onto carnitine, an essential step forthe mitochondrial uptake of long-chain fatty acids and theirsubsequent beta-oxidation in the mitochondrion. Plays an importantrole in triglyceride metabolism. Multi-pass membrane protein {ECO:0000269|PubMed:11350182,ECO:0000269|PubMed:14517221}.;Mitochondrion outer membrane{ECO:0000269|PubMed:11350182, ECO:0000269|PubMed:14517221} carnitine metabolic process;carnitine shuttle;cellular response to fatty acid;circadian rhythm;eating behavior;epithelial cell differentiation;fatty acid beta-oxidation;glucose metabolic process;long-chain fatty acid metabolic process;positive regulation of fatty acid beta-oxidation;protein homooligomerization;regulation of insulin secretion;regulation of lipid metabolic process;response to drug;response to organic cyclic compound;triglyceride metabolic process carnitine O-palmitoyltransferase activity;identical protein binding;palmitoleoyltransferase activity integral component of mitochondrial outer membrane;membrane;mitochondrial outer membrane;mitochondrion Adipocytokine signaling pathway;AMPK signaling pathway;Fatty acid degradation;Fatty acid metabolism;Glucagon signaling pathway;Insulin resistance;PPAR signaling pathway;Thermogenesis Carnitine palmitoyltransferase I deficiency;Disorders of mitochondrial fatty-acid oxidation Oxfenicine;Perhexiline Import of palmitoyl-CoA into the mitochondrial matrix;PPARA activates gene expression;RORA activates gene expression;Signaling by Retinoic Acid -0.178717389702797 -0.450971782207489 -1.15300846099854 -0.155181482434273 -1.40605926513672 -1.80504679679871 -1.44028449058533 -1.15605878829956 0.688609957695007 0.843653440475464 0.77789968252182 0.353846609592438 0.801957249641418 0.353846609592438 1.27015554904938 0.933606207370758 0.622820854187012 1.09893226623535 + Cluster -671 1 1 1 10.6 10.6 10.6 14.234 0 3.3063 1639600000 4 4.85677104289629 1.92307692307692E-05 E9PRG8 E9PRG8 Uncharacterized protein C11orf98 C11orf98 60 0.0354026444256306 0.0774092376232147 -1.34024274349213 -0.961810886859894 -1.53465914726257 -1.43671083450317 -1.35704731941223 -1.08445763587952 0.629324674606323 1.0371470451355 1.0371470451355 0.370166569948196 0.222499117255211 0.49466598033905 0.716559827327728 0.728732883930206 1.10333859920502 1.26253473758698 + Cluster -671 10 10 10 59.3 59.3 59.3 15.55 0 233.13 199070000000 207 6.92711653048706 0 P08708 P08708 40S ribosomal protein S17 RPS17 561 erythrocyte homeostasis;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;ribosomal small subunit biogenesis;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;focal adhesion;membrane;nucleoplasm;ribosome Ribosome Diamond-Blackfan anemia Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic -0.358633548021317 -0.276579469442368 -1.48477673530579 -0.501913785934448 -1.0765073299408 -1.34692907333374 -1.81338107585907 -1.01298570632935 0.841793596744537 1.00932395458221 1.22999250888824 0.546214699745178 0.242248579859734 0.428255259990692 0.717260837554932 0.824958264827728 0.94059419631958 1.09106481075287 + Cluster -671 1 1 1 2 2 2 44.314 0.0015964 1.6406 356340000 3 5.16347019567548 1.82926829268293E-05 Q8NEZ2;Q8NEZ2-3;Q8NEZ2-2 Q8NEZ2;Q8NEZ2-3;Q8NEZ2-2 Vacuolar protein sorting-associated protein 37A VPS37A 2239 Component of the ESCRT-I complex, a regulator ofvesicular trafficking process. Required for the sorting ofendocytic ubiquitinated cargos into multivesicular bodies. May beinvolved in cell growth and differentiation Peripheral membraneprotein. Nucleus.;Late endosome membrane endosomal transport;endosome transport via multivesicular body sorting pathway;macroautophagy;multivesicular body assembly;protein targeting to membrane;protein targeting to vacuole;ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway;viral budding via host ESCRT complex;viral life cycle centrosome;cytosol;endosome membrane;ESCRT I complex;intracellular membrane-bounded organelle;late endosome membrane;nucleoplasm Endocytosis Hereditary spastic paraplegia Budding and maturation of HIV virion;Endosomal Sorting Complex Required For Transport (ESCRT);Membrane binding and targetting of GAG proteins -0.112823210656643 -0.0253491159528494 -1.2925341129303 -0.652899324893951 -1.07517063617706 -1.82028985023499 -1.646968126297 -1.13352203369141 0.510356187820435 0.978687763214111 0.939130783081055 0.308367401361465 0.85235071182251 0.732561886310577 0.789676249027252 0.890148758888245 0.84265547990799 0.915621221065521 + Cluster -671 12 2 2 25.2 7.4 7.4 49.775 0 99.607 218370000000 61 7.07528169658341 0 Q3ZCM7 Q3ZCM7 Tubulin beta-8 chain TUBB8 1889 Tubulin is the major constituent of microtubules. Itbinds two moles of GTP, one at an exchangeable site on the betachain and one at a non-exchangeable site on the alpha chain (Bysimilarity). TUBB8 has a key role in meiotic spindle assembly andoocyte maturation (PubMed:26789871). Cytoplasm, cytoskeleton{ECO:0000269|PubMed:26789871}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:26789871}. microtubule cytoskeleton organization;microtubule-based process;mitotic cell cycle;oocyte maturation;spindle assembly involved in female meiosis GTP binding;GTPase activity;structural constituent of cytoskeleton cytoplasm;extracellular exosome;meiotic spindle;microtubule Gap junction;Pathogenic Escherichia coli infection;Phagosome Oocyte maturation defect Batabulin;Brentuximab vedotin;Cabazitaxel;Cevipabulin;Colchicine;Denintuzumab mafodotin;Docetaxel;Enfortumab vedotin;Eribulin;Estramustine;Glembatumumab vedotin;Indibulin;Ixabepilone;Lexibulin;Lifastuzumab vedotin;Lisavanbulin;Maytansine;Mivobulin isethionate;Paclitaxel;Paclitaxel poliglumex;Podophyllotoxin;Soblidotin;Taltobulin;Tasidotin hydrochloride;Trastuzumab emtansine;Verubulin;Vinblastine;Vincristine;Vindesine;Vinepidine sulfate;Vinflunine;Vinglycinate sulfate;Vinleurosine sulfate;Vinorelbine;Vinrosidine sulfate;Vinzolidine sulfate Carboxyterminal post-translational modifications of tubulin;Cilium Assembly;COPI-dependent Golgi-to-ER retrograde traffic;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;Gap junction assembly;HSP90 chaperone cycle for steroid hormone receptors (SHR);Kinesins;MHC class II antigen presentation;Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane;Mitotic Prometaphase;Recruitment of NuMA to mitotic centrosomes;Recycling pathway of L1;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;RHO GTPases activate IQGAPs;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;Translocation of SLC2A4 (GLUT4) to the plasma membrane -0.583675026893616 -0.093206949532032 -1.18154990673065 -0.497945874929428 -1.25102090835571 -1.82376766204834 -1.35792005062103 -1.18591284751892 0.634554743766785 0.896647214889526 0.896647214889526 0.506609261035919 0.62180894613266 0.72584742307663 0.720064461231232 0.610949575901031 1.22200930118561 1.13986098766327 + Cluster -671 4 4 4 23.4 23.4 23.4 23.845 0 37.957 4161100000 23 5.85011114204495 1.08695652173913E-05 Q16763 Q16763 Ubiquitin-conjugating enzyme E2 S UBE2S 1862 Accepts ubiquitin from the E1 complex and catalyzes itscovalent attachment to other proteins (PubMed:22496338). Catalyzes'Lys-11'-linked polyubiquitination. Acts as an essential factor ofthe anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression throughmitosis. Acts by specifically elongating 'Lys-11'-linkedpolyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 onAPC/C substrates, enhancing the degradation of APC/C substrates bythe proteasome and promoting mitotic exit (PubMed:19820702,PubMed:19822757, PubMed:27259151). Also acts by elongatingubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro;it is however unclear whether UBE2D1/UBCH5 acts as an E2 enzymefor the APC/C in vivo. Also involved in ubiquitination andsubsequent degradation of VHL, resulting in an accumulation ofHIF1A (PubMed:16819549). In vitro able to promotepolyubiquitination using all 7 ubiquitin Lys residues, except'Lys-48'-linked polyubiquitination (PubMed:20061386,PubMed:20622874). anaphase-promoting complex-dependent catabolic process;cell division;cellular protein modification process;exit from mitosis;free ubiquitin chain polymerization;positive regulation of ubiquitin protein ligase activity;protein K11-linked ubiquitination;protein K27-linked ubiquitination;protein K29-linked ubiquitination;protein K63-linked ubiquitination;protein K6-linked ubiquitination;protein ubiquitination;ubiquitin-dependent protein catabolic process anaphase-promoting complex binding;ATP binding;ubiquitin conjugating enzyme activity;ubiquitin-protein transferase activity anaphase-promoting complex;cytosol;nucleoplasm Ubiquitin mediated proteolysis Antigen processing: Ubiquitination & Proteasome degradation;Synthesis of active ubiquitin: roles of E1 and E2 enzymes -0.0218527261167765 -0.533125460147858 -1.0940535068512 -0.802895307540894 -1.21282029151917 -1.3127965927124 -1.61115181446075 -1.35282695293427 0.87883585691452 0.983302712440491 1.3936220407486 0.279180079698563 0.478590130805969 0.490512758493423 0.651567757129669 0.854285001754761 0.918688893318176 1.01293742656708 + Cluster -671 2 2 2 43.3 43.3 43.3 10.061 0 28.399 6343100000 10 5.63278534494377 8.7719298245614E-06 Q13015 Q13015 Protein AF1q MLLT11 1585 Cofactor for the transcription factor TCF7(PubMed:26079538). Involved in regulation of lymphoid developmentby driving multipotent hematopoietic progenitor cells towards a Tcell fate (PubMed:21715312). Nucleus {ECO:0000269|PubMed:21715312,ECO:0000269|PubMed:26079538}. Cytoplasm{ECO:0000269|PubMed:21715312, ECO:0000269|PubMed:26079538}.Cytoplasm, cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:21715312}. Note=Continuous nuclear export isfollowed by degradation. {ECO:0000269|PubMed:21715312}. extrinsic apoptotic signaling pathway;intrinsic apoptotic signaling pathway;positive regulation of apoptotic process;positive regulation of mitochondrial depolarization;positive regulation of release of cytochrome c from mitochondria;positive regulation of transcription, DNA-templated cytosol;intracellular;microtubule organizing center;nucleoplasm -0.131085693836212 -0.0351964682340622 -1.10506069660187 -0.556777060031891 -0.87099826335907 -1.86589729785919 -2.01226568222046 -0.933471381664276 0.345446020364761 0.748805999755859 1.13312256336212 0.498801499605179 0.970488309860229 0.515677690505981 0.944744288921356 0.747398614883423 1.05596530437469 0.550301969051361 + Cluster -671 4 4 4 4.2 4.2 4.2 146.2 0 19.705 1553300000 10 5.61849239968075 8.54700854700855E-06 O60271;O60271-2;O60271-9;O60271-4;O60271-5;O60271-3 O60271;O60271-2;O60271-9;O60271-4;O60271-5;O60271-3 C-Jun-amino-terminal kinase-interacting protein 4 SPAG9 261 The JNK-interacting protein (JIP) group of scaffoldproteins selectively mediates JNK signaling by aggregatingspecific components of the MAPK cascade to form a functional JNKsignaling module. Isoform 5 may play a role in spermatozoa-egg-interaction. Cytoplasm. Cytoplasm, perinuclear region.Note=Perinuclear distribution in response to stress signals suchas UV radiation.Isoform 5: Cytoplasmic vesicle, secretoryvesicle, acrosome. Note=Associated with the plasma membrane of theacrosomal compartment and also localizes in the acrosome matrix. activation of JUN kinase activity;positive regulation of cell migration;positive regulation of muscle cell differentiation;positive regulation of neuron differentiation;protein homooligomerization;retrograde transport, endosome to Golgi;striated muscle cell differentiation;vesicle-mediated transport JUN kinase binding;kinesin binding;MAP-kinase scaffold activity;receptor signaling complex scaffold activity acrosomal vesicle;cytoplasm;cytosol;extracellular exosome;microtubule organizing center;perinuclear region of cytoplasm CDO in myogenesis CHUK-NFKB2-REL-IKBKG-SPAG9-NFKB1-NFKBIE-COPB2-TNIP1-NFKBIA-RELA-TNIP2 complex -0.015340318903327 -0.178294390439987 -1.04512548446655 -0.97767186164856 -1.11426424980164 -1.37648022174835 -1.61394381523132 -1.51992642879486 0.567835807800293 0.73662143945694 1.24305391311646 0.215887844562531 0.777631342411041 0.880799770355225 0.656343519687653 1.09710204601288 0.901437282562256 0.764333724975586 + Cluster -671 6 6 6 15.5 15.5 15.5 58.805 0 66.73 5196000000 22 7.32811932373688 0 P49643;P49643-2 P49643 DNA primase large subunit PRIM2 1108 DNA primase is the polymerase that synthesizes small RNAprimers for the Okazaki fragments made during discontinuous DNAreplication. DNA replication, synthesis of RNA primer;G1/S transition of mitotic cell cycle;telomere maintenance via semi-conservative replication 4 iron, 4 sulfur cluster binding;DNA primase activity;metal ion binding;single-stranded DNA binding alpha DNA polymerase:primase complex;nucleoplasm DNA replication Activation of the pre-replicative complex;DNA replication initiation;Inhibition of replication initiation of damaged DNA by RB1/E2F1;Polymerase switching;Polymerase switching on the C-strand of the telomere;Processive synthesis on the lagging strand;Removal of the Flap Intermediate;Telomere C-strand synthesis initiation DNA polymerase alpha-primase complex;DNA synthesome complex (13 subunits);DNA synthesome complex (15 subunits);DNA synthesome complex (17 subunits);DNA synthesome core complex 0.0242353808134794 0.0242353808134794 -1.31758320331573 -0.800303936004639 -1.31758320331573 -1.45949923992157 -1.76992070674896 -0.815326333045959 1.11496222019196 1.35027182102203 0.81652444601059 -0.103908121585846 1.00095891952515 0.565383732318878 0.415601164102554 0.757317185401917 0.757317185401917 0.757317185401917 + Cluster -671 23 23 23 64.7 64.7 64.7 43.786 0 323.31 226530000000 319 5.03171477445931 2.23463687150838E-05 Q9UQ80;Q9UQ80-2 Q9UQ80;Q9UQ80-2 Proliferation-associated protein 2G4 PA2G4 3209 May play a role in a ERBB3-regulated signal transductionpathway. Seems be involved in growth regulation. Acts acorepressor of the androgen receptor (AR) and is regulated by theERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcriptionof some E2F1-regulated promoters, probably by recruiting histoneacetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and5.8S mature rRNAs, several rRNA precursors and probably U3 smallnucleolar RNA. May be involved in regulation of intermediate andlate steps of rRNA processing. May be involved in ribosomeassembly. Mediates cap-independent translation of specific viralIRESs (internal ribosomal entry site) (By similarity). Regulatescell proliferation, differentiation, and survival. Isoform 1suppresses apoptosis whereas isoform 2 promotes celldifferentiation (By similarity). Isoform 1: Cytoplasm{ECO:0000269|PubMed:16832058, ECO:0000269|PubMed:19037095}.Nucleus, nucleolus {ECO:0000269|PubMed:16832058,ECO:0000269|PubMed:19037095}. Note=Translocates to the nucleusupon treatment with HRG. Phosphorylation at Ser-361 by PKC/PRKCDregulates its nucleolar localization.{ECO:0000269|PubMed:16832058}.Isoform 2: Cytoplasm{ECO:0000269|PubMed:16832058, ECO:0000269|PubMed:19037095}. cell cycle arrest;cell proliferation;negative regulation of apoptotic process;negative regulation of transcription, DNA-templated;neutrophil degranulation;positive regulation of cell differentiation;regulation of translation;ribosomal large subunit export from nucleus;rRNA processing DNA binding;DNA-binding transcription factor activity;RNA binding;ubiquitin protein ligase binding azurophil granule lumen;cytoplasm;extracellular exosome;extracellular region;membrane;nucleolus;nucleus Neutrophil degranulation -0.142273023724556 0.15597066283226 -1.5462406873703 -1.0952410697937 -1.15890681743622 -1.29718589782715 -0.894133687019348 -0.951622843742371 0.591042697429657 1.63459646701813 0.265669643878937 -0.794514715671539 0.762657701969147 0.417049795389175 0.857460975646973 1.069291472435 1.15314722061157 0.973231911659241 + Cluster -671 18 18 6 52.4 52.4 16.7 37.512 0 288.03 87580000000 133 4.04885209553477 0.000132743362831858 P62136;P62136-2;P62136-3 P62136;P62136-2;P62136-3 Serine/threonine-protein phosphatase PP1-alpha catalytic subunit PPP1CA 1333 Protein phosphatase that associates with over 200regulatory proteins to form highly specific holoenzymes whichdephosphorylate hundreds of biological targets. Proteinphosphatase 1 (PP1) is essential for cell division, andparticipates in the regulation of glycogen metabolism, musclecontractility and protein synthesis. Involved in regulation ofionic conductances and long-term synaptic plasticity. May play animportant role in dephosphorylating substrates such as thepostsynaptic density-associated Ca(2+)/calmodulin dependentprotein kinase II. Component of the PTW/PP1 phosphatase complex,which plays a role in the control of chromatin structure and cellcycle progression during the transition from mitosis intointerphase. Regulates NEK2 function in terms of kinase activityand centrosome number and splitting, both in the presence andabsence of radiation-induced DNA damage. Regulator of neural tubeand optic fissure closure, and enteric neural crest cell (ENCCs)migration during development. In balance with CSNK1D and CSNK1E,determines the circadian period length, through the regulation ofthe speed and rhythmicity of PER1 and PER2 phosphorylation. Maydephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418'residue of FOXP3 in regulatory T-cells (Treg) from patients withrheumatoid arthritis, thereby inactivating FOXP3 and renderingTreg cells functionally defective (PubMed:23396208).Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323) Cytoplasm. Nucleus. Nucleus, nucleoplasm.Nucleus, nucleolus. Note=Primarily nuclear and largely excludedfrom the nucleolus. Highly mobile in cells and can be relocalizedthrough interaction with targeting subunits. NOM1 plays a role intargeting this protein to the nucleolus. In the presence of PPP1R8relocalizes from the nucleus to nuclear speckles. beta-catenin destruction complex disassembly;branching morphogenesis of an epithelial tube;cell cycle;cell division;circadian regulation of gene expression;dephosphorylation;entrainment of circadian clock by photoperiod;glycogen metabolic process;lung development;negative regulation of protein binding;peptidyl-serine dephosphorylation;peptidyl-threonine dephosphorylation;positive regulation of extrinsic apoptotic signaling pathway in absence of ligand;protein dephosphorylation;regulation of canonical Wnt signaling pathway;regulation of circadian rhythm;regulation of glycogen biosynthetic process;regulation of glycogen catabolic process;regulation of translational initiation by eIF2 alpha dephosphorylation;response to lead ion cadherin binding involved in cell-cell adhesion;metal ion binding;phosphatase activity;phosphoprotein phosphatase activity;protein phosphatase 1 binding;protein serine/threonine phosphatase activity;ribonucleoprotein complex binding cell-cell adherens junction;cytoplasm;cytosol;dendritic spine;extracellular exosome;glutamatergic synapse;glycogen granule;nucleolus;nucleoplasm;nucleus;perikaryon;plasma membrane;presynapse;protein phosphatase type 1 complex;PTW/PP1 phosphatase complex Adrenergic signaling in cardiomyocytes;Alcoholism;Amphetamine addiction;cAMP signaling pathway;Cellular senescence;cGMP-PKG signaling pathway;Dopaminergic synapse;Focal adhesion;Herpes simplex virus 1 infection;Hippo signaling pathway;Inflammatory mediator regulation of TRP channels;Insulin resistance;Insulin signaling pathway;Long-term potentiation;mRNA surveillance pathway;Oocyte meiosis;Oxytocin signaling pathway;Platelet activation;Proteoglycans in cancer;Regulation of actin cytoskeleton;Vascular smooth muscle contraction Circadian Clock;DARPP-32 events;Downregulation of TGF-beta receptor signaling;Triglyceride catabolism CDC5L complex;KCNQ1 macromolecular complex;PNUTS-PP1 complex;PPP1CA-PPP1R13L complex 0.589048266410828 0.091614805161953 -1.35771214962006 -0.760795056819916 -1.4351065158844 -1.97205853462219 -1.34025704860687 -0.623595118522644 1.20443475246429 1.23252761363983 1.17330396175385 0.233690842986107 0.59596848487854 0.143089234828949 0.557345926761627 0.435083210468292 0.4563227891922 0.777094483375549 + Cluster -671 5 5 5 41 41 41 17 0 25.368 1230600000 9 5.15216394221582 1.80722891566265E-05 P41223;P41223-2 P41223;P41223-2 Protein BUD31 homolog BUD31 996 may increase AR transcriptionalactivity (PubMed:25091737).;Involved in the pre-mRNA splicing process(PubMed:28502770, PubMed:28076346). May play a role as regulatorof AR transcriptional activity Nucleus {ECO:0000269|PubMed:25091737,ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.Note=Detected in chromatin at the promoter of AR target genes.{ECO:0000305|PubMed:25091737}. mRNA splicing, via spliceosome;positive regulation of androgen receptor activity nuclear hormone receptor binding;nuclear receptor transcription coactivator activity nucleoplasm;nucleus;spliceosomal complex;U2-type catalytic step 2 spliceosome Spliceosome mRNA Splicing - Major Pathway Spliceosome 0.2630495429039 -0.30704653263092 -1.40415000915527 -0.889411747455597 -1.46454906463623 -1.34145414829254 -1.3737633228302 -1.01946306228638 0.980998873710632 1.24081516265869 1.15873980522156 -0.0515229068696499 0.544872522354126 0.274232655763626 0.567539632320404 0.939421772956848 1.00605809688568 0.875632643699646 + Cluster -671 5 5 5 25.2 25.2 25.2 23.662 0 81.002 7418200000 16 5.28690912561138 1.34228187919463E-05 P09496-2;P09496;P09496-4;P09496-3;P09496-5 P09496-2;P09496;P09496-4;P09496-3 Clathrin light chain A CLTA 579 Clathrin is the major protein of the polyhedral coat ofcoated pits and vesicles. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization ofkinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:21297582) Cytoplasmic side. Cytoplasm,cytoskeleton, spindle {ECO:0000269|PubMed:21297582,ECO:0000305|PubMed:15858577}. Note=Cytoplasmic face of coated pitsand vesicles. In complex with TACC3 and CKAP5 (forming theTACC3/ch-TOG/clathrin complex) localized to inter-microtubulebridges in mitotic spindles. {ECO:0000305}.; Cytoplasmic side. Membrane, coated pit; Peripheralmembrane protein;Cytoplasmic vesicle membrane;Peripheral membrane protein antigen processing and presentation of exogenous peptide antigen via MHC class II;cell cycle;cell division;clathrin coat assembly;clathrin-dependent endocytosis;intracellular protein transport;low-density lipoprotein particle clearance;low-density lipoprotein particle receptor catabolic process;membrane organization clathrin heavy chain binding;GTPase binding;peptide binding;protein-containing complex binding;structural molecule activity clathrin coat;clathrin coat of coated pit;clathrin coat of trans-Golgi network vesicle;clathrin complex;clathrin vesicle coat;clathrin-coated endocytic vesicle;cytoplasmic vesicle;cytosol;endolysosome membrane;membrane;plasma membrane;postsynaptic endocytic zone cytoplasmic component;presynaptic endocytic zone membrane;spindle;synaptic vesicle membrane;trans-Golgi network membrane Bacterial invasion of epithelial cells;Endocrine and other factor-regulated calcium reabsorption;Endocytosis;Huntington disease;Lysosome;Synaptic vesicle cycle Cargo recognition for clathrin-mediated endocytosis;Clathrin-mediated endocytosis;Entry of Influenza Virion into Host Cell via Endocytosis;EPH-ephrin mediated repulsion of cells;Formation of annular gap junctions;Gap junction degradation;Golgi Associated Vesicle Biogenesis;LDL clearance;Lysosome Vesicle Biogenesis;MHC class II antigen presentation;Recycling pathway of L1;Retrograde neurotrophin signalling;VLDLR internalisation and degradation;WNT5A-dependent internalization of FZD2, FZD5 and ROR2;WNT5A-dependent internalization of FZD4 0.0933776795864105 -0.247162237763405 -1.50360667705536 -0.945152282714844 -1.13473737239838 -1.58272910118103 -1.36831283569336 -1.05173575878143 0.95987606048584 1.05532145500183 0.717886209487915 -0.101236194372177 0.816654860973358 0.912774920463562 0.601395189762115 0.90910804271698 1.00767052173615 0.860607624053955 + Cluster -671 1 1 1 4.4 4.4 4.4 24.817 0 8.0331 1555800000 6 6.17009781764565 0 P00846 P00846 ATP synthase subunit a MT-ATP6 474 it may play a direct role in the translocation ofprotons across the membrane.;Mitochondrial membrane ATP synthase (F(1)F(0) ATPsynthase or Complex V) produces ATP from ADP in the presence of aproton gradient across the membrane which is generated by electrontransport complexes of the respiratory chain. F-type ATPasesconsist of two structural domains, F(1) - containing theextramembraneous catalytic core and F(0) - containing the membraneproton channel, linked together by a central stalk and aperipheral stalk. During catalysis, ATP synthesis in the catalyticdomain of F(1) is coupled via a rotary mechanism of the centralstalk subunits to proton translocation. Key component of theproton channel Multi-passmembrane protein.;Mitochondrion inner membrane aging;ATP biosynthetic process;ATP hydrolysis coupled cation transmembrane transport;ATP synthesis coupled proton transport;cristae formation;mitochondrial ATP synthesis coupled proton transport;response to hyperoxia proton transmembrane transporter activity;transmembrane transporter activity integral component of membrane;mitochondrial inner membrane;mitochondrial proton-transporting ATP synthase complex;proton-transporting ATP synthase complex;proton-transporting ATP synthase complex, coupling factor F(o) Alzheimer disease;Huntington disease;Metabolic pathways;Oxidative phosphorylation;Parkinson disease;Thermogenesis ATP synthase deficiency;Infantile bilateral striatal necrosis;Kearns-Sayre syndrome;Leber hereditary optic atrophy;NARP syndrome Cristae formation;Formation of ATP by chemiosmotic coupling F1F0-ATP synthase, mitochondrial 0.0891501903533936 -0.931737124919891 -1.18009376525879 -1.00692629814148 -0.576726496219635 -1.33375954627991 -1.54795730113983 -1.15292978286743 1.50790739059448 1.44875955581665 0.476095229387283 -0.117805458605289 1.04641580581665 0.532104015350342 0.649114370346069 0.699462950229645 0.699462950229645 0.699462950229645 + Cluster -671 16 6 6 44.6 19.8 19.8 32.852 0 43.361 24718000000 36 3.322518217765 0.000580246913580247 P05141;Q9H0C2 P05141 ADP/ATP translocase 2;ADP/ATP translocase 2, N-terminally processed SLC25A5 501 Catalyzes the exchange of cytoplasmic ADP withmitochondrial ATP across the mitochondrial inner membrane. As partof the mitotic spindle-associated MMXD complex it may play a rolein chromosome segregation.;Catalyzes the exchange of cytoplasmic ADP withmitochondrial ATP across the mitochondrial inner membrane. Mayserve to mediate energy generating and energy consuming processesin the distal flagellum, possibly as a nucleotide shuttle betweenflagellar glycolysis, protein phosphorylation and mechanisms ofmotility. Multi-passmembrane protein.; Multi-passmembrane protein. Cell projection, cilium, flagellum. Note=Insperm flagellum this protein is located in the fibrous sheath, anon-mitochondrial region.;Mitochondrion inner membrane cellular response to leukemia inhibitory factor;chromosome segregation;negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;positive regulation of cell proliferation;regulation of insulin secretion;viral process adenine transmembrane transporter activity;ATP:ADP antiporter activity;RNA binding;ubiquitin protein ligase binding integral component of membrane;integral component of plasma membrane;membrane;membrane raft;mitochondrial inner membrane;mitochondrial nucleoid;mitochondrion;MMXD complex;motile cilium;myelin sheath;nucleus Calcium signaling pathway;Cellular senescence;cGMP-PKG signaling pathway;Human T-cell leukemia virus 1 infection;Huntington disease;Influenza A;Necroptosis;Parkinson disease Regulation of insulin secretion;Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization ANP32A-ANP32B-PSMA3-PTMA-SLC25A5 complex;MMXD complex;Nop56p-associated pre-rRNA complex;prohibitin 2 complex, mitochondrial -0.395960688591003 -0.0132860504090786 -1.27199769020081 -0.726664125919342 -0.624991595745087 -2.10355830192566 -1.2145231962204 -1.15228402614594 0.780886173248291 1.17652678489685 1.00123381614685 -0.269715845584869 0.708496928215027 1.05976831912994 0.794012784957886 0.627285242080688 0.954594612121582 0.670176982879639 + Cluster -671 7 7 7 41.4 41.4 41.4 15.423 0 76.234 51525000000 77 4.35924336751652 6.87285223367698E-05 P62847;P62847-2;P62847-3;P62847-4 P62847;P62847-2;P62847-3;P62847-4 40S ribosomal protein S24 RPS24 1371 Required for processing of pre-rRNA and maturation of40S ribosomal subunits. erythrocyte homeostasis;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;ribosomal small subunit biogenesis;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome;translation initiation factor binding cytosol;cytosolic small ribosomal subunit;membrane;nucleoplasm;nucleus;small ribosomal subunit Ribosome Diamond-Blackfan anemia Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic -0.176186352968216 0.00457516871392727 -1.55455005168915 -0.7292839884758 -0.906890690326691 -1.63470995426178 -1.24736225605011 -1.22170162200928 0.753879904747009 1.32565999031067 0.565225541591644 -0.407917141914368 0.88249933719635 0.749833822250366 0.988495767116547 0.692648768424988 1.08560240268707 0.830181360244751 + Cluster -671 9 9 9 64.1 64.1 64.1 18.681 0 291.01 29072000000 58 5.09777140994467 1.72413793103448E-05 Q9H773 Q9H773 dCTP pyrophosphatase 1 DCTPP1 2813 Hydrolyzes deoxynucleoside triphosphates (dNTPs) to thecorresponding nucleoside monophosphates. Has a strong preferencefor dCTP and its analogs including 5-iodo-dCTP and 5-methyl-dCTPfor which it may even have a higher efficiency. May protect DNA orRNA against the incorporation of these genotoxic nucleotideanalogs through their catabolism. Mitochondrion {ECO:0000269|PubMed:24467396}.Nucleus {ECO:0000269|PubMed:24467396}. Cytoplasm, cytosol{ECO:0000269|PubMed:24467396}. dCTP catabolic process;DNA protection;nucleoside triphosphate catabolic process;protein homotetramerization dCTP diphosphatase activity;identical protein binding;magnesium ion binding;nucleoside-triphosphate diphosphatase activity;pyrimidine deoxyribonucleotide binding cytosol;mitochondrion;nucleus Metabolic pathways;Pyrimidine metabolism Interconversion of nucleotide di- and triphosphates -0.199983507394791 -0.257921010255814 -1.202467918396 -0.346864432096481 -1.00172388553619 -2.32358431816101 -1.31239426136017 -0.763386964797974 0.687386453151703 0.836195886135101 0.668617188930511 -0.167510807514191 1.12096703052521 0.897746026515961 1.0434045791626 0.756786465644836 0.89337283372879 0.671360611915588 + Cluster -671 5 5 5 20.1 20.1 20.1 34.063 0 91.474 8629100000 15 4.34691714583462 6.8259385665529E-05 O43765 O43765 Small glutamine-rich tetratricopeptide repeat-containing protein alpha SGTA 242 Co-chaperone that binds misfolded and hydrophobicpatches-containing client proteins in the cytosol. Mediates theirtargeting to the endoplasmic reticulum but also regulates theirsorting to the proteasome when targeting fails (PubMed:28104892).Functions in tail-anchored/type II transmembrane proteins membraneinsertion constituting with ASNA1 and the BAG6 complex a targetingmodule (PubMed:28104892). Functions upstream of the BAG6 complexand ASNA1, binding more rapidly the transmembrane domain of newlysynthesized proteins (PubMed:28104892, PubMed:25535373). It isalso involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interactionwith BAG6: collaborates with the BAG6 complex to maintainhydrophobic substrates in non-ubiquitinated states(PubMed:23129660, PubMed:25179605). Competes with RNF126 forinteraction with BAG6, preventing the ubiquitination of clientproteins associated with the BAG6 complex (PubMed:27193484). Bindsdirectly to HSC70 and HSP70 and regulates their ATPase activity(PubMed:18759457). Cytoplasm {ECO:0000269|PubMed:16580629}.Nucleus {ECO:0000269|PubMed:16580629}. Note=Co-localizes withHSP90AB1 in the cytoplasm. Increased nuclear accumulation seenduring cell apoptosis. {ECO:0000269|PubMed:16580629}. chaperone-mediated protein folding;negative regulation of ER-associated ubiquitin-dependent protein catabolic process;negative regulation of ubiquitin-dependent protein catabolic process;positive regulation of chaperone-mediated protein folding;positive regulation of ER-associated ubiquitin-dependent protein catabolic process;posttranslational protein targeting to endoplasmic reticulum membrane;tail-anchored membrane protein insertion into ER membrane;ubiquitin-dependent ERAD pathway;viral process BAT3 complex binding;identical protein binding;protein self-association;protein-containing complex scaffold activity cytoplasm;cytosol;extrinsic component of synaptic vesicle membrane;membrane;nucleus;TRC complex -0.363012850284576 -0.0776119083166122 -1.29803705215454 -0.363012850284576 -1.1669614315033 -1.83138632774353 -1.61095559597015 -0.785491108894348 0.629281640052795 0.449665278196335 1.12774777412415 -0.103466250002384 1.27902817726135 0.58039778470993 0.894477844238281 0.951528131961823 1.10297572612762 0.584832966327667 + Cluster -671 1 1 1 2 2 2 50.197 0.0012858 1.7403 305150000 2 4.69619966865674 3.00429184549356E-05 O75530;O75530-2;O75530-3 O75530;O75530-2;O75530-3 Polycomb protein EED EED 341 Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3,leading to transcriptional repression of the affected target gene.Also recognizes 'Lys-26' trimethylated histone H1 with the effectof inhibiting PRC2 complex methyltransferase activity onnucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognitionhas the opposite effect, enabling the propagation of thisrepressive mark. The PRC2/EED-EZH2 complex may also serve as arecruiting platform for DNA methyltransferases, thereby linkingtwo epigenetic repression systems. Genes repressed by thePRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A Nucleus. Chromosome. Note=Transientlycolocalizes with XIST at inactive X chromosomes. cellular response to leukemia inhibitory factor;chromatin silencing;histone H3-K27 methylation;negative regulation of G0 to G1 transition;negative regulation of gene expression, epigenetic;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;positive regulation of histone H3-K27 methylation;regulation of adaxial/abaxial pattern formation;regulation of gene expression by genetic imprinting;spinal cord development chromatin binding;histone methyltransferase activity;identical protein binding;RNA polymerase II proximal promoter sequence-specific DNA binding cytosol;ESC/E(Z) complex;nucleoplasm;nucleus;pronucleus;sex chromatin Activation of anterior HOX genes in hindbrain development during early embryogenesis;Oxidative Stress Induced Senescence;PKMTs methylate histone lysines;PRC2 methylates histones and DNA;Regulation of PTEN gene transcription;Transcriptional Regulation by E2F6 CUL4A-DDB1-EED complex;EED-EZH polycomb complex;EED-EZH2 complex;EED-EZH2-PHF19 complex;EED-EZH-YY1 polycomb complex;Ezh2 methyltransferase complex, cytosolic;HIC1-PCL3L-PCR2 complex;Polycomb repressive complex 2 (PRC 2);Polycomb repressive complex 4 -0.200892090797424 -0.49602335691452 -1.0143461227417 -0.526026904582977 -0.749894976615906 -1.56731402873993 -1.75262212753296 -1.63892793655396 0.716215252876282 0.763199985027313 1.18974566459656 0.821515917778015 0.683223843574524 0.715407192707062 0.785768449306488 1.05112159252167 0.591396570205688 0.628453195095062 + Cluster -671 4 4 4 9.7 9.7 9.7 65.459 0 47.365 2516400000 11 5.52439572436808 8.19672131147541E-06 O94925-3;O94925 O94925-3;O94925 Glutaminase kidney isoform, mitochondrial GLS 395 Catalyzes the first reaction in the primary pathway forthe renal catabolism of glutamine. Plays a role in maintainingacid-base homeostasis. Regulates the levels of theneurotransmitter glutamate in the brain. Isoform 2 lacks catalyticactivity. Isoform 1: Cytoplasm, cytosol.Isoform 3: Mitochondrion. cellular amino acid biosynthetic process;chemical synaptic transmission;glutamate biosynthetic process;glutamate secretion;glutamine catabolic process;protein homotetramerization;regulation of respiratory gaseous exchange by neurological system process;suckling behavior glutaminase activity cytosol;mitochondrial matrix;mitochondrion Alanine, aspartate and glutamate metabolism;Arginine biosynthesis;Central carbon metabolism in cancer;D-Glutamine and D-glutamate metabolism;GABAergic synapse;Glutamatergic synapse;Metabolic pathways;MicroRNAs in cancer;Proximal tubule bicarbonate reclamation Amino acid synthesis and interconversion (transamination);Glutamate Neurotransmitter Release Cycle;TP53 Regulates Metabolic Genes 0.134730339050293 -0.454638808965683 -0.963029801845551 -0.742563486099243 -0.87687885761261 -1.67402863502502 -1.69310593605042 -1.42199444770813 0.156022980809212 1.21281743049622 0.862385213375092 0.800950169563293 0.481387168169022 0.692531585693359 0.739065527915955 1.23386633396149 0.629590690135956 0.882892489433289 + Cluster -671 2 2 2 6.9 6.9 6.9 41.28 0 11.912 577490000 5 6.78485660406156 0 P82650 P82650 28S ribosomal protein S22, mitochondrial MRPS22 1439 Mitochondrion {ECO:0000269|PubMed:25838379}. mitochondrial translational elongation;mitochondrial translational termination structural constituent of ribosome mitochondrial inner membrane;mitochondrial ribosome;mitochondrial small ribosomal subunit;mitochondrion Combined oxidative phosphorylation deficiency Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -0.00925970263779163 -0.0454211682081223 -0.792490422725677 -0.93338006734848 -0.93338006734848 -1.81557524204254 -1.31815659999847 -1.65907192230225 -0.162015795707703 0.545064389705658 0.796222865581512 0.720464885234833 1.01251351833344 0.855135798454285 0.863379895687103 1.19499826431274 0.945222735404968 0.735748529434204 + Cluster -671 4 4 4 29.9 29.9 29.9 22.521 0 49.295 6907700000 13 7.91646836925293 0 Q9NPD8 Q9NPD8 Ubiquitin-conjugating enzyme E2 T UBE2T 2881 Accepts ubiquitin from the E1 complex and catalyzes itscovalent attachment to other proteins. Catalyzesmonoubiquitination. Involved in mitomycin-C (MMC)-induced DNArepair. Acts as a specific E2 ubiquitin-conjugating enzyme for theFanconi anemia complex by associating with E3 ubiquitin-proteinligase FANCL and catalyzing monoubiquitination of FANCD2, a keystep in the DNA damage pathway (PubMed:16916645, PubMed:17938197,PubMed:19111657, PubMed:19589784, PubMed:28437106). Also mediatesmonoubiquitination of FANCL and FANCI (PubMed:16916645,PubMed:17938197, PubMed:19111657, PubMed:19589784). May contributeto ubiquitination and degradation of BRCA1 (PubMed:19887602). Invitro able to promote polyubiquitination using all 7 ubiquitin Lysresidues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:20061386) Nucleus {ECO:0000269|PubMed:17938197,ECO:0000269|PubMed:19887602}. Note=Accumulates to chromatin. cellular response to DNA damage stimulus;DNA repair;interstrand cross-link repair;protein autoubiquitination;protein K11-linked ubiquitination;protein K27-linked ubiquitination;protein K29-linked ubiquitination;protein K48-linked ubiquitination;protein K63-linked ubiquitination;protein K6-linked ubiquitination;protein monoubiquitination;protein ubiquitination ATP binding;chromatin binding;ubiquitin conjugating enzyme activity;ubiquitin protein ligase binding;ubiquitin-protein transferase activity nucleolus;nucleoplasm;nucleus Fanconi anemia pathway Fanconi anemia Fanconi Anemia Pathway;Synthesis of active ubiquitin: roles of E1 and E2 enzymes -0.177133575081825 0.527121901512146 -0.683400928974152 -0.683400928974152 -1.29506695270538 -1.64983761310577 -1.64983761310577 -1.64983761310577 0.215998902916908 0.962525308132172 0.394130021333694 0.962525308132172 0.705253005027771 0.962525308132172 0.962525308132172 0.527121901512146 0.784394204616547 0.784394204616547 + Cluster -671 53 53 53 67.7 67.7 67.7 82.431 0 323.31 1115700000000 976 6.48388509503415 0 Q92499;Q92499-2;Q92499-3 Q92499;Q92499-2;Q92499-3 ATP-dependent RNA helicase DDX1 DDX1 2323 Acts as an ATP-dependent RNA helicase, able to unwindboth RNA-RNA and RNA-DNA duplexes. Possesses 5' single-strandedRNA overhang nuclease activity. Possesses ATPase activity onvarious RNA, but not DNA polynucleotides. May play a role in RNAclearance at DNA double-strand breaks (DSBs), thereby facilitatingthe template-guided repair of transcriptionally active regions ofthe genome. Together with RELA, acts as a coactivator to enhanceNF-kappa-B-mediated transcriptional activation. Acts as a positivetranscriptional regulator of cyclin CCND2 expression. Binds to thecyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds topoly(A) RNA. May be involved in 3'-end cleavage andpolyadenylation of pre-mRNAs. Component of the tRNA-splicingligase complex required to facilitate the enzymatic turnover ofcatalytic subunit RTCB: together with archease (ZBTB8OS), acts byfacilitating the guanylylation of RTCB, a key intermediate step intRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of acascade of antiviral responses including the induction ofproinflammatory cytokines via the adapter molecule TICAM1.Specifically binds (via helicase ATP-binding domain) on both shortand long poly(I:C) dsRNA (By similarity) Nucleus. Cytoplasm. Cytoplasmic granule.Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q91VR5}. Mitochondrion{ECO:0000250|UniProtKB:Q91VR5}. Note=Localized with MBNL1, TIAL1and YBX1 in stress granules upon stress. Localized with CSTF2 incleavage bodies. Forms large aggregates called DDX1 bodies.Relocalized into multiple foci (IR-induced foci or IRIF) after IRtreatment, a process that depends on the presence of chromosomalDNA and/or RNA-DNA duplexes. Relocalized at sites of DNA double-strand breaks (DSBs) in an ATM-dependent manner after IRtreatment. Colocalized with RELA in the nucleus upon TNF-alphainduction. Enters into the nucleus in case of active transcriptionwhile it accumulates in cytosol when transcription level is low(PubMed:24608264). Colocalizes in the cytosol with DDX21, DHX36and TICAM1. Colocalizes in the mitochondria with TICAM1 andpoly(I:C) RNA ligand. The multi-helicase-TICAM1 complex maytranslocate to the mitochondria upon poly(I:C) stimulation (Bysimilarity). {ECO:0000250|UniProtKB:Q91VR5,ECO:0000269|PubMed:24608264}.Cytoplasm {ECO:0000269|PubMed:20573827}.Note=(Microbial infection) Relocalized to the cytoplasm with aperinuclear staining pattern in avian infectious bronchitis virus(IBV)-infected cells (PubMed:20573827). Required for properlocalization of HIV-1 Rev (PubMed:15567440).{ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:20573827}. defense response to virus;DNA duplex unwinding;double-strand break repair;innate immune response;multicellular organism development;nucleic acid phosphodiester bond hydrolysis;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of myeloid dendritic cell cytokine production;protein localization to cytoplasmic stress granule;regulation of translational initiation;response to exogenous dsRNA;spliceosomal complex assembly;tRNA splicing, via endonucleolytic cleavage and ligation ATP binding;ATP-dependent helicase activity;chromatin binding;DNA binding;DNA/RNA helicase activity;double-stranded RNA binding;exonuclease activity;nuclease activity;poly(A) binding;RNA binding;RNA helicase activity;transcription coregulator activity cleavage body;cytoplasm;cytoplasmic stress granule;cytosol;membrane;mitochondrion;nucleoplasm;nucleus;ribonucleoprotein complex;tRNA-splicing ligase complex tRNA processing in the nucleus Large Drosha complex;tRNA Splicing Ligase Complex -0.0642168298363686 -0.0642168298363686 -0.644920527935028 0.0132293757051229 -0.593753576278687 -2.01171612739563 -1.60866796970367 -1.85801661014557 -0.0784064009785652 0.801309466362 0.701174855232239 0.505701780319214 1.12322127819061 1.1415981054306 1.20538902282715 0.372702538967133 0.635482907295227 0.424105554819107 + Cluster -671 7 7 7 6.6 6.6 6.6 191.58 0 56.058 1795800000 13 3.84509051175507 0.000227390180878553 Q7LBC6;Q7LBC6-2;Q7LBC6-3 Q7LBC6;Q7LBC6-2 Lysine-specific demethylase 3B KDM3B 2065 Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code.Demethylation of Lys residue generates formaldehyde and succinate.May have tumor suppressor activity. Nucleus {ECO:0000250}. histone H3-K9 demethylation;response to cisplatin antioxidant activity;chromatin DNA binding;dioxygenase activity;histone demethylase activity;histone demethylase activity (H3-K9 specific);metal ion binding;transcription regulatory region sequence-specific DNA binding chromatin;nucleoplasm;nucleus Thermogenesis HDMs demethylate histones 0.126754865050316 -0.241080895066261 -0.523024439811707 -0.763950109481812 -0.941166460514069 -1.60988700389862 -1.80996191501617 -1.60488784313202 -0.150333777070045 0.55670577287674 1.159059882164 0.561712443828583 1.10059630870819 0.673545479774475 0.973101675510406 1.01257836818695 0.652797400951385 0.827440142631531 + Cluster -671 5 5 5 16.3 16.3 16.3 45.566 0 55.862 4269400000 17 6.18075716483381 0 P51398;P51398-2;P51398-3 P51398;P51398-2;P51398-3 28S ribosomal protein S29, mitochondrial DAP3 1152 Involved in mediating interferon-gamma-induced celldeath. Mitochondrion {ECO:0000269|PubMed:11162496,ECO:0000269|PubMed:20563667}. apoptotic signaling pathway;mitochondrial translational elongation;mitochondrial translational termination GTP binding;RNA binding;structural constituent of ribosome mitochondrial inner membrane;mitochondrial small ribosomal subunit;mitochondrion;nucleoplasm Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -0.247771665453911 -0.165505215525627 -1.22657096385956 -0.513700008392334 -1.06160640716553 -1.80588853359222 -1.35677659511566 -1.31053447723389 0.12235152721405 0.636782169342041 0.477970480918884 0.278567969799042 1.22228181362152 0.946695625782013 0.91090452671051 1.22980511188507 0.899847030639648 0.963147699832916 + Cluster -671 7 7 7 17.6 17.6 17.6 52.891 0 45.483 5287400000 21 7.69584009624448 0 P50579;P50579-3;P50579-2 P50579;P50579-3;P50579-2 Methionine aminopeptidase 2 METAP2 1141 Cotranslationally removes the N-terminal methionine fromnascent proteins. The N-terminal methionine is often cleaved whenthe second residue in the primary sequence is small and uncharged(Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalyticactivity of human METAP2 toward Met-Val peptides is consistentlytwo orders of magnitude higher than that of METAP1, suggestingthat it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo.Protects eukaryotic initiation factor EIF2S1 fromtranslation-inhibiting phosphorylation by inhibitory kinases suchas EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in theregulation of protein synthesis. Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03175,ECO:0000269|PubMed:21537465}. Note=About 30% of expressed METAP2associates with polysomes. N-terminal protein amino acid modification;peptidyl-methionine modification;protein initiator methionine removal;protein processing;regulation of rhodopsin mediated signaling pathway aminopeptidase activity;metal ion binding;metalloaminopeptidase activity;metalloexopeptidase activity;RNA binding cytoplasm;cytosol;plasma membrane Inactivation, recovery and regulation of the phototransduction cascade 0.0583525560796261 0.0223517548292875 -1.05866885185242 -1.09017956256866 -1.11065983772278 -1.60491192340851 -1.48326754570007 -1.23338091373444 0.103791683912277 0.31309574842453 0.242548823356628 0.518940627574921 1.0086225271225 1.13779246807098 1.10053169727325 0.918328404426575 1.19493782520294 0.961774528026581 + Cluster -671 16 16 16 29.2 29.2 29.2 90.069 0 215.78 24385000000 83 11.1946427814469 0 P23921 P23921 Ribonucleoside-diphosphate reductase large subunit RRM1 791 Provides the precursors necessary for DNA synthesis.Catalyzes the biosynthesis of deoxyribonucleotides from thecorresponding ribonucleotides. Cytoplasm. cell proliferation in forebrain;deoxyribonucleotide biosynthetic process;DNA replication;male gonad development;mitotic cell cycle;protein heterotetramerization;pyrimidine nucleobase metabolic process;response to ionizing radiation;retina development in camera-type eye ATP binding;disordered domain specific binding;identical protein binding;ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor cell projection;cytosol;neuronal cell body;nuclear envelope;ribonucleoside-diphosphate reductase complex Drug metabolism - other enzymes;Glutathione metabolism;Metabolic pathways;Purine metabolism;Pyrimidine metabolism Caracemide;Cladribine;Clofarabine;Fludarabine;Gemcitabine;Tezacitabine Interconversion of nucleotide di- and triphosphates -0.360116809606552 -0.169800013303757 -0.637647032737732 -0.637647032737732 -0.749626874923706 -1.3547123670578 -1.84573006629944 -1.72047901153564 -0.160164326429367 0.715730547904968 1.02994394302368 0.173905938863754 1.26930463314056 0.697186291217804 1.03485345840454 0.950741469860077 0.82273006439209 0.941527247428894 + Cluster -671 2 2 2 21.2 21.2 21.2 17.417 0 9.7612 3789200000 9 5.84799522858458 1.0752688172043E-05 O14561 O14561 Acyl carrier protein, mitochondrial NDUFAB1 116 Carrier of the growing fatty acid chain in fatty acidbiosynthesis (By similarity). Accessory and non-catalytic subunitof the mitochondrial membrane respiratory chain NADH dehydrogenase(Complex I), which functions in the transfer of electrons fromNADH to the respiratory chain (PubMed:27626371) Mitochondrion {ECO:0000269|PubMed:12611891,ECO:0000269|PubMed:28892042}. fatty acid biosynthetic process;lipid A biosynthetic process;mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;protein lipoylation acyl binding;acyl carrier activity;calcium ion binding;fatty acid binding;NADH dehydrogenase (ubiquinone) activity;phosphopantetheine binding cytosol;mitochondrial inner membrane;mitochondrial matrix;mitochondrial membrane;mitochondrial respiratory chain complex I;mitochondrion;nucleoplasm Alzheimer disease;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Retrograde endocannabinoid signaling;Thermogenesis Complex I biogenesis;Glyoxylate metabolism and glycine degradation;Mitochondrial Fatty Acid Beta-Oxidation;Respiratory electron transport Respiratory chain complex I (beta subunit) mitochondrial;Respiratory chain complex I (holoenzyme), mitochondrial 0.390564858913422 -0.323132932186127 -1.30796658992767 -1.05167746543884 -0.995959222316742 -1.37134504318237 -1.27669167518616 -1.54880654811859 0.085389070212841 0.521764874458313 0.286949694156647 0.595073342323303 1.09898030757904 0.595073342323303 1.09898030757904 1.32226228713989 0.833567917346954 1.04697358608246 + Cluster -671 4 4 4 11.3 11.3 11.3 52.259 0 40.923 4571600000 13 8.66608908468819 0 O95864;O95864-3;O95864-4;O95864-2 O95864;O95864-3 Fatty acid desaturase 2 FADS2 449 Acts as a fatty acyl-coenzyme A (CoA) desaturase thatintroduces a cis double bond at carbon 6 of the fatty acyl chain.Involved in biosynthesis of highly unsaturated fatty acids (HUFA)from the essential polyunsaturated fatty acids (PUFA) linoleicacid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3)precursors. Catalyzes the first and rate limiting step in thispathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively (PubMed:12713571). Subsequently, in thebiosynthetic pathway of HUFA n-3 series, desaturatestetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3),which is then converted to docosahexaenoate (DHA)(22:6n-3), animportant lipid for nervous system function (By similarity).Desaturates palmitate to produce the mono-unsaturated fatty acidsapienate, the most abundant fatty acid in sebum(PubMed:12713571). Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathwayof LA (18:2n-6) (By similarity). Multi-pass membrane protein {ECO:0000305}.;Endoplasmic reticulum membrane{ECO:0000305} alpha-linolenic acid metabolic process;linoleic acid metabolic process;unsaturated fatty acid biosynthetic process linoleoyl-CoA desaturase activity;stearoyl-CoA 9-desaturase activity endoplasmic reticulum membrane;integral component of plasma membrane;membrane alpha-Linolenic acid metabolism;Biosynthesis of unsaturated fatty acids;Fatty acid metabolism;Metabolic pathways;PPAR signaling pathway alpha-linolenic acid (ALA) metabolism;Linoleic acid (LA) metabolism 0.0166185665875673 0.0725683569908142 -1.11932742595673 -0.623733937740326 -0.695029556751251 -1.48352146148682 -1.52871870994568 -1.85497307777405 0.217690214514732 0.72141021490097 0.960793972015381 -0.189695701003075 1.17595100402832 0.990979552268982 1.20777904987335 0.73760598897934 0.808653354644775 0.584949672222137 + Cluster -671 5 5 5 25.3 25.3 25.3 24.347 0 22.126 3599000000 11 5.638848602467 8.84955752212389E-06 Q9UL25 Q9UL25 Ras-related protein Rab-21 RAB21 3157 Regulates integrin internalization and recycling, butdoes not influence the traffic of endosomally translocatedreceptors in general (By similarity). As a result, may regulatecell adhesion and migration (By similarity). During the mitosis ofadherent cells, controls the endosomal trafficking of integrinswhich is required for the successful completion of cytokinesis(PubMed:18804435). Involved in neurite growth (By similarity).Following SBF2/MTMT13-mediated activation in response tostarvation-induced autophagy, binds to and regulates SNARE proteinVAMP8 endolysosomal transport required for SNARE-mediatedautophagosome-lysosome fusion (PubMed:25648148) in polarized cells, observed in vesicles in the apicalcytoplasm (PubMed:10887961). During mitosis, in mid-telophase,localized in the ingressing cleavage furrow (PubMed:18804435). Inlate telophase, detected at the opposite poles of the daughtercells, in vesicles at the base of lamellipodia formed by theseparating daughter cells (PubMed:18804435).{ECO:0000250|UniProtKB:P35282, ECO:0000269|PubMed:10887961,ECO:0000269|PubMed:18804435}.; Lipid-anchor {ECO:0000305}. Golgiapparatus, trans-Golgi network {ECO:0000269|PubMed:19745841}.Golgi apparatus membrane {ECO:0000305}. Early endosome membrane{ECO:0000269|PubMed:16525121, ECO:0000269|PubMed:25648148}.Cytoplasmic vesicle membrane {ECO:0000269|PubMed:10887961}.Cleavage furrow {ECO:0000269|PubMed:18804435}. Note=Colocalizeswith ANKRD27 and VAMP7 in neurites (By similarity). Innonpolarized epithelial Caco-2 cells, found in the endoplasmicreticulum;Endoplasmic reticulum membrane{ECO:0000269|PubMed:10887961} anterograde axonal transport;intracellular protein transport;positive regulation of dendrite morphogenesis;positive regulation of early endosome to late endosome transport;positive regulation of receptor-mediated endocytosis;Rab protein signal transduction;regulation of axon extension;regulation of exocytosis GDP binding;GTP binding;GTPase activity axon cytoplasm;cleavage furrow;cytoplasmic side of early endosome membrane;cytoplasmic side of plasma membrane;cytoplasmic vesicle membrane;cytosol;early endosome;early endosome membrane;endoplasmic reticulum membrane;endosome;extracellular exosome;focal adhesion;Golgi cisterna membrane;synapse;trans-Golgi network;vesicle membrane RAB GEFs exchange GTP for GDP on RABs;RAB geranylgeranylation 0.254189282655716 -0.204210296273232 -1.17234551906586 -0.937948524951935 -0.851879000663757 -1.74269568920135 -1.68745076656342 -1.26329779624939 0.693889856338501 1.033562541008 0.916019201278687 0.194325417280197 1.14035320281982 0.642959594726563 0.766244530677795 0.643906354904175 0.625978291034698 0.948399245738983 + Cluster -671 3 3 3 7 7 7 54.234 0 5.4759 1489600000 7 6.4757252134493 0 Q9BR76 Q9BR76 Coronin-1B CORO1B 2623 Regulates leading edge dynamics and cell motility infibroblasts. May be involved in cytokinesis and signaltransduction (By similarity). Cytoplasm, cytoskeleton{ECO:0000269|PubMed:16027158}. Cytoplasm, cytoskeleton, stressfiber {ECO:0000269|PubMed:16027158}. Note=Localized to the leadingedge in fibroblasts, as well as weakly along actin stress fibers.{ECO:0000269|PubMed:16027158}. actin cytoskeleton organization;actin filament branching;actin filament bundle assembly;cell migration;cellular response to platelet-derived growth factor stimulus;endothelial cell chemotaxis;negative regulation of Arp2/3 complex-mediated actin nucleation;negative regulation of smooth muscle cell chemotaxis;positive regulation of lamellipodium morphogenesis;protein localization to cell leading edge;regulation of Arp2/3 complex-mediated actin nucleation;ruffle organization;wound healing actin filament binding;Arp2/3 complex binding;cadherin binding;identical protein binding actin filament;cell leading edge;cell periphery;cytoplasm;cytosol;extracellular exosome;focal adhesion;lamellipodium;perinuclear region of cytoplasm;plasma membrane;stress fiber 0.505861222743988 -0.0229518804699183 -1.24311506748199 -1.09482705593109 -1.33813154697418 -1.35617661476135 -1.78352630138397 -1.04436218738556 0.790503203868866 0.67673397064209 0.944338440895081 0.0222505629062653 0.96145087480545 0.691579580307007 0.887714684009552 0.835480749607086 0.839420795440674 0.727756500244141 + Cluster -671 3 3 3 20.9 20.9 20.9 19.463 0 7.3878 1071200000 5 7.60217874913274 0 P62633;P62633-2;P62633-4;P62633-8;P62633-5;P62633-6;P62633-7;P62633-3 P62633;P62633-2;P62633-4;P62633-8;P62633-5;P62633-6;P62633-7;P62633-3 Cellular nucleic acid-binding protein CNBP 1361 Single-stranded DNA-binding protein, with specificity tothe sterol regulatory element (SRE). Involved in sterol-mediatedrepression. Cytoplasm {ECO:0000250}. Endoplasmicreticulum {ECO:0000250}. cholesterol biosynthetic process;negative regulation of transcription by RNA polymerase II;positive regulation of cell proliferation;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;regulation of transcription, DNA-templated DNA-binding transcription factor activity;DNA-binding transcription repressor activity, RNA polymerase II-specific;RNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;single-stranded DNA binding;single-stranded RNA binding;zinc ion binding cytosol;endoplasmic reticulum;nucleus Myotonic dystrophy -0.00993506703525782 -0.333726286888123 -0.851306021213531 -0.74045729637146 -0.799128651618958 -1.73341906070709 -1.73341906070709 -1.53859424591064 0.394923985004425 1.09703886508942 1.06274223327637 0.28757905960083 0.860605955123901 0.744566857814789 0.952908456325531 0.76354455947876 0.771904468536377 0.804171144962311 + Cluster -671 5 5 5 38 38 38 16.762 0 75.232 17621000000 26 6.20758140398496 0 P20674 P20674 Cytochrome c oxidase subunit 5A, mitochondrial COX5A 747 This is the heme A-containing chain of cytochrome coxidase, the terminal oxidase in mitochondrial electron transport. Mitochondrion inner membrane. mitochondrial electron transport, cytochrome c to oxygen cytochrome-c oxidase activity;electron transfer activity;metal ion binding mitochondrial inner membrane;mitochondrial respiratory chain complex IV Alzheimer disease;Cardiac muscle contraction;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Thermogenesis Respiratory electron transport;TP53 Regulates Metabolic Genes Cytochrome c oxidase, mitochondrial 0.149494394659996 -0.201181694865227 -0.74086582660675 -0.642249882221222 -1.00152432918549 -1.88058662414551 -1.88058662414551 -1.16642260551453 0.439498156309128 0.437055975198746 0.980539917945862 0.170327097177505 1.277214884758 0.963390052318573 1.09909129142761 0.864181101322174 0.500240743160248 0.632384061813354 + Cluster -671 9 9 9 61.8 61.8 61.8 22.391 0 166.67 19521000000 82 5.41917501241564 7.63358778625954E-06 P37802;P37802-2;Q9UI15 P37802;P37802-2 Transgelin-2 TAGLN2 965 central nervous system development;epithelial cell differentiation;negative regulation of transcription by RNA polymerase II;platelet degranulation actin filament binding;cadherin binding cytosol;extracellular exosome;extracellular region;myelin sheath;nucleus;vesicle Platelet degranulation -1.20588183403015 -0.218041971325874 -1.44762134552002 -0.218041971325874 -1.05848824977875 -1.75091540813446 -1.09179091453552 -0.581082284450531 0.413761407136917 0.524533569812775 0.84287291765213 0.550008356571198 0.151376590132713 0.84287291765213 0.51211279630661 0.726790606975555 1.24526596069336 1.76226890087128 + Cluster -671 1 1 1 4.8 4.8 4.8 37.492 0 9.3836 2362000000 6 3.56305159276676 0.000383966244725738 P52564;P52564-2 P52564;P52564-2 Dual specificity mitogen-activated protein kinase kinase 6 MAP2K6 1178 and for IFNG-dependent gene transcription. Has a role in osteoclastdifferentiation through NF-kappa-B transactivation by TNFSF11, andin endochondral ossification and since SOX9 is another likelydownstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediatesapoptotic cell death in thymocytes. Acts also as a regulator formelanocytes dendricity, through the modulation of Rho familyGTPases.;Dual specificity protein kinase which acts as anessential component of the MAP kinase signal transduction pathway.With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of athreonine and a tyrosine residue in the MAP kinases p38 MAPK11,MAPK12, MAPK13 and MAPK14 and plays an important role in theregulation of cellular responses to cytokines and all kinds ofstresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are bothessential for the activation of MAPK11 and MAPK13 induced byenvironmental stress, whereas MAP2K6/MKK6 is the major MAPK11activator in response to TNF. MAP2K6/MKK6 also phosphorylates andactivates PAK6. The p38 MAP kinase signal transduction pathwayleads to direct activation of transcription factors. Nucleartargets of p38 MAP kinase include the transcription factors ATF2and ELK1. Within the p38 MAPK signal transduction pathway,MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14activation, and is therefore required for STAT4 activation andSTAT4-regulated gene expression in response to IL-12 stimulation.The pathway is also crucial for IL-6-induced SOCS3 expression anddown-regulation of IL-6-mediated gene induction Nucleus {ECO:0000269|PubMed:9768359}.Cytoplasm {ECO:0000269|PubMed:9768359}. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:9768359}. Note=Binds to microtubules. activation of MAPK activity;activation of protein kinase activity;apoptotic process;cardiac muscle contraction;cell cycle arrest;cellular response to sorbitol;DNA damage induced protein phosphorylation;negative regulation of cold-induced thermogenesis;nucleotide-binding oligomerization domain containing signaling pathway;ovulation cycle process;positive regulation of apoptotic process;positive regulation of nitric-oxide synthase biosynthetic process;positive regulation of prostaglandin secretion;response to drug;response to ischemia;signal transduction;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade ATP binding;identical protein binding;MAP kinase kinase activity;protein kinase binding;protein serine/threonine kinase activity;protein tyrosine kinase activity cytoplasm;cytoskeleton;cytosol;nucleoplasm;nucleus Amyotrophic lateral sclerosis (ALS);Cellular senescence;Epstein-Barr virus infection;Fc epsilon RI signaling pathway;Fluid shear stress and atherosclerosis;GnRH signaling pathway;Hepatitis B;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Inflammatory mediator regulation of TRP channels;Kaposi sarcoma-associated herpesvirus infection;MAPK signaling pathway;Osteoclast differentiation;PD-L1 expression and PD-1 checkpoint pathway in cancer;Rap1 signaling pathway;TNF signaling pathway;Toll-like receptor signaling pathway;Toxoplasmosis;Yersinia infection activated TAK1 mediates p38 MAPK activation;CDO in myogenesis;Interleukin-1 signaling;NOD1/2 Signaling Pathway;Oxidative Stress Induced Senescence;PI5P Regulates TP53 Acetylation;Uptake and function of anthrax toxins -1.07611560821533 0.0386638380587101 -0.923112809658051 -0.689078152179718 -1.47776830196381 -1.12029337882996 -1.59288763999939 -0.405139863491058 -0.0274311657994986 -0.127099081873894 1.17659378051758 0.674147367477417 0.457194030284882 0.295945376157761 0.641539454460144 1.29702091217041 1.28150510787964 1.57631623744965 + Cluster -671 2 2 2 27.2 27.2 27.2 15.892 0 77.324 13414000000 23 3.8961767202349 0.000197889182058047 Q9Y2V2 Q9Y2V2 Calcium-regulated heat stable protein 1 CARHSP1 3242 Binds mRNA and regulates the stability of target mRNA.Binds single-stranded DNA (in vitro) Cytoplasm {ECO:0000269|PubMed:21177848}.Cytoplasm, P-body {ECO:0000269|PubMed:21177848}. Cytoplasmicgranule {ECO:0000269|PubMed:21177848}. Note=Detected atcytoplasmic stress granules and P-bodies. Detected at exosomegranules where mRNA is degraded (By similarity). {ECO:0000250}. intracellular signal transduction;regulation of mRNA stability DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;mRNA 3'-UTR binding;phosphatase binding cytoplasm;cytoplasmic exosome (RNase complex);cytosol;P granule;P-body -1.58300471305847 -0.119536824524403 -0.742474496364594 -0.317709445953369 -0.921676754951477 -1.22024834156036 -1.78186178207397 -0.972029447555542 0.20956926047802 0.428203761577606 1.28440463542938 0.776035070419312 0.303849130868912 0.405586391687393 0.776035070419312 1.19015550613403 1.09454751014709 1.19015550613403 + Cluster -671 2 2 1 6.9 6.9 4.1 49.008 0 22.026 1848600000 8 3.82076646918386 0.000238578680203046 Q9UNW9;P51513-2 Q9UNW9;P51513-2 RNA-binding protein Nova-2;RNA-binding protein Nova-1 NOVA2;NOVA1 3190 May regulate RNA splicing or metabolism in a specificsubset of developing neurons (By similarity). Binds single strandRNA.;May regulate RNA splicing or metabolism in a specificsubset of developing neurons. Nucleus {ECO:0000250}.;Nucleus. chemical synaptic transmission;locomotory behavior;mRNA splicing, via spliceosome;negative regulation of cold-induced thermogenesis;regulation of RNA metabolic process;RNA processing;RNA splicing mRNA binding;RNA binding intracellular membrane-bounded organelle;nucleolus;nucleus -1.44860541820526 -0.451868087053299 -0.769806504249573 -0.411325871944427 -1.14843499660492 -0.956266283988953 -1.49023270606995 -0.514074802398682 -0.211290374398232 -0.0833875089883804 1.15794718265533 0.209631249308586 0.716902434825897 0.242627307772636 0.716902434825897 1.71784436702728 1.23046207427979 1.49297547340393 + Cluster -671 8 8 8 29.9 29.9 29.9 50.144 0 112.49 10231000000 32 3.90590715131031 0.000184491978609626 Q9UKX7;Q9UKX7-2 Q9UKX7;Q9UKX7-2 Nuclear pore complex protein Nup50 NUP50 3154 Component of the nuclear pore complex that has a directrole in nuclear protein import (PubMed:20016008). Activelydisplaces NLSs from importin-alpha, and facilitates disassembly ofthe importin-alpha:beta-cargo complex and importin recycling(PubMed:20016008). Interacts with regulatory proteins of cellcycle progression including CDKN1B (By similarity). Thisinteraction is required for correct intracellular transport anddegradation of CDKN1B (By similarity) Nucleoplasmic side{ECO:0000250|UniProtKB:O08587}. Note=Localizes to thenucleoplasmic fibrils of the nuclear pore complex (By similarity).Dissociates from the NPC structure early during prophase ofmitosis (PubMed:12802065). Associates with the newly formednuclear membrane during telophase (PubMed:12802065). In thetestis, the localization changes during germ cell differentiationfrom the nuclear surface in spermatocytes to the whole nucleus(interior) in spermatids and back to the nuclear surface inspermatozoa (By similarity). {ECO:0000250|UniProtKB:O08587,ECO:0000269|PubMed:12802065}.; Peripheral membrane protein{ECO:0000250|UniProtKB:O08587};Nucleus, nuclear pore complex{ECO:0000269|PubMed:12802065}. Nucleus membrane{ECO:0000250|UniProtKB:O08587} mRNA export from nucleus;positive regulation of GTPase activity;protein import into nucleus;viral process Ran GTPase binding cytoplasm;intracellular membrane-bounded organelle;nuclear membrane;nuclear pore;nucleoplasm;nucleus RNA transport ISG15 antiviral mechanism;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Rev-mediated nuclear export of HIV RNA;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs -1.21737551689148 -0.347452312707901 -0.77884566783905 -0.484003037214279 -0.890186429023743 -1.42953705787659 -1.56570863723755 -1.23252046108246 0.0367244854569435 0.672280430793762 1.03609979152679 0.519144237041473 0.598517656326294 0.622542917728424 0.779147863388062 1.24335205554962 1.01486086845398 1.42295873165131 + Cluster -671 7 7 7 48.5 48.5 48.5 22.367 0 93.294 26368000000 35 5.48030149935352 7.8740157480315E-06 Q9NR31;Q9NR31-2;Q9Y6B6 Q9NR31;Q9NR31-2 GTP-binding protein SAR1a SAR1A 2910 Involved in transport from the endoplasmic reticulum tothe Golgi apparatus (By similarity). Required to maintain SEC16Alocalization at discrete locations on the ER membrane perhaps bypreventing its dissociation. SAR1A-GTP-dependent assembly ofSEC16A on the ER membrane forms an organized scaffold definingendoplasmic reticulum exit sites (ERES).;Involved in transport from the endoplasmic reticulum tothe Golgi apparatus. Activated by the guanine nucleotide exchangefactor PREB. Involved in the selection of the protein cargo andthe assembly of the COPII coat complex. Peripheral membrane protein {ECO:0000250}. Golgiapparatus, Golgi stack membrane {ECO:0000250}; Peripheral membraneprotein {ECO:0000250}. Note=Associated with the endoplasmicreticulum and Golgi stacks, in particular in the juxta-nuclearGolgi region. {ECO:0000250}.;Endoplasmic reticulum {ECO:0000250}. Golgiapparatus {ECO:0000250}.;Endoplasmic reticulum membrane{ECO:0000250} antigen processing and presentation of exogenous peptide antigen via MHC class II;antigen processing and presentation of peptide antigen via MHC class I;cargo loading into COPII-coated vesicle;COPII vesicle coating;endoplasmic reticulum to Golgi vesicle-mediated transport;intracellular protein transport;membrane organization;positive regulation of protein exit from endoplasmic reticulum;regulation of COPII vesicle coating;vesicle organization GTP binding;GTPase activity;metal ion binding COPII vesicle coat;cytosol;endoplasmic reticulum;endoplasmic reticulum exit site;endoplasmic reticulum membrane;ER to Golgi transport vesicle membrane;Golgi cisterna membrane;Golgi membrane Legionellosis;Protein processing in endoplasmic reticulum Chylomicron retention disease Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Cargo concentration in the ER;Chylomicron assembly;COPII-mediated vesicle transport;MHC class II antigen presentation;Regulation of cholesterol biosynthesis by SREBP (SREBF) Coat protein complex II (SAR1B, PREB, SEC23A , SEC24B, SEC23IP) -1.50270390510559 0.185560837388039 -0.540755927562714 -0.229023054242134 -1.18161737918854 -1.3495866060257 -1.54630601406097 -0.97611403465271 -0.229023054242134 0.103868260979652 1.29170966148376 1.02149879932404 0.409586131572723 0.540087580680847 0.505295991897583 1.23212945461273 1.46957588195801 0.79581743478775 + Cluster -671 15 15 10 45.1 45.1 35.7 55.364 0 154.17 57948000000 78 3.59027560716069 0.000376086956521739 Q92769;Q92769-3 Q92769;Q92769-3 Histone deacetylase 2 HDAC2 2351 Responsible for the deacetylation of lysine residues onthe N-terminal part of the core histones (H2A, H2B, H3 and H4).Histone deacetylation gives a tag for epigenetic repression andplays an important role in transcriptional regulation, cell cycleprogression and developmental events. Histone deacetylases act viathe formation of large multiprotein complexes. Formstranscriptional repressor complexes by associating with MAD, SIN3,YY1 and N-COR. Interacts in the late S-phase of DNA-replicationwith DNMT1 in the other transcriptional repressor complex composedof DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates itstranscriptional repressor activity. Component of aRCOR/GFI/KDM1A/HDAC complex that suppresses, via histonedeacetylase (HDAC) recruitment, a number of genes implicated inmultilineage blood cell development. May be involved in thetranscriptional repression of circadian target genes, such asPER1, mediated by CRY1 through histone deacetylation. Involved inMTA1-mediated transcriptional corepression of TFF1 and CDKN1A Nucleus {ECO:0000269|PubMed:24970816}.Cytoplasm {ECO:0000269|PubMed:24970816}. ATP-dependent chromatin remodeling;behavioral response to ethanol;blood coagulation;cardiac muscle hypertrophy;cellular response to dopamine;cellular response to heat;cellular response to hydrogen peroxide;cellular response to retinoic acid;cellular response to transforming growth factor beta stimulus;chromatin remodeling;circadian regulation of gene expression;dendrite development;embryonic digit morphogenesis;epidermal cell differentiation;eyelid development in camera-type eye;fungiform papilla formation;hair follicle placode formation;histone deacetylation;histone H3 deacetylation;histone H4 deacetylation;maintenance of chromatin silencing;negative regulation of apoptotic process;negative regulation of dendritic spine development;negative regulation of DNA binding;negative regulation of DNA-binding transcription factor activity;negative regulation of MHC class II biosynthetic process;negative regulation of neuron projection development;negative regulation of peptidyl-lysine acetylation;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;odontogenesis of dentin-containing tooth;positive regulation of cell proliferation;positive regulation of collagen biosynthetic process;positive regulation of epithelial to mesenchymal transition;positive regulation of interleukin-1 production;positive regulation of oligodendrocyte differentiation;positive regulation of proteolysis;positive regulation of receptor biosynthetic process;positive regulation of transcription by RNA polymerase II;positive regulation of transcription, DNA-templated;positive regulation of tumor necrosis factor production;positive regulation of tyrosine phosphorylation of STAT protein;response to amphetamine;response to caffeine;response to cocaine;response to hyperoxia;response to lipopolysaccharide;response to nicotine chromatin binding;deacetylase activity;enzyme binding;heat shock protein binding;histone deacetylase activity;histone deacetylase binding;NAD-dependent histone deacetylase activity (H3-K14 specific);NF-kappaB binding;promoter-specific chromatin binding;protein deacetylase activity;RNA binding;RNA polymerase II repressing transcription factor binding;sequence-specific DNA binding;transcription factor binding cytoplasm;ESC/E(Z) complex;histone deacetylase complex;nuclear chromatin;nucleoplasm;nucleus;NuRD complex;protein-containing complex;Sin3 complex;Sin3-type complex Alcoholism;Cell cycle;Chronic myeloid leukemia;Epstein-Barr virus infection;Human papillomavirus infection;Huntington disease;Longevity regulating pathway - multiple species;Notch signaling pathway;Pathways in cancer;Thyroid hormone signaling pathway;Transcriptional misregulation in cancer;Viral carcinogenesis Abexinostat;Belinostat;Entinostat;Fimepinostat;Mocetinostat;Nanatinostat;Panobinostat;Quisinostat;Remetinostat;Romidepsin;Tinostamustine;Tucidinostat;Vorinostat Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Constitutive Signaling by NOTCH1 PEST Domain Mutants;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Factors involved in megakaryocyte development and platelet production;HDACs deacetylate histones;MECP2 regulates neuronal receptors and channels;NoRC negatively regulates rRNA expression;NOTCH1 Intracellular Domain Regulates Transcription;p75NTR negatively regulates cell cycle via SC1;Regulation of MECP2 expression and activity;Regulation of PTEN gene transcription;Regulation of TP53 Activity through Acetylation;RNA Polymerase I Transcription Initiation;SUMOylation of chromatin organization proteins AJUBA-GFI1-HDAC2 complex;ALL-1 supercomplex;anti-BHC110 complex;Anti-HDAC2 complex;ATR-HDAC2 complex;ATR-HDAC2-CHD4 complex;BHC complex;BHC110 complex;BRAF53-BRCA2 complex;BRCA1-HDAC1-HDAC2 complex;BRG1-SIN3A complex;BRG1-SIN3A-HDAC containing SWI/SNF remodeling complex I;BRMS1-SIN3-HDAC complex;BRM-SIN3A complex;BRM-SIN3A-HDAC complex;CDH4-HDAC2-MTA2-RBBP7-TWIST1 complex;CoREST-HDAC complex;CoREST-HDAC2 complex;CtBP complex;CtBP core complex;DNTTIP1-ZNF541-HDAC1-HDAC2 complex;ESR1-CDK7-CCNH-MNAT1-MTA1-HDAC2 complex;HCF-1 complex;HDAC2-asscociated core complex;ING2 complex;LARC complex (LCR-associated remodeling complex);MAD1-mSin3A-HDAC2 complex;MeCP1 complex;MeCP2-SIN3A-HDAC complex;Mi2/NuRD complex;MiDAC complex;mSin3A complex;mSin3A-HDAC1-HDAC2 complex;MTA1 complex;MTA1-HDAC core complex;MTA2 complex;NCOR2 complex;NCOR-SIN3-HDAC-HESX1 complex;NCOR-SIN3-RPD3 complex;NRD complex (Nucleosome remodeling and deacetylation complex);NuRD.1 complex;SAP complex (Sin3-associated protein complex);Sin3 complex;SIN3 complex;SIN3-HDAC-SAP30-ARID4 complex;SIN3-ING1b complex I;SIN3-ING1b complex II;SIN3-SAP25 complex;SNF2h-cohesin-NuRD complex;SNF2h-HDAC12 complex;TBX20-HDAC2 repressor complex;XFIM complex -1.34809958934784 -0.145918264985085 -0.953369140625 -0.225838914513588 -0.915014564990997 -1.58481001853943 -1.45713376998901 -0.603428602218628 0.155565336346626 0.186093926429749 1.85893964767456 0.789479494094849 0.242389068007469 0.475961655378342 0.0925024673342705 1.08205425739288 1.1753134727478 1.1753134727478 + Cluster -671 5 5 5 22.7 22.7 22.7 42.502 0 144.35 22920000000 38 3.15296187281912 0.0008096 Q7L2H7;Q7L2H7-2 Q7L2H7;Q7L2H7-2 Eukaryotic translation initiation factor 3 subunit M EIF3M 2055 Component of the eukaryotic translation initiationfactor 3 (eIF-3) complex, which is required for several steps inthe initiation of protein synthesis (PubMed:17403899,PubMed:25849773, PubMed:27462815). The eIF-3 complex associateswith the 40S ribosome and facilitates the recruitment of eIF-1,eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNArecruitment to the 43S PIC and scanning of the mRNA for AUGrecognition. The eIF-3 complex is also required for disassemblyand recycling of post-termination ribosomal complexes andsubsequently prevents premature joining of the 40S and 60Sribosomal subunits prior to initiation (PubMed:17403899). The eIF-3 complex specifically targets and initiates translation of asubset of mRNAs involved in cell proliferation, including cellcycling, differentiation and apoptosis, and uses different modesof RNA stem-loop binding to exert either translational activationor repression (PubMed:25849773). Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03012}. cytoplasmic translational initiation;formation of cytoplasmic translation initiation complex;translational initiation translation initiation factor activity;translation initiation factor binding cytosol;eukaryotic 43S preinitiation complex;eukaryotic 48S preinitiation complex;eukaryotic translation initiation factor 3 complex;eukaryotic translation initiation factor 3 complex, eIF3m Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Ribosomal scanning and start codon recognition;Translation initiation complex formation eIF3 complex (EIF3S6, EIF3S5, EIF3S4, EIF3S3, EIF3S6IP, EIF3S2, EIF3S9, EIF3S12, EIF3S10, EIF3S8, EIF3S1, EIF3S7, PCID1) -0.834502100944519 -0.220567613840103 -0.834502100944519 -0.616552412509918 -1.21488785743713 -1.14136755466461 -1.73217880725861 -1.00502061843872 0.0423455722630024 0.583484292030334 1.62095665931702 0.252914607524872 0.444262087345123 0.271804094314575 0.705175399780273 1.0879533290863 1.14115035533905 1.44953262805939 + Cluster -671 5 5 5 33.7 33.7 33.7 18.648 0 113.71 43945000000 46 4.6452934588999 4.11522633744856E-05 Q14011;Q14011-2;Q14011-3 Q14011;Q14011-2 Cold-inducible RNA-binding protein CIRBP 1673 Cold-inducible mRNA binding protein that plays aprotective role in the genotoxic stress response by stabilizingtranscripts of genes involved in cell survival. Acts as atranslational activator. Seems to play an essential role in cold-induced suppression of cell proliferation. Binds specifically tothe 3'-untranslated regions (3'-UTRs) of stress-responsivetranscripts RPA2 and TXN. Acts as a translational repressor (Bysimilarity). Promotes assembly of stress granules (SGs), whenoverexpressed. Nucleus, nucleoplasm{ECO:0000269|PubMed:11574538}. Cytoplasm{ECO:0000269|PubMed:11574538}. Note=Translocates from the nucleusto the cytoplasm after exposure to UV radiation. Translocates fromthe nucleus to the cytoplasm into stress granules upon variouscytoplasmic stresses, such as osmotic and heat shocks. Itsrecruitment into stress granules occurs in the absence of TIARproteins (By similarity). {ECO:0000250}. mRNA stabilization;positive regulation of mRNA splicing, via spliceosome;positive regulation of translation;response to cold;response to UV;stress granule assembly mRNA 3'-UTR binding;poly(U) RNA binding;RNA binding;small ribosomal subunit rRNA binding;translation repressor activity cytoplasm;cytoplasmic stress granule;nucleolus;nucleoplasm;nucleus;ribonucleoprotein complex;spliceosomal complex Spliceosome -1.50965046882629 -0.0921469554305077 -0.923565804958344 0.148542866110802 -0.971028745174408 -1.64529871940613 -1.34735715389252 -0.971067190170288 0.0820216611027718 0.253930598497391 1.38062739372253 0.794677376747131 0.0752714574337006 0.724809944629669 0.734435200691223 0.758618593215942 1.12821614742279 1.37896394729614 + Cluster -671 3 3 3 6.8 6.8 6.8 61.492 0 15.207 3012300000 8 3.29440840974752 0.000598967297762478 Q13112 Q13112 Chromatin assembly factor 1 subunit B CHAF1B 1594 histones H2A/H2B can bind to thischromatin precursor subsequent to DNA replication to complete thehistone octamer.;Complex that is thought to mediate chromatin assembly inDNA replication and DNA repair. Assembles histone octamers ontoreplicating DNA in vitro. CAF-1 performs the first step of thenucleosome assembly process, bringing newly synthesized histonesH3 and H4 to replicating DNA Nucleus {ECO:0000269|PubMed:9614144}.Cytoplasm {ECO:0000269|PubMed:9614144}. Note=DNA replication foci.Cytoplasmic in M phase. cell cycle;chromatin assembly;DNA repair;DNA replication;DNA replication-dependent nucleosome assembly;nucleosome assembly chromatin binding;histone binding;unfolded protein binding CAF-1 complex;cytoplasm;nuclear chromatin;nucleoplasm;nucleus;protein-containing complex ASF1-histone containing complex;ASF1-interacting protein complex;Chromatin assembly complex (CAF-1 complex);Histone H3.1 complex -1.81652557849884 0.109334714710712 -0.683041214942932 -0.496114432811737 -0.825212240219116 -1.15365278720856 -1.53251481056213 -1.14339137077332 0.169773161411285 0.920984029769897 0.582944810390472 0.607590615749359 0.402911484241486 0.642193615436554 0.672918021678925 1.32256889343262 1.60078346729279 0.618449568748474 + Cluster -671 1 1 1 11.8 11.8 11.8 34.645 0 15.571 1538100000 3 3.63895978201374 0.000333333333333333 P13051;P13051-2 P13051;P13051-2 Uracil-DNA glycosylase UNG 649 Excises uracil residues from the DNA which can arise asa result of misincorporation of dUMP residues by DNA polymerase ordue to deamination of cytosine. Isoform 1: Mitochondrion.Isoform 2: Nucleus. base-excision repair;base-excision repair, AP site formation via deaminated base removal;depyrimidination;DNA repair;negative regulation of apoptotic process;positive regulation of isotype switching;somatic hypermutation of immunoglobulin genes;somatic recombination of immunoglobulin gene segments;viral process damaged DNA binding;ribosomal small subunit binding;uracil DNA N-glycosylase activity mitochondrion;nucleoplasm;nucleus Base excision repair;Primary immunodeficiency Hyper IgM syndromes, autosomal recessive type Cleavage of the damaged pyrimidine;Displacement of DNA glycosylase by APEX1;Recognition and association of DNA glycosylase with site containing an affected pyrimidine -1.72791624069214 -0.237083867192268 -0.758685231208801 -0.210202991962433 -1.27066791057587 -1.20557022094727 -1.45561254024506 -0.823083817958832 0.5187868475914 0.560437738895416 0.926892876625061 0.550241529941559 0.227275997400284 0.550241529941559 0.66919207572937 0.713213503360748 1.48627030849457 1.48627030849457 + Cluster -671 4 4 4 52.1 52.1 52.1 13.293 0 44.369 4401700000 35 3.24768930932329 0.00068135593220339 P52435;Q9GZM3;Q9H1A7;Q9GZM3-2 P52435;Q9GZM3;Q9H1A7 DNA-directed RNA polymerase II subunit RPB11-a;DNA-directed RNA polymerase II subunit RPB11-b1;DNA-directed RNA polymerase II subunit RPB11-b2 POLR2J;POLR2J2;POLR2J3 1177 DNA-dependent RNA polymerase catalyzes the transcriptionof DNA into RNA using the four ribonucleoside triphosphates assubstrates. Component of RNA polymerase II which synthesizes mRNAprecursors and many functional non-coding RNAs. Pol II is thecentral component of the basal RNA polymerase II transcriptionmachinery. It is composed of mobile elements that move relative toeach other. RPB11 is part of the core element with the centrallarge cleft (By similarity). Nucleus {ECO:0000250}.;Nucleus {ECO:0000269|PubMed:9852112}. 7-methylguanosine mRNA capping;fibroblast growth factor receptor signaling pathway;mRNA splicing, via spliceosome;regulation of gene silencing by miRNA;RNA metabolic process;snRNA transcription by RNA polymerase II;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;transcription initiation from RNA polymerase II promoter;transcription-coupled nucleotide-excision repair DNA binding;DNA-directed 5'-3' RNA polymerase activity;LRR domain binding;protein dimerization activity;RNA polymerase II activity nucleoplasm;nucleus;RNA polymerase II, core complex Huntington disease;RNA polymerase Abortive elongation of HIV-1 transcript in the absence of Tat;Activation of anterior HOX genes in hindbrain development during early embryogenesis;Dual incision in TC-NER;Estrogen-dependent gene expression;FGFR2 alternative splicing;Formation of HIV elongation complex in the absence of HIV Tat;Formation of HIV-1 elongation complex containing HIV-1 Tat;Formation of RNA Pol II elongation complex;Formation of TC-NER Pre-Incision Complex;Formation of the Early Elongation Complex;Formation of the HIV-1 Early Elongation Complex;Gap-filling DNA repair synthesis and ligation in TC-NER;HIV elongation arrest and recovery;HIV Transcription Initiation;MicroRNA (miRNA) biogenesis;mRNA Capping;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;Pausing and recovery of HIV elongation;Pausing and recovery of Tat-mediated HIV elongation;PIWI-interacting RNA (piRNA) biogenesis;Processing of Capped Intron-Containing Pre-mRNA;RNA Pol II CTD phosphorylation and interaction with CE;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Promoter Escape;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription Elongation;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;Signaling by FGFR2 IIIa TM;Tat-mediated elongation of the HIV-1 transcript;Tat-mediated HIV elongation arrest and recovery;TP53 Regulates Transcription of DNA Repair Genes;Transcription of the HIV genome;Transcriptional regulation by small RNAs;Transcriptional regulation of pluripotent stem cells;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Viral Messenger RNA Synthesis BRCA1-core RNA polymerase II complex;BRCA1-RNA polymerase II complex;RNA polymerase II (RNAPII);RNA polymerase II core complex;RNA polymerase II holoenzyme complex -0.859811961650848 -0.0350942499935627 -1.51591944694519 -0.336788207292557 -1.05345392227173 -1.61242282390594 -1.58817064762115 -0.516773879528046 0.273788720369339 0.656727373600006 1.09609568119049 -0.067242793738842 0.758009016513824 0.830880999565125 0.442904204130173 1.23540115356445 1.03826582431793 1.25360476970673 + Cluster -671 7 2 2 4.2 1.3 1.3 227.87 0 11.007 3503100000 15 4.38332964449185 5.96491228070175E-05 Q7Z406;Q7Z406-6;Q7Z406-2;Q7Z406-5;Q7Z406-4 Q7Z406;Q7Z406-6;Q7Z406-2;Q7Z406-5;Q7Z406-4 Myosin-14 MYH14 2076 Cellular myosin that appears to play a role incytokinesis, cell shape, and specialized functions such assecretion and capping. actin filament-based movement;actomyosin structure organization;mitochondrion morphogenesis;neuronal action potential;regulation of cell shape;sensory perception of sound;skeletal muscle contraction;skeletal muscle tissue development;vocalization behavior actin filament binding;actin-dependent ATPase activity;ATP binding;ATPase activity;calmodulin binding;microfilament motor activity actomyosin;brush border;cytosol;extracellular exosome;growth cone;membrane;myelin sheath;myosin II complex;myosin II filament;stress fiber Regulation of actin cytoskeleton;Tight junction Deafness, autosomal dominant EPHA-mediated growth cone collapse;RHO GTPases activate CIT;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases Activate ROCKs;Sema4D induced cell migration and growth-cone collapse -0.862620890140533 -0.263132870197296 -1.34502780437469 -0.227096453309059 -1.96329236030579 -0.810609996318817 -1.05773377418518 -0.693441450595856 0.196687623858452 0.291603952646255 0.800895512104034 0.118131399154663 0.680559813976288 0.236549288034439 0.434037566184998 1.67515289783478 1.26866471767426 1.52067291736603 + Cluster -671 2 2 2 8.6 8.6 8.6 36.504 0 78.977 4161500000 12 3.67380589225869 0.000324884792626728 Q7L5D6;Q7L5D6-2 Q7L5D6;Q7L5D6-2 Golgi to ER traffic protein 4 homolog GET4 2060 As part of a cytosolic protein quality control complex,the BAG6/BAT3 complex, maintains misfolded and hydrophobicpatches-containing proteins in a soluble state and participates totheir proper delivery to the endoplasmic reticulum oralternatively can promote their sorting to the proteasome wherethey undergo degradation (PubMed:20676083, PubMed:21636303,PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex isinvolved in the post-translational delivery of tail-anchored/typeII transmembrane proteins to the endoplasmic reticulum membrane.Recruited to ribosomes, it interacts with the transmembrane regionof newly synthesized tail-anchored proteins and together with SGTAand ASNA1 mediates their delivery to the endoplasmic reticulum(PubMed:20676083, PubMed:28104892, PubMed:25535373). Clientproteins that cannot be properly delivered to the endoplasmicreticulum are ubiquitinated and sorted to the proteasome(PubMed:28104892). Similarly, the BAG6/BAT3 complex also functionsas a sorting platform for proteins of the secretory pathway thatare mislocalized to the cytosol either delivering them to theproteasome for degradation or to the endoplasmic reticulum(PubMed:21743475). The BAG6/BAT3 complex also plays a role in theendoplasmic reticulum-associated degradation (ERAD), a qualitycontrol mechanism that eliminates unwanted proteins of theendoplasmic reticulum through their retrotranslocation to thecytosol and their targeting to the proteasome. It maintains theseretrotranslocated proteins in an unfolded yet soluble statecondition in the cytosol to ensure their proper delivery to theproteasome (PubMed:21636303). Cytoplasm, cytosol{ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303,ECO:0000269|PubMed:29042515}. cytoplasmic sequestering of protein;maintenance of unfolded protein involved in ERAD pathway;protein insertion into ER membrane;tail-anchored membrane protein insertion into ER membrane chaperone binding BAT3 complex;cytoplasm;cytosol;nucleolus;nucleoplasm Bag6-Ubl4A-Trc35 Complex -1.24561107158661 -0.00467892270535231 -0.974200785160065 0.00287335622124374 -1.51609361171722 -1.34717035293579 -1.5831310749054 -0.795796990394592 -0.0302125718444586 0.704457759857178 0.67680412530899 0.3492052257061 0.837081372737885 0.481730341911316 0.67680412530899 1.08337271213531 1.36668431758881 1.31788218021393 + Cluster -671 2 2 2 8.9 8.9 8.9 55.846 0 70.997 2706600000 9 4.36415925681194 6.9204152249135E-05 Q13325;Q13325-2 Q13325;Q13325-2 Interferon-induced protein with tetratricopeptide repeats 5 IFIT5 1620 Interferon-induced RNA-binding protein involved in thehuman innate immune response. Has a broad and adaptable RNAstructure recognition important for RNA recognition specificity inantiviral defense. Binds precursor and processed tRNAs as well aspoly-U-tailed tRNA fragments (PubMed:25092312, PubMed:23317505,PubMed:23774268). Specifically binds single-stranded RNA bearing a5'-triphosphate group (PPP-RNA), thereby acting as a sensor ofviral single-stranded RNAs. Single-stranded PPP-RNAs, which lack2'-O-methylation of the 5' cap and bear a 5'-triphosphate groupinstead, are specific from viruses, providing a molecularsignature to distinguish between self and non-self mRNAs by thehost during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner (PubMed:23334420). Also recognizes andselectively binds AT-rich dsDNA (PubMed:23774268). Additionally,as a mediator in innate immunity, regulates positively IKK-NFKBsignaling by sinergizing the recruitment of IKK to MAP3K7(PubMed:26334375). Cell projection, ruffle membrane{ECO:0000269|PubMed:23317505}. Note=Colocalized with DDX58/RIG-Iat cell surface ruffles. Localizes to actin-rich protrusions fromthe apical cell surface. defense response to virus;innate immune response;negative regulation of viral genome replication;positive regulation of I-kappaB kinase/NF-kappaB signaling double-stranded DNA binding;poly(U) RNA binding;RNA binding;RNA cap binding;single-stranded RNA binding;tRNA binding actin cytoskeleton;apical part of cell;cytosol;intracellular membrane-bounded organelle;plasma membrane;ruffle membrane -1.15361547470093 -0.29612597823143 -1.29865062236786 -0.482228070497513 -1.09740829467773 -1.77792179584503 -1.35888481140137 -0.254719138145447 0.802509188652039 0.0555251203477383 0.661553263664246 0.323225021362305 0.961625516414642 0.46636438369751 0.923278093338013 1.37012445926666 1.10753667354584 1.04781246185303 + Cluster -671 5 5 5 53.5 53.5 53.5 10.112 0 54.63 26271000000 36 3.811925355432 0.000244949494949495 P49458;P49458-2 P49458 Signal recognition particle 9 kDa protein SRP9 1100 Signal-recognition-particle assembly has a crucial rolein targeting secretory proteins to the rough endoplasmic reticulummembrane. SRP9 together with SRP14 and the Alu portion of the SRPRNA, constitutes the elongation arrest domain of SRP. The complexof SRP9 and SRP14 is required for SRP RNA binding. Cytoplasm. negative regulation of translational elongation;SRP-dependent cotranslational protein targeting to membrane;SRP-dependent cotranslational protein targeting to membrane, translocation 7S RNA binding;RNA binding;signal recognition particle binding cytosol;signal recognition particle receptor complex;signal recognition particle, endoplasmic reticulum targeting Protein export SRP-dependent cotranslational protein targeting to membrane -1.47612273693085 0.0501613989472389 -1.59010231494904 -0.144609734416008 -1.13197147846222 -1.20191740989685 -1.30669403076172 -0.660361647605896 0.480954617261887 -0.0264086741954088 0.913173079490662 0.339515119791031 0.51473993062973 0.51473993062973 0.913173079490662 1.34076285362244 1.18933296203613 1.28163516521454 + Cluster -671 27 27 27 35.7 35.7 35.7 123.63 0 323.31 130850000000 207 3.52845216534806 0.000397148676171079 O00410;O00410-2;O00410-3;O60518 O00410;O00410-2;O00410-3 Importin-5 IPO5 84 Functions in nuclear protein import as nuclear transportreceptor. Serves as receptor for nuclear localization signals(NLS) in cargo substrates. Is thought to mediate docking of theimportin/substrate complex to the nuclear pore complex (NPC)through binding to nucleoporin and the complex is subsequentlytranslocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ranbinds to the importin, the importin/substrate complex dissociatesand importin is re-exported from the nucleus to the cytoplasmwhere GTP hydrolysis releases Ran. The directionality of nuclearimport is thought to be conferred by an asymmetric distribution ofthe GTP- and GDP-bound forms of Ran between the cytoplasm andnucleus (By similarity). Mediates the nuclear import of ribosomalproteins RPL23A, RPS7 and RPL5. Binds to a beta-like importreceptor binding (BIB) domain of RPL23A. In vitro, mediatesnuclear import of H2A, H2B, H3 and H4 histones. Binds to CPEB3 andmediates its nuclear import following neuronal stimulation (Bysimilarity). In case of HIV-1 infection, binds and mediates thenuclear import of HIV-1 Rev.;May function in nuclear protein import as nucleartransport receptor. nuclear rim. Found particularly in the nuclear rimand nucleolus.;Cytoplasm {ECO:0000250}. Nucleus{ECO:0000250}.;Cytoplasm. Nucleus. Nucleus, nucleolus.Note=Nucleus cellular response to amino acid stimulus;negative regulation of cyclin-dependent protein serine/threonine kinase activity;NLS-bearing protein import into nucleus;positive regulation of protein import into nucleus;ribosomal protein import into nucleus;viral process GTPase inhibitor activity;nuclear localization sequence binding;protein transporter activity;Ran GTPase binding;RNA binding cytoplasm;membrane;nuclear membrane;nuclear periphery;nuclear pore;nucleolus;nucleus vRNP Assembly -1.12368261814117 -0.447084158658981 -1.3185111284256 -0.841784298419952 -1.10363161563873 -0.868837893009186 -1.2570366859436 -0.578114151954651 0.273474544286728 -0.0891440808773041 1.15918028354645 0.356260716915131 0.555631101131439 0.192207381129265 0.529853463172913 1.51751530170441 1.31155240535736 1.73215174674988 + Cluster -671 10 10 10 32.8 32.8 32.8 45.745 0 88.48 27105000000 48 3.84703873908103 0.000227979274611399 O60884 O60884 DnaJ homolog subfamily A member 2 DNAJA2 297 Co-chaperone of Hsc70. Stimulates ATP hydrolysis and thefolding of unfolded proteins mediated by HSPA1A/B (in vitro)(PubMed:24318877). Lipid-anchor{ECO:0000305}.;Membrane {ECO:0000305} positive regulation of cell proliferation;protein refolding;response to heat ATP binding;ATPase activator activity;chaperone binding;heat shock protein binding;metal ion binding;unfolded protein binding cytosol;extracellular exosome;membrane Protein processing in endoplasmic reticulum HSP90 chaperone cycle for steroid hormone receptors (SHR) BAX-DNAJA2-HSPA1B complex -1.19781410694122 -0.386724650859833 -0.812714397907257 -0.454298824071884 -0.944673418998718 -1.65585672855377 -1.57567131519318 -0.862840235233307 0.523128092288971 1.08555519580841 1.00433325767517 0.465281397104263 0.0684076845645905 0.822062432765961 0.648681819438934 0.61830335855484 1.36193823814392 1.29290223121643 + Cluster -671 17 17 17 59.3 59.3 59.3 32.854 0 323.31 453600000000 291 3.98104184080862 0.000141242937853107 P08865 P08865 40S ribosomal protein SA RPSA 564 Required for the assembly and/or stability of the 40Sribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of40S ribosomal subunits. Also functions as a cell surface receptorfor laminin. Plays a role in cell adhesion to the basementmembrane and in the consequent activation of signalingtransduction pathways. May play a role in cell fate determinationand tissue morphogenesis. Acts as a PPP1R16B-dependent substrateof PPP1CA. Cell membrane. Cytoplasm. Nucleus{ECO:0000255|HAMAP-Rule:MF_03016}. Note=67LR is found at thesurface of the plasma membrane, with its C-terminal laminin-binding domain accessible to extracellular ligands. 37LRP is foundat the cell surface, in the cytoplasm and in the nucleus (Bysimilarity). Colocalizes with PPP1R16B in the cell membrane.{ECO:0000255|HAMAP-Rule:MF_03016}. cell adhesion;endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA);nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;ribosomal small subunit assembly;rRNA export from nucleus;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation laminin binding;laminin receptor activity;ribosome binding;RNA binding;structural constituent of ribosome;virus receptor activity cytoplasm;cytosol;cytosolic small ribosomal subunit;extracellular exosome;membrane;nucleoplasm;nucleus;plasma membrane Ribosome Congenital asplenia Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic -1.32949578762054 -0.706486701965332 -0.593418598175049 -0.87228912115097 -0.969981908798218 -1.33724963665009 -1.63821387290955 -0.471054792404175 0.556514859199524 1.18496477603912 0.555699825286865 0.29683044552803 0.411991208791733 0.629426538944244 0.367539316415787 1.15511727333069 1.25677514076233 1.50333106517792 + Cluster -671 6 6 6 26.9 26.9 26.9 25.835 0 70.991 6600800000 24 3.67071228790555 0.000323394495412844 Q96CT7 Q96CT7 Coiled-coil domain-containing protein 124 CCDC124 2417 Required for proper progression of late cytokineticstages. Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:23894443}.Midbody {ECO:0000269|PubMed:23894443}. Note=Colocalizes withgamma-tubulin at interphase, prophase, metaphase, and anaphase.Relocates from centrosome to midbody at telophase. cell cycle;cell division RNA binding cytosol;microtubule organizing center;midbody;plasma membrane -1.01422703266144 -0.711657106876373 -0.811076521873474 0.0979218110442162 -1.1642233133316 -1.29212486743927 -1.83108496665955 -1.04674220085144 0.557356059551239 1.1244570016861 1.054083943367 0.256945490837097 0.339731156826019 0.634541392326355 0.760165274143219 0.518237471580505 1.18434679508209 1.3433495759964 + Cluster -671 3 3 3 2.1 2.1 2.1 288.89 0 26.981 627260000 6 3.49433530887673 0.000429141716566866 P42345 P42345 Serine/threonine-protein kinase mTOR MTOR 1012 Serine/threonine protein kinase which is a centralregulator of cellular metabolism, growth and survival in responseto hormones, growth factors, nutrients, energy and stress signals.MTOR directly or indirectly regulates the phosphorylation of atleast 800 proteins. Functions as part of 2 structurally andfunctionally distinct signaling complexes mTORC1 and mTORC2 (mTORcomplex 1 and 2). Activated mTORC1 up-regulates protein synthesisby phosphorylating key regulators of mRNA translation and ribosomesynthesis. This includes phosphorylation of EIF4EBP1 and releaseof its inhibition toward the elongation initiation factor 4E(eiF4E). Moreover, phosphorylates and activates RPS6KB1 andRPS6KB2 that promote protein synthesis by modulating the activityof their downstream targets including ribosomal protein S6,eukaryotic translation initiation factor EIF4B, and the inhibitorof translation initiation PDCD4. Stimulates the pyrimidinebiosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, anddelayed regulation, through transcriptional enhancement of thepentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a laterstep in synthesis, this function is dependent on the mTORC1complex. Regulates ribosome synthesis by activating RNA polymeraseIII-dependent transcription through phosphorylation and inhibitionof MAF1 an RNA polymerase III-repressor. In parallel to proteinsynthesis, also regulates lipid synthesis through SREBF1/SREBP1and LPIN1. To maintain energy homeostasis mTORC1 may also regulatemitochondrial biogenesis through regulation of PPARGC1A. mTORC1also negatively regulates autophagy through phosphorylation ofULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventingactivation of ULK1. Also prevents autophagy throughphosphorylation of the autophagy inhibitor DAP. mTORC1 exerts afeedback control on upstream growth factor signaling that includesphosphorylation and activation of GRB10 a INSR-dependent signalingsuppressor. Among other potential targets mTORC1 may phosphorylateCLIP1 and regulate microtubules. As part of the mTORC2 complexMTOR may regulate other cellular processes including survival andorganization of the cytoskeleton. Plays a critical role in thephosphorylation at 'Ser-473' of AKT1, a pro-survival effector ofphosphoinositide 3-kinase, facilitating its activation by PDK1.mTORC2 may regulate the actin cytoskeleton, throughphosphorylation of PRKCA, PXN and activation of the Rho-typeguanine nucleotide exchange factors RHOA and RAC1A or RAC1B.mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'(PubMed:12087098, PubMed:12150925, PubMed:12150926,PubMed:12231510, PubMed:12718876, PubMed:14651849,PubMed:15268862, PubMed:15467718, PubMed:15545625,PubMed:15718470, PubMed:18497260, PubMed:18762023,PubMed:18925875, PubMed:20516213, PubMed:20537536,PubMed:21659604, PubMed:23429703, PubMed:23429704,PubMed:25799227, PubMed:26018084). Regulates osteoclastogenesis byadjusting the expression of CEBPB isoforms (By similarity) Cytoplasmic side{ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}.Lysosome {ECO:0000269|PubMed:18497260,ECO:0000269|PubMed:20381137}. Cytoplasm{ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:18497260}.Nucleus, PML body {ECO:0000250|UniProtKB:Q9JLN9}. Microsomemembrane {ECO:0000269|PubMed:9434772}. Note=Shuttles betweencytoplasm and nucleus. Accumulates in the nucleus in response tohypoxia (By similarity). Targeting to lysosomes depends on aminoacid availability and RRAGA and RRAGB (PubMed:18497260,PubMed:20381137). {ECO:0000250|UniProtKB:Q9JLN9,ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:20381137}.; Cytoplasmic side{ECO:0000269|PubMed:14578359}. Golgi apparatus membrane{ECO:0000269|PubMed:14578359}; Cytoplasmic side{ECO:0000269|PubMed:14578359}. Mitochondrion outer membrane{ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}; Peripheral membrane protein{ECO:0000269|PubMed:14578359};Endoplasmic reticulum membrane{ECO:0000269|PubMed:14578359};Peripheral membrane protein {ECO:0000269|PubMed:11930000,ECO:0000269|PubMed:14578359} activation of protein kinase B activity;anoikis;brain development;cardiac muscle cell development;cardiac muscle contraction;cell aging;cell cycle arrest;cellular response to amino acid starvation;cellular response to amino acid stimulus;cellular response to hypoxia;cellular response to leucine;cellular response to leucine starvation;cellular response to nutrient levels;cellular response to starvation;'de novo' pyrimidine nucleobase biosynthetic process;energy reserve metabolic process;germ cell development;heart morphogenesis;heart valve morphogenesis;long-term memory;maternal process involved in female pregnancy;mRNA stabilization;multicellular organism growth;negative regulation of autophagy;negative regulation of calcineurin-NFAT signaling cascade;negative regulation of cell size;negative regulation of cholangiocyte apoptotic process;negative regulation of iodide transmembrane transport;negative regulation of macroautophagy;negative regulation of muscle atrophy;negative regulation of protein phosphorylation;negative regulation of protein ubiquitination;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;phosphorylation;positive regulation of actin filament polymerization;positive regulation of cell growth involved in cardiac muscle cell development;positive regulation of cholangiocyte proliferation;positive regulation of cytoplasmic translational initiation;positive regulation of dendritic spine development;positive regulation of eating behavior;positive regulation of endothelial cell proliferation;positive regulation of epithelial to mesenchymal transition;positive regulation of gene expression;positive regulation of glial cell proliferation;positive regulation of granulosa cell proliferation;positive regulation of keratinocyte migration;positive regulation of lamellipodium assembly;positive regulation of lipid biosynthetic process;positive regulation of myotube differentiation;positive regulation of neuron death;positive regulation of neuron maturation;positive regulation of nitric oxide biosynthetic process;positive regulation of oligodendrocyte differentiation;positive regulation of peptidyl-tyrosine phosphorylation;positive regulation of phosphoprotein phosphatase activity;positive regulation of protein kinase B signaling;positive regulation of protein phosphorylation;positive regulation of sensory perception of pain;positive regulation of skeletal muscle hypertrophy;positive regulation of smooth muscle cell proliferation;positive regulation of stress fiber assembly;positive regulation of transcription by RNA polymerase III;positive regulation of transcription of nucleolar large rRNA by RNA polymerase I;positive regulation of translation;positive regulation of wound healing, spreading of epidermal cells;post-embryonic development;protein autophosphorylation;protein catabolic process;protein phosphorylation;regulation of actin cytoskeleton organization;regulation of brown fat cell differentiation;regulation of carbohydrate utilization;regulation of cell growth;regulation of cell size;regulation of cellular response to heat;regulation of fatty acid beta-oxidation;regulation of glycogen biosynthetic process;regulation of GTPase activity;regulation of macroautophagy;regulation of membrane permeability;regulation of myelination;regulation of osteoclast differentiation;regulation of response to food;regulation of translation at synapse, modulating synaptic transmission;response to activity;response to amino acid;response to cocaine;response to insulin;response to morphine;response to nutrient;ruffle organization;social behavior;spinal cord development;T-helper 1 cell lineage commitment;TOR signaling;TORC1 signaling;visual learning;voluntary musculoskeletal movement;wound healing ATP binding;identical protein binding;kinase activity;phosphoprotein binding;protein domain specific binding;protein kinase activity;protein kinase binding;protein serine/threonine kinase activity;ribosome binding;RNA polymerase III type 1 promoter DNA binding;RNA polymerase III type 2 promoter DNA binding;RNA polymerase III type 3 promoter DNA binding;TFIIIC-class transcription factor complex binding;translation regulator activity cytoplasm;cytosol;dendrite;endomembrane system;endoplasmic reticulum membrane;glutamatergic synapse;Golgi membrane;lysosomal membrane;lysosome;membrane;mitochondrial outer membrane;neuronal cell body;nucleoplasm;nucleus;PML body;postsynaptic cytosol;TORC1 complex;TORC2 complex Acute myeloid leukemia;Adipocytokine signaling pathway;AMPK signaling pathway;Apelin signaling pathway;Autophagy - animal;Autophagy - other;Breast cancer;Cellular senescence;Central carbon metabolism in cancer;Choline metabolism in cancer;Colorectal cancer;EGFR tyrosine kinase inhibitor resistance;Endocrine resistance;ErbB signaling pathway;Gastric cancer;Glioma;Hepatocellular carcinoma;Herpes simplex virus 1 infection;HIF-1 signaling pathway;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Human papillomavirus infection;Insulin resistance;Insulin signaling pathway;Jak-STAT signaling pathway;Kaposi sarcoma-associated herpesvirus infection;Longevity regulating pathway;Longevity regulating pathway - multiple species;MicroRNAs in cancer;mTOR signaling pathway;Pancreatic cancer;Pathways in cancer;PD-L1 expression and PD-1 checkpoint pathway in cancer;Phospholipase D signaling pathway;PI3K-Akt signaling pathway;Prostate cancer;Proteoglycans in cancer;Th17 cell differentiation;Thermogenesis;Thyroid hormone signaling pathway;Type II diabetes mellitus Smith-Kingsmore syndrome Apitolisib;Bimiralisib;Dactolisib;Everolimus;Gedatolisib;Olcorolimus;Omipalisib;Ridaforolimus;Samotolisib;Sirolimus;Temsirolimus;Zotarolimus CD28 dependent PI3K/Akt signaling;Constitutive Signaling by AKT1 E17K in Cancer;Energy dependent regulation of mTOR by LKB1-AMPK;HSF1-dependent transactivation;Macroautophagy;mTOR signalling;mTORC1-mediated signalling;PIP3 activates AKT signaling;Regulation of PTEN gene transcription;Regulation of TP53 Degradation;TP53 Regulates Metabolic Genes;VEGFR2 mediated vascular permeability mTOR complex (MTOR, RAPTOR);mTOR complex (MTOR, RAPTOR, MLST8);mTOR complex (MTOR, RICTOR, MLST8);mTORC1 complex;mTORC2 complex -0.475459516048431 -0.988149523735046 -0.576384544372559 -0.746850311756134 -0.906054079532623 -0.829070031642914 -1.67627739906311 -1.16909158229828 0.397255092859268 0.867980003356934 1.1262491941452 -0.334374308586121 0.0371360033750534 1.16517627239227 0.812281787395477 0.442621141672134 0.857951164245605 1.99506068229675 + Cluster -671 1 1 1 4 4 4 41.141 0.001599 1.6711 3785100000 1 3.17516256474776 0.000777957860615883 Q15049;Q15049-2 Q15049;Q15049-2 Membrane protein MLC1 MLC1 1762 Regulates the response of astrocytes to hypo-osmosis bypromoting calcium influx. Multi-pass membraneprotein {ECO:0000305}. Cell membrane{ECO:0000269|PubMed:22328087}. Cytoplasm, perinuclear region{ECO:0000269|PubMed:22328087}. Endoplasmic reticulum{ECO:0000269|PubMed:22328087}.;Membrane {ECO:0000305} caveolin-mediated endocytosis;cellular response to cholesterol;ion transport;positive regulation of intracellular transport;protein complex oligomerization;regulation of response to osmotic stress;vesicle-mediated transport protein transporter activity;protein-containing complex binding apical plasma membrane;basolateral plasma membrane;caveola;cell-cell junction;cytoplasm;cytoplasmic vesicle;early endosome;endoplasmic reticulum;endosome;integral component of membrane;lysosome;membrane raft;perinuclear region of cytoplasm;plasma membrane;recycling endosome Megaloencephalic leukoencephalopathy with subcortical cysts HEPACAM-MLC1-Na,K-ATPase-Kir4.1-AQP4-TRPV4 complex;MLC1-Na,K-ATPase-Kir4.1-AQP4-TRPV4-syntrophin complex -0.649593472480774 -0.329780101776123 -0.144085884094238 -0.649593472480774 -1.41564404964447 -1.16024827957153 -2.04831099510193 -0.830072045326233 -0.301290690898895 0.383378744125366 1.07261395454407 0.173966139554977 0.717522323131561 0.567328691482544 1.12388122081757 0.820928990840912 1.19722521305084 1.47177362442017 + Cluster -671 12 12 12 42.1 42.1 42.1 29.506 0 171.86 33700000000 75 4.56100162947957 4.81927710843374E-05 P61289;P61289-2;P61289-3 P61289;P61289-2;P61289-3 Proteasome activator complex subunit 3 PSME3 1307 Subunit of the 11S REG-gamma (also called PA28-gamma)proteasome regulator, a doughnut-shaped homoheptamer whichassociates with the proteasome. 11S REG-gamma activates thetrypsin-like catalytic subunit of the proteasome but inhibits thechymotrypsin-like and postglutamyl-preferring (PGPH) subunits.Facilitates the MDM2-p53/TP53 interaction which promotesubiquitination- and MDM2-dependent proteasomal degradation ofp53/TP53, limiting its accumulation and resulting in inhibitedapoptosis after DNA damage. May also be involved in cell cycleregulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition(PubMed:25361978). Nucleus {ECO:0000269|PubMed:10657252,ECO:0000269|PubMed:12629132}. Cytoplasm {ECO:0000250}.Note=Localizes to the cytoplasm during mitosis following nuclearenvelope breakdown at this distinct stage of the cell cycle whichallows its interaction with MAP3K3 kinase. {ECO:0000250}. apoptotic process;cell cycle;negative regulation of extrinsic apoptotic signaling pathway;positive regulation of endopeptidase activity;post-translational protein modification;protein deubiquitination;regulation of G1/S transition of mitotic cell cycle;regulation of proteasomal protein catabolic process endopeptidase activator activity;identical protein binding;MDM2/MDM4 family protein binding;p53 binding cytoplasm;cytosol;membrane;nucleoplasm;nucleus;proteasome activator complex;proteasome complex Antigen processing and presentation;Hepatitis C;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 PA28gamma complex;PA28gamma-20S proteasome -0.670373022556305 -0.297332853078842 0.00966500118374825 -0.617352366447449 -1.43440163135529 -1.03941142559052 -1.93136727809906 -1.40500676631927 0.18781989812851 0.914642453193665 1.46404266357422 0.209046483039856 0.087941437959671 0.785479009151459 0.914642453193665 0.74645984172821 0.976298451423645 1.09920752048492 + Cluster -671 5 5 5 38.4 38.4 38.4 14.463 0 39.586 96029000000 101 3.83592407547912 0.000228205128205128 P62899;P62899-3;P62899-2 P62899;P62899-3;P62899-2 60S ribosomal protein L31 RPL31 1380 cytoplasmic translation;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic large ribosomal subunit;extracellular exosome;focal adhesion;membrane;polysomal ribosome Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic -0.478016346693039 0.391348570585251 -1.89006543159485 -1.30041182041168 -1.49580836296082 -0.406768828630447 -0.724354386329651 -0.951973080635071 0.910874664783478 0.728140890598297 0.609758019447327 0.741944432258606 -0.184377014636993 0.193919315934181 -0.00631006667390466 0.926959812641144 1.48335421085358 1.45178544521332 + Cluster -671 8 8 8 23.1 23.1 23.1 62.717 0 141.06 9532300000 26 3.16932376173858 0.000785829307568438 Q8WZA9 Q8WZA9 Immunity-related GTPase family Q protein IRGQ 2322 GTP binding -0.423558115959167 -0.493032366037369 -1.61610269546509 -1.19182252883911 -1.42323076725006 -1.17154252529144 -0.704262673854828 -0.535432398319244 0.842678844928741 0.588108062744141 0.717959105968475 0.344651788473129 0.273794203996658 0.00462669413536787 0.482073813676834 1.20952594280243 1.31040847301483 1.78515696525574 + Cluster -671 2 2 2 3.4 3.4 3.4 132.37 0 37.425 2787300000 7 3.62753235173038 0.000343680709534368 Q96KQ7;Q96KQ7-2;Q96KQ7-3 Q96KQ7;Q96KQ7-2;Q96KQ7-3 Histone-lysine N-methyltransferase EHMT2 EHMT2 2501 Histone methyltransferase that specifically mono- anddimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2,respectively) in euchromatin. H3K9me represents a specific tag forepigenetic transcriptional repression by recruiting HP1 proteinsto methylated histones. Also mediates monomethylation of 'Lys-56'of histone H3 (H3K56me1) in G1 phase, leading to promoteinteraction between histone H3 and PCNA and regulating DNAreplication. Also weakly methylates 'Lys-27' of histone H3(H3K27me). Also required for DNA methylation, the histonemethyltransferase activity is not required for DNA methylation,suggesting that these 2 activities function independently.Probably targeted to histone H3 by different DNA-binding proteinslike E2F6, MGA, MAX and/or DP1. May also methylate histone H1. Inaddition to the histone methyltransferase activity, alsomethylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1,ERCC6, KLF12 and itself. Nucleus {ECO:0000269|PubMed:11316813}.Chromosome {ECO:0000269|PubMed:11316813}. Note=Associates witheuchromatic regions. Does not associate with heterochromatin. cellular response to starvation;DNA methylation;histone lysine methylation;histone methylation;negative regulation of G0 to G1 transition;negative regulation of transcription by RNA polymerase II;peptidyl-lysine dimethylation;regulation of DNA replication C2H2 zinc finger domain binding;histone methyltransferase activity (H3-K27 specific);histone methyltransferase activity (H3-K9 specific);histone-lysine N-methyltransferase activity;p53 binding;promoter-specific chromatin binding;protein-lysine N-methyltransferase activity;zinc ion binding nuclear chromatin;nuclear speck;nucleoplasm;nucleus Longevity regulating pathway;Lysine degradation ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;PKMTs methylate histone lysines;Regulation of TP53 Activity through Methylation;RNA Polymerase I Transcription Initiation;Senescence-Associated Secretory Phenotype (SASP);Transcriptional Regulation by E2F6 CBX3-EHMT2-NR3C1 complex;CtBP complex;CtBP core complex;DNMT1-EHMT2 complex;DNMT1-EHMT2-PCNA complex;E2F-6 complex -0.722158133983612 -0.538831114768982 -1.28730320930481 -0.554195046424866 -1.5148161649704 -1.23527729511261 -1.35687375068665 -0.548127710819244 1.12159013748169 0.685931622982025 1.29913282394409 0.565675020217896 0.0435173064470291 0.221883878111839 0.324146509170532 1.47059142589569 0.733130395412445 1.29198348522186 + Cluster -671 4 4 4 20.2 20.2 20.2 52.417 0 58.641 10758000000 31 3.28255373939016 0.000606164383561644 Q92733 Q92733 Proline-rich protein PRCC PRCC 2348 May regulate cell cycle progression through interactionwith MAD2L2. Nucleus {ECO:0000269|PubMed:11717438}. mitotic cell cycle checkpoint;mRNA splicing, via spliceosome nuclear speck;nucleoplasm;nucleus Renal cell carcinoma;Transcriptional misregulation in cancer mRNA Splicing - Major Pathway -0.673198282718658 -0.137392431497574 -1.66978013515472 -0.766656577587128 -1.13224732875824 -0.993117809295654 -1.76698398590088 -0.665699779987335 0.849586486816406 0.772422254085541 1.09825158119202 0.446349948644638 0.390671968460083 0.263291031122208 0.454805374145508 1.26254189014435 1.10424363613129 1.16291213035583 + Cluster -671 1 1 1 9 9 9 20.64 0 9.5134 922320000 4 4.3761563612779 6.27177700348432E-05 P79522;P79522-2 P79522;P79522-2 Proline-rich protein 3 PRR3 1436 metal ion binding;RNA binding -0.58914315700531 -0.561632096767426 -1.38096153736115 -0.757999122142792 -1.31899511814117 -0.903461515903473 -1.23980093002319 -1.0878654718399 0.517505645751953 0.870867967605591 1.15384459495544 0.248274296522141 -0.0309331435710192 0.335293620824814 0.653790831565857 1.3534482717514 1.22787654399872 1.50989043712616 + Cluster -671 14 14 14 25.7 25.7 25.7 83.677 0 172.58 17575000000 57 4.40453733435922 6.04982206405694E-05 Q16891;Q16891-2;Q16891-4;Q16891-3 Q16891;Q16891-2;Q16891-4;Q16891-3 MICOS complex subunit MIC60 IMMT 1872 Component of the MICOS complex, a large protein complexof the mitochondrial inner membrane that plays crucial roles inthe maintenance of crista junctions, inner membrane architecture,and formation of contact sites to the outer membrane. Plays animportant role in the maintenance of the MICOS complex stabilityand the mitochondrial cristae morphology (PubMed:22114354,PubMed:25781180). Mitochondrion inner membrane{ECO:0000269|PubMed:25764979, ECO:0000269|PubMed:25997101};Single-pass membrane protein {ECO:0000255}. Mitochondrion{ECO:0000269|PubMed:25781180}. cristae formation;mitochondrial calcium ion homeostasis RNA binding membrane;MICOS complex;mitochondrial inner membrane;mitochondrion;myelin sheath Cristae formation MIB complex;MICOS complex;MINOS complex -0.0387705527245998 -0.494614064693451 -0.979004502296448 -1.4656103849411 -1.06941366195679 -1.13214099407196 -1.09981727600098 -1.24189782142639 0.408401280641556 0.946087777614594 1.5379775762558 0.568837940692902 -0.0723390355706215 0.308286607265472 0.185026362538338 1.53382098674774 1.14281463623047 0.962355077266693 + Cluster -671 5 5 5 4.1 4.1 4.1 196.04 0 85.323 2161800000 15 4.81011184132416 2.32558139534884E-05 Q5SRE5;Q5SRE5-2 Q5SRE5;Q5SRE5-2 Nucleoporin NUP188 homolog NUP188 1929 May function as a component of the nuclear pore complex(NPC). Nucleus, nuclear pore complex {ECO:0000305}. mRNA export from nucleus;protein import into nucleus;viral process structural constituent of nuclear pore membrane;nuclear envelope;nuclear pore inner ring RNA transport ISG15 antiviral mechanism;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Rev-mediated nuclear export of HIV RNA;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs -0.697939872741699 -0.617371320724487 -0.828231394290924 -0.457703858613968 -1.26297557353973 -0.965246081352234 -1.608189702034 -1.05815458297729 0.223070487380028 0.74855250120163 1.68911588191986 0.991727769374847 0.0198711566627026 -0.0667280107736588 0.249051079154015 1.01177072525024 1.24614500999451 1.38323569297791 + Cluster -671 4 4 4 7.2 7.2 7.2 64.244 0 14.916 6331600000 11 4.06278618796793 0.000130952380952381 Q96AY3;Q96AY3-2 Q96AY3 Peptidyl-prolyl cis-trans isomerase FKBP10 FKBP10 2403 PPIases accelerate the folding of proteins duringprotein synthesis. Endoplasmic reticulum lumen{ECO:0000255|PROSITE-ProRule:PRU10138}. calcium ion binding;FK506 binding;peptidyl-prolyl cis-trans isomerase activity endoplasmic reticulum lumen Bruck syndrome;Osteogenesis imperfecta PLOD2-FKBP10 complex -0.328010559082031 -0.561780214309692 -0.600275576114655 -0.550017714500427 -0.983157575130463 -1.19609463214874 -1.66802585124969 -1.57736313343048 -0.151869386434555 1.13491868972778 1.39771270751953 1.103431224823 0.245830222964287 -0.0253845863044262 0.584975242614746 1.07372903823853 1.05069100856781 1.05069100856781 + Cluster -671 8 8 8 29.8 29.8 29.8 39.233 0 68.742 7485200000 27 5.50120745838357 7.93650793650794E-06 P11177;P11177-2;P11177-3 P11177;P11177-2;P11177-3 Pyruvate dehydrogenase E1 component subunit beta, mitochondrial PDHB 619 The pyruvate dehydrogenase complex catalyzes the overallconversion of pyruvate to acetyl-CoA and CO(2), and thereby linksthe glycolytic pathway to the tricarboxylic cycle Mitochondrion matrix. acetyl-CoA biosynthetic process from pyruvate;glucose metabolic process;mitochondrial acetyl-CoA biosynthetic process from pyruvate;tricarboxylic acid cycle pyruvate dehydrogenase (acetyl-transferring) activity;pyruvate dehydrogenase activity mitochondrial matrix;mitochondrion;nucleoplasm;nucleus;pyruvate dehydrogenase complex Carbon metabolism;Central carbon metabolism in cancer;Citrate cycle (TCA cycle);Glucagon signaling pathway;Glycolysis / Gluconeogenesis;HIF-1 signaling pathway;Metabolic pathways;Pyruvate metabolism Pyruvate dehydrogenase complex deficiency;Pyruvate dehydrogenase E1-beta deficiency Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Regulation of pyruvate dehydrogenase (PDH) complex;Signaling by Retinoic Acid -0.091550350189209 -0.806753873825073 -1.38415396213531 -0.250962793827057 -1.19443166255951 -0.956600308418274 -1.4860657453537 -1.20565831661224 0.644857466220856 1.29565274715424 1.06686401367188 1.37082707881927 -0.0298981219530106 -0.153621226549149 0.0984858796000481 1.19838786125183 0.942310631275177 0.942310631275177 + Cluster -671 3 3 3 16.4 16.4 16.4 30.156 0 3.0135 235120000 4 4.07280976227095 0.00012874251497006 Q13084 Q13084 39S ribosomal protein L28, mitochondrial MRPL28 1590 Mitochondrion {ECO:0000269|PubMed:25278503,ECO:0000269|PubMed:28892042}. mitochondrial translational elongation;mitochondrial translational termination;translation RNA binding;structural constituent of ribosome cytosol;mitochondrial inner membrane;mitochondrial large ribosomal subunit;mitochondrial ribosome;mitochondrion Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 39S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -0.751869976520538 -1.0221072435379 -0.272021621465683 -0.777560889720917 -0.904437780380249 -1.1415901184082 -1.44524395465851 -1.42604768276215 -0.252641022205353 0.837375223636627 1.07545650005341 0.603355884552002 0.372418016195297 0.549998462200165 0.574273943901062 1.03666579723358 1.51062405109406 1.43335235118866 + Cluster -671 19 19 19 52 52 52 49.541 0 229.28 82499000000 132 5.25814519085628 1.30718954248366E-05 P49411 P49411 Elongation factor Tu, mitochondrial TUFM 1096 Promotes the GTP-dependent binding of aminoacyl-tRNA tothe A-site of ribosomes during protein biosynthesis. Plays also arole in the regulation of autophagy and innate immunity. RecruitsATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint ofthe RIG-I/DDX58-MAVS pathway. In turn, inhibits RLR-mediated typeI interferon while promoting autophagy Mitochondrion {ECO:0000269|PubMed:22749352}. mitochondrial translational elongation;response to ethanol;translational elongation GTP binding;GTPase activity;RNA binding;translation elongation factor activity extracellular exosome;membrane;mitochondrial nucleoid;mitochondrion;myelin sheath;synapse Combined oxidative phosphorylation deficiency Mitochondrial translation elongation Nop56p-associated pre-rRNA complex -0.813764333724976 -0.212523281574249 -1.01937806606293 -0.863564193248749 -0.941068112850189 -1.33861017227173 -1.28142690658569 -1.44332492351532 -0.0735066682100296 1.00398087501526 0.737255752086639 0.632449150085449 0.473159581422806 0.660275638103485 0.556227385997772 1.14565026760101 1.44926524162292 1.32890284061432 + Cluster -671 4 4 4 17.9 17.9 17.9 33.419 0 18.975 1745700000 6 6.78059763478442 0 Q9P015 Q9P015 39S ribosomal protein L15, mitochondrial MRPL15 3035 Mitochondrion {ECO:0000269|PubMed:25278503,ECO:0000269|PubMed:25838379, ECO:0000269|PubMed:28892042}. cellular response to leukemia inhibitory factor;mitochondrial translational elongation;mitochondrial translational termination RNA binding;structural constituent of ribosome mitochondrial inner membrane;mitochondrial large ribosomal subunit;mitochondrion Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 39S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial 0.0234054662287235 -0.73581862449646 -0.89856481552124 -0.916909217834473 -1.2155214548111 -1.31815493106842 -1.35233783721924 -1.35233783721924 -0.0972386375069618 0.916696786880493 1.02069342136383 0.524903237819672 0.559657394886017 0.475990563631058 0.524903237819672 1.35237991809845 1.12133586406708 1.36691737174988 + Cluster -671 9 9 9 39.7 39.7 39.7 31.387 0 176.61 22306000000 51 6.69510634568061 0 P30084 P30084 Enoyl-CoA hydratase, mitochondrial ECHS1 864 Straight-chain enoyl-CoA thioesters from C4 up to atleast C16 are processed, although with decreasing catalytic rate.Has high substrate specificity for crotonyl-CoA and moderatespecificity for acryloyl-CoA, 3-methylcrotonyl-CoA andmethacrylyl-CoA. It is noteworthy that binds tiglyl-CoA, buthydrates only a small amount of this substrate Mitochondrion matrix. fatty acid beta-oxidation enoyl-CoA hydratase activity mitochondrial matrix;mitochondrion beta-Alanine metabolism;Butanoate metabolism;Carbon metabolism;Fatty acid degradation;Fatty acid elongation;Fatty acid metabolism;Lysine degradation;Metabolic pathways;Propanoate metabolism;Tryptophan metabolism;Valine, leucine and isoleucine degradation Beta oxidation of butanoyl-CoA to acetyl-CoA;Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA;Beta oxidation of hexanoyl-CoA to butanoyl-CoA;Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA;Beta oxidation of octanoyl-CoA to hexanoyl-CoA -0.501693964004517 -0.363386213779449 -1.07481479644775 -0.97436398267746 -0.763204276561737 -1.43439662456512 -1.48159801959991 -1.39296686649323 0.0474412627518177 0.96990430355072 0.929914772510529 0.70862603187561 0.384562283754349 0.674894392490387 0.641052305698395 1.09611976146698 1.27629554271698 1.25761389732361 + Cluster -671 1 1 1 3.1 3.1 3.1 33.535 0.00032563 1.9814 1124600000 3 7.28460341594404 0 P49406 P49406 39S ribosomal protein L19, mitochondrial MRPL19 1094 Mitochondrion {ECO:0000269|PubMed:10600119,ECO:0000269|PubMed:11543634, ECO:0000269|PubMed:25278503,ECO:0000269|PubMed:25838379, ECO:0000269|PubMed:28892042}. mitochondrial translational elongation;mitochondrial translational termination structural constituent of ribosome mitochondrial inner membrane;mitochondrial large ribosomal subunit;mitochondrion;nuclear membrane;nucleus Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 39S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -1.35985720157623 -0.512063324451447 0.0968470796942711 0.00883298553526402 -0.722661912441254 -1.10957288742065 -2.04487943649292 -1.02456784248352 -0.116259030997753 1.45784759521484 1.38576459884644 1.17516601085663 0.0310998000204563 -0.212865576148033 0.34206622838974 0.744891583919525 0.875700771808624 0.984510600566864 + Cluster -671 28 5 5 63.5 16.2 16.2 49.67 0 198.66 738200000000 444 3.17696700126222 0.000775974025974026 P07437;A6NNZ2 P07437 Tubulin beta chain TUBB 538 Tubulin is the major constituent of microtubules. Itbinds two moles of GTP, one at an exchangeable site on the betachain and one at a non-exchangeable site on the alpha chain (Bysimilarity).;Tubulin is the major constituent of microtubules. Itbinds two moles of GTP, one at an exchangeable site on the betachain and one at a non-exchangeable site on the alpha chain. Cytoplasm, cytoskeleton {ECO:0000250}.;Cytoplasm, cytoskeleton{ECO:0000269|PubMed:26637975}. cell division;cellular process;ciliary basal body-plasma membrane docking;cytoskeleton-dependent intracellular transport;G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;microtubule-based process;mitotic cell cycle;natural killer cell mediated cytotoxicity;neutrophil degranulation;regulation of G2/M transition of mitotic cell cycle;regulation of synapse organization;spindle assembly GTP binding;GTPase activating protein binding;GTPase activity;MHC class I protein binding;protein domain specific binding;protein-containing complex binding;structural constituent of cytoskeleton;structural molecule activity;ubiquitin protein ligase binding azurophil granule lumen;cell body;cytoplasm;cytoplasmic ribonucleoprotein granule;cytoskeleton;extracellular exosome;extracellular region;membrane raft;microtubule;nuclear envelope lumen;nucleus Gap junction;Pathogenic Escherichia coli infection;Phagosome Complex cortical dysplasia with other brain malformations;Congenital symmetric circumferential skin creases Batabulin;Brentuximab vedotin;Cabazitaxel;Cevipabulin;Colchicine;Denintuzumab mafodotin;Docetaxel;Enfortumab vedotin;Eribulin;Estramustine;Glembatumumab vedotin;Indibulin;Ixabepilone;Lexibulin;Lifastuzumab vedotin;Lisavanbulin;Maytansine;Mivobulin isethionate;Paclitaxel;Paclitaxel poliglumex;Podophyllotoxin;Soblidotin;Taltobulin;Tasidotin hydrochloride;Trastuzumab emtansine;Verubulin;Vinblastine;Vincristine;Vindesine;Vinepidine sulfate;Vinflunine;Vinglycinate sulfate;Vinleurosine sulfate;Vinorelbine;Vinrosidine sulfate;Vinzolidine sulfate Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;Carboxyterminal post-translational modifications of tubulin;Cilium Assembly;COPI-dependent Golgi-to-ER retrograde traffic;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;Gap junction assembly;HSP90 chaperone cycle for steroid hormone receptors (SHR);Kinesins;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;MHC class II antigen presentation;Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane;Mitotic Prometaphase;Neutrophil degranulation;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Recycling pathway of L1;Regulation of PLK1 Activity at G2/M Transition;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;RHO GTPases activate IQGAPs;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;Translocation of SLC2A4 (GLUT4) to the plasma membrane ASCOM complex;SNW1 complex;TBCD-ARL2-tubulin(beta) complex;TBCD-ARL2-tubulin(beta)-TBCE complex;TBCD-tubulin(alpha)-tubulin(beta) complex -1.01693451404572 0.385317981243134 -1.5374253988266 -0.342123359441757 -0.512775421142578 -1.50629186630249 -1.23921477794647 -1.14397394657135 0.142461031675339 1.16137254238129 1.63749492168427 1.04101896286011 -0.143471091985703 0.156861931085587 0.036171268671751 0.915646374225616 1.0502188205719 0.915646374225616 + Cluster -671 5 5 5 10.9 10.9 10.9 69.917 0 22.114 2963800000 12 3.95413875385442 0.000158333333333333 Q9NQW7;Q9NQW7-3;Q9NQW7-2;Q9NQW7-4 Q9NQW7;Q9NQW7-3;Q9NQW7-2;Q9NQW7-4 Xaa-Pro aminopeptidase 1 XPNPEP1 2903 Contributes to the degradation of bradykinin. Catalyzesthe removal of a penultimate prolyl residue from the N-termini ofpeptides, such as Arg-Pro-Pro. Cytoplasm {ECO:0000250}. bradykinin catabolic process;proteolysis aminopeptidase activity;manganese ion binding;metalloaminopeptidase activity;protein homodimerization activity cytoplasm;cytosol;extracellular exosome -0.965290725231171 0.423313736915588 -1.27202093601227 -0.390496462583542 -0.865646123886108 -1.13838970661163 -1.59503209590912 -1.13838970661163 -0.247992038726807 1.10575139522552 1.38820195198059 1.01323115825653 -0.159956976771355 0.180387496948242 0.344176083803177 0.793993651866913 1.29768145084381 1.22647774219513 + Cluster -671 10 10 10 21.3 21.3 21.3 79.467 0 51.173 10152000000 18 4.26236281308703 8.76623376623377E-05 P28331;P28331-3;P28331-4;P28331-5;P28331-2 P28331;P28331-3;P28331-4;P28331-5;P28331-2 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial NDUFS1 842 Core subunit of the mitochondrial membrane respiratorychain NADH dehydrogenase (Complex I) that is believed to belong tothe minimal assembly required for catalysis. Complex I functionsin the transfer of electrons from NADH to the respiratory chain.The immediate electron acceptor for the enzyme is believed to beubiquinone (By similarity). This is the largest subunit of complexI and it is a component of the iron-sulfur (IP) fragment of theenzyme. It may form part of the active site crevice where NADH isoxidized. Mitochondrion inner membrane. apoptotic mitochondrial changes;ATP metabolic process;cellular respiration;mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;reactive oxygen species metabolic process;regulation of mitochondrial membrane potential 2 iron, 2 sulfur cluster binding;4 iron, 4 sulfur cluster binding;electron transfer activity;metal ion binding;NADH dehydrogenase (ubiquinone) activity mitochondrial intermembrane space;mitochondrial matrix;mitochondrial respiratory chain complex I;mitochondrion;myelin sheath;plasma membrane respiratory chain complex I Alzheimer disease;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Retrograde endocannabinoid signaling;Thermogenesis Mitochondrial complex I deficiency Complex I biogenesis;Respiratory electron transport Respiratory chain complex I (holoenzyme), mitochondrial;Respiratory chain complex I (incomplete intermediate), mitochondrial;Respiratory chain complex I (lambda subunit) mitochondrial -0.623683393001556 -0.125009194016457 -1.03541672229767 -0.26280614733696 -1.21782088279724 -1.36808621883392 -1.75225722789764 -0.934907376766205 0.473176896572113 1.15428459644318 1.21916389465332 1.03646636009216 -0.37742668390274 0.554426372051239 0.468336254358292 0.215229317545891 1.3323175907135 1.24401259422302 + Cluster -671 11 11 11 32.9 32.9 32.9 34.93 0 150.21 88185000000 87 4.0019032735519 0.000138728323699422 Q96AG4 Q96AG4 Leucine-rich repeat-containing protein 59 LRRC59 2399 Required for nuclear import of FGF1, but not that ofFGF2. Might regulate nuclear import of exogenous FGF1 byfacilitating interaction with the nuclear import machinery and bytransporting cytosolic FGF1 to, and possibly through, the nuclearpores. Single-pass type II membrane protein {ECO:0000250}. Endoplasmic reticulummembrane; Single-pass type II membrane protein. Nucleus envelope.Note=Localization in the nuclear envelope depends upon the nuclearimport machinery, including KPNB1.;Microsome membrane {ECO:0000250} cadherin binding;RNA binding cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;membrane;mitochondrial nucleoid;nuclear envelope;organelle membrane -1.13139200210571 -0.00972196832299232 -1.23300039768219 -0.565021812915802 -1.06297540664673 -1.48500752449036 -1.27339231967926 -0.932124197483063 0.672156095504761 1.05763721466064 1.32784616947174 0.803596675395966 0.0510721206665039 0.225193306803703 0.225193306803703 0.763764679431915 1.50153517723083 1.06464087963104 + Cluster -671 12 12 12 41.5 41.5 41.5 48.141 0 154.78 91470000000 116 3.99954454801041 0.000137931034482759 P27797 P27797 Calreticulin CALR 832 Calcium-binding chaperone that promotes folding,oligomeric assembly and quality control in the endoplasmicreticulum (ER) via the calreticulin/calnexin cycle. This lectininteracts transiently with almost all of the monoglucosylatedglycoproteins that are synthesized in the ER. Interacts with theDNA-binding domain of NR3C1 and mediates its nuclear export.Involved in maternal gene expression regulation. May participatein oocyte maturation via the regulation of calcium homeostasis (Bysimilarity). Endoplasmic reticulum lumen{ECO:0000269|PubMed:10358038, ECO:0000269|PubMed:11149926}.Cytoplasm, cytosol {ECO:0000269|PubMed:11149926}. Secreted,extracellular space, extracellular matrix {ECO:0000305}. Cellsurface {ECO:0000269|PubMed:10358038}. Sarcoplasmic reticulumlumen {ECO:0000250|UniProtKB:P28491}. Note=Also found in cellsurface (T cells), cytosol and extracellular matrix(PubMed:10358038). Associated with the lytic granules in thecytolytic T-lymphocytes. {ECO:0000269|PubMed:10358038,ECO:0000269|PubMed:8418194}. antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent;antigen processing and presentation of peptide antigen via MHC class I;ATF6-mediated unfolded protein response;cardiac muscle cell differentiation;cellular calcium ion homeostasis;cellular response to lithium ion;cellular senescence;chaperone-mediated protein folding;cortical actin cytoskeleton organization;glucocorticoid receptor signaling pathway;negative regulation of cell cycle arrest;negative regulation of intracellular steroid hormone receptor signaling pathway;negative regulation of neuron differentiation;negative regulation of retinoic acid receptor signaling pathway;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;negative regulation of translation;negative regulation of trophoblast cell migration;peptide antigen assembly with MHC class I protein complex;positive regulation of cell cycle;positive regulation of cell proliferation;positive regulation of dendritic cell chemotaxis;positive regulation of endothelial cell migration;positive regulation of gene expression;positive regulation of NIK/NF-kappaB signaling;positive regulation of phagocytosis;positive regulation of substrate adhesion-dependent cell spreading;protein export from nucleus;protein folding;protein folding in endoplasmic reticulum;protein localization to nucleus;protein maturation by protein folding;protein stabilization;receptor-mediated endocytosis;regulation of apoptotic process;regulation of meiotic nuclear division;regulation of transcription, DNA-templated;response to drug;response to estradiol;response to testosterone;sequestering of calcium ion;spermatogenesis;vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane androgen receptor binding;calcium ion binding;carbohydrate binding;chaperone binding;complement component C1q binding;DNA binding;hormone binding;integrin binding;iron ion binding;mRNA binding;peptide binding;protein binding involved in protein folding;RNA binding;ubiquitin protein ligase binding;unfolded protein binding;zinc ion binding acrosomal vesicle;cell surface;collagen-containing extracellular matrix;cytoplasm;cytosol;endocytic vesicle lumen;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum quality control compartment;endoplasmic reticulum-Golgi intermediate compartment membrane;external side of plasma membrane;extracellular exosome;extracellular region;extracellular space;focal adhesion;Golgi apparatus;integral component of lumenal side of endoplasmic reticulum membrane;intracellular;membrane;MHC class I peptide loading complex;nuclear envelope;nucleus;perinuclear region of cytoplasm;phagocytic vesicle membrane;polysome;sarcoplasmic reticulum lumen;smooth endoplasmic reticulum Antigen processing and presentation;Chagas disease (American trypanosomiasis);Epstein-Barr virus infection;Herpes simplex virus 1 infection;Human cytomegalovirus infection;Human immunodeficiency virus 1 infection;Human T-cell leukemia virus 1 infection;Phagosome;Protein processing in endoplasmic reticulum Essential thrombocytosis;Myelofibrosis Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Assembly of Viral Components at the Budding Site;ATF6 (ATF6-alpha) activates chaperone genes;Calnexin/calreticulin cycle;ER-Phagosome pathway;Scavenging by Class A Receptors;Scavenging by Class F Receptors Calreticulin homo-oligomer complex;H2AX complex I;H2AX complex II;H2AX complex, isolated from cells without IR exposure -1.20932996273041 -0.0589970424771309 -1.07302904129028 -0.312913328409195 -0.803527772426605 -1.52866303920746 -1.14385390281677 -1.06479275226593 0.56886500120163 1.4927476644516 1.46858322620392 0.778440296649933 -0.618921637535095 0.394459515810013 0.222042128443718 0.631441712379456 1.20204031467438 1.05540871620178 + Cluster -671 6 6 6 24.9 24.9 24.9 38.926 0 132.71 14420000000 31 3.32851797130211 0.000575971731448763 P61962;P61962-2 P61962 DDB1- and CUL4-associated factor 7 DCAF7 1325 Involved in craniofacial development. Acts upstream ofthe EDN1 pathway and is required for formation of the upper jawequivalent, the palatoquadrate. The activity required for EDN1pathway function differs between the first and second arches (Bysimilarity). Associates with DIAPH1 and controls GLI1transcriptional activity. Could be involved in normal and diseaseskin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. Cytoplasm. Nucleus. Note=Overexpression ofDIAHP1 or active RHOA causes translocation from the nucleus tocytoplasm. multicellular organism development;post-translational protein modification;protein ubiquitination Cul4-RING E3 ubiquitin ligase complex;cytoplasm;cytosol;nuclear body;nuclear matrix;nucleoplasm;nucleus;protein-containing complex Association of TriC/CCT with target proteins during biosynthesis;Neddylation -1.06351900100708 0.00294519681483507 -1.28588223457336 -0.0209093987941742 -0.389756590127945 -1.56804168224335 -1.71060991287231 -0.975203096866608 0.520863592624664 1.43173348903656 1.38789021968842 1.08449339866638 -0.293608963489532 -0.0321274511516094 0.675448954105377 0.504680871963501 0.92145699262619 0.810145556926727 + Cluster -671 9 9 9 12.3 12.3 12.3 106.49 0 36.669 5381100000 16 3.40497981842129 0.000509293680297398 P36776;P36776-3;P36776-2 P36776;P36776-3;P36776-2 Lon protease homolog, mitochondrial LONP1 955 ATP-dependent serine protease that mediates theselective degradation of misfolded, unassembled or oxidativelydamaged polypeptides as well as certain short-lived regulatoryproteins in the mitochondrial matrix. May also have a chaperonefunction in the assembly of inner membrane protein complexes.Participates in the regulation of mitochondrial gene expressionand in the maintenance of the integrity of the mitochondrialgenome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. May regulatemitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation ofregulatory proteins binding to adjacent sites in mitochondrialpromoters (PubMed:12198491, PubMed:15870080, PubMed:17420247,PubMed:8248235). Endogenous substrates include mitochondrialsteroidogenic acute regulatory (StAR) protein, helicase Twinkle(TWNK) and the large ribosomal subunit protein bL32m. bL32m isprotected from degradation by LONP1 when it is bound to a nucleicacid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575) Mitochondrion matrix {ECO:0000255|HAMAP-Rule:MF_03120, ECO:0000269|PubMed:7961901}. aging;cellular response to oxidative stress;chaperone-mediated protein complex assembly;mitochondrial DNA metabolic process;mitochondrial genome maintenance;mitochondrion organization;oxidation-dependent protein catabolic process;protein homooligomerization;protein quality control for misfolded or incompletely synthesized proteins;proteolysis involved in cellular protein catabolic process;response to aluminum ion;response to hormone;response to hypoxia ADP binding;ATP binding;ATP-dependent peptidase activity;DNA polymerase binding;G-quadruplex DNA binding;mitochondrial promoter sequence-specific DNA binding;sequence-specific DNA binding;serine-type endopeptidase activity;single-stranded DNA binding;single-stranded RNA binding cytosol;membrane;mitochondrial matrix;mitochondrial nucleoid;mitochondrion;nucleoplasm;nucleus CODAS syndrome -0.719881534576416 0.211043357849121 -0.965714812278748 -0.449579209089279 -0.719881534576416 -1.2104457616806 -1.63062429428101 -0.906012058258057 0.321085870265961 1.92350697517395 1.11264085769653 1.26114237308502 -1.05931770801544 0.0312682315707207 0.477861762046814 0.921992063522339 0.812357842922211 0.588557541370392 + Cluster -671 8 6 6 30.1 24.4 24.4 40.925 0 55.571 15580000000 32 3.57302967852918 0.000378205128205128 O60256;O60256-4;O60256-2;O60256-3 O60256;O60256-4;O60256-2;O60256-3 Phosphoribosyl pyrophosphate synthase-associated protein 2 PRPSAP2 259 Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis. 5-phosphoribose 1-diphosphate biosynthetic process;bone development;nucleobase-containing compound metabolic process;nucleoside metabolic process;nucleotide biosynthetic process;purine nucleotide biosynthetic process enzyme inhibitor activity;magnesium ion binding;ribose phosphate diphosphokinase activity cytoplasm;ribose phosphate diphosphokinase complex -0.839625716209412 -0.308518141508102 -0.987218260765076 -0.436124444007874 -0.728715062141418 -1.57740926742554 -1.57740926742554 -1.08088481426239 0.896047830581665 1.56052029132843 1.42239880561829 0.969137489795685 -0.0169716347008944 -0.0169716347008944 0.31756380200386 0.512058198451996 0.996074140071869 0.896047830581665 + Cluster -671 14 14 13 24 24 23 67.567 0 284.57 192160000000 234 4.1300624298388 0.000114197530864198 P27824;P27824-2;P27824-3 P27824;P27824-2;P27824-3 Calnexin CANX 834 Calcium-binding protein that interacts with newlysynthesized glycoproteins in the endoplasmic reticulum. It may actin assisting protein assembly and/or in the retention within theER of unassembled protein subunits. It seems to play a major rolein the quality control apparatus of the ER by the retention ofincorrectly folded proteins. Associated with partial T-cellantigen receptor complexes that escape the ER of immaturethymocytes, it may function as a signaling complex regulatingthymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse. Single-pass type I membrane protein{ECO:0000255}. Endoplasmic reticulum{ECO:0000269|PubMed:22314232}. Melanosome{ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}.Note=Identified by mass spectrometry in melanosome fractions fromstage I to stage IV (PubMed:12643545, PubMed:17081065). Thepalmitoylated form preferentially localizes to the perinuclearrough ER (PubMed:22314232). {ECO:0000269|PubMed:12643545,ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:22314232}.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:22314232} aging;antigen processing and presentation of exogenous peptide antigen via MHC class II;antigen processing and presentation of peptide antigen via MHC class I;chaperone-mediated protein folding;clathrin-dependent endocytosis;interleukin-27-mediated signaling pathway;interleukin-35-mediated signaling pathway;protein folding;protein folding in endoplasmic reticulum;protein secretion;synaptic vesicle endocytosis apolipoprotein binding;calcium ion binding;carbohydrate binding;ionotropic glutamate receptor binding;RNA binding;unfolded protein binding axon;dendrite cytoplasm;dendritic spine;endoplasmic reticulum;endoplasmic reticulum lumen;endoplasmic reticulum membrane;endoplasmic reticulum quality control compartment;extracellular exosome;glutamatergic synapse;integral component of lumenal side of endoplasmic reticulum membrane;integral component of postsynaptic membrane;integral component of presynaptic active zone membrane;melanosome;membrane;mitochondria-associated endoplasmic reticulum membrane;myelin sheath;neuronal cell body;ribosome;rough endoplasmic reticulum;smooth endoplasmic reticulum Antigen processing and presentation;Human T-cell leukemia virus 1 infection;Phagosome;Protein processing in endoplasmic reticulum;Thyroid hormone synthesis Antigen Presentation: Folding, assembly and peptide loading of class I MHC;Assembly of Viral Components at the Budding Site;Calnexin/calreticulin cycle;Interleukin-27 signaling;Interleukin-35 Signalling;MHC class II antigen presentation SELK multiprotein complex -1.41029441356659 -0.356149345636368 -0.247813791036606 -0.104816474020481 -0.577386558055878 -1.41065061092377 -1.32945287227631 -1.38002598285675 -0.0889050960540771 0.943995952606201 2.03120517730713 0.676438689231873 -0.0501845329999924 0.646170377731323 -0.127517715096474 0.480515003204346 1.22584545612335 1.07902681827545 + Cluster -671 6 6 5 20.3 20.3 20.3 43.171 0 31.68 3831000000 13 3.06412645945462 0.000955927051671733 P54727;P54727-2 P54727;P54727-2 UV excision repair protein RAD23 homolog B RAD23B 1227 it preferentially binds to cisplatinand UV-damaged double-stranded DNA and also binds to a variety ofchemically and structurally diverse DNA adducts. XPC:RAD23Bcontacts DNA both 5' and 3' of a cisplatin lesion with apreference for the 5' side. XPC:RAD23B induces a bend in DNA uponbinding. XPC:RAD23B stimulates the activity of DNA glycosylasesTDG and SMUG1.;Multiubiquitin chain receptor involved in modulation ofproteasomal degradation. Binds to polyubiquitin chains. Proposedto be capable to bind simultaneously to the 26S proteasome and topolyubiquitinated substrates and to deliver ubiquitinated proteinsto the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins byassociation with PNGase and delivering deglycosylated proteins tothe proteasome.Involved in global genome nucleotide excision repair(GG-NER) by acting as component of the XPC complex. Cooperativelywith CETN2 appears to stabilize XPC. May protect XPC fromproteasomal degradation.The XPC complex is proposed to represent the firstfactor bound at the sites of DNA damage and together with othercore recognition factors, XPA, RPA and the TFIIH complex, is partof the pre-incision (or initial recognition) complex. The XPCcomplex recognizes a wide spectrum of damaged DNA characterized bydistortions of the DNA helix such as single-stranded loops,mismatched bubbles or single-stranded overhangs. The orientationof XPC complex binding appears to be crucial for inducing aproductive NER. XPC complex is proposed to recognize and tointeract with unpaired bases on the undamaged DNA strand which isfollowed by recruitment of the TFIIH complex and subsequentscanning for lesions in the opposite strand in a 5'-to-3'direction by the NER machinery. Cyclobutane pyrimidine dimers(CPDs) which are formed upon UV-induced DNA damage esacpedetection by the XPC complex due to a low degree of structuralperurbation. Instead they are detected by the UV-DDB complex whichin turn recruits and cooperates with the XPC complex in therespective DNA repair. In vitro, the XPC:RAD23B dimer issufficient to initiate NER upon entering mitosis, relocalizes in the cytoplasm withoutassociation with chromatin.;Nucleus. Cytoplasm. Note=The intracellulardistribution is cell cycle dependent. Localized to the nucleus andthe cytoplasm during G1 phase. Nuclear levels decrease during S-phase cellular response to interleukin-7;embryonic organ development;global genome nucleotide-excision repair;nucleotide-excision repair;nucleotide-excision repair, DNA damage recognition;nucleotide-excision repair, preincision complex assembly;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination;protein folding;regulation of proteasomal ubiquitin-dependent protein catabolic process;spermatogenesis damaged DNA binding;polyubiquitin modification-dependent protein binding;proteasome binding;single-stranded DNA binding;ubiquitin binding cytosol;nucleoplasm;nucleus;proteasome complex;XPC complex Nucleotide excision repair;Protein processing in endoplasmic reticulum DNA Damage Recognition in GG-NER;Formation of Incision Complex in GG-NER;Josephin domain DUBs;N-glycan trimming in the ER and Calnexin/Calreticulin cycle -1.60622608661652 -0.20187583565712 -0.298939675092697 0.0259188339114189 -0.184557020664215 -1.36468982696533 -1.62359941005707 -1.28156387805939 0.131554827094078 1.20221269130707 1.60877931118011 1.52827084064484 -0.269547879695892 0.260911494493484 -0.0607297308743 0.508042573928833 0.771816313266754 0.854222416877747 + Cluster -671 4 4 4 36.1 36.1 36.1 22.782 0 65.846 10092000000 15 3.08674237937963 0.000927131782945736 P04792 P04792 Heat shock protein beta-1 HSPB1 491 Small heat shock protein which functions as a molecularchaperone probably maintaining denatured proteins in a folding-competent state (PubMed:10383393, PubMed:20178975). Plays a rolein stress resistance and actin organization (PubMed:19166925).Through its molecular chaperone activity may regulate numerousbiological processes including the phosphorylation and the axonaltransport of neurofilament proteins (PubMed:23728742) Cytoplasm {ECO:0000269|PubMed:10777697,ECO:0000269|PubMed:28144995}. Nucleus{ECO:0000269|PubMed:19464326}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:10777697}. Note=Cytoplasmic in interphasecells. Colocalizes with mitotic spindles in mitotic cells.Translocates to the nucleus during heat shock and resides in sub-nuclear structures known as SC35 speckles or nuclear splicingspeckles. {ECO:0000269|PubMed:19464326}. anterograde axonal protein transport;cellular response to vascular endothelial growth factor stimulus;chaperone-mediated protein folding;intracellular signal transduction;negative regulation of apoptotic process;negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;negative regulation of protein kinase activity;platelet aggregation;positive regulation of angiogenesis;positive regulation of blood vessel endothelial cell migration;positive regulation of endothelial cell chemotaxis;positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway;positive regulation of interleukin-1 beta production;positive regulation of tumor necrosis factor biosynthetic process;regulation of autophagy;regulation of I-kappaB kinase/NF-kappaB signaling;regulation of mRNA stability;regulation of protein phosphorylation;regulation of translational initiation;response to unfolded protein;response to virus;retina homeostasis identical protein binding;protein binding involved in protein folding;protein homodimerization activity;protein kinase binding;protein kinase C binding;protein kinase C inhibitor activity;RNA binding;ubiquitin binding axon cytoplasm;cytoplasm;cytoskeleton;cytosol;extracellular exosome;extracellular space;focal adhesion;nucleus;plasma membrane;proteasome complex;spindle;Z disc Amoebiasis;MAPK signaling pathway;VEGF signaling pathway Distal hereditary motor neuropathies AUF1 (hnRNP D0) binds and destabilizes mRNA;MAPK6/MAPK4 signaling;VEGFA-VEGFR2 Pathway -1.68039393424988 -0.0577569156885147 -0.701634109020233 -0.263682425022125 -0.418476939201355 -1.19149816036224 -1.52079212665558 -1.21492326259613 0.367972552776337 1.00917422771454 1.5100713968277 1.41338968276978 -0.277781695127487 -0.0113058257848024 0.28369128704071 0.666367053985596 0.957618534564972 1.12996065616608 + Cluster -671 2 2 2 10.6 10.6 10.6 33.843 0 21.668 1917600000 9 3.13838490971304 0.00083015873015873 Q8NBJ7;Q8NBJ7-5;Q8NBJ7-2;Q8NBJ7-4;Q8NBJ7-3 Q8NBJ7;Q8NBJ7-5;Q8NBJ7-2;Q8NBJ7-4;Q8NBJ7-3 Sulfatase-modifying factor 2 SUMF2 2220 Lacks formylglycine generating activity and is unable toconvert newly synthesized inactive sulfatases to their activeform. Inhibits the activation of sulfatases by SUMF1 Endoplasmic reticulum lumen{ECO:0000269|PubMed:15708861, ECO:0000269|PubMed:15962010,ECO:0000269|PubMed:18266766}. glycosphingolipid metabolic process;post-translational protein modification metal ion binding endoplasmic reticulum;endoplasmic reticulum lumen Glycosphingolipid metabolism;The activation of arylsulfatases -1.845618724823 -0.395312279462814 -0.603708326816559 -0.292185604572296 -0.466523259878159 -1.168661236763 -1.02926599979401 -1.270716547966 -0.127122983336449 1.45288407802582 1.02326583862305 0.772892355918884 -0.239652052521706 0.163197547197342 0.296029806137085 0.945701658725739 1.47899353504181 1.30580222606659 + Cluster -671 1 1 1 9.7 9.7 9.7 16.698 0 42.969 5214600000 9 3.2166127874335 0.000718543046357616 Q9P0J0;Q9P0J0-2 Q9P0J0;Q9P0J0-2 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 NDUFA13 3039 Accessory subunit of the mitochondrial membranerespiratory chain NADH dehydrogenase (Complex I), that is believednot to be involved in catalysis (PubMed:27626371). Complex Ifunctions in the transfer of electrons from NADH to therespiratory chain. The immediate electron acceptor for the enzymeis believed to be ubiquinone (PubMed:27626371). Involved in theinterferon/all-trans-retinoic acid (IFN/RA) induced cell death.This apoptotic activity is inhibited by interaction with viralIRF1. Prevents the transactivation of STAT3 target genes. May playa role in CARD15-mediated innate mucosal responses and serve toregulate intestinal epithelial cell responses to microbes(PubMed:15753091). Matrix side. Nucleus {ECO:0000269|PubMed:12628925}.Note=Localizes mainly in the mitochondrion (PubMed:12628925). Maybe translocated into the nucleus upon IFN/RA treatment.{ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:15059901}.; Single-pass membrane protein{ECO:0000255};Mitochondrion inner membrane{ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:15059901,ECO:0000269|PubMed:15367666} apoptotic signaling pathway;cellular response to interferon-beta;cellular response to retinoic acid;extrinsic apoptotic signaling pathway;mitochondrial respiratory chain complex I assembly;negative regulation of cell growth;negative regulation of intrinsic apoptotic signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of peptidase activity;positive regulation of protein catabolic process;protein import into mitochondrial inner membrane;reactive oxygen species metabolic process ATP binding;NADH dehydrogenase (ubiquinone) activity;NADH dehydrogenase activity cytoplasm;integral component of membrane;mitochondrial inner membrane;mitochondrial membrane;mitochondrial respirasome;mitochondrial respiratory chain complex I;mitochondrion;nucleoplasm Alzheimer disease;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Retrograde endocannabinoid signaling;Thermogenesis Mitochondrial complex I deficiency Complex I biogenesis;Respiratory electron transport Respiratory chain complex I (holoenzyme), mitochondrial;Respiratory chain complex I (lambda subunit) mitochondrial -1.69232320785522 -0.029103459790349 -0.579606175422668 -0.246704459190369 -0.579606175422668 -1.18181872367859 -1.40508270263672 -1.44653904438019 -0.262065976858139 1.3280336856842 0.641459822654724 1.04455602169037 0.134125515818596 0.394245833158493 0.490996062755585 0.643369436264038 1.42423832416534 1.32182514667511 + Cluster -671 1 1 1 7.6 7.6 7.6 21.08 0 131.7 4907700000 8 3.60751837092222 0.000347921225382932 Q9UNL2;Q9UNL2-2 Q9UNL2;Q9UNL2-2 Translocon-associated protein subunit gamma SSR3 3184 TRAP proteins are part of a complex whose function is tobind calcium to the ER membrane and thereby regulate the retentionof ER resident proteins. Multi-passmembrane protein.;Endoplasmic reticulum membrane SRP-dependent cotranslational protein targeting to membrane endoplasmic reticulum membrane;integral component of membrane Protein processing in endoplasmic reticulum SRP-dependent cotranslational protein targeting to membrane Translocon-associated protein (TRAP) complex -1.76420533657074 -0.340201705694199 -0.918917834758759 0.0256214030086994 -0.67569363117218 -0.930126786231995 -1.51073026657104 -1.22655034065247 0.186905458569527 0.976771056652069 1.49956715106964 0.449673473834991 0.183082938194275 0.197204276919365 0.361122906208038 1.04469525814056 0.993881464004517 1.44790065288544 + Cluster -671 4 4 4 5.9 5.9 5.9 150.07 0 90.345 4004600000 15 3.07570526238854 0.000940184049079755 Q6Y7W6;Q6Y7W6-4;Q6Y7W6-5;Q6Y7W6-3 Q6Y7W6;Q6Y7W6-4;Q6Y7W6-5;Q6Y7W6-3 PERQ amino acid-rich with GYF domain-containing protein 2 GIGYF2 2026 Key component of the 4EHP-GYF2 complex, a multiproteincomplex that acts as a repressor of translation initiation(PubMed:22751931). In 4EHP-GYF2 the complex, acts as a factor thatbridges EIF4E2 to ZFP36/TTP, linking translation repression withmRNA decay (By similarity). May act cooperatively with GRB10 toregulate tyrosine kinase receptor signaling, including IGF1 andinsulin receptors (PubMed:12771153) adult locomotory behavior;cellular protein metabolic process;feeding behavior;homeostasis of number of cells within a tissue;insulin-like growth factor receptor signaling pathway;mitotic G1 DNA damage checkpoint;mRNA destabilization;multicellular organism growth;musculoskeletal movement;negative regulation of translation;neuromuscular process controlling balance;post-embryonic development;posttranscriptional gene silencing;spinal cord motor neuron differentiation cadherin binding;proline-rich region binding;RNA binding cytoplasmic stress granule;cytosol;endoplasmic reticulum;endosome;Golgi apparatus;integral component of membrane;membrane;perikaryon;protein-containing complex;proximal dendrite Parkinson disease -1.55087161064148 -0.571920573711395 -0.779170274734497 -0.537975788116455 -0.587894916534424 -1.22547233104706 -1.28364646434784 -1.36856508255005 0.315690577030182 1.0721207857132 1.04069137573242 0.765238344669342 0.303632766008377 0.317805707454681 0.378197640180588 0.955080270767212 1.24393272399902 1.51312685012817 + Cluster -671 3 3 3 25 25 25 20.776 0 26.593 3003100000 7 4.04488029161225 0.000131964809384164 O96000;O96000-2 O96000;O96000-2 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 NDUFB10 455 Accessory subunit of the mitochondrial membranerespiratory chain NADH dehydrogenase (Complex I), that is believednot to be involved in catalysis. Complex I functions in thetransfer of electrons from NADH to the respiratory chain. Theimmediate electron acceptor for the enzyme is believed to beubiquinone. Matrix side {ECO:0000305}.; Peripheral membrane protein{ECO:0000305};Mitochondrion inner membrane{ECO:0000305|PubMed:12611891} mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly NADH dehydrogenase (ubiquinone) activity mitochondrial inner membrane;mitochondrial respiratory chain complex I Alzheimer disease;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Retrograde endocannabinoid signaling;Thermogenesis Complex I biogenesis;Respiratory electron transport Respiratory chain complex I (beta subunit) mitochondrial;Respiratory chain complex I (holoenzyme), mitochondrial -1.00028324127197 -0.582258641719818 -0.370141685009003 -0.942802608013153 -0.861539423465729 -1.41933441162109 -1.34549713134766 -1.26765155792236 0.344385355710983 0.851879596710205 1.67921590805054 0.758999347686768 0.167984530329704 0.184720993041992 0.389707386493683 0.85368686914444 1.31986737251282 1.23906135559082 + Cluster -671 2 2 2 5.6 5.6 5.6 45.884 0 8.9755 1218400000 9 4.28109204024897 8.19672131147541E-05 Q03154;Q03154-2;Q03154-3;Q03154-4 Q03154;Q03154-2;Q03154-3;Q03154-4 Aminoacylase-1 ACY1 1504 Involved in the hydrolysis of N-acylated or N-acetylatedamino acids (except L-aspartate). Cytoplasm. cellular amino acid metabolic process;xenobiotic metabolic process aminoacylase activity;identical protein binding;metal ion binding;metallopeptidase activity cytosol;extracellular exosome 2-Oxocarboxylic acid metabolism;Arginine biosynthesis;Biosynthesis of amino acids;Metabolic pathways Aminoacylase 1 deficiency Aflatoxin activation and detoxification;Defective ACY1 causes encephalopathy -1.59552609920502 0.11958497017622 -0.444500088691711 -0.210277706384659 -1.2541116476059 -1.02294552326202 -1.65754795074463 -1.0571596622467 -0.129462018609047 0.763595938682556 1.28514933586121 0.966095566749573 0.132777005434036 0.203394994139671 0.386613339185715 0.814097046852112 1.27162456512451 1.42859816551208 + Cluster -671 4 4 4 53.2 53.2 53.2 13.178 0 112.26 7898200000 23 3.40582071586791 0.00051024208566108 Q99622 Q99622 Protein C10 C12orf57 2581 In brain, may be required for corpus callusumdevelopment. Cytoplasm {ECO:0000269|PubMed:23453666}. camera-type eye morphogenesis;cognition;corpus callosum morphogenesis;post-embryonic development;psychomotor behavior;regulation of skeletal muscle contraction;third ventricle development cytoplasm;nuclear speck -1.32638120651245 -0.119654051959515 -0.783848285675049 -0.242530435323715 -0.8671954870224 -1.58653235435486 -1.55720460414886 -1.0725919008255 -0.0536461621522903 0.994331240653992 1.18484938144684 0.954771459102631 0.103816971182823 0.37911194562912 0.599437773227692 1.02545630931854 1.05540692806244 1.31240272521973 + Cluster -671 17 17 17 46 46 46 47.463 0 299.31 63806000000 99 4.42326939593483 6.2043795620438E-05 O00231;O00231-2 O00231;O00231-2 26S proteasome non-ATPase regulatory subunit 11 PSMD11 73 Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. In the complex,PSMD11 is required for proteasome assembly. Plays a key role inincreased proteasome activity in embryonic stem cells (ESCs): itshigh expression in ESCs promotes enhanced assembly of the 26Sproteasome, followed by higher proteasome activity Nucleus {ECO:0000250}. Cytoplasm, cytosol{ECO:0000250}. neutrophil degranulation;post-translational protein modification;proteasome assembly;protein deubiquitination;stem cell differentiation;ubiquitin-dependent protein catabolic process structural molecule activity cytosol;extracellular region;ficolin-1-rich granule lumen;membrane;nucleoplasm;nucleus;proteasome accessory complex;proteasome complex;proteasome regulatory particle, lid subcomplex;secretory granule lumen Epstein-Barr virus infection;Proteasome ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;Neutrophil degranulation;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 PA700 complex;PA700-20S-PA28 complex -1.21058309078217 0.0848810225725174 -0.57392144203186 0.109402135014534 -0.553752422332764 -1.94532918930054 -1.63331532478333 -1.04961133003235 -0.0935836732387543 1.08569741249084 1.28221845626831 1.37819015979767 0.755613088607788 0.132035925984383 -0.00555555243045092 0.708979308605194 0.354951292276382 1.1736832857132 + Cluster -671 6 6 6 17.3 17.3 17.3 51.735 0 65.822 7219000000 28 3.3533899823029 0.000554954954954955 Q53EL6;Q53EL6-2 Q53EL6;Q53EL6-2 Programmed cell death protein 4 PDCD4 1902 Inhibits translation initiation and cap-dependenttranslation. May excert its function by hindering the interactionbetween EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A.Modulates the activation of JUN kinase. Down-regulates theexpression of MAP4K1, thus inhibiting events important in drivinginvasion, namely, MAPK85 activation and consequent JUN-dependenttranscription. May play a role in apoptosis. Tumor suppressor.Inhibits tumor promoter-induced neoplastic transformation. BindsRNA (By similarity). Nucleus {ECO:0000250|UniProtKB:Q61823}.Cytoplasm {ECO:0000250|UniProtKB:Q61823}. Note=Shuttles betweenthe nucleus and cytoplasm (By similarity). Predominantly nuclearunder normal growth conditions, and when phosphorylated at Ser-457(PubMed:16357133). {ECO:0000269|PubMed:16357133}. apoptotic process;BMP signaling pathway;cell aging;cellular response to lipopolysaccharide;epithelial to mesenchymal transition involved in cardiac fibroblast development;interleukin-12-mediated signaling pathway;negative regulation of apoptotic process;negative regulation of cell cycle;negative regulation of cytokine production involved in inflammatory response;negative regulation of JUN kinase activity;negative regulation of myofibroblast differentiation;negative regulation of transcription, DNA-templated;negative regulation of vascular smooth muscle cell differentiation;negative regulation of vascular smooth muscle cell proliferation;positive regulation of endothelial cell apoptotic process;positive regulation of inflammatory response;positive regulation of NIK/NF-kappaB signaling;positive regulation of vascular associated smooth muscle cell apoptotic process RNA binding cytoplasm;cytosol;nucleus MicroRNAs in cancer;Proteoglycans in cancer Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation Emerin complex 52 -1.29989576339722 -0.253518372774124 -1.0591094493866 -0.0218330752104521 -0.769212484359741 -1.55685007572174 -1.75911748409271 -0.591878890991211 0.205229490995407 1.23795247077942 1.14805197715759 0.947263836860657 0.106522716581821 0.213833540678024 0.254241973161697 0.689916670322418 0.999437093734741 1.50896561145782 + Cluster -671 1 1 1 1.2 1.2 1.2 140.26 0 3.8143 422430000 2 3.41369519826233 0.000509398496240602 Q9UPT8 Q9UPT8 Zinc finger CCCH domain-containing protein 4 ZC3H4 3204 negative regulation of transcription, DNA-templated DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;metal ion binding;RNA binding;RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding cytosol;nucleoplasm;nucleus -1.77965748310089 -0.462252259254456 -0.5778768658638 0.248589560389519 -0.426249235868454 -1.50567948818207 -1.26848840713501 -1.04281985759735 -0.449527442455292 1.1178685426712 1.27703237533569 0.78113842010498 -0.0523048676550388 0.363927870988846 0.329343110322952 0.896511971950531 1.06827735900879 1.48216676712036 + Cluster -671 1 1 1 6.5 6.5 6.5 36.908 0 7.2898 1924600000 3 3.3157670013705 0.000585237258347979 Q9BYD6 Q9BYD6 39S ribosomal protein L1, mitochondrial MRPL1 2719 Mitochondrion {ECO:0000250|UniProtKB:A6QPQ5,ECO:0000305|PubMed:11279069}. maturation of LSU-rRNA;mitochondrial translational elongation;mitochondrial translational termination;translation RNA binding;structural constituent of ribosome cytosolic large ribosomal subunit;mitochondrial inner membrane;mitochondrion Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 39S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -1.80828988552094 0.0230384916067123 -0.844842255115509 -0.205800473690033 -0.566429257392883 -1.60431361198425 -1.15451216697693 -1.04627597332001 0.162748083472252 1.02491629123688 1.55884861946106 0.502474009990692 0.0666186213493347 0.326141119003296 0.326141119003296 0.761033594608307 1.34861886501312 1.1298850774765 + Cluster -671 6 4 4 10.7 7.1 7.1 82.564 0 40.541 5363500000 11 3.04036348180012 0.00099702380952381 Q9BQ39 Q9BQ39 ATP-dependent RNA helicase DDX50 DDX50 2611 Nucleus, nucleolus{ECO:0000269|PubMed:12429849}. ATP binding;helicase activity;RNA binding membrane;nucleolus;plasma membrane -1.69245159626007 -0.0740934535861015 -0.865691423416138 0.132595300674438 -0.716447651386261 -1.71663463115692 -1.25144588947296 -0.968464136123657 0.0743778347969055 1.29656362533569 1.06012499332428 0.88307797908783 0.0331904515624046 0.395781517028809 0.26781639456749 0.608279168605804 1.26139628887177 1.27202522754669 + Cluster -671 2 2 2 2.9 2.9 2.9 169.3 0 34.647 266290000 3 3.13985195438583 0.000828298887122417 Q9BVV6;Q9BVV6-2;Q9BVV6-4;Q9BVV6-3 Q9BVV6;Q9BVV6-2;Q9BVV6-4;Q9BVV6-3 Protein TALPID3 KIAA0586 2689 Required for ciliogenesis and sonic hedgehog/SHHsignaling. Required for the centrosomal recruitment of RAB8A andfor the targeting of centriole satellite proteins to centrosomessuch as of PCM1. May play a role in early ciliogenesis in thedisappearance of centriolar satellites that preceeds ciliaryvesicle formation (PubMed:24421332). Involved in regulation ofcell intracellular organization. Involved in regulation of cellpolarity (By similarity). Required for asymmetrical localizationof CEP120 to daughter centrioles (By similarity) Cytoplasm, cytoskeleton, microtubuleorganizing center, centrosome {ECO:0000269|PubMed:19144723}.Photoreceptor inner segment {ECO:0000269|PubMed:26386247}.Cytoplasm, cytoskeleton, microtubule organizing center,centrosome, centriole {ECO:0000269|PubMed:24421332,ECO:0000269|PubMed:26386247}. Cytoplasm, cytoskeleton, ciliumbasal body {ECO:0000269|PubMed:26386247}. Note=Forms a ring-likestructure at the extreme distal end of both mother and daughtercentrioles (PubMed:24421332). In photoreceptor cells localized tothe joint between the inner and outer segments, specificallylocalized at the mother centriole (basal body) and the adjacentcentriole as well as between the two centrioles but not in theconnecting cilium (PubMed:26386247). {ECO:0000269|PubMed:24421332,ECO:0000269|PubMed:26386247}. cilium assembly;regulation of establishment of protein localization;smoothened signaling pathway centriole;centrosome;ciliary basal body;photoreceptor inner segment Joubert syndrome;Short-rib thoracic dysplasia -1.48393654823303 -0.243112936615944 -0.678649246692657 -0.0882256701588631 -0.946686923503876 -1.31148731708527 -1.42572176456451 -1.07254803180695 0.125915363430977 1.23013651371002 1.64287102222443 0.642965137958527 0.0979281440377235 0.0979281440377235 0.0979281440377235 0.898346185684204 1.01512813568115 1.40122163295746 + Cluster -671 4 4 4 12.6 12.6 12.6 49.901 0 74.647 6762900000 30 3.42751430873707 0.000493383742911153 P49642 P49642 DNA primase small subunit PRIM1 1107 DNA primase is the polymerase that synthesizes small RNAprimers for the Okazaki fragments made during discontinuous DNAreplication. DNA replication, synthesis of RNA primer;G1/S transition of mitotic cell cycle;telomere maintenance via semi-conservative replication DNA primase activity;metal ion binding;single-stranded DNA binding alpha DNA polymerase:primase complex;membrane;nucleoplasm DNA replication Activation of the pre-replicative complex;DNA replication initiation;Inhibition of replication initiation of damaged DNA by RB1/E2F1;Polymerase switching;Polymerase switching on the C-strand of the telomere;Processive synthesis on the lagging strand;Removal of the Flap Intermediate;Telomere C-strand synthesis initiation DNA polymerase alpha-primase complex;DNA synthesome complex (13 subunits);DNA synthesome complex (15 subunits);DNA synthesome complex (17 subunits);DNA synthesome core complex -1.48427748680115 -0.322896957397461 -0.680885314941406 0.0575704723596573 -0.571037173271179 -1.37535560131073 -1.61177921295166 -1.25931107997894 0.335099220275879 1.57088208198547 1.52123737335205 0.525397777557373 -0.0395608879625797 0.309711873531342 0.35874530673027 0.745936989784241 0.843262851238251 1.07725989818573 + Cluster -671 4 4 4 29.4 29.4 29.4 20.198 0 102.9 38631000000 61 3.18768743074566 0.000760195758564437 P61923;P61923-5;P61923-4;P61923-2;P61923-3 P61923;P61923-5;P61923-4 Coatomer subunit zeta-1 COPZ1 1321 the complexalso influences the Golgi structural integrity, as well as theprocessing, activity, and endocytic recycling of LDL receptors (Bysimilarity).;The coatomer is a cytosolic protein complex that bindsto dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosyntheticprotein transport from the ER, via the Golgi up to the trans Golginetwork. Coatomer complex is required for budding from Golgimembranes, and is essential for the retrograde Golgi-to-ERtransport of dilysine-tagged proteins. In mammals, the coatomercan only be recruited by membranes associated to ADP-ribosylationfactors (ARFs), which are small GTP-binding proteins Cytoplasmic side {ECO:0000250}. Note=The coatomeris cytoplasmic or polymerized on the cytoplasmic side of theGolgi, as well as on the vesicles/buds originating from it.{ECO:0000250}.; Peripheral membrane protein {ECO:0000250}; Peripheral membrane protein{ECO:0000250};Cytoplasm {ECO:0000250}. Golgi apparatusmembrane {ECO:0000250};Cytoplasmic side {ECO:0000250}. Cytoplasmic vesicle, COPI-coatedvesicle membrane {ECO:0000250} endoplasmic reticulum to Golgi vesicle-mediated transport;intracellular protein transport;intra-Golgi vesicle-mediated transport;retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum;toxin transport COPI vesicle coat;cytosol;endoplasmic reticulum membrane;Golgi membrane;transport vesicle COPI-dependent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport -1.14338552951813 -0.423810511827469 -0.922865569591522 0.0712779685854912 -0.563548564910889 -1.67354583740234 -1.65254330635071 -0.951977670192719 0.0210784021764994 1.40860438346863 1.46190786361694 0.675822675228119 -0.0145095754414797 0.316780120134354 0.429477572441101 0.716749489307404 1.07395589351654 1.1705322265625 + Cluster -671 2 2 2 27.7 27.7 27.7 9.3959 0 21.741 10845000000 20 3.71128115817549 0.000287769784172662 P14406 P14406 Cytochrome c oxidase subunit 7A2, mitochondrial COX7A2 668 This protein is one of the nuclear-coded polypeptidechains of cytochrome c oxidase, the terminal oxidase inmitochondrial electron transport. Mitochondrion inner membrane. mitochondrial respirasome assembly;regulation of oxidative phosphorylation cytochrome-c oxidase activity mitochondrial respirasome Alzheimer disease;Cardiac muscle contraction;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Thermogenesis -0.864382684230804 -0.585782825946808 -0.551855027675629 -0.298073917627335 -0.70671021938324 -1.50171315670013 -1.45043909549713 -1.42865228652954 -0.298073917627335 1.37985706329346 1.14519309997559 1.05074787139893 -0.0224255081266165 0.604051768779755 0.223386809229851 0.78337687253952 1.24366283416748 1.27783215045929 + Cluster -671 7 7 7 40.6 40.6 40.6 21.452 0 58.187 15210000000 37 4.78427886644811 2.71493212669683E-05 P00374;P00374-2 P00374;P00374-2 Dihydrofolate reductase DHFR 463 Key enzyme in folate metabolism. Contributes to the denovo mitochondrial thymidylate biosynthesis pathway. Catalyzes anessential reaction for de novo glycine and purine synthesis, andfor DNA precursor synthesis. Binds its own mRNA and that of DHFR2 Mitochondrion{ECO:0000250|UniProtKB:P00375}. Cytoplasm{ECO:0000250|UniProtKB:P00375}. axon regeneration;dihydrofolate metabolic process;folic acid metabolic process;negative regulation of translation;one-carbon metabolic process;oxidation-reduction process;positive regulation of nitric-oxide synthase activity;regulation of removal of superoxide radicals;regulation of transcription involved in G1/S transition of mitotic cell cycle;response to methotrexate;tetrahydrobiopterin biosynthetic process;tetrahydrofolate biosynthetic process;tetrahydrofolate metabolic process dihydrofolate reductase activity;drug binding;folate reductase activity;folic acid binding;methotrexate binding;mRNA binding;NADP binding;NADPH binding;sequence-specific mRNA binding;translation repressor activity, mRNA regulatory element binding cytosol;mitochondrion Antifolate resistance;Folate biosynthesis;Metabolic pathways;One carbon pool by folate Dihydrofolate reductase deficiency Edatrexate;Methotrexate;Pemetrexed;Piritrexim isethionate;Pralatrexate;Talotrexin ammonium;Trimetrexate Activation of E2F1 target genes at G1/S;Metabolism of folate and pterines;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation -0.776690661907196 -0.301940113306046 -0.748559296131134 -0.272140026092529 -0.817091643810272 -1.45375537872314 -1.60011029243469 -1.22591912746429 -0.0589761957526207 1.16766393184662 1.74936962127686 1.04891872406006 -0.187733724713326 0.176420897245407 0.32514226436615 0.673046708106995 1.04169774055481 1.2606565952301 + Cluster -671 4 4 4 20.9 20.9 20.9 21.258 0 60.864 42759000000 66 4.54037475229305 4.70588235294118E-05 P60953;P60953-1 P60953;P60953-1 Cell division control protein 42 homolog CDC42 1281 Plasma membrane-associated small GTPase which cyclesbetween an active GTP-bound and an inactive GDP-bound state. Inactive state binds to a variety of effector proteins to regulatecellular responses. Involved in epithelial cell polarizationprocesses. Regulates the bipolar attachment of spindlemicrotubules to kinetochores before chromosome congression inmetaphase. Plays a role in the extension and maintenance of theformation of thin, actin-rich surface projections calledfilopodia. Mediates CDC42-dependent cell migration. Required forDOCK10-mediated spine formation in Purkinje cells and hippocampalneurons. Facilitates filopodia formation upon DOCK11-activation(By similarity). Also plays a role in phagocytosis throughorganization of the F-actin cytoskeleton associated with formingphagocytic cups. Cytoplasmic side {ECO:0000305}. Cytoplasm,cytoskeleton, microtubule organizing center, centrosome{ECO:0000269|PubMed:15642749}. Cytoplasm, cytoskeleton, spindle{ECO:0000269|PubMed:15642749}. Midbody{ECO:0000269|PubMed:15642749}. Note=Localizes to spindle duringprometaphase cells. Moves to the central spindle as cellsprogressed through anaphase to telophase (PubMed:15642749).Localizes at the end of cytokinesis in the intercellular bridgeformed between two daughter cells (PubMed:15642749). Itslocalization is regulated by the activities of guanine nucleotideexchange factor ECT2 and GTPase activating protein RACGAP1(PubMed:15642749). Colocalizes with NEK6 in the centrosome(PubMed:20873783). In its active GTP-bound form localizes to theleading edge membrane of migrating dendritic cells (Bysimilarity). {ECO:0000250|UniProtKB:P60766,ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:20873783}.; Lipid-anchor{ECO:0000305};Cell membrane {ECO:0000305} actin cytoskeleton organization;actin filament branching;actin filament organization;blood coagulation;Cdc42 protein signal transduction;cell junction assembly;cell projection assembly;dendritic spine morphogenesis;endocytosis;ephrin receptor signaling pathway;establishment of epithelial cell apical/basal polarity;establishment of Golgi localization;establishment or maintenance of cell polarity;Fc-gamma receptor signaling pathway involved in phagocytosis;Golgi organization;integrin-mediated signaling pathway;interleukin-12-mediated signaling pathway;macrophage differentiation;modification of synaptic structure;negative regulation of epidermal growth factor receptor signaling pathway;negative regulation of protein complex assembly;neuropilin signaling pathway;organelle transport along microtubule;phagocytosis, engulfment;positive regulation of actin cytoskeleton reorganization;positive regulation of catalytic activity;positive regulation of cell growth;positive regulation of cytokinesis;positive regulation of DNA replication;positive regulation of filopodium assembly;positive regulation of intracellular protein transport;positive regulation of JNK cascade;positive regulation of lamellipodium assembly;positive regulation of muscle cell differentiation;positive regulation of neuron apoptotic process;positive regulation of pseudopodium assembly;positive regulation of stress fiber assembly;positive regulation of substrate adhesion-dependent cell spreading;positive regulation of synapse structural plasticity;regulation of actin cytoskeleton organization;regulation of attachment of spindle microtubules to kinetochore;regulation of cell shape;regulation of filopodium assembly;regulation of lamellipodium assembly;regulation of modification of postsynaptic structure;regulation of small GTPase mediated signal transduction;regulation of stress fiber assembly;Rho protein signal transduction;sprouting angiogenesis;submandibular salivary gland formation;substantia nigra development;T cell costimulation;vascular endothelial growth factor receptor signaling pathway;viral RNA genome replication;Wnt signaling pathway, planar cell polarity pathway apolipoprotein A-I receptor binding;GBD domain binding;GTP binding;GTPase activity;identical protein binding;mitogen-activated protein kinase kinase kinase binding;protein kinase binding;protein serine/threonine kinase activity;thioesterase binding;ubiquitin protein ligase activity cell cortex;cell projection;cytoplasm;cytoplasmic ribonucleoprotein granule;cytosol;dendritic spine;endoplasmic reticulum membrane;extracellular exosome;filopodium;focal adhesion;Golgi membrane;Golgi transport complex;membrane;microtubule organizing center;midbody;mitotic spindle;neuron projection;neuronal cell body;plasma membrane;protein-containing complex;Schaffer collateral - CA1 synapse;secretory granule;spindle midzone Adherens junction;AGE-RAGE signaling pathway in diabetic complications;Axon guidance;Bacterial invasion of epithelial cells;Chemokine signaling pathway;Endocytosis;Epithelial cell signaling in Helicobacter pylori infection;Fc gamma R-mediated phagocytosis;Focal adhesion;GnRH signaling pathway;Human papillomavirus infection;Leukocyte transendothelial migration;MAPK signaling pathway;Neurotrophin signaling pathway;Non-alcoholic fatty liver disease (NAFLD);Pancreatic cancer;Pathogenic Escherichia coli infection;Pathways in cancer;Proteoglycans in cancer;Rap1 signaling pathway;Ras signaling pathway;Regulation of actin cytoskeleton;Renal cell carcinoma;Salmonella infection;Shigellosis;T cell receptor signaling pathway;Tight junction;VEGF signaling pathway;Viral carcinogenesis;Yersinia infection CD28 dependent Vav1 pathway;CDO in myogenesis;DCC mediated attractive signaling;EGFR downregulation;EPHB-mediated forward signaling;Factors involved in megakaryocyte development and platelet production;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;GPVI-mediated activation cascade;Inactivation of CDC42 and RAC1;MAPK6/MAPK4 signaling;Regulation of actin dynamics for phagocytic cup formation;Rho GTPase cycle;RHO GTPases Activate Formins;RHO GTPases activate IQGAPs;RHO GTPases activate KTN1;RHO GTPases activate PAKs;RHO GTPases Activate WASPs and WAVEs;VEGFA-VEGFR2 Pathway ACK1 signaling complex;APC-IQGAP1-Cdc42 complex;PAR6-CDC42 complex -1.37026226520538 -0.169901147484779 -0.557797193527222 -0.194082722067833 -0.734773874282837 -1.20911848545074 -1.63633334636688 -0.906690716743469 -0.262263357639313 1.08294475078583 1.45734798908234 1.30792605876923 -0.37014228105545 -0.0194673035293818 0.293533325195313 0.652788877487183 1.4637359380722 1.17255568504333 + Cluster -671 6 6 6 18.4 18.4 18.4 42.981 0 73.047 5601500000 14 3.46676211148827 0.000459882583170254 P10644;P10644-2 P10644;P10644-2 cAMP-dependent protein kinase type I-alpha regulatory subunit;cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed PRKAR1A 611 Regulatory subunit of the cAMP-dependent protein kinasesinvolved in cAMP signaling in cells. Cell membrane {ECO:0000269|PubMed:23115245}. activation of protein kinase A activity;blood coagulation;cardiac muscle cell proliferation;cellular response to glucagon stimulus;cGMP-mediated signaling;female meiotic nuclear division;intracellular signal transduction;mesoderm formation;negative regulation of activated T cell proliferation;negative regulation of cAMP-dependent protein kinase activity;negative regulation of meiotic nuclear division;regulation of transcription by RNA polymerase II;renal water homeostasis;sarcomere organization 3',5'-cyclic-GMP phosphodiesterase activity;cAMP binding;cAMP-dependent protein kinase inhibitor activity;cAMP-dependent protein kinase regulator activity;protein domain specific binding;protein kinase A catalytic subunit binding;ubiquitin protein ligase binding cAMP-dependent protein kinase complex;ciliary base;cytoplasm;cytosol;glutamatergic synapse;membrane;neuromuscular junction;nucleotide-activated protein kinase complex;plasma membrane raft;protein-containing complex Insulin signaling pathway Acrodysostosis;Carney complex;Cushing syndrome;Pigmented micronodular adrenocortical disease;Pituitary adenomas DARPP-32 events;Factors involved in megakaryocyte development and platelet production;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Hedgehog 'off' state;PKA activation;PKA activation in glucagon signalling;Vasopressin regulates renal water homeostasis via Aquaporins -1.09677314758301 -0.257027268409729 -0.439635366201401 -0.231733947992325 -0.768464386463165 -1.32562160491943 -1.58066785335541 -1.24955761432648 -0.101729534566402 1.35159528255463 1.60929894447327 1.22159087657928 -0.375449597835541 0.159848123788834 0.188951432704926 0.711242318153381 1.27059268951416 0.913540780544281 + Cluster -671 4 4 4 21.4 21.4 21.4 18.998 0 52.797 11640000000 23 4.04827175987803 0.000132352941176471 P51571 P51571 Translocon-associated protein subunit delta SSR4 1156 TRAP proteins are part of a complex whose function is tobind calcium to the ER membrane and thereby regulate the retentionof ER resident proteins. Single-passtype I membrane protein.;Endoplasmic reticulum membrane extracellular exosome;integral component of membrane;Sec61 translocon complex Protein processing in endoplasmic reticulum Congenital disorders of glycosylation type I SRP-dependent cotranslational protein targeting to membrane Translocon-associated protein (TRAP) complex -1.33498418331146 -0.361573934555054 -0.395032167434692 -0.195187747478485 -0.614287316799164 -1.30485510826111 -1.75247311592102 -1.22580075263977 0.0908261239528656 1.18192136287689 1.71116733551025 1.017054438591 -0.116149954497814 0.203795373439789 0.285357058048248 0.679192781448364 1.0260956287384 1.10493421554565 + Cluster -671 3 3 3 12.5 12.5 12.5 38.989 0 36.015 11236000000 20 3.71100840855098 0.000287081339712919 P49770 P49770 Translation initiation factor eIF-2B subunit beta EIF2B2 1118 Catalyzes the exchange of eukaryotic initiation factor2-bound GDP for GTP. central nervous system development;myelination;oligodendrocyte development;ovarian follicle development;regulation of translational initiation;response to glucose;response to heat;response to peptide hormone;T cell receptor signaling pathway;translational initiation ATP binding;GTP binding;translation initiation factor activity cytoplasm;cytosol;eukaryotic translation initiation factor 2B complex Herpes simplex virus 1 infection;RNA transport Leukoencephalopathy with vanishing white matter Recycling of eIF2:GDP EIF2B1-EIF2B2-EIF2B3-EIF2B4-EIF2B5 complex;EIF2B2-EIF2B3-EIF2B4-EIF2B5 complex -1.3051495552063 -0.346083790063858 -0.463955223560333 -0.323931485414505 -0.590411901473999 -1.46944165229797 -1.5212310552597 -1.15851163864136 0.192922919988632 1.28990852832794 1.65388548374176 0.932158708572388 -0.369965195655823 0.496863901615143 0.146320894360542 0.505908608436584 1.23583364486694 1.09487891197205 + Cluster -671 12 12 11 32.3 32.3 30.8 56.381 0 218.43 41842000000 78 3.54870609976712 0.000386363636363636 P05091;P05091-2 P05091;P05091-2 Aldehyde dehydrogenase, mitochondrial ALDH2 499 Mitochondrion matrix. alcohol metabolic process;carbohydrate metabolic process;ethanol catabolic process;ethanol oxidation aldehyde dehydrogenase (NAD) activity;aldehyde dehydrogenase [NAD(P)+] activity;electron transfer activity;glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity;NAD binding extracellular exosome;mitochondrial matrix Arginine and proline metabolism;Ascorbate and aldarate metabolism;beta-Alanine metabolism;Fatty acid degradation;Glycerolipid metabolism;Glycolysis / Gluconeogenesis;Histidine metabolism;Lysine degradation;Metabolic pathways;Pyruvate metabolism;Tryptophan metabolism;Valine, leucine and isoleucine degradation Acute alcohol sensitivity;Alcohol dependence Cyanamide;Disulfiram Ethanol oxidation;Metabolism of serotonin -0.761452734470367 -0.761452734470367 -0.997157096862793 -0.426227003335953 -0.913168787956238 -1.15069735050201 -1.56450605392456 -0.919905781745911 0.606476366519928 1.20828235149384 1.66646337509155 0.797461569309235 -0.268680453300476 0.288932383060455 -0.0573052652180195 0.649147570133209 1.27462244033813 1.32916724681854 + Cluster -671 8 8 8 33.3 33.3 33.3 39.681 0 65.33 8999200000 29 3.56269944407228 0.000383157894736842 P35249;P35249-2 P35249;P35249-2 Replication factor C subunit 4 RFC4 928 The elongation of primed DNA templates by DNA polymerasedelta and epsilon requires the action of the accessory proteinsproliferating cell nuclear antigen (PCNA) and activator 1. Thissubunit may be involved in the elongation of the multiprimed DNAtemplate. Nucleus {ECO:0000305}. DNA damage response, detection of DNA damage;DNA replication;DNA strand elongation involved in DNA replication;DNA-dependent DNA replication;error-free translesion synthesis;error-prone translesion synthesis;nucleotide-excision repair, DNA gap filling;nucleotide-excision repair, DNA incision;nucleotide-excision repair, DNA incision, 5'-to lesion;positive regulation of DNA-directed DNA polymerase activity;telomere maintenance via semi-conservative replication;transcription-coupled nucleotide-excision repair;translesion synthesis ATP binding;DNA binding;enzyme binding Ctf18 RFC-like complex;DNA replication factor C complex;Elg1 RFC-like complex;nucleoplasm;nucleus DNA replication;Mismatch repair;Nucleotide excision repair Activation of ATR in response to replication stress;Dual Incision in GG-NER;Dual incision in TC-NER;G2/M DNA damage checkpoint;Gap-filling DNA repair synthesis and ligation in GG-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;HDR through Homologous Recombination (HRR);HDR through Single Strand Annealing (SSA);PCNA-Dependent Long Patch Base Excision Repair;Polymerase switching;Polymerase switching on the C-strand of the telomere;Presynaptic phase of homologous DNA pairing and strand exchange;Processing of DNA double-strand break ends;Recognition of DNA damage by PCNA-containing replication complex;Regulation of TP53 Activity through Phosphorylation;Termination of translesion DNA synthesis;Translesion Synthesis by POLH;Translesion synthesis by POLI;Translesion synthesis by POLK;Translesion synthesis by REV1 9-1-1-RAD17-RFC complex;BASC (Ab 80) complex (BRCA1-associated genome surveillance complex);BASC (Ab 81) complex (BRCA1-associated genome surveillance complex);BASC complex (BRCA1-associated genome surveillance complex);BRD4-RFC complex;CHTF18-RFC2-5 complex;CTF18-cohesion-RFC complex;CTF18-cohesion-RFC-POLH complex;PCNA-CHL12-RFC2-5 complex;PCNA-RFC2-5 complex;RAD17-RFC complex;RC complex (Replication competent complex);RFC complex;RFC core complex;RFC2-5 subcomplex;RFC2-RIalpha complex -1.38559377193451 -0.288996070623398 -0.434899181127548 -0.740674376487732 -0.651452541351318 -1.66271758079529 -1.30003094673157 -1.05234086513519 0.436423152685165 1.43864405155182 1.36313807964325 0.105172462761402 -0.0471052750945091 0.865318477153778 0.289829641580582 1.04192101955414 1.30781447887421 0.715549170970917 + Cluster -671 12 12 12 18.7 18.7 18.7 93.487 0 54.369 11556000000 33 3.24020214994681 0.000692953020134228 Q8N1F7;Q8N1F7-2 Q8N1F7;Q8N1F7-2 Nuclear pore complex protein Nup93 NUP93 2183 Plays a role in the nuclear pore complex (NPC) assemblyand/or maintenance (PubMed:9348540). May anchor nucleoporins, butnot NUP153 and TPR, to the NPC. During renal development,regulates podocyte migration and proliferation through SMAD4signaling (PubMed:26878725). Peripheral membrane protein{ECO:0000250|UniProtKB:Q66HC5}. Nucleus, nuclear pore complex{ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283,ECO:0000269|PubMed:9348540}. Nucleus envelope{ECO:0000269|PubMed:26878725, ECO:0000269|PubMed:9348540}.Note=Localizes at the nuclear basket and at or near the nuclearentry to the gated channel of the pore.{ECO:0000269|PubMed:9348540}.;Nucleus membrane{ECO:0000250|UniProtKB:Q66HC5} mRNA export from nucleus;nuclear envelope organization;nuclear pore complex assembly;poly(A)+ mRNA export from nucleus;positive regulation of SMAD protein signal transduction;protein import into nucleus;renal system development;SMAD protein signal transduction;viral process structural constituent of nuclear pore membrane;nuclear envelope;nuclear membrane;nuclear periphery;nuclear pore RNA transport Nephrotic syndrome ISG15 antiviral mechanism;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Rev-mediated nuclear export of HIV RNA;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs CEN complex -0.69489711523056 -0.176537454128265 -1.13083064556122 -0.148830279707909 -0.121978908777237 -2.32583665847778 -1.65189146995544 -0.777309954166412 -0.332604318857193 0.84287828207016 1.03343200683594 0.630273759365082 0.488515168428421 0.689967274665833 1.0699782371521 0.958079695701599 0.766242206096649 0.881350040435791 + Cluster -671 6 6 6 19.2 19.2 19.2 65.443 0 221 5474900000 19 3.8218606101252 0.000239795918367347 P23368;P23368-2 P23368;P23368-2 NAD-dependent malic enzyme, mitochondrial ME2 780 Mitochondrion matrix. malate metabolic process;pyruvate metabolic process;regulation of NADP metabolic process;tricarboxylic acid cycle electron transfer activity;malate dehydrogenase (decarboxylating) (NAD+) activity;malate dehydrogenase (decarboxylating) (NADP+) activity;malic enzyme activity;metal ion binding;NAD binding;oxaloacetate decarboxylase activity mitochondrial matrix;mitochondrion Carbon metabolism;Pyruvate metabolism Citric acid cycle (TCA cycle) -1.17175722122192 0.192649856209755 -1.17175722122192 -0.224587708711624 -0.795175969600677 -1.86611104011536 -1.51615178585052 -1.11710166931152 0.606562614440918 0.978874087333679 1.04122936725616 0.344833940267563 0.476824045181274 0.61636209487915 1.04122936725616 0.606562614440918 0.99685150384903 0.960663318634033 + Cluster -671 6 6 6 25.7 25.7 25.7 39.724 0 84.075 19194000000 29 3.99006351949224 0.000142857142857143 P11766 P11766 Alcohol dehydrogenase class-3 ADH5 631 Class-III ADH is remarkably ineffective in oxidizingethanol, but it readily catalyzes the oxidation of long-chainprimary alcohols and the oxidation of S-(hydroxymethyl)glutathione. Cytoplasm {ECO:0000305}. ethanol oxidation;formaldehyde catabolic process;peptidyl-cysteine S-nitrosylation;positive regulation of blood pressure;respiratory system process;response to lipopolysaccharide;response to nitrosative stress;response to redox state;retinoid metabolic process alcohol dehydrogenase activity, zinc-dependent;electron transfer activity;fatty acid binding;formaldehyde dehydrogenase activity;protein homodimerization activity;S-(hydroxymethyl)glutathione dehydrogenase activity;zinc ion binding cytosol;extracellular exosome;mitochondrion Carbon metabolism;Chemical carcinogenesis;Drug metabolism - cytochrome P450;Fatty acid degradation;Glycolysis / Gluconeogenesis;Metabolic pathways;Metabolism of xenobiotics by cytochrome P450;Retinol metabolism;Tyrosine metabolism Ethanol oxidation -1.45617091655731 -0.157216638326645 -0.92874675989151 -0.0465158186852932 -0.511727452278137 -1.90210938453674 -1.66804695129395 -0.908289790153503 0.29311466217041 1.03462517261505 0.896207511425018 0.505795240402222 0.473195374011993 0.784304440021515 0.784304440021515 0.582176029682159 1.20958232879639 1.01551842689514 + Cluster -671 2 2 2 20.1 20.1 20.1 19.291 0 46.742 3226900000 8 3.54190110996163 0.000388090349075975 Q9GZN8;Q9GZN8-2 Q9GZN8;Q9GZN8-2 UPF0687 protein C20orf27 C20orf27 2744 -0.86977630853653 0.273450881242752 -1.08949840068817 -0.153087422251701 -0.410419344902039 -2.70312309265137 -1.28970539569855 -0.624819993972778 0.25488269329071 1.27411675453186 0.88285893201828 0.57081663608551 0.57081663608551 0.748213469982147 0.57081663608551 0.453688323497772 0.895480751991272 0.645288288593292 + Cluster -671 5 5 5 21.1 21.1 21.1 40.556 0 68.5 9080200000 20 3.05305981367636 0.000978915662650602 P40938;P40938-2 P40938;P40938-2 Replication factor C subunit 3 RFC3 991 The elongation of primed DNA templates by DNA polymerasedelta and epsilon requires the action of the accessory proteinsproliferating cell nuclear antigen (PCNA) and activator 1. Nucleus {ECO:0000305}. DNA damage response, detection of DNA damage;DNA replication;DNA strand elongation involved in DNA replication;DNA synthesis involved in DNA repair;DNA-dependent DNA replication;error-free translesion synthesis;error-prone translesion synthesis;nucleotide-excision repair, DNA gap filling;nucleotide-excision repair, DNA incision;nucleotide-excision repair, DNA incision, 5'-to lesion;positive regulation of DNA-directed DNA polymerase activity;response to organophosphorus;telomere maintenance via semi-conservative replication;transcription-coupled nucleotide-excision repair;translesion synthesis DNA clamp loader activity Ctf18 RFC-like complex;DNA replication factor C complex;nucleoplasm;nucleus DNA replication;Mismatch repair;Nucleotide excision repair Activation of ATR in response to replication stress;Dual Incision in GG-NER;Dual incision in TC-NER;G2/M DNA damage checkpoint;Gap-filling DNA repair synthesis and ligation in GG-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;HDR through Homologous Recombination (HRR);HDR through Single Strand Annealing (SSA);PCNA-Dependent Long Patch Base Excision Repair;Polymerase switching;Polymerase switching on the C-strand of the telomere;Presynaptic phase of homologous DNA pairing and strand exchange;Processing of DNA double-strand break ends;Recognition of DNA damage by PCNA-containing replication complex;Regulation of TP53 Activity through Phosphorylation;Termination of translesion DNA synthesis;Translesion Synthesis by POLH;Translesion synthesis by POLI;Translesion synthesis by POLK;Translesion synthesis by REV1 9-1-1-RAD17-RFC complex;BRD4-RFC complex;CHTF18-RFC2-5 complex;CTF18-cohesion-RFC complex;CTF18-cohesion-RFC-POLH complex;CTF18-CTF8-DCC1-RFC3 complex;PCNA-CHL12-RFC2-5 complex;PCNA-RFC2-5 complex;RAD17-RFC complex;RC complex (Replication competent complex);RFC complex;RFC2-5 subcomplex -1.15056455135345 0.0454470217227936 -1.66805803775787 -0.0444039963185787 -0.382816106081009 -2.08578324317932 -1.14909696578979 -0.838607370853424 0.0869783908128738 0.99903279542923 0.99903279542923 0.521544933319092 0.36317104101181 0.565313220024109 0.625366866588593 0.927639484405518 1.06669580936432 1.11910784244537 + Cluster -671 11 11 11 39.7 39.7 39.7 22.876 0 298.81 238920000000 193 3.55779368483625 0.000385416666666667 P46782 P46782 40S ribosomal protein S5;40S ribosomal protein S5, N-terminally processed RPS5 1056 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;regulation of translational fidelity;ribosomal small subunit assembly;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation mRNA binding;RNA binding;rRNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleoplasm;ribonucleoprotein complex Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic -1.00938081741333 -0.0825157538056374 -0.765900373458862 -0.347868055105209 -0.444866746664047 -1.81401383876801 -0.969596445560455 -1.26464223861694 0.103967756032944 2.46602988243103 0.876300036907196 0.380931884050369 0.0720834732055664 0.180808693170547 0.0720834732055664 0.710197567939758 0.918190777301788 0.918190777301788 + Cluster -671 1 1 1 8.1 8.1 8.1 21.943 0 9.4745 2812700000 11 3.03822593690817 0.000995562130177515 O14925;Q5SRD1;Q5SRD1-2 O14925;Q5SRD1;Q5SRD1-2 Mitochondrial import inner membrane translocase subunit Tim23;Putative mitochondrial import inner membrane translocase subunit Tim23B TIMM23;TIMM23B 141 Essential component of the TIM23 complex, a complex thatmediates the translocation of transit peptide-containing proteinsacross the mitochondrial inner membrane.;May participate in the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. thePAM complex (By similarity). Multi-pass membrane protein{ECO:0000255}.;Mitochondrion inner membrane {ECO:0000250};Mitochondrion inner membrane{ECO:0000269|PubMed:25997101};Multi-pass membrane protein {ECO:0000250}. protein import into mitochondrial matrix;protein targeting to mitochondrion P-P-bond-hydrolysis-driven protein transmembrane transporter activity;protein transmembrane transporter activity integral component of mitochondrial inner membrane;mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrion;TIM23 mitochondrial import inner membrane translocase complex Mitochondrial protein import APP-TIM23 complex;TIM (TIM17A, TIM17B, TIM23, TIM44) complex, mitochondrial;TIM17A-TIM23 complex;TIM17A-TIM23 complex, mitochondrial;TIM17B-TIM23 complex, mitochondrial;TIM23-TOM22-TIM50-HSD3B2 complex;TIM50-TIM23 complex, mitochondrial;TIMM8A-TIMM13-TIMM23 complex -0.972716808319092 0.0315900780260563 -1.01422941684723 -0.137900918722153 -0.835391461849213 -1.98007047176361 -1.3380936384201 -0.818924605846405 0.284951895475388 1.6500072479248 1.47754693031311 0.743133366107941 -0.0409069061279297 0.172885283827782 0.134400114417076 0.944292962551117 0.87209290266037 0.827333390712738 + Cluster -671 29 1 1 68.8 7.8 7.8 51.028 0 23.028 22442000000 16 3.80673693370561 0.000243107769423559 P61978-2;P61978 P61978-2;P61978 Heterogeneous nuclear ribonucleoprotein K HNRNPK 1329 One of the major pre-mRNA-binding proteins. Bindstenaciously to poly(C) sequences. Likely to play a role in thenuclear metabolism of hnRNAs, particularly for pre-mRNAs thatcontain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNAdamage, acting at the level of both transcription activation andrepression. When sumoylated, acts as a transcriptional coactivatorof p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFNinduction (By similarity). As far as transcription repression isconcerned, acts by interacting with long intergenic RNA p21(lincRNA-p21), a non-coding RNA induced by p53/TP53. Thisinteraction is necessary for the induction of apoptosis, but notcell cycle arrest. Cytoplasm {ECO:0000269|PubMed:1729596}.Nucleus, nucleoplasm {ECO:0000269|PubMed:16360036,ECO:0000269|PubMed:1729596, ECO:0000269|PubMed:18775702,ECO:0000269|PubMed:22721921}. Cell projection, podosome{ECO:0000269|PubMed:22721921}. Note=Recruited to p53/TP53-responsive promoters, in the presence of functional p53/TP53(PubMed:16360036). In case of ASFV infection, there is a shift inthe localization which becomes predominantly nuclear(PubMed:18775702). mRNA splicing, via spliceosome;negative regulation of apoptotic process;negative regulation of mRNA splicing, via spliceosome;positive regulation of low-density lipoprotein particle receptor biosynthetic process;positive regulation of receptor-mediated endocytosis;positive regulation of transcription by RNA polymerase II;regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter;regulation of low-density lipoprotein particle clearance;RNA metabolic process;RNA processing;signal transduction;viral process cadherin binding;DNA-binding transcription activator activity, RNA polymerase II-specific;identical protein binding;protein domain specific binding;RNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;single-stranded DNA binding catalytic step 2 spliceosome;cell projection;cytoplasm;cytoplasmic stress granule;extracellular exosome;focal adhesion;membrane;nuclear chromatin;nucleoplasm;nucleus;podosome MicroRNAs in cancer;Spliceosome;Viral carcinogenesis Au-Kline syndrome mRNA Splicing - Major Pathway;Processing of Capped Intron-Containing Pre-mRNA;SUMOylation of RNA binding proteins C complex spliceosome;Emerin complex 25;Emerin complex 52 -0.734550654888153 -0.160782128572464 -1.30167412757874 -0.0940636098384857 -0.902567327022552 -1.88075435161591 -1.3902200460434 -0.800290703773499 0.0212771687656641 1.54507219791412 1.10790193080902 -0.0113240480422974 0.228798106312752 0.740568399429321 0.460221588611603 0.93235856294632 1.13250339031219 1.10752558708191 + Cluster -671 3 3 3 31.3 31.3 31.3 13.015 0 52.401 63516000000 118 3.85793656421748 0.000220779220779221 P62854;Q5JNZ5 P62854;Q5JNZ5 40S ribosomal protein S26;Putative 40S ribosomal protein S26-like 1 RPS26;RPS26P11 1373 Cytoplasm, cytosol{ECO:0000269|PubMed:25957688}. Cytoplasm{ECO:0000305|PubMed:23636399, ECO:0000305|PubMed:25901680}. Roughendoplasmic reticulum {ECO:0000250|UniProtKB:P49171}.Note=Detected on cytosolic polysomes (PubMed:25957688). Detectedin ribosomes that are associated with the rough endoplasmicreticulum (By similarity). {ECO:0000250|UniProtKB:P49171,ECO:0000269|PubMed:25957688}. cytoplasmic translation;negative regulation of RNA splicing;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation cadherin binding;mRNA binding;RNA binding;structural constituent of ribosome cytoplasmic side of rough endoplasmic reticulum membrane;cytosol;cytosolic small ribosomal subunit;extracellular exosome;membrane;nucleoplasm;polysomal ribosome;small ribosomal subunit Ribosome Diamond-Blackfan anemia Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic -0.404001384973526 0.0687347128987312 -1.44254755973816 -0.87670511007309 -0.404001384973526 -2.01654958724976 -0.396100878715515 -0.980739414691925 -0.661286413669586 1.00891292095184 0.777855038642883 -0.355319291353226 0.15428052842617 0.903842449188232 0.903842449188232 0.897188544273376 1.38464105129242 1.43795335292816 + Cluster -671 9 9 9 45.7 45.7 45.7 21.634 0 273.4 105120000000 148 3.6879446901886 0.000309859154929577 Q07020;Q07020-2 Q07020;Q07020-2 60S ribosomal protein L18 RPL18 1534 Component of the large ribosomal subunit Cytoplasm, cytosol{ECO:0000269|PubMed:25957688}. Cytoplasm{ECO:0000305|PubMed:23636399, ECO:0000305|PubMed:25901680}. Roughendoplasmic reticulum {ECO:0000250|UniProtKB:Q95342}.Note=Detected on cytosolic polysomes (PubMed:25957688). Detectedin ribosomes that are associated with the rough endoplasmicreticulum (By similarity). {ECO:0000250|UniProtKB:Q95342,ECO:0000269|PubMed:25957688}. cytoplasmic translation;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic large ribosomal subunit;endoplasmic reticulum;focal adhesion;membrane;nucleolus;nucleus;polysomal ribosome;rough endoplasmic reticulum Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic -0.65871661901474 -0.174575746059418 -1.337681889534 -0.489121943712234 -0.653360784053802 -1.78228533267975 -1.32280039787292 -1.35209167003632 0.218229234218597 1.33549213409424 1.01861238479614 0.317656278610229 0.387199074029922 0.658497035503387 0.739720642566681 0.88800036907196 1.08400440216064 1.12322306632996 + Cluster -671 2 2 2 2.3 2.3 2.3 155.64 0 11.717 1544800000 8 5.35638959999019 1.3986013986014E-05 O14802 O14802 DNA-directed RNA polymerase III subunit RPC1 POLR3A 135 DNA-dependent RNA polymerase catalyzes the transcriptionof DNA into RNA using the four ribonucleoside triphosphates assubstrates. Largest and catalytic core component of RNA polymeraseIII which synthesizes small RNAs, such as 5S rRNA and tRNAs. Formsthe polymerase active center together with the second largestsubunit. A single-stranded DNA template strand of the promoter ispositioned within the central active site cleft of Pol III. Abridging helix emanates from RPC1 and crosses the cleft near thecatalytic site and is thought to promote translocation of Pol IIIby acting as a ratchet that moves the RNA-DNA hybrid through theactive site by switching from straight to bent conformations ateach step of nucleotide addition (By similarity). Plays a key rolein sensing and limiting infection by intracellular bacteria andDNA viruses. Acts as nuclear and cytosolic DNA sensor involved ininnate immune response. Can sense non-self dsDNA that serves astemplate for transcription into dsRNA. The non-self RNA polymeraseIII transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs)induce type I interferon and NF- Kappa-B through the RIG-Ipathway. Nucleus. defense response to virus;innate immune response;positive regulation of interferon-beta production;transcription by RNA polymerase III;transcription, DNA-templated chromatin binding;DNA binding;DNA-directed 5'-3' RNA polymerase activity;metal ion binding cytosol;membrane;nucleoplasm;RNA polymerase III complex Cytosolic DNA-sensing pathway;RNA polymerase Hypomyelinating leukodystrophy Cytosolic sensors of pathogen-associated DNA;RNA Polymerase III Abortive And Retractive Initiation;RNA Polymerase III Chain Elongation;RNA Polymerase III Transcription Initiation From Type 1 Promoter;RNA Polymerase III Transcription Initiation From Type 2 Promoter;RNA Polymerase III Transcription Initiation From Type 3 Promoter;RNA Polymerase III Transcription Termination -0.680436670780182 -0.198049649596214 -1.26263511180878 -0.370003223419189 -0.680436670780182 -1.99067878723145 -1.25559890270233 -0.945165455341339 0.140309050679207 1.70939004421234 1.11328995227814 0.440791845321655 0.243571430444717 0.243571430444717 0.440791845321655 0.818733632564545 1.01595401763916 1.21660113334656 + Cluster -671 21 21 21 78 78 78 30.791 0 323.31 558140000000 454 4.284861471408 8.22368421052632E-05 P60174;P60174-1;P60174-4 P60174;P60174-1;P60174-4 Triosephosphate isomerase TPI1 1271 Triosephosphate isomerase is an extremely efficientmetabolic enzyme that catalyzes the interconversion betweendihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate(G3P) in glycolysis and gluconeogenesis Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU10127}. canonical glycolysis;gluconeogenesis;glyceraldehyde-3-phosphate biosynthetic process;glycerol catabolic process;glycolytic process;methylglyoxal biosynthetic process methylglyoxal synthase activity;protein homodimerization activity;triose-phosphate isomerase activity;ubiquitin protein ligase binding cytosol;extracellular exosome;extracellular space;nucleus Biosynthesis of amino acids;Carbon metabolism;Fructose and mannose metabolism;Glycolysis / Gluconeogenesis;Inositol phosphate metabolism;Metabolic pathways Anemia due to disorders of glycolytic enzymes Gluconeogenesis;Glycolysis -0.545048296451569 -0.0720901489257813 -1.12847185134888 -0.646301805973053 -0.870381355285645 -2.24631333351135 -0.908865809440613 -0.628407895565033 0.257435858249664 1.46117770671844 1.24468898773193 0.284432649612427 -0.379046112298965 0.606679499149323 0.565685570240021 0.547526657581329 1.22864997386932 1.22864997386932 + Cluster -671 7 7 7 33 33 33 23.432 0 85.002 40107000000 84 3.4817204714309 0.000437375745526839 P50914 P50914 60S ribosomal protein L14 RPL14 1145 Component of the large ribosomal subunit nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;ribosomal large subunit biogenesis;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation cadherin binding;RNA binding;structural constituent of ribosome cytosol;cytosolic large ribosomal subunit;extracellular exosome;membrane;postsynaptic density Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle) -0.997172296047211 0.163343206048012 -1.27976107597351 -0.303477197885513 -0.791859865188599 -1.95335149765015 -1.26871585845947 -0.625205636024475 0.462259113788605 1.84669411182404 0.844321608543396 0.373569846153259 -0.229550555348396 0.559680223464966 0.452577829360962 0.517993271350861 1.05513656139374 1.17351818084717 + Cluster -671 3 3 3 3.1 3.1 3.1 162.12 0 17.992 1434700000 9 3.11842336384817 0.000877165354330709 Q12769 Q12769 Nuclear pore complex protein Nup160 NUP160 1563 Involved in poly(A)+ RNA transport Nucleus, nuclear pore complex{ECO:0000269|PubMed:11564755, ECO:0000269|PubMed:11684705}. mRNA export from nucleus;viral process structural constituent of nuclear pore cytosol;nuclear envelope;nuclear pore;nuclear pore outer ring RNA transport Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;ISG15 antiviral mechanism;Mitotic Prometaphase;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Resolution of Sister Chromatid Cohesion;Rev-mediated nuclear export of HIV RNA;RHO GTPases Activate Formins;Separation of Sister Chromatids;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs NPC subcomplex (NUP98, NUP107, NUP133, NUP160);Nup 107-160 subcomplex -0.600631713867188 -0.692222058773041 -0.416207849979401 -0.236496642231941 -0.539339661598206 -2.04217028617859 -1.62459516525269 -1.25632345676422 0.296997368335724 1.47260713577271 1.42421686649323 0.592859268188477 0.183964982628822 0.634977757930756 0.614490926265717 0.992539048194885 0.822463750839233 0.37286964058876 + Cluster -671 3 3 3 10.1 10.1 10.1 54.854 0 32.092 1903600000 4 3.81180935421069 0.000244332493702771 Q96GA3 Q96GA3 Protein LTV1 homolog LTV1 2460 ribosomal small subunit biogenesis;ribosomal small subunit export from nucleus cytosol;EGO complex;late endosome membrane;nucleoplasm;nucleus;preribosome, small subunit precursor Major pathway of rRNA processing in the nucleolus and cytosol -0.762132346630096 -0.408526599407196 -0.722672820091248 -0.392683386802673 -0.354586601257324 -1.35803031921387 -1.72687029838562 -1.62096214294434 0.106373824179173 1.48864603042603 1.6397465467453 0.706299185752869 0.240047559142113 0.240047559142113 0.391056686639786 0.519454419612885 1.08961188793182 0.925180613994598 + Cluster -671 4 4 4 12.5 12.5 12.5 50.464 0 19.015 3678000000 8 4.40998472594621 6.11510791366906E-05 Q3ZCQ8-2;Q3ZCQ8;Q3ZCQ8-3 Q3ZCQ8-2;Q3ZCQ8;Q3ZCQ8-3 Mitochondrial import inner membrane translocase subunit TIM50 TIMM50 1890 however such activity may not be relevant invivo.;Essential component of the TIM23 complex, a complex thatmediates the translocation of transit peptide-containing proteinsacross the mitochondrial inner membrane. Has some phosphataseactivity in vitro Single-pass membrane protein{ECO:0000269|PubMed:15044455}.Isoform 2: Nucleus speckle{ECO:0000269|PubMed:16008839}. Note=Nuclear and enriched inspeckles with snRNPs. {ECO:0000269|PubMed:16008839}.;Mitochondrion inner membrane{ECO:0000269|PubMed:15044455} mitochondrial membrane organization;protein dephosphorylation;protein import into mitochondrial matrix;release of cytochrome c from mitochondria interleukin-2 receptor binding;phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein tyrosine phosphatase activity;ribonucleoprotein complex binding;RNA binding integral component of membrane;mitochondrial inner membrane;mitochondrion;nuclear speck;nucleoplasm;TIM23 mitochondrial import inner membrane translocase complex 3-Methylglutaconic aciduria Mitochondrial protein import TIM23-TOM22-TIM50-HSD3B2 complex;TIM50-COIL complex;TIM50-SMN1 complex;TIM50-TIM23 complex, mitochondrial -0.626585483551025 0.254298955202103 -0.955264270305634 -0.277659565210342 -0.723438560962677 -1.92318642139435 -1.59432435035706 -1.21847724914551 0.547224402427673 1.64742803573608 1.4579963684082 -0.0559657402336597 0.298101127147675 0.751920640468597 0.636520206928253 0.420683890581131 0.680364012718201 0.680364012718201 + Cluster -671 8 8 8 32.6 32.6 32.6 41.401 0 99.921 16688000000 32 3.65340299013072 0.000331065759637188 Q8TDN6 Q8TDN6 Ribosome biogenesis protein BRX1 homolog BRIX1 2271 Required for biogenesis of the 60S ribosomal subunit. Nucleus, nucleolus. ribosomal large subunit assembly RNA binding nucleolus;nucleus Nop56p-associated pre-rRNA complex -0.754553437232971 0.258526533842087 -1.23954594135284 -0.721513152122498 -1.1523152589798 -1.52897620201111 -1.61164259910583 -0.711188018321991 1.08443558216095 1.23786151409149 1.45503258705139 0.0816642791032791 0.201541870832443 0.225502640008926 0.650175273418427 0.66649055480957 1.03040087223053 0.828102827072144 + Cluster -671 4 4 4 16.2 16.2 16.2 46.578 0 72.338 3243700000 12 3.89968318582931 0.000188829787234043 Q96EE3-1;Q96EE3 Q96EE3-1;Q96EE3 Nucleoporin SEH1 SEH1L 2431 Component of the Nup107-160 subcomplex of the nuclearpore complex (NPC). The Nup107-160 subcomplex is required for theassembly of a functional NPC. The Nup107-160 subcomplex is alsorequired for normal kinetochore microtubule attachment, mitoticprogression and chromosome segregation. This subunit plays a rolein recruitment of the Nup107-160 subcomplex to the kinetochore Chromosome, centromere, kinetochore{ECO:0000269|PubMed:15146057, ECO:0000269|PubMed:17363900}.Nucleus, nuclear pore complex {ECO:0000269|PubMed:15146057,ECO:0000269|PubMed:17363900}. Lysosome membrane{ECO:0000269|PubMed:28199306}. attachment of mitotic spindle microtubules to kinetochore;cell division;cellular protein-containing complex localization;cellular response to amino acid starvation;cytokine production involved in inflammatory response;defense response to Gram-positive bacterium;mitotic metaphase plate congression;mRNA export from nucleus;nuclear pore organization;positive regulation of TOR signaling;positive regulation of TORC1 signaling;viral process structural molecule activity condensed chromosome kinetochore;cytosol;GATOR2 complex;lysosomal membrane;nuclear envelope;nuclear pore outer ring;Seh1-associated complex mTOR signaling pathway;RNA transport Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;ISG15 antiviral mechanism;Mitotic Prometaphase;NEP/NS2 Interacts with the Cellular Export Machinery;NS1 Mediated Effects on Host Pathways;Nuclear import of Rev protein;Nuclear Pore Complex (NPC) Disassembly;Regulation of Glucokinase by Glucokinase Regulatory Protein;Regulation of HSF1-mediated heat shock response;Resolution of Sister Chromatid Cohesion;Rev-mediated nuclear export of HIV RNA;RHO GTPases Activate Formins;Separation of Sister Chromatids;snRNP Assembly;SUMOylation of chromatin organization proteins;SUMOylation of DNA damage response and repair proteins;SUMOylation of DNA replication proteins;SUMOylation of RNA binding proteins;SUMOylation of SUMOylation proteins;SUMOylation of ubiquitinylation proteins;Transcriptional regulation by small RNAs;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Ribonucleoproteins into the Host Nucleus;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA;tRNA processing in the nucleus;Viral Messenger RNA Synthesis;Vpr-mediated nuclear import of PICs GATOR complex;GATOR2 complex;Nuclear pore complex;Nup 107-160 subcomplex;SOG complex -0.385714888572693 0.0195095278322697 -1.11609590053558 -0.502377450466156 -0.728674292564392 -1.81947290897369 -1.49560511112213 -1.32793164253235 0.664128184318542 1.55407536029816 1.55407536029816 0.727517068386078 0.224511921405792 0.203921779990196 0.378908097743988 0.885659635066986 0.664128184318542 0.499436914920807 + Cluster -671 10 10 10 24.9 24.9 24.9 43.159 0 161 31910000000 43 5.28590858003955 1.33333333333333E-05 Q9P035;Q9P035-2 Q9P035;Q9P035-2 Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 3 HACD3 3038 Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to thechain of long- and very long-chain fatty acids/VLCFAs per cycle.This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoAintermediate into trans-2,3-enoyl-CoA, within each cycle of fattyacid elongation. Thereby, it participates in the production ofVLCFAs of different chain lengths that are involved in multiplebiological processes as precursors of membrane lipids and lipidmediators. May be involved in Rac1-signaling pathways leading tothe modulation of gene expression. Promotes insulin receptor/INSRautophosphorylation and is involved in INSR internalization(PubMed:25687571). Multi-pass membrane protein{ECO:0000269|PubMed:18554506}.;Endoplasmic reticulum membrane{ECO:0000269|PubMed:18554506} activation of JUN kinase activity;fatty acid elongation;I-kappaB kinase/NF-kappaB signaling;positive regulation by virus of viral protein levels in host cell;positive regulation of viral genome replication;Rac protein signal transduction;Rho protein signal transduction;small GTPase mediated signal transduction;sphingolipid biosynthetic process;very long-chain fatty acid biosynthetic process 3-hydroxyacyl-CoA dehydratase activity;3-hydroxy-arachidoyl-CoA dehydratase activity;3-hydroxy-behenoyl-CoA dehydratase activity;3-hydroxy-lignoceroyl-CoA dehydratase activity;enzyme binding;GTPase activator activity;very-long-chain 3-hydroxyacyl-CoA dehydratase activity cytosol;endoplasmic reticulum;endoplasmic reticulum membrane;focal adhesion;integral component of membrane;mitochondrion;nuclear membrane Biosynthesis of unsaturated fatty acids;Fatty acid elongation;Fatty acid metabolism;Metabolic pathways Synthesis of very long-chain fatty acyl-CoAs -0.517062783241272 -0.0914711728692055 -0.874371349811554 -0.389331787824631 -0.995616912841797 -1.69796049594879 -1.84987568855286 -1.13325273990631 0.282676547765732 1.02907121181488 1.61274814605713 0.840249478816986 0.557890772819519 0.191508367657661 0.449625581502914 0.819026231765747 0.907147526741028 0.858998894691467 + Cluster -671 2 2 2 9 9 9 41.488 0 16.477 7839600000 13 5.35054282838596 1.38888888888889E-05 Q8TCT9;Q8TCT9-5;Q8TCT9-2;Q8TCT9-4 Q8TCT9;Q8TCT9-5;Q8TCT9-2;Q8TCT9-4 Minor histocompatibility antigen H13 HM13 2265 Catalyzes intramembrane proteolysis of some signalpeptides after they have been cleaved from a preprotein, resultingin the release of the fragment from the ER membrane into thecytoplasm. Required to generate lymphocyte cell surface (HLA-E)epitopes derived from MHC class I signal peptides(PubMed:11714810). May be necessary for the removal of the signalpeptide that remains attached to the hepatitis C virus coreprotein after the initial proteolytic processing of thepolyprotein (PubMed:12145199). Involved in the intramembranecleavage of the integral membrane protein PSEN1 (PubMed:12077416,PubMed:11714810, PubMed:14741365). Cleaves the integral membraneprotein XBP1 isoform 1 in a DERL1/RNF139-dependent manner(PubMed:25239945). May play a role in graft rejection (Bysimilarity). Lumenal side {ECO:0000269|PubMed:12077416,ECO:0000269|PubMed:15385547}.Isoform 4: Cell membrane{ECO:0000250|UniProtKB:Q9D8V0}; Multi-pass membrane protein{ECO:0000250|UniProtKB:Q9D8V0}.; Multi-pass membrane protein{ECO:0000305}; Multi-pass membrane protein{ECO:0000305}. Membrane {ECO:0000269|PubMed:12077416,ECO:0000269|PubMed:15385547};Endoplasmic reticulum membrane{ECO:0000269|PubMed:15998642} membrane protein proteolysis;membrane protein proteolysis involved in retrograde protein transport, ER to cytosol;protein homotetramerization;signal peptide processing aspartic endopeptidase activity, intramembrane cleaving;peptidase activity;protein homodimerization activity;ubiquitin protein ligase binding cell surface;Derlin-1 retrotranslocation complex;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of cytoplasmic side of endoplasmic reticulum membrane;integral component of lumenal side of endoplasmic reticulum membrane;membrane;plasma membrane;rough endoplasmic reticulum -0.163119167089462 -0.248729228973389 -1.10483849048615 -0.712811470031738 -0.657442450523376 -1.30333995819092 -1.56222057342529 -1.41876208782196 0.404666304588318 1.04533922672272 2.23831248283386 0.274608343839645 0.251101821660995 0.284740149974823 0.190207898616791 0.816433668136597 0.727889597415924 0.937964141368866 + Cluster -671 3 3 3 17.3 17.3 17.3 33.31 0 25.149 13251000000 14 4.39449824403921 5.98591549295775E-05 Q9BPW8 Q9BPW8 Protein NipSnap homolog 1 NIPSNAP1 2607 sensory perception of pain neurotransmitter binding mitochondrion;synaptic membrane -0.347126066684723 -0.530557513237 -0.530557513237 -0.855507135391235 0.380866020917892 -1.91564929485321 -1.07840716838837 -2.19426321983337 0.380866020917892 1.14948236942291 1.14948236942291 0.966050982475281 0.6411013007164 0.6411013007164 0.6411013007164 0.740284085273743 0.380866020917892 0.380866020917892 + Cluster -671 14 14 14 95.7 95.7 95.7 15.054 0 323.31 505940000000 478 3.2786480810574 0.000615384615384615 P07737;CON__P02584 P07737 Profilin-1 PFN1 539 Binds to actin and affects the structure of thecytoskeleton. At high concentrations, profilin prevents thepolymerization of actin, whereas it enhances it at lowconcentrations. By binding to PIP2, it inhibits the formation ofIP3 and DG. Inhibits androgen receptor (AR) and HTT aggregationand binding of G-actin is essential for its inhibition of AR Cytoplasm, cytoskeleton. actin cytoskeleton organization;modification of postsynaptic actin cytoskeleton;negative regulation of actin filament bundle assembly;negative regulation of actin filament polymerization;negative regulation of stress fiber assembly;neural tube closure;positive regulation of actin filament bundle assembly;positive regulation of actin filament polymerization;positive regulation of ATPase activity;positive regulation of epithelial cell migration;positive regulation of ruffle assembly;protein stabilization;regulation of actin filament polymerization;regulation of transcription by RNA polymerase II;synapse maturation;Wnt signaling pathway, planar cell polarity pathway actin binding;actin monomer binding;adenyl-nucleotide exchange factor activity;cadherin binding;phosphatidylinositol-4,5-bisphosphate binding;proline-rich region binding;Rho GTPase binding;RNA binding blood microparticle;cell cortex;cytoplasm;cytoskeleton;cytosol;extracellular exosome;focal adhesion;glutamatergic synapse;membrane;nucleus Rap1 signaling pathway;Regulation of actin cytoskeleton;Salmonella infection;Shigellosis Amyotrophic lateral sclerosis (ALS) PCP/CE pathway;Platelet degranulation;RHO GTPases Activate Formins;Signaling by ROBO receptors Profilin 1 complex;RIAM-profilin complex;RIAM-Rap1-GTP-profilin complex -0.381997436285019 0.0725527852773666 -1.17937076091766 -0.473791897296906 -0.572292923927307 -1.94863533973694 -1.44267702102661 -1.58982074260712 0.573314189910889 1.04946708679199 1.48575460910797 0.422523349523544 0.617574870586395 0.675595998764038 0.730197072029114 0.712722599506378 0.512714624404907 0.73616886138916 + Cluster -671 6 6 6 9.1 9.1 9.1 114.76 0 61.095 3738100000 12 5.06479742890416 1.71428571428571E-05 Q9H2U1;Q9H2U1-3;Q9H2U1-2 Q9H2U1;Q9H2U1-3;Q9H2U1-2 ATP-dependent RNA helicase DHX36 DHX36 2785 Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:16150737, PubMed:18854321,PubMed:20472641, PubMed:21586581). Plays a role in many biologicalprocesses such as genomic integrity, gene expression regulationsand as a sensor to initiate antiviral responses (PubMed:14731398,PubMed:18279852, PubMed:21993297, PubMed:22238380,PubMed:25579584). G4 structures correspond to helical structurescontaining guanine tetrads (By similarity). Binds with highaffinity to and unwinds G4 structures that are formed in nucleicacids (G4-ADN and G4-RNA) (PubMed:16150737, PubMed:18842585,PubMed:20472641, PubMed:21586581, PubMed:24369427,PubMed:26195789). Plays a role in genomic integrity(PubMed:22238380). Converts the G4-RNA structure present intelomerase RNA template component (TREC) into a double-strandedRNA to promote P1 helix formation that acts as a template boundaryensuring accurate reverse transcription (PubMed:20472641,PubMed:21149580, PubMed:21846770, PubMed:22238380,PubMed:24151078, PubMed:25579584). Plays a role in transcriptionalregulation (PubMed:21586581, PubMed:21993297). Resolves G4-DNAstructures in promoters of genes, such as YY1, KIT/c-kit and ALPLand positively regulates their expression (PubMed:21993297). Playsa role in post-transcriptional regulation (PubMed:27940037).Unwinds a G4-RNA structure located in the 3'-UTR polyadenylationsite of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-endprocessing in response to ultraviolet (UV)-induced DNA damage(PubMed:27940037). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the controlof dendritic spine size (By similarity). Plays a role in theregulation of cytoplasmic mRNA translation and mRNA stability(PubMed:24369427, PubMed:26489465). Binds to both G4-RNAstructures and alternative non-quadruplex-forming sequence withinthe 3'-UTR of the PITX1 mRNA regulating negatively PITX1 proteinexpression (PubMed:24369427). Binds to both G4-RNA structure inthe 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR ofNKX2-5 mRNA to either stimulate protein translation or induce mRNAdecay in an ELAVL1-dependent manner, respectively(PubMed:26489465). Binds also to ARE sequences present in severalmRNAs mediating exosome-mediated 3'-5' mRNA degradation(PubMed:14731398, PubMed:18279852). Involved in cytoplasmicurokinase-type plasminogen activator (uPA) mRNA decay(PubMed:14731398). Component of a multi-helicase-TICAM1 complexthat acts as a cytoplasmic sensor of viral double-stranded RNA(dsRNA) and plays a role in the activation of a cascade ofantiviral responses including the induction of proinflammatorycytokines via the adapter molecule TICAM1 (By similarity).Required for early embryonic development and hematopoiesis.Involved in the regulation of cardioblast differentiation andproliferation during heart development. Involved in spermatogoniadifferentiation. May play a role in ossification (By similarity) Nucleus {ECO:0000269|PubMed:18279852,ECO:0000269|PubMed:18854321}. Cytoplasm{ECO:0000269|PubMed:18279852, ECO:0000269|PubMed:18854321}.Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q8VHK9}. Cytoplasm,Stress granule {ECO:0000269|PubMed:18854321}. Nucleus speckle{ECO:0000269|PubMed:18279852}. Chromosome, telomere{ECO:0000269|PubMed:20472641}. Mitochondrion{ECO:0000250|UniProtKB:Q8VHK9}. Perikaryon{ECO:0000250|UniProtKB:D4A2Z8}. Cell projection, dendrite{ECO:0000250|UniProtKB:D4A2Z8}. Cell projection, axon{ECO:0000250|UniProtKB:D4A2Z8}. Note=Predominantly localized inthe nucleus (PubMed:18279852). Colocalizes with SRSF2 in nuclearspeckles (PubMed:18279852). Colocalizes with DDX5 in nucleolarcaps upon transcription inhibition (PubMed:18279852). Accumulatesand colocalized with TIA1 in cytoplasmic stress granules (SGs) inan arsenite-, heat shock- and RNA-binding-dependent manner(PubMed:18854321). Shuttles into and out of SGs in an ATPase-dependent manner (PubMed:18854321). Colocalizes in the cytosolwith the multi-helicase-TICAM1 complex that translocates to themitochondria upon poly(I:C) RNA ligand stimulation (Bysimilarity). {ECO:0000250|UniProtKB:Q8VHK9,ECO:0000269|PubMed:18279852, ECO:0000269|PubMed:18854321}.Isoform 1: Nucleus{ECO:0000269|PubMed:14731398}. Cytoplasm{ECO:0000269|PubMed:14731398}. Note=Preferentially localized inthe nucleus (PubMed:14731398). Excluded from nucleoli(PubMed:14731398). {ECO:0000269|PubMed:14731398}.Isoform 2: Nucleus{ECO:0000269|PubMed:14731398}. Cytoplasm{ECO:0000269|PubMed:14731398}. Note=Preferentially localized inthe cytoplasm (PubMed:14731398). Excluded from nucleoli(PubMed:14731398). {ECO:0000269|PubMed:14731398}. 3'-UTR-mediated mRNA destabilization;cellular response to arsenite ion;cellular response to heat;cellular response to UV;defense response to virus;G-quadruplex DNA unwinding;innate immune response;negative regulation of translation;ossification;positive regulation of cardioblast differentiation;positive regulation of cytoplasmic translation;positive regulation of dendritic spine morphogenesis;positive regulation of gene expression;positive regulation of hematopoietic progenitor cell differentiation;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of interferon-alpha secretion;positive regulation of intracellular mRNA localization;positive regulation of mRNA 3'-end processing;positive regulation of myeloid dendritic cell cytokine production;positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;positive regulation of telomere maintenance;positive regulation of telomere maintenance via telomere lengthening;positive regulation of transcription by RNA polymerase II;positive regulation of transcription initiation from RNA polymerase II promoter;positive regulation of type I interferon production;regulation of embryonic development;regulation of mRNA stability;regulation of transcription by RNA polymerase III;regulation of transcription from RNA polymerase II promoter involved in spermatogenesis;response to exogenous dsRNA;RNA secondary structure unwinding;spermatogenesis;telomerase RNA stabilization ATP binding;ATP-dependent 3'-5' RNA helicase activity;ATP-dependent DNA helicase activity;ATP-dependent RNA helicase activity;DNA-dependent ATPase activity;double-stranded RNA binding;G-quadruplex DNA binding;G-quadruplex RNA binding;histone deacetylase binding;magnesium ion binding;mRNA 3'-UTR AU-rich region binding;mRNA 3'-UTR binding;mRNA 5'-UTR binding;pre-miRNA binding;RNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;single-stranded DNA binding;telomerase RNA binding;transcription regulatory region DNA binding axon;chromosome, telomeric region;cytoplasm;cytoplasmic stress granule;cytosol;dendrite;extracellular exosome;mitochondrion;nuclear speck;nucleus;perikaryon RNA degradation DEx/H-box helicases activate type I IFN and inflammatory cytokines production -0.840587079524994 -0.557795703411102 -0.642859935760498 -0.557795703411102 -0.930944204330444 -1.12449908256531 -1.97990787029266 -0.885428071022034 0.318879157304764 0.480001658201218 1.78641295433044 -0.156819015741348 0.333151072263718 0.875050842761993 0.67207133769989 0.944425463676453 1.34019029140472 0.926453948020935 + Cluster -671 5 5 5 11.6 11.6 11.6 53.248 0 61.077 8218000000 13 3.5597249390468 0.000386221294363257 Q9ULV4;Q9ULV4-2;Q9ULV4-3;Q6QEF8;Q6QEF8-3;Q6QEF8-4;Q6QEF8-2;Q6QEF8-5 Q9ULV4;Q9ULV4-2;Q9ULV4-3 Coronin-1C CORO1C 3164 Plays a role in directed cell migration by regulatingthe activation and subcellular location of RAC1 (PubMed:25074804,PubMed:25925950). Increases the presence of activated RAC1 at theleading edge of migrating cells (PubMed:25074804,PubMed:25925950). Required for normal organization of thecytoskeleton, including the actin cytoskeleton, microtubules andthe vimentin intermediate filaments (By similarity). Plays a rolein endoplasmic reticulum-associated endosome fission: localizes toendosome membrane tubules and promotes recruitment of TMCC1,leading to recruitment of the endoplasmic reticulum to endosometubules for fission (PubMed:30220460). Endosome membrane fissionof early and late endosomes is essential to separate regionsdestined for lysosomal degradation from carriers to be recycled tothe plasma membrane (PubMed:30220460). Required for normal cellproliferation, cell migration, and normal formation oflamellipodia (By similarity). Required for normal distribution ofmitochondria within cells (By similarity) Cytoplasmic side{ECO:0000269|PubMed:19651142, ECO:0000269|PubMed:25074804,ECO:0000269|PubMed:25925950}. Cell projection, lamellipodium{ECO:0000269|PubMed:12377779, ECO:0000269|PubMed:19651142}. Cellprojection, ruffle membrane {ECO:0000269|PubMed:25074804}.Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10828594,ECO:0000269|PubMed:12377779, ECO:0000269|PubMed:19651142,ECO:0000269|PubMed:25074804}. Cytoplasm, cell cortex{ECO:0000269|PubMed:10828594, ECO:0000269|PubMed:19651142}.Endosome membrane {ECO:0000269|PubMed:30220460}. Note=All isoformscolocalize with the actin cytoskeleton in the cytosol, andespecially in the cell cortex (PubMed:10828594, PubMed:19651142,PubMed:25074804). Colocalizes with F-actin at the leading edge oflamellipodia. Partially colocalizes with microtubules and vimentinintermediate filaments (PubMed:10828594, PubMed:19651142,PubMed:25074804). Localizes to endosome membrane tubules/buds(PubMed:30220460). {ECO:0000269|PubMed:10828594,ECO:0000269|PubMed:19651142, ECO:0000269|PubMed:25074804,ECO:0000269|PubMed:30220460}.Isoform 3: Cell membrane, sarcolemma{ECO:0000269|PubMed:19651142}. Cytoplasm, myofibril, sarcomere{ECO:0000269|PubMed:19651142}. Cell junction, synapse{ECO:0000269|PubMed:19651142}. Cell membrane{ECO:0000269|PubMed:19651142}; Cytoplasmic side{ECO:0000269|PubMed:19651142}. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:19651142}. Cytoplasm, cell cortex{ECO:0000269|PubMed:19651142}. Note=Colocalizes with the thinfilaments of the sarcomere and with the postsynaptic area and thejunctional sarcoplasm of motor end plates. Colocalizes with theactin cytoskeleton in the cytosol, and especially in the cellcortex. {ECO:0000269|PubMed:19651142}.; Peripheral membrane protein{ECO:0000269|PubMed:19651142, ECO:0000269|PubMed:25074804,ECO:0000269|PubMed:25925950}; Peripheral membrane protein{ECO:0000269|PubMed:19651142};Cell membrane {ECO:0000269|PubMed:12377779,ECO:0000269|PubMed:19651142, ECO:0000269|PubMed:25074804,ECO:0000269|PubMed:25925950} actin cytoskeleton organization;activation of GTPase activity;establishment of protein localization;negative regulation of epithelial cell migration;negative regulation of focal adhesion assembly;negative regulation of protein kinase activity by regulation of protein phosphorylation;negative regulation of protein phosphorylation;negative regulation of substrate adhesion-dependent cell spreading;neural crest cell migration;phagocytosis;positive regulation of lamellipodium morphogenesis;regulation of epithelial cell migration;regulation of fibroblast migration;regulation of focal adhesion assembly;regulation of protein phosphorylation;regulation of ruffle assembly;regulation of substrate adhesion-dependent cell spreading;signal transduction actin filament binding;Rac GTPase binding actin cytoskeleton;cell cortex;flotillin complex;focal adhesion;lamellipodium;lateral plasma membrane;ruffle membrane;sarcolemma;sarcomere;synapse -0.678915023803711 -0.158498734235764 -1.05215442180634 -0.119297012686729 -1.35460960865021 -1.37700891494751 -1.64567112922668 -1.27280807495117 0.486095517873764 0.255929470062256 1.41319143772125 0.143345072865486 1.14515233039856 0.574293494224548 0.763552904129028 0.988427758216858 1.06396222114563 0.825012803077698 + Cluster -671 11 11 11 54.3 54.3 54.3 17.222 0 97.174 139580000000 117 4.50933935559158 5.74712643678161E-05 P62277 P62277 40S ribosomal protein S13 RPS13 1347 negative regulation of RNA splicing;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation mRNA 5'-UTR binding;mRNA binding;RNA binding;small ribosomal subunit rRNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleolus;nucleoplasm;nucleus;postsynaptic density;ribosome Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TNF-alpha/Nf-kappa B signaling complex (RPL6, RPL30, RPS13, CHUK, DDX3X, NFKB2, NFKBIB, REL, IKBKG, NFKB1, MAP3K8, RELB, GLG1, NFKBIA, RELA, TNIP2, GTF2I);TNF-alpha/NF-kappa B signaling complex 6 -0.462395191192627 -0.286722183227539 -1.01557338237762 -0.356198996305466 -0.898520231246948 -1.71413135528564 -1.81529641151428 -1.15278041362762 0.314947664737701 1.12539219856262 1.26944661140442 0.0202955026179552 0.598867416381836 0.789278745651245 0.878938794136047 0.850081026554108 0.960352718830109 0.894017577171326 + Cluster -671 1 1 1 2.3 2.3 2.3 106.91 0 6.0079 1220300000 6 5.00113470636662 2.20994475138122E-05 Q13111;Q13111-3 Q13111;Q13111-3 Chromatin assembly factor 1 subunit A CHAF1A 1593 Core component of the CAF-1 complex, a complex thoughtto mediate chromatin assembly in DNA replication and DNA repair.Assembles histone octamers onto replicating DNA in vitro. CAF-1performs the first step of the nucleosome assembly process,bringing newly synthesized histones H3 and H4 to replicating DNA;histones H2A/H2B can bind to this chromatin precursor subsequentto DNA replication to complete the histone octamer. CHAF1A bindsto histones H3 and H4. It may play a role in heterochromatinmaintenance in proliferating cells by bringing newly synthesizedcbx proteins to heterochromatic DNA replication foci (Bysimilarity). Nucleus {ECO:0000269|PubMed:10052459}.Note=DNA replication foci. cell cycle;chromatin assembly;DNA repair;DNA replication;DNA replication-dependent nucleosome assembly;nucleosome assembly chromatin binding;chromo shadow domain binding;identical protein binding;unfolded protein binding CAF-1 complex;nuclear chromatin;nucleus;protein-containing complex ASF1-interacting protein complex;Chromatin assembly complex (CAF-1 complex);Histone H3.1 complex;Replication-coupled CAF-1-MBD1-ETDB1 complex;WINAC complex -0.775029957294464 -0.229671433568001 -0.70548552274704 -0.236709028482437 -1.13515877723694 -1.63437640666962 -1.59307599067688 -1.39037346839905 0.189065456390381 1.15494501590729 1.33185958862305 0.27683162689209 0.49673718214035 0.678728938102722 0.678728938102722 0.636789739131927 1.2355854511261 1.02060842514038 + Cluster -671 1 1 1 2.8 2.8 2.8 38.771 0.00032616 2.0128 637660000 4 4.8070324682447 2.31481481481481E-05 Q96J01;Q96J01-2 Q96J01;Q96J01-2 THO complex subunit 3 THOC3 2492 Required for efficient export of polyadenylated RNA andspliced mRNA. Acts as component of the THO subcomplex of the TREXcomplex which is thought to couple mRNA transcription, processingand nuclear export, and which specifically associates with splicedmRNA and not with unspliced pre-mRNA. TREX is recruited to splicedmRNAs by a transcription-independent mechanism, binds to mRNAupstream of the exon-junction complex (EJC) and is recruited in asplicing- and cap-dependent manner to a region near the 5' end ofthe mRNA where it functions in mRNA export to the cytoplasm viathe TAP/NFX1 pathway. The TREX complex is essential for the exportof Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAsand infectious virus production. Nucleus {ECO:0000305}. Nucleus speckle{ECO:0000305}. mRNA 3'-end processing;mRNA export from nucleus;RNA export from nucleus;RNA splicing;viral mRNA export from host cell nucleus RNA binding nuclear speck;nucleoplasm;THO complex part of transcription export complex;transcription export complex RNA transport;Spliceosome Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;Transport of Mature mRNA derived from an Intron-Containing Transcript hTREX84 complex;Spliceosome;TREX complex -0.972110748291016 -0.170996084809303 -0.515688061714172 -0.378786206245422 -0.676028192043304 -1.5948578119278 -1.78644061088562 -1.45973873138428 0.240744292736053 1.01172590255737 1.57450580596924 0.227391973137856 0.787117540836334 0.453197151422501 0.787117540836334 0.502068400382996 1.13147294521332 0.83930504322052 + Cluster -671 14 14 13 39.4 39.4 36.5 45.626 0 158.56 27048000000 71 4.05561768580747 0.000133136094674556 P62195;P62195-2;Q8NB90-3 P62195;P62195-2 26S protease regulatory subunit 8 PSMC5 1337 ATP-dependent chaperone which uses the energy providedby ATP hydrolysis to generate mechanical force to disassembleprotein complexes. May be involved in morphological and functionalmitochondrial transformations during spermatogenesis;Component of the 26S proteasome, a multiprotein complexinvolved in the ATP-dependent degradation of ubiquitinatedproteins. This complex plays a key role in the maintenance ofprotein homeostasis by removing misfolded or damaged proteins,which could impair cellular functions, and by removing proteinswhose functions are no longer required. Therefore, the proteasomeparticipates in numerous cellular processes, including cell cycleprogression, apoptosis, or DNA damage repair. PSMC5 belongs to theheterohexameric ring of AAA (ATPases associated with diversecellular activities) proteins that unfolds ubiquitinated targetproteins that are concurrently translocated into a proteolyticchamber and degraded into peptides. Cytoplasm {ECO:0000250|UniProtKB:Q3UMC0}.Mitochondrion {ECO:0000250|UniProtKB:Q3UMC0}.;Cytoplasm {ECO:0000305}. Nucleus{ECO:0000305}. brain development;cell differentiation;modulation of chemical synaptic transmission;negative regulation of programmed cell death;negative regulation of transcription, DNA-templated;positive regulation of inclusion body assembly;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of transcription, DNA-templated;post-translational protein modification;proteasome-mediated ubiquitin-dependent protein catabolic process;protein deubiquitination;regulation of transcription by RNA polymerase II;spermatogenesis ATP binding;ATPase activity;proteasome-activating ATPase activity;TBP-class protein binding;thyrotropin-releasing hormone receptor binding;transcription factor binding blood microparticle;cytoplasm;cytoplasmic vesicle;cytosol;cytosolic proteasome complex;extracellular exosome;inclusion body;membrane;mitochondrion;nuclear proteasome complex;nucleoplasm;nucleus;postsynapse;proteasome accessory complex;proteasome complex;proteasome regulatory particle, base subcomplex Epstein-Barr virus infection;Proteasome;Ribosome biogenesis in eukaryotes Symptomatic generalized epilepsies ABC-family proteins mediated transport;Activation of NF-kappaB in B cells;Antigen processing: Ubiquitination & Proteasome degradation;APC/C:Cdc20 mediated degradation of Securin;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;Asymmetric localization of PCP proteins;AUF1 (hnRNP D0) binds and destabilizes mRNA;Autodegradation of Cdh1 by Cdh1:APC/C;Autodegradation of the E3 ubiquitin ligase COP1;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;CDK-mediated phosphorylation and removal of Cdc6;CDT1 association with the CDC6:ORC:origin complex;CLEC7A (Dectin-1) signaling;Cross-presentation of soluble exogenous antigens (endosomes);Dectin-1 mediated noncanonical NF-kB signaling;Defective CFTR causes cystic fibrosis;Degradation of AXIN;Degradation of beta-catenin by the destruction complex;Degradation of DVL;Degradation of GLI1 by the proteasome;Degradation of GLI2 by the proteasome;Downstream TCR signaling;ER-Phagosome pathway;FBXL7 down-regulates AURKA during mitotic entry and in early mitosis;FCERI mediated NF-kB activation;G2/M Checkpoints;GLI3 is processed to GLI3R by the proteasome;Hedgehog ligand biogenesis;Hedgehog 'on' state;Hh mutants that don't undergo autocatalytic processing are degraded by ERAD;Interleukin-1 signaling;MAPK6/MAPK4 signaling;Neddylation;Negative regulation of NOTCH4 signaling;NIK-->noncanonical NF-kB signaling;Orc1 removal from chromatin;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of activated PAK-2p34 by proteasome mediated degradation;Regulation of expression of SLITs and ROBOs;Regulation of ornithine decarboxylase (ODC);Regulation of PTEN stability and activity;Regulation of RAS by GAPs;Regulation of RUNX2 expression and activity;Regulation of RUNX3 expression and activity;RUNX1 regulates transcription of genes involved in differentiation of HSCs;SCF(Skp2)-mediated degradation of p27/p21;SCF-beta-TrCP mediated degradation of Emi1;Separation of Sister Chromatids;The role of GTSE1 in G2/M progression after G2 checkpoint;TNFR2 non-canonical NF-kB pathway;Ubiquitin Mediated Degradation of Phosphorylated Cdc25A;Ubiquitin-dependent degradation of Cyclin D1;Ub-specific processing proteases;UCH proteinases;Vif-mediated degradation of APOBEC3G;Vpu mediated degradation of CD4 26S proteasome;PA700 complex;PA700-20S-PA28 complex -0.982537508010864 -0.195879951119423 -0.389902234077454 -0.195879951119423 -0.778041958808899 -1.85357165336609 -1.96634030342102 -1.21660578250885 0.80709844827652 1.21172881126404 1.25992500782013 0.571049749851227 0.689512073993683 0.733195185661316 0.571049749851227 0.459442704916 0.740317046642303 0.535440623760223 + Cluster -671 9 9 9 42.8 42.8 42.8 26.888 0 323.31 116800000000 146 3.45689593174744 0.000463320463320463 Q86V81 Q86V81 THO complex subunit 4 ALYREF 2112 ALYREF/THOC4 mediates the recruitment of the TREXcomplex to the intronless viral mRNA. Required for TREX complexassembly and for linking DDX39B to the cap-binding complex (CBC).In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclearexport of HSP70 mRNA; both proteins enhance the RNA bindingactivity of NXF1 and are required for NXF1 localization to thenuclear rim. Involved in the nuclear export of intronless mRNA;Export adapter involved in nuclear export of spliced andunspliced mRNA. Binds mRNA which is thought to be transferred tothe NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway). Componentof the TREX complex which is thought to couple mRNA transcription,processing and nuclear export, and specifically associates withspliced mRNA and not with unspliced pre-mRNA. TREX is recruited tospliced mRNAs by a transcription-independent mechanism, binds tomRNA upstream of the exon-junction complex (EJC) and is recruitedin a splicing- and cap-dependent manner to a region near the 5'end of the mRNA where it functions in mRNA export to thecytoplasm. TREX recruitment occurs via an interaction betweenALYREF/THOC4 and the cap-binding protein NCBP1. The TREX complexis essential for the export of Kaposi's sarcoma-associatedherpesvirus (KSHV) intronless mRNAs and infectious virusproduction;proposed to be recruited to intronless mRNA by ATP-bound DDX39B.Involved in transcription elongation and genome stability Nucleus {ECO:0000269|PubMed:10488337,ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332,ECO:0000305|PubMed:18974867}. Nucleus speckle{ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332}.Cytoplasm {ECO:0000269|PubMed:19324961}. Note=Colocalizes with thecore EJC, ALYREF/THOC4, NXF1 and DDX39B in the nucleus and nuclearspeckles. Travels to the cytoplasm as part of the exon junctioncomplex (EJC) bound to mRNA (PubMed:19324961). Localizes toregions surrounding nuclear speckles known as perispeckles inwhich TREX complex assembly seems to occur (PubMed:23826332).{ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:23826332}. mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;osteoblast differentiation;positive regulation of DNA-templated transcription, elongation;regulation of DNA recombination;replication fork processing;RNA export from nucleus;viral mRNA export from host cell nucleus;viral process RNA binding catalytic step 2 spliceosome;cytosol;extracellular exosome;membrane;nuclear speck;nucleoplasm;transcription export complex Herpes simplex virus 1 infection;mRNA surveillance pathway;RNA transport;Spliceosome Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Transport of Mature mRNA derived from an Intron-Containing Transcript;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA C complex spliceosome;Exon junction complex;Spliceosome;Splicing-associated factors complex;TREX complex -0.647231698036194 -0.389721244573593 -0.857138752937317 -0.708834290504456 -0.754653573036194 -2.01436948776245 -1.49125933647156 -1.05870306491852 0.414883553981781 1.12626850605011 1.19792699813843 0.773013949394226 0.23951330780983 0.529441893100739 0.698192715644836 0.936848282814026 1.13038408756256 0.875438272953033 + Cluster -671 7 7 7 20.6 20.6 20.6 53.488 0 116.87 12699000000 30 5.32211871515434 1.36054421768707E-05 Q9UBB4;Q9UBB4-2 Q9UBB4;Q9UBB4-2 Ataxin-10 ATXN10 3064 Necessary for the survival of cerebellar neurons.Induces neuritogenesis by activating the Ras-MAP kinase pathway.May play a role in the maintenance of a critical intracellularglycosylation level and homeostasis. Cytoplasm, perinuclear region{ECO:0000269|PubMed:16498633}. cilium assembly;nervous system development;neuron projection development;protein homotrimerization enzyme binding;identical protein binding cytoplasm;cytosol;dendrite;extracellular space;membrane;neuronal cell body;perinuclear region of cytoplasm;plasma membrane Spinocerebellar ataxia (SCA) -0.55914580821991 -0.423000603914261 -0.699680209159851 -0.585732758045197 -0.759610414505005 -1.78146123886108 -1.85238313674927 -1.19866812229156 0.248616129159927 0.798364281654358 1.44820261001587 0.666417300701141 0.654610157012939 0.57954603433609 0.685381352901459 0.860810577869415 0.923722803592682 0.994010984897614 + Cluster -671 4 4 4 15.2 15.2 15.2 45.834 0 22.643 1164900000 8 5.44562091561928 7.75193798449612E-06 P82933 P82933 28S ribosomal protein S9, mitochondrial MRPS9 1444 Mitochondrion {ECO:0000269|PubMed:25838379}. DNA damage response, detection of DNA damage;maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);mitochondrial translational elongation;mitochondrial translational termination RNA binding;structural constituent of ribosome mitochondrial inner membrane;mitochondrial small ribosomal subunit;mitochondrion;nucleolus Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -0.477194309234619 -0.477194309234619 -0.477194309234619 -0.477194309234619 -1.28063094615936 -1.54497921466827 -1.54497921466827 -1.54497921466827 0.257755637168884 0.772479891777039 0.772479891777039 0.772479891777039 0.772479891777039 0.772479891777039 0.772479891777039 0.257755637168884 1.33697748184204 1.33697748184204 + Cluster -671 32 32 1 83.2 83.2 4.5 41.792 0 323.31 5883100000000 3234 5.2542111063755 1.2987012987013E-05 P63261 P63261 Actin, cytoplasmic 2;Actin, cytoplasmic 2, N-terminally processed ACTG1 1406 Actins are highly conserved proteins that are involvedin various types of cell motility and are ubiquitously expressedin all eukaryotic cells. Cytoplasm, cytoskeleton{ECO:0000269|PubMed:28493397}. cell junction assembly;cellular response to interferon-gamma;ephrin receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;membrane organization;platelet aggregation;retina homeostasis;sarcomere organization;synaptic vesicle endocytosis ATP binding;identical protein binding;profilin binding;structural constituent of cytoskeleton;ubiquitin protein ligase binding actin filament;blood microparticle;calyx of Held;cytoskeleton;cytosol;dense body;extracellular exosome;extracellular space;filamentous actin;focal adhesion;membrane;myelin sheath;myofibril;nucleus;phagocytic vesicle;plasma membrane;Schaffer collateral - CA1 synapse Adherens junction;Apoptosis;Arrhythmogenic right ventricular cardiomyopathy (ARVC);Bacterial invasion of epithelial cells;Dilated cardiomyopathy (DCM);Fluid shear stress and atherosclerosis;Focal adhesion;Hepatocellular carcinoma;Hippo signaling pathway;Hypertrophic cardiomyopathy (HCM);Influenza A;Leukocyte transendothelial migration;Oxytocin signaling pathway;Pathogenic Escherichia coli infection;Phagosome;Platelet activation;Proteoglycans in cancer;Rap1 signaling pathway;Regulation of actin cytoskeleton;Salmonella infection;Shigellosis;Thermogenesis;Thyroid hormone signaling pathway;Tight junction;Vibrio cholerae infection;Viral myocarditis;Yersinia infection Baraitser-Winter syndrome;Bilateral sudden sensorineural hearing loss;Deafness, autosomal dominant Adherens junctions interactions;Cell-extracellular matrix interactions;Clathrin-mediated endocytosis;EPHB-mediated forward signaling;EPH-ephrin mediated repulsion of cells;Formation of annular gap junctions;Gap junction degradation;Interaction between L1 and Ankyrins;MAP2K and MAPK activation;Paradoxical activation of RAF signaling by kinase inactive BRAF;Recycling pathway of L1;Regulation of actin dynamics for phagocytic cup formation;RHO GTPases Activate Formins;RHO GTPases activate IQGAPs;RHO GTPases Activate WASPs and WAVEs;Signaling by BRAF and RAF fusions;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Signaling by RAS mutants;Translocation of SLC2A4 (GLUT4) to the plasma membrane;VEGFA-VEGFR2 Pathway BAF complex;CTGF/Hcs24-actin(beta/gamma) complex;Profilin 1 complex -0.690949976444244 -0.133456617593765 -0.690949976444244 -0.546016871929169 -0.771576344966888 -1.80858039855957 -1.56874239444733 -1.50306522846222 0.0804778933525085 1.3904550075531 1.02258682250977 0.667179465293884 0.512361228466034 0.7921382188797 0.495701372623444 1.01483035087585 1.0046147108078 0.732992768287659 + Cluster -671 6 6 5 30.7 30.7 25.9 35.594 0 215.25 27980000000 43 5.62569939282477 8.69565217391304E-06 P67775;P62714;P67775-2 P67775;P62714;P67775-2 Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform;Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform PPP2CA;PPP2CB 1363 PP2A can modulate the activity of phosphorylase B kinasecasein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase;PP2A is the major phosphatase for microtubule-associatedproteins (MAPs). PP2A can modulate the activity of phosphorylase Bkinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2kinase. Cooperates with SGO2 to protect centromeric cohesin fromseparase-mediated cleavage in oocytes specifically during meiosisI (By similarity). Can dephosphorylate SV40 large T antigen andp53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259' Cytoplasm {ECO:0000269|PubMed:16541025}.Nucleus {ECO:0000269|PubMed:16541025}. Chromosome, centromere{ECO:0000269|PubMed:16541025}. Cytoplasm, cytoskeleton, spindlepole {ECO:0000269|PubMed:16541025}. Note=In prometaphase cells,but not in anaphase cells, localizes at centromeres. Duringmitosis, also found at spindle poles.;Cytoplasm {ECO:0000269|PubMed:16541025}.Nucleus {ECO:0000269|PubMed:16541025}. Chromosome, centromere{ECO:0000269|PubMed:16541025}. Cytoplasm, cytoskeleton, spindlepole {ECO:0000269|PubMed:16541025}. Note=In prometaphase cells,but not in anaphase cells, localizes at centromeres. Duringmitosis, also found at spindle poles. Centromeric localizationrequires the presence of SGO2 (By similarity). {ECO:0000250}. apoptotic mitochondrial changes;apoptotic process;ceramide metabolic process;inactivation of MAPK activity;meiotic cell cycle;mesoderm development;negative regulation of cell growth;negative regulation of epithelial to mesenchymal transition;negative regulation of Ras protein signal transduction;negative regulation of tyrosine phosphorylation of STAT protein;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;peptidyl-serine dephosphorylation;peptidyl-threonine dephosphorylation;positive regulation of microtubule binding;positive regulation of protein serine/threonine kinase activity;proteasome-mediated ubiquitin-dependent protein catabolic process;protein dephosphorylation;regulation of cell adhesion;regulation of cell differentiation;regulation of DNA replication;regulation of gene expression;regulation of growth;regulation of microtubule binding;regulation of protein phosphorylation;regulation of transcription, DNA-templated;regulation of Wnt signaling pathway;response to endoplasmic reticulum stress;response to hydrogen peroxide;response to lead ion;response to organic substance;RNA splicing;second-messenger-mediated signaling GABA receptor binding;metal ion binding;phosphoprotein phosphatase activity;protein C-terminus binding;protein heterodimerization activity;protein serine/threonine phosphatase activity;tau protein binding chromosome, centromeric region;cytosol;extracellular exosome;membrane;membrane raft;microtubule cytoskeleton;mitochondrion;nucleus;plasma membrane;protein phosphatase type 2A complex;spindle pole;synapse Adrenergic signaling in cardiomyocytes;AMPK signaling pathway;Autophagy - animal;Autophagy - other;Chagas disease (American trypanosomiasis);Dopaminergic synapse;Hepatitis C;Hippo signaling pathway;Human papillomavirus infection;Long-term depression;mRNA surveillance pathway;Oocyte meiosis;PI3K-Akt signaling pathway;Sphingolipid signaling pathway;TGF-beta signaling pathway;Tight junction Fostriecin sodium Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;APC truncation mutants have impaired AXIN binding;AXIN missense mutants destabilize the destruction complex;Beta-catenin phosphorylation cascade;CTLA4 inhibitory signaling;Cyclin A/B1/B2 associated events during G2/M transition;Cyclin D associated events in G1;DARPP-32 events;Degradation of beta-catenin by the destruction complex;Disassembly of the destruction complex and recruitment of AXIN to the membrane;ERK/MAPK targets;ERKs are inactivated;Glycolysis;Inhibition of replication initiation of damaged DNA by RB1/E2F1;Initiation of Nuclear Envelope Reformation;Integration of energy metabolism;MASTL Facilitates Mitotic Progression;Misspliced GSK3beta mutants stabilize beta-catenin;Mitotic Prometaphase;Negative regulation of MAPK pathway;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Platelet sensitization by LDL;PP2A-mediated dephosphorylation of key metabolic factors;RAF activation;Regulation of TP53 Degradation;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;S33 mutants of beta-catenin aren't phosphorylated;S37 mutants of beta-catenin aren't phosphorylated;S45 mutants of beta-catenin aren't phosphorylated;Separation of Sister Chromatids;Spry regulation of FGF signaling;T41 mutants of beta-catenin aren't phosphorylated;Truncations of AMER1 destabilize the destruction complex IGBP1-MID1-PPP2CA complex;LPP-PPP2CA-PPP2R3A complex;PP2A A/C-SG2NA complex;PP2A A/C-striatin complex;PP2A-NR3A complex;PPP2CA-PPP2R1A complex;PPP2CA-PPP2R1A-PPP2R3A complex;PPP2R1A-PPP2R1B-PPP2CA-PPME1-EIF4A1 complex;protein phosphatase 2A C-subunit-synapsin complex;RAF1-PPP2-PIN1 complex;STRIPAK complex -0.686216533184052 -0.434290885925293 -0.260884255170822 -0.481203943490982 -0.382232934236526 -1.80362665653229 -1.59015715122223 -1.66851949691772 -0.364982753992081 1.07064485549927 1.39729034900665 0.852036356925964 0.387343019247055 0.596427440643311 0.758552432060242 0.820047497749329 0.805471301078796 0.984301209449768 + Cluster -671 6 6 6 27.3 27.3 27.3 30.241 0 70.476 8504500000 20 4.75855647337789 2.66666666666667E-05 O75489;O75489-2 O75489 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 336 Core subunit of the mitochondrial membrane respiratorychain NADH dehydrogenase (Complex I) that is believed to belong tothe minimal assembly required for catalysis. Complex I functionsin the transfer of electrons from NADH to the respiratory chain.The immediate electron acceptor for the enzyme is believed to beubiquinone (By similarity). Mitochondrion inner membrane. mitochondrial electron transport, NADH to ubiquinone;mitochondrial respiratory chain complex I assembly;negative regulation of cell growth;negative regulation of intrinsic apoptotic signaling pathway;reactive oxygen species metabolic process;substantia nigra development electron transfer activity;NADH dehydrogenase (ubiquinone) activity;NADH dehydrogenase activity mitochondrial matrix;mitochondrial membrane;mitochondrial respiratory chain complex I;mitochondrion;myelin sheath;nuclear body Alzheimer disease;Huntington disease;Metabolic pathways;Non-alcoholic fatty liver disease (NAFLD);Oxidative phosphorylation;Parkinson disease;Retrograde endocannabinoid signaling;Thermogenesis Leigh syndrome;Mitochondrial complex I deficiency Complex I biogenesis;Respiratory electron transport Ecsit complex (ECSIT, NDUFS3, NDUFAF1);Ecsit complex (ECSIT, NDUFS3, TOM20);Respiratory chain complex I (early intermediate NDUFAF1 assembly), mitochondrial;Respiratory chain complex I (holoenzyme), mitochondrial;Respiratory chain complex I (intermediate I/200kD and III/250kD), mitochondrial;Respiratory chain complex I (intermediate IV/310kD), mitochondrial;Respiratory chain complex I (intermediate V/380kD and VI/480kD), mitochondrial;Respiratory chain complex I (intermediate VII/650kD), mitochondrial;Respiratory chain complex I (intermediate), mitochondrial;Respiratory chain complex I (lambda subunit) mitochondrial -0.767412126064301 -0.300705671310425 -0.635774254798889 -0.828844130039215 -0.828844130039215 -1.12213408946991 -2.11324048042297 -1.2168151140213 0.116363808512688 0.651078820228577 1.106112241745 0.464493930339813 0.827211439609528 0.464493930339813 0.938768744468689 1.32918107509613 0.762468278408051 1.15359771251678 + Cluster -671 13 13 13 38.5 38.5 38.5 37.432 0 217.05 43451000000 77 5.39471931653603 7.40740740740741E-06 O76003 O76003 Glutaredoxin-3 GLRX3 374 Together with BOLA2, acts as a cytosolic iron-sulfur(Fe-S) cluster assembly factor that facilitates [2Fe-2S] clusterinsertion into a subset of cytosolic proteins (PubMed:26613676,PubMed:27519415). Acts as a critical negative regulator of cardiachypertrophy and a positive inotropic regulator (By similarity).Required for hemoglobin maturation (PubMed:23615448). Does notpossess any thyoredoxin activity since it lacks the conservedmotif that is essential for catalytic activity Cytoplasm, cytosol{ECO:0000305|PubMed:27519415}. Cytoplasm, cell cortex{ECO:0000269|PubMed:10636891}. Cytoplasm, myofibril, sarcomere, Zline {ECO:0000250|UniProtKB:Q9CQM9}. Note=Under the plasmamembrane (By similarity). After PMA stimulation, GLRX3 andPRKCQ/PKC-theta translocate to a more extended submembrane area(By similarity). In the Z line, found associated with CSRP3 (Bysimilarity). {ECO:0000250|UniProtKB:Q9CQM9}. [2Fe-2S] cluster assembly;cell redox homeostasis;cellular iron ion homeostasis;negative regulation of cardiac muscle hypertrophy;protein maturation by iron-sulfur cluster transfer;regulation of the force of heart contraction electron transfer activity;glutathione disulfide oxidoreductase activity;identical protein binding;iron-sulfur cluster binding;metal ion binding;protein disulfide oxidoreductase activity;protein kinase C binding;RNA binding cell cortex;cytosol;dendrite;nucleus;Z disc Iron uptake and transport BOLA2-GLRX3 complex -1.41603887081146 -0.170276328921318 -0.319301396608353 -0.170276328921318 -0.480992197990417 -1.58584702014923 -1.91824793815613 -1.17603445053101 -0.136595577001572 0.479012221097946 1.45998013019562 0.479012221097946 0.946084558963776 0.433902710676193 0.882189095020294 0.595812499523163 1.03893208503723 1.05868446826935 + Cluster -671 8 8 8 54.9 54.9 54.9 20.455 0 81.3 12476000000 22 3.50523971531018 0.000423387096774194 P36405 P36405 ADP-ribosylation factor-like protein 3 ARL3 947 Small GTP-binding protein which cycles between aninactive GDP-bound and an active GTP-bound form, and the rate ofcycling is regulated by guanine nucleotide exchange factors (GEF)and GTPase-activating proteins (GAP) (PubMed:16525022,PubMed:18588884). Required for normal cytokinesis and ciliasignaling (PubMed:22085962). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cyclebetween inactive GDP-bound and active GTP-bound forms. Requiredfor targeting proteins to the cilium, including myristoylatedNPHP3 and prenylated INPP5E (PubMed:30269812). Targets NPHP3 tothe ciliary membrane by releasing myristoylated NPHP3 from UNC119Bcargo adapter into the cilium (PubMed:22085962). Required forPKD1:PKD2 complex targeting from the trans-Golgi network to thecilium (By similarity). Cytoplasmic side. Cytoplasm, cytoskeleton,spindle. Nucleus. Cytoplasm, cytoskeleton, microtubule organizingcenter, centrosome. Cytoplasm. Cell projection, cilium{ECO:0000269|PubMed:30269812}. Note=Detected predominantly in thephotoreceptor connecting cilium. Present on the mitotic spindle.Centrosome-associated throughout the cell cycle. Not detected tointerphase microtubules.; Peripheralmembrane protein;Golgi apparatus membrane cilium assembly;Golgi to plasma membrane transport;intraciliary transport;kidney development;mitotic cytokinesis;photoreceptor cell development;post-Golgi vesicle-mediated transport;protein localization to ciliary membrane;small GTPase mediated signal transduction;smoothened signaling pathway GDP binding;GTP binding;GTPase activating protein binding;GTPase activity;magnesium ion binding;microtubule binding centrosome;cilium;cytoplasmic microtubule;extracellular exosome;Golgi apparatus;Golgi membrane;microtubule cytoskeleton;midbody;nucleus;photoreceptor connecting cilium;spindle microtubule Trafficking of myristoylated proteins to the cilium -0.576674699783325 -0.312141627073288 -0.551848411560059 -0.180485486984253 -0.868317782878876 -1.67324090003967 -1.54942512512207 -1.36054968833923 -0.466235101222992 0.144687280058861 1.61519479751587 0.586245775222778 1.06867969036102 0.131016507744789 1.03740215301514 1.03673911094666 0.753241717815399 1.16571164131165 + Cluster -671 6 6 6 38.3 38.3 38.3 23.225 0 36.174 15199000000 21 4.19607015690281 9.58466453674121E-05 Q99627;Q99627-2 Q99627;Q99627-2 COP9 signalosome complex subunit 8 COPS8 2583 Component of the COP9 signalosome complex (CSN), acomplex involved in various cellular and developmental processes.The CSN complex is an essential regulator of the ubiquitin (Ubl)conjugation pathway by mediating the deneddylation of the cullinsubunits of SCF-type E3 ligase complexes, leading to decrease theUbl ligase activity of SCF-type complexes such as SCF, CSA orDDB2. The complex is also involved in phosphorylation of p53/TP53,c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly viaits association with CK2 and PKD kinases. CSN-dependentphosphorylation of TP53 and JUN promotes and protects degradationby the Ubl system, respectively. Cytoplasm {ECO:0000269|PubMed:9535219}.Nucleus {ECO:0000269|PubMed:9535219}. activation of NF-kappaB-inducing kinase activity;COP9 signalosome assembly;negative regulation of cell proliferation;nucleotide-excision repair, DNA damage recognition;post-translational protein modification;protein deneddylation;protein phosphorylation;transcription-coupled nucleotide-excision repair COP9 signalosome;cytosol;extracellular exosome;nucleoplasm;nucleus;perinuclear region of cytoplasm Cargo recognition for clathrin-mediated endocytosis;DNA Damage Recognition in GG-NER;Formation of TC-NER Pre-Incision Complex;Neddylation CNS-P53 complex;COP9 signalosome complex;CSA complex;CSA-POLIIa complex;DDB2 complex;Ubiquitin E3 ligase (CSN1, CSN8, HRT1, SKP1, SKP2, CUL1, CUL2, CUL3) -1.59288430213928 -0.353555977344513 -0.514985501766205 0.123357176780701 -0.566751658916473 -1.37691509723663 -1.68133783340454 -1.43838381767273 -0.140972957015038 1.01585721969604 1.10768747329712 0.795476078987122 0.2842738032341 0.65522313117981 0.638102352619171 1.10900783538818 1.03892409801483 0.897877991199493 + Cluster -671 1 1 1 8.7 8.7 8.7 25.65 0 12.802 2388400000 3 3.81668625394921 0.000240506329113924 P82930 P82930 28S ribosomal protein S34, mitochondrial MRPS34 1443 Required for mitochondrial translation, plays a role inmaintaining the stability of the small ribosomal subunit and the12S rRNA that are required for mitoribosome formation Mitochondrion {ECO:0000269|PubMed:11279123}. mitochondrial translation;mitochondrial translational elongation;mitochondrial translational termination structural constituent of ribosome mitochondrial inner membrane;mitochondrial small ribosomal subunit;mitochondrion Combined oxidative phosphorylation deficiency Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial -1.36374962329865 -0.23059768974781 -0.164025455713272 -0.205742314457893 -0.830635190010071 -1.46381783485413 -1.89443564414978 -1.24875998497009 -0.0438762307167053 0.905251026153564 1.52777051925659 0.531966328620911 0.503801941871643 0.558245778083801 0.579957246780396 0.862474739551544 0.988086223602295 0.988086223602295 + Cluster -671 3 3 3 16.6 16.6 16.6 25.764 0 28.247 8237400000 12 3.80048527804661 0.0002475 Q9BRX8;Q9BRX8-2 Q9BRX8;Q9BRX8-2 Redox-regulatory protein FAM213A FAM213A 2636 Involved in redox regulation of the cell(PubMed:26438880, PubMed:19951071). Acts as an antioxidant(PubMed:19951071, PubMed:26438880). Inhibits TNFSF11-induced NFKB1and JUN activation and osteoclast differentiation(PubMed:19951071). May affect bone resorption and help to maintainbone mass (PubMed:19951071). Acts as a negative regulator ofmacrophage-mediated inflammation by inhibiting macrophageproduction of inflammatory cytokines, probably through suppressionof the MAPK signaling pathway (PubMed:26438880) Cytoplasm {ECO:0000269|PubMed:19951071}.Secreted {ECO:0000269|PubMed:26438880}. Note=Secreted from matureadipocytes but not from preadipocytes.{ECO:0000269|PubMed:26438880}. oxidation-reduction process;regulation of osteoclast differentiation antioxidant activity cytoplasm;extracellular region -0.880343079566956 0.0162754245102406 -0.401487708091736 -0.495412945747375 0.00625920761376619 -2.03967022895813 -1.70975863933563 -1.38941788673401 -0.284300178289413 0.824485421180725 1.13999259471893 0.0867973193526268 1.3504444360733 0.812464475631714 0.924647569656372 0.625044643878937 0.767046213150024 0.646933317184448 + Cluster -671 4 4 4 12 12 12 58.011 0 20.52 4655900000 10 3.45984947670895 0.000463035019455253 Q8IZ40 Q8IZ40 REST corepressor 2 RCOR2 2169 May act as a component of a corepressor complex thatrepresses transcription. Nucleus {ECO:0000255|PROSITE-ProRule:PRU00512, ECO:0000255|PROSITE-ProRule:PRU00624}. negative regulation of transcription, DNA-templated DNA-binding transcription factor activity;DNA-binding transcription factor activity, RNA polymerase II-specific;enzyme binding;transcription corepressor activity;transcription factor binding;transcription regulatory region DNA binding nucleus;transcription factor complex;transcriptional repressor complex -1.022092461586 -0.367469519376755 -0.297421962022781 0.301129877567291 -0.352508306503296 -1.88726532459259 -1.6822110414505 -1.61572074890137 -0.272495180368423 0.942034065723419 1.16856610774994 1.16104936599731 0.354478865861893 0.662446916103363 0.896629691123962 0.384885907173157 0.835537195205688 0.790426671504974 + Cluster -671 4 4 4 12.2 12.2 12.2 57.889 0 34.645 3079600000 7 3.3841424863659 0.000523020257826888 P78395 P78395 Melanoma antigen preferentially expressed in tumors PRAME 1430 Functions as a transcriptional repressor, inhibiting thesignaling of retinoic acid through the retinoic acid receptorsRARA, RARB and RARG. Prevents retinoic acid-induced cellproliferation arrest, differentiation and apoptosis Nucleus {ECO:0000305|PubMed:16620968}. Cellmembrane {ECO:0000269|PubMed:16620968}. apoptotic process;cell differentiation;negative regulation of apoptotic process;negative regulation of cell differentiation;negative regulation of retinoic acid receptor signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of cell proliferation;regulation of growth retinoic acid receptor binding cytoplasm;nucleus;plasma membrane PRAME complex;PRAME-Cullin2 ubiquitin ligase complex;PRAME-ElonginBC ubiquitin ligase -1.67598378658295 -0.203734591603279 -0.274794936180115 -0.222925186157227 -0.281302094459534 -1.62373912334442 -1.7043616771698 -1.36728000640869 -0.00374437100253999 0.928852200508118 1.30743622779846 0.455980569124222 0.763691782951355 0.515008211135864 0.724450349807739 0.785121262073517 0.903772056102753 0.973553001880646 + Cluster -671 5 5 5 17.2 17.2 17.2 55.827 0 89.035 7329000000 18 3.42220723349328 0.000502824858757062 Q13610 Q13610 Periodic tryptophan protein 1 homolog PWP1 1653 Chromatin-associated factor that regulates transcription(PubMed:29065309). Regulates Pol I-mediated rRNA biogenesis and,probably, Pol III-mediated transcription (PubMed:29065309).Regulates the epigenetic status of rDNA (PubMed:29065309) Nucleus {ECO:0000269|PubMed:7828893}.Nucleus, nucleolus {ECO:0000269|PubMed:29065309}. Chromosome{ECO:0000269|PubMed:29065309}. Note=Associates with chromatinregions of rDNA. {ECO:0000269|PubMed:29065309}. histone H4-K20 trimethylation;negative regulation of peptidyl-serine phosphorylation of STAT protein;positive regulation of stem cell differentiation;positive regulation of transcription of nucleolar large rRNA by RNA polymerase I;ribosome biogenesis;transcription, DNA-templated H4K20me3 modified histone binding chromosome;Golgi apparatus;nucleolus;nucleus Nop56p-associated pre-rRNA complex -0.466316670179367 -0.402231991291046 -0.983394026756287 -0.133944526314735 -0.550047874450684 -1.99974977970123 -1.45990705490112 -1.47463691234589 -0.215172737836838 1.02541971206665 1.09705305099487 0.909993767738342 0.947220921516418 0.440562725067139 0.514003813266754 0.868277192115784 1.03333592414856 0.849534511566162 + Cluster -671 7 7 7 27.3 27.3 27.3 35.079 0 77.513 13796000000 27 5.16107968117678 1.81818181818182E-05 P13804;P13804-2 P13804;P13804-2 Electron transfer flavoprotein subunit alpha, mitochondrial ETFA 659 Heterodimeric electron transfer flavoprotein thataccepts electrons from several mitochondrial dehydrogenases,including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosinedehydrogenase (PubMed:27499296, PubMed:15159392, PubMed:15975918,PubMed:9334218, PubMed:10356313). It transfers the electrons tothe main mitochondrial respiratory chain via ETF-ubiquinoneoxidoreductase (ETF dehydrogenase) (PubMed:9334218). Required fornormal mitochondrial fatty acid oxidation and normal amino acidmetabolism (PubMed:12815589, PubMed:1882842, PubMed:1430199) Mitochondrion matrix {ECO:0000305}. fatty acid beta-oxidation using acyl-CoA dehydrogenase electron transfer activity;flavin adenine dinucleotide binding;oxidoreductase activity mitochondrial matrix;mitochondrion Glutaric acidemia;Secondary hyperammonemia Respiratory electron transport 2.00688147544861 0.405908197164536 -1.69748079776764 -1.4092139005661 -1.16811978816986 -0.922030687332153 -0.387092232704163 0.169164448976517 1.39968407154083 -0.44416806101799 -0.650285422801971 -0.26665672659874 1.10789716243744 0.850207030773163 0.54293966293335 0.674232602119446 0.189664632081985 -0.401531606912613 + Cluster -671 1 1 1 1.3 1.3 1.3 138.66 0 35.013 1071000000 3 3.17894044809019 0.000773615635179153 Q9UNS1;Q9UNS1-2 Q9UNS1;Q9UNS1-2 Protein timeless homolog TIMELESS 3188 Plays an important role in the control of DNAreplication, maintenance of replication fork stability,maintenance of genome stability throughout normal DNA replication,DNA repair and in the regulation of the circadian clock(PubMed:9856465, PubMed:17141802, PubMed:17296725,PubMed:23418588, PubMed:26344098). Required to stabilizereplication forks during DNA replication by forming a complex withTIPIN: this complex regulates DNA replication processes under bothnormal and stress conditions, stabilizes replication forks andinfluences both CHEK1 phosphorylation and the intra-S phasecheckpoint in response to genotoxic stress (PubMed:17141802,PubMed:17296725). TIMELESS promotes TIPIN nuclear localization(PubMed:17141802, PubMed:17296725). Involved in cell survivalafter DNA damage or replication stress by promoting DNA repair(PubMed:17141802, PubMed:17296725, PubMed:26344098,PubMed:30356214). In response to double-strand breaks (DSBs),accumulates at DNA damage sites and promotes homologousrecombination repair via its interaction with PARP1(PubMed:26344098, PubMed:30356214). May be specifically requiredfor the ATR-CHEK1 pathway in the replication checkpoint induced byhydroxyurea or ultraviolet light (PubMed:15798197). Involved inthe determination of period length and in the DNA damage-dependentphase advancing of the circadian clock (PubMed:23418588).Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-inducedtransactivation of PER1 possibly via translocation of PER1 intothe nucleus (PubMed:9856465). May also play an important role inepithelial cell morphogenesis and formation of branching tubules(By similarity). Nucleus {ECO:0000269|PubMed:17141802}.Chromosome {ECO:0000269|PubMed:26344098}. Note=In response todouble-strand breaks (DSBs), accumulates at DNA damage sites viaits interaction with PARP1. {ECO:0000269|PubMed:26344098}. branching morphogenesis of an epithelial tube;cell cycle phase transition;cell division;cellular response to bleomycin;cellular response to cisplatin;cellular response to DNA damage stimulus;cellular response to hydroxyurea;circadian rhythm;detection of abiotic stimulus;DNA repair;DNA replication checkpoint;lung development;morphogenesis of an epithelium;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;positive regulation of double-strand break repair;regulation of circadian rhythm;replication fork arrest;replication fork protection DNA binding;protein heterodimerization activity;protein homodimerization activity nuclear chromatin;nuclear chromosome;nucleoplasm;nucleus;replication fork protection complex Processing of DNA double-strand break ends 2.41724848747253 0.0816476792097092 -1.82937800884247 -1.46560001373291 -1.19617187976837 -0.489455044269562 -0.869308590888977 -0.489455044269562 1.37046051025391 -0.0785497725009918 0.404862552881241 0.0700331628322601 0.708640277385712 0.404862552881241 0.338409692049026 0.313061684370041 0.227044194936752 0.0816476792097092 + Cluster -671 18 18 18 57.3 57.3 57.3 29.225 0 251.39 90224000000 143 3.57284507115242 0.00037953091684435 P18124 P18124 60S ribosomal protein L7 RPL7 716 Component of the large ribosomal subunit(PubMed:12962325). Binds to G-rich structures in 28S rRNA and inmRNAs. Plays a regulatory role in the translation apparatus;inhibits cell-free translation of mRNAs maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;ribosomal large subunit biogenesis;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation DNA binding;mRNA binding;protein homodimerization activity;RNA binding;structural constituent of ribosome cytoplasm;cytosol;cytosolic large ribosomal subunit;focal adhesion;membrane;nucleolus;nucleus;polysome;postsynaptic density;ribonucleoprotein complex Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle) 1.72741985321045 0.0835877507925034 -1.65651047229767 -1.27539527416229 -1.32059490680695 -1.25590550899506 -0.735690534114838 -0.785049438476563 1.22391855716705 0.604041218757629 0.0711287707090378 -0.587575554847717 0.929090917110443 0.977219223976135 0.782769441604614 0.30865079164505 0.514481544494629 0.394413620233536 + Cluster -671 13 13 13 60.7 60.7 60.7 16.06 0 106.81 54580000000 88 4.66738691529927 3.36134453781513E-05 P39019 P39019 40S ribosomal protein S19 RPS19 974 Required for pre-rRNA processing and maturation of 40Sribosomal subunits. Nucleus {ECO:0000269|PubMed:12586610,ECO:0000269|PubMed:17517689}. Note=Located more specifically inthe nucleoli. antimicrobial humoral immune response mediated by antimicrobial peptide;defense response to Gram-negative bacterium;erythrocyte differentiation;killing of cells of other organism;maturation of SSU-rRNA;maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);monocyte chemotaxis;negative regulation of respiratory burst involved in inflammatory response;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;nucleolus organization;positive regulation of cellular component movement;positive regulation of respiratory burst involved in inflammatory response;protein tetramerization;response to extracellular stimulus;ribosomal small subunit assembly;ribosomal small subunit biogenesis;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation fibroblast growth factor binding;protein homodimerization activity;protein kinase binding;RNA binding;structural constituent of ribosome cytoplasm;cytosol;cytosolic small ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleolus;nucleoplasm;postsynaptic density;ribosome Ribosome Diamond-Blackfan anemia Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic 1.28842437267303 0.450379639863968 -1.58818340301514 -1.4527850151062 -1.07067930698395 -1.99557101726532 -0.968046069145203 -0.186289310455322 0.957791805267334 0.147816553711891 0.896211862564087 0.958999276161194 0.00433870358392596 0.85374242067337 0.28874534368515 0.843739986419678 0.450379639863968 0.120984330773354 + Cluster -671 15 15 15 29.9 29.9 29.9 72.979 0 136.53 15157000000 40 4.47596157222376 6.06060606060606E-05 Q9BTE3;Q9BTE3-2;Q9BTE3-3 Q9BTE3;Q9BTE3-2;Q9BTE3-3 Mini-chromosome maintenance complex-binding protein MCMBP 2653 probably acts bydestabilizing interactions of each individual subunits of the MCMcomplex. Required for sister chromatid cohesion;Associated component of the MCM complex that acts as aregulator of DNA replication. Binds to the MCM complex during lateS phase and promotes the disassembly of the MCM complex fromchromatin, thereby acting as a key regulator of pre-replicationcomplex (pre-RC) unloading from replicated DNA. Can dissociate theMCM complex without addition of ATP Nucleus {ECO:0000269|PubMed:17296731}.Note=Associates with chromatin. Highly associated with chromatinin G1/S and S phases, reduced binding to chromatin in G2, andfurther decreased binding in early M phase. It then reassociateswith chromatin in late M phase. Dissociates from chromatin laterthan component of the MCM complex. cell division;DNA-dependent DNA replication;sister chromatid cohesion chromatin binding cytosol;MCM complex;nuclear chromatin;nucleoplasm;nucleus;plasma membrane 0.322832077741623 -0.503284633159637 -0.705110669136047 -1.78411602973938 -1.54986464977264 -0.0767595246434212 -1.50578367710114 -1.2115306854248 1.098149061203 -0.0767595246434212 0.911250352859497 0.150218084454536 0.280445396900177 0.61764007806778 0.911250352859497 0.850722968578339 0.850722968578339 1.41997814178467 + Cluster -671 10 9 2 18.1 17 3.9 71.407 0 212.48 35796000000 62 3.56005048644025 0.000385744234800839 P29692-2 P29692-2 Elongation factor 1-delta EEF1D 855 Isoform 1: EF-1-beta and EF-1-delta stimulate theexchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to theribosome.Isoform 2: Regulates induction of heat-shock-responsivegenes through association with heat shock transcription factorsand direct DNA-binding at heat shock promoter elements (HSE). Isoform 2: Nucleus{ECO:0000269|PubMed:21597468}. cellular response to ionizing radiation;mRNA transcription;positive regulation of I-kappaB kinase/NF-kappaB signaling;regulation of cell death;translational elongation activating transcription factor binding;cadherin binding;DNA binding;heat shock protein binding;translation elongation factor activity;translation factor activity, RNA binding cytoplasm;cytosol;eukaryotic translation elongation factor 1 complex;fibrillar center;nucleus Eukaryotic Translation Elongation 1.25745987892151 -0.308847695589066 -2.03648519515991 -1.34404027462006 -1.74027848243713 -0.51803731918335 -0.73625248670578 -0.577338099479675 0.853501856327057 0.365134865045547 0.427510499954224 -0.0256194490939379 0.500279366970062 0.245002448558807 0.319308757781982 1.23116672039032 0.893390417098999 1.19414412975311 + + Cluster -671 1 1 1 0.9 0.9 0.9 112.22 1 -2 551980000 2 3.6252225682247 0.000342920353982301 Q6ZMZ3;Q6ZMZ3-2 Q6ZMZ3;Q6ZMZ3-2 Nesprin-3 SYNE3 2030 As a component of the LINC (LInker of Nucleoskeleton andCytoskeleton) complex involved in the connection between thenuclear lamina and the cytoskeleton. The nucleocytoplasmicinteractions established by the LINC complex play an importantrole in the transmission of mechanical forces across the nuclearenvelope and in nuclear movement and positioning. Probableanchoring protein which tethers the nucleus to the cytoskeleton bybinding PLEC which can associate with the intermediate filamentsystem. Plays a role in the regulation of aortic epithelial cellmorphology, and is required for flow-induced centrosomepolarization and directional migration in aortic endothelialcells. Single-pass type IV membraneprotein {ECO:0000269|PubMed:21937718}. Nucleus envelope{ECO:0000269|PubMed:21937718}. Rough endoplasmic reticulum{ECO:0000250}.;Nucleus outer membrane{ECO:0000269|PubMed:21937718} cytoskeletal anchoring at nuclear membrane;cytoskeleton organization;establishment of protein localization to membrane;nuclear migration;nucleus localization;regulation of cell shape actin filament binding cytoplasm;integral component of membrane;meiotic nuclear membrane microtubule tethering complex;membrane;nuclear envelope;nuclear membrane;nuclear outer membrane;rough endoplasmic reticulum 0.916475713253021 -0.773964047431946 -1.89271867275238 -1.13914036750793 -1.61019015312195 -0.818348586559296 -0.61417281627655 -0.697578132152557 1.39320540428162 0.153961256146431 0.254576504230499 -0.127317950129509 0.512358903884888 0.586446821689606 0.750076472759247 1.29846549034119 1.00344848632813 0.804415643215179 + Cluster -671 2 2 2 8.6 8.6 8.6 40.633 0 19.818 345150000 5 3.63297684824739 0.000335555555555556 P26992 P26992 Ciliary neurotrophic factor receptor subunit alpha CNTFR 823 Binds to CNTF. The alpha subunit provides the receptorspecificity. Lipid-anchor, GPI-anchor.;Cell membrane brainstem development;ciliary neurotrophic factor-mediated signaling pathway;cytokine-mediated signaling pathway;negative regulation of neuron apoptotic process;nervous system development;positive regulation of cell proliferation;sex differentiation;signal transduction;skeletal muscle organ development;suckling behavior ciliary neurotrophic factor receptor activity;cytokine binding;cytokine receptor activity;interleukin-27 receptor binding;signaling receptor binding anchored component of membrane;apical plasma membrane;ciliary neurotrophic factor receptor complex;CNTFR-CLCF1 complex;external side of plasma membrane;extrinsic component of membrane;plasma membrane;receptor complex Cytokine-cytokine receptor interaction;Jak-STAT signaling pathway Dapiclermin IL-6-type cytokine receptor ligand interactions CNTF-CNTFR-gp130-LIFR complex 0.651081323623657 -0.471180707216263 -1.67951595783234 -1.14753913879395 -1.7481461763382 -1.04852545261383 -0.499127417802811 -0.785257518291473 0.31257838010788 0.422670394182205 0.389144510030746 -0.0829308852553368 0.467921942472458 0.655634820461273 0.480484157800674 0.905605912208557 1.5053836107254 1.67171823978424 + Cluster -671 4 3 3 16.2 13.5 13.5 33.729 0 12.979 888440000 4 4.43866473503936 6.25E-05 P11802;P11802-2 P11802;P11802-2 Cyclin-dependent kinase 4 CDK4 632 Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexesthat phosphorylate and inhibit members of the retinoblastoma (RB)protein family including RB1 and regulate the cell-cycle duringG(1)/S transition. Phosphorylation of RB1 allows dissociation ofthe transcription factor E2F from the RB/E2F complexes and thesubsequent transcription of E2F target genes which are responsiblefor the progression through the G(1) phase. Hypophosphorylates RB1in early G(1) phase. Cyclin D-CDK4 complexes are major integratorsof various mitogenenic and antimitogenic signals. Alsophosphorylates SMAD3 in a cell-cycle-dependent manner andrepresses its transcriptional activity. Component of the ternarycomplex, cyclin D/CDK4/CDKN1B, required for nuclear translocationand activity of the cyclin D-CDK4 complex Cytoplasm. Nucleus. Membrane.Note=Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complexin the cytoplasm as cells progress through G(1) phase. The complexaccumulates on the nuclear membrane and enters the nucleus ontransition from G(1) to S phase. Also present in nucleoli andheterochromatin lumps. Colocalizes with RB1 after release into thenucleus. adipose tissue development;animal organ regeneration;cell division;cellular response to insulin stimulus;cellular response to interleukin-4;cellular response to ionomycin;cellular response to lipopolysaccharide;cellular response to phorbol 13-acetate 12-myristate;circadian rhythm;G1/S transition of mitotic cell cycle;lens development in camera-type eye;negative regulation of cell cycle arrest;positive regulation of apoptotic process;positive regulation of cell cycle;positive regulation of cell proliferation;positive regulation of cell size;positive regulation of fibroblast proliferation;positive regulation of G2/M transition of mitotic cell cycle;positive regulation of translation;protein phosphorylation;regulation of gene expression;regulation of insulin receptor signaling pathway;regulation of lipid biosynthetic process;regulation of lipid catabolic process;regulation of multicellular organism growth;response to drug;response to hyperoxia;response to lead ion;response to testosterone;response to toxic substance;signal transduction;transcription initiation from RNA polymerase II promoter ATP binding;cyclin binding;cyclin-dependent protein serine/threonine kinase activity;cyclin-dependent protein serine/threonine kinase regulator activity;protein-containing complex binding bicellular tight junction;chromatin;cyclin D2-CDK4 complex;cyclin-dependent protein kinase holoenzyme complex;cytosol;nuclear membrane;nucleolus;nucleoplasm;nucleus;perinuclear region of cytoplasm;transcription factor complex AGE-RAGE signaling pathway in diabetic complications;Bladder cancer;Breast cancer;Cell cycle;Cellular senescence;Chronic myeloid leukemia;Cushing syndrome;Endocrine resistance;Epstein-Barr virus infection;Glioma;Hepatitis C;Hepatocellular carcinoma;Human cytomegalovirus infection;Human papillomavirus infection;Human T-cell leukemia virus 1 infection;Influenza A;Kaposi sarcoma-associated herpesvirus infection;Measles;Melanoma;Non-small cell lung cancer;p53 signaling pathway;Pancreatic cancer;Pathways in cancer;PI3K-Akt signaling pathway;Small cell lung cancer;T cell receptor signaling pathway;Tight junction;Viral carcinogenesis Cervical cancer;Glioma;Melanoma Abemaciclib;Alvocidib;Lerociclib;Palbociclib;Ribociclib;Trilaciclib Cyclin D associated events in G1;Meiotic recombination;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;PTK6 Regulates Cell Cycle;RMTs methylate histone arginines;SCF(Skp2)-mediated degradation of p27/p21;Senescence-Associated Secretory Phenotype (SASP);Transcriptional regulation by RUNX2;Transcriptional regulation of white adipocyte differentiation;Ubiquitin-dependent degradation of Cyclin D1 CCND1-CDK4 complex;CCND2-CDK4 complex;CCND3-CDK4 complex;Cell cycle kinase complex CDK4;CyclinD1-CDK4-CDK6 complex;CyclinD1-CDK4-p21 complex;CyclinD3-CDK4-CDK6 complex;CyclinD3-CDK4-CDK6-p21 complex;p16-cyclin D2-CDK4 complex;p34(SEI-1)-CDK4-CyclinD2 complex 1.6922914981842 -0.150808811187744 -1.34590482711792 -1.80207049846649 -0.998452186584473 -0.675425052642822 -0.706547856330872 -1.24652850627899 0.235724598169327 1.43107664585114 0.371305763721466 -0.706547856330872 0.371305763721466 0.462645292282104 0.698705852031708 0.536059677600861 0.916585147380829 0.916585147380829 + Cluster -671 16 16 16 65.1 65.1 65.1 17.718 0 130.67 28741000000 93 3.08226490728332 0.000936532507739938 P62269 P62269 40S ribosomal protein S18 RPS18 1345 Located at the top of the head of the 40S subunit, itcontacts several helices of the 18S rRNA. Cytoplasm. nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;rRNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleoplasm;nucleus;postsynaptic density;ribosome;small ribosomal subunit Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic 0.979623854160309 -0.263063699007034 -1.56092512607574 -1.14650189876556 -1.32801496982574 -1.50119340419769 -0.990357637405396 -1.03257632255554 1.04387307167053 1.30618298053741 0.852614104747772 -0.199919909238815 0.360754311084747 0.672328054904938 0.532160401344299 0.779367029666901 0.716282188892365 0.779367029666901 + Cluster -671 4 4 4 58.1 58.1 58.1 9.7251 0 46.734 11347000000 14 5.12283645709453 1.76470588235294E-05 P62306 P62306 Small nuclear ribonucleoprotein F SNRPF 1350 Plays role in pre-mRNA splicing as core component of theSMN-Sm complex that mediates spliceosomal snRNP assembly and ascomponent of the spliceosomal U1, U2, U4 and U5 small nuclearribonucleoproteins (snRNPs), the building blocks of thespliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628,PubMed:23333303, PubMed:25555158, PubMed:26912367,PubMed:28502770, PubMed:28781166, PubMed:28076346). Component ofboth the pre-catalytic spliceosome B complex and activatedspliceosome C complexes (PubMed:11991638, PubMed:28502770,PubMed:28781166, PubMed:28076346). Is also a component of theminor U12 spliceosome (PubMed:15146077). As part of the U7 snRNPit is involved in histone 3'-end processing (PubMed:12975319) Cytoplasm, cytosol{ECO:0000269|PubMed:18984161}. Nucleus{ECO:0000269|PubMed:11574479, ECO:0000269|PubMed:11991638,ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28076346,ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166}.Note=SMN-mediated assembly into core snRNPs occurs in the cytosolbefore SMN-mediated transport to the nucleus to be included inspliceosomes. {ECO:0000305}. histone mRNA metabolic process;import into nucleus;mRNA splicing, via spliceosome;RNA splicing;spliceosomal snRNP assembly;termination of RNA polymerase II transcription RNA binding catalytic step 2 spliceosome;cytosol;methylosome;nucleoplasm;nucleus;pICln-Sm protein complex;small nuclear ribonucleoprotein complex;small nucleolar ribonucleoprotein complex;SMN-Sm protein complex;spliceosomal complex;U1 snRNP;U12-type spliceosomal complex;U2-type catalytic step 2 spliceosome;U2-type precatalytic spliceosome;U4 snRNP;U4/U6 x U5 tri-snRNP complex;U7 snRNP Spliceosome Cleavage of Growing Transcript in the Termination Region;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs;SLBP independent Processing of Histone Pre-mRNAs;snRNP Assembly (E.F.G) complex;12S U11 snRNP;17S U2 snRNP;18S U11/U12 snRNP;6S methyltransferase and RG-containing Sm proteins complex;C complex spliceosome;SMN complex;SMN complex, U7 snRNA specific;Spliceosome 1.39579510688782 0.0917115658521652 -1.74989855289459 -1.54264545440674 -1.24939370155334 -0.9029580950737 -0.982644319534302 -0.766665697097778 0.688156425952911 0.00331809371709824 -0.226955428719521 0.0394039899110794 1.22015964984894 0.711640238761902 0.904694736003876 1.34389579296112 0.47415965795517 0.548226118087769 + Cluster -671 2 2 2 11.2 11.2 11.2 28.134 0 27.176 911610000 5 5.64640348834924 8.92857142857143E-06 Q9Y2R9 Q9Y2R9 28S ribosomal protein S7, mitochondrial MRPS7 3237 Mitochondrion {ECO:0000269|PubMed:25838379}. mitochondrial translation;mitochondrial translational elongation;mitochondrial translational termination;ribosomal small subunit assembly;translation mRNA binding;RNA binding;rRNA binding;structural constituent of ribosome mitochondrial inner membrane;mitochondrial small ribosomal subunit Ribosome Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial 1.14657163619995 -0.0808221101760864 -1.28509175777435 -1.86701619625092 -1.37815880775452 -0.84625232219696 -1.20921504497528 -1.03558552265167 0.798237264156342 0.167715057730675 0.501075863838196 0.395756512880325 0.93306565284729 0.296915084123611 0.796524822711945 1.37057757377625 0.708634853363037 0.587067604064941 + Cluster -671 11 11 11 28.5 28.5 28.5 43.295 0 48.653 6913800000 28 5.86668167108708 1.11111111111111E-05 P08559;P08559-3;P08559-4;P08559-2;P29803 P08559;P08559-3;P08559-4;P08559-2 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial PDHA1 556 The pyruvate dehydrogenase complex catalyzes the overallconversion of pyruvate to acetyl-CoA and CO(2), and thereby linksthe glycolytic pathway to the tricarboxylic cycle Mitochondrion matrix. acetyl-CoA biosynthetic process from pyruvate;glucose metabolic process;mitochondrial acetyl-CoA biosynthetic process from pyruvate;pyruvate metabolic process;tricarboxylic acid cycle pyruvate dehydrogenase (acetyl-transferring) activity;pyruvate dehydrogenase (NAD+) activity;pyruvate dehydrogenase activity mitochondrial matrix;mitochondrion;myelin sheath;nucleolus;nucleus;pyruvate dehydrogenase complex Carbon metabolism;Central carbon metabolism in cancer;Citrate cycle (TCA cycle);Glucagon signaling pathway;Glycolysis / Gluconeogenesis;HIF-1 signaling pathway;Metabolic pathways;Pyruvate metabolism Pyruvate dehydrogenase complex deficiency;Pyruvate dehydrogenase E1-alpha deficiency Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Regulation of pyruvate dehydrogenase (PDH) complex;Signaling by Retinoic Acid 1.72828924655914 -0.360507756471634 -0.992027223110199 -2.02754282951355 -1.28520035743713 -1.08930456638336 -0.903183460235596 -0.831115543842316 0.613929510116577 0.313671052455902 -0.00471846805885434 0.194723516702652 1.06384313106537 0.563770532608032 0.692331373691559 1.14145851135254 0.594478249549866 0.58710503578186 + Cluster -671 4 4 4 47.7 47.7 47.7 12.349 0 54.291 2689100000 16 4.31278934847905 8.33333333333333E-05 Q9GZT3;Q9GZT3-2 Q9GZT3;Q9GZT3-2 SRA stem-loop-interacting RNA-binding protein, mitochondrial SLIRP 2749 RNA-binding protein that acts as a nuclear receptorcorepressor. Probably acts by binding the SRA RNA, and repressingthe SRA-mediated nuclear receptor coactivation. Binds the STR7loop of SRA RNA. Also able to repress glucocorticoid (GR),androgen (AR), thyroid (TR) and VDR-mediated transactivation Mitochondrion {ECO:0000269|PubMed:16762838}.Nucleus {ECO:0000269|PubMed:16762838}. Note=Predominantlymitochondrial. Some fraction is nuclear. In the nucleus, it isrecruited to nuclear receptor target promoters. flagellated sperm motility;mitochondrion morphogenesis;negative regulation of mitochondrial RNA catabolic process;single fertilization;spermatid development RNA binding acrosomal vesicle;mitochondrion;nucleus;perinuclear region of cytoplasm;ribonucleoprotein complex;sperm flagellum 0.535282790660858 -0.123170219361782 -1.61856281757355 -1.07532286643982 -1.51781594753265 -1.3579238653183 -1.34240674972534 -0.845936000347137 1.02826976776123 0.486176609992981 0.526373147964478 0.0663771852850914 0.96271163225174 0.708308577537537 0.796316564083099 1.11783671379089 0.791610598564148 0.861874759197235 + Cluster -671 19 3 3 46.7 15.1 15.1 42.051 0 29.827 430170000000 134 7.29758905051523 0 P68133;P68032;P62736;P63267;P63267-2 P68133;P68032;P62736;P63267;P63267-2 Actin, alpha skeletal muscle;Actin, alpha cardiac muscle 1;Actin, aortic smooth muscle;Actin, gamma-enteric smooth muscle ACTA1;ACTC1;ACTA2;ACTG2 1414 Actins are highly conserved proteins that are involvedin various types of cell motility and are ubiquitously expressedin all eukaryotic cells. Cytoplasm, cytoskeleton. actin filament-based movement;actin-myosin filament sliding;actomyosin structure organization;cardiac muscle contraction;cardiac muscle tissue morphogenesis;cardiac myofibril assembly;cellular response to organonitrogen compound;glomerular mesangial cell development;heart contraction;mesenchyme migration;muscle contraction;muscle filament sliding;negative regulation of apoptotic process;positive regulation of gene expression;positive regulation of transcription, DNA-templated;regulation of blood pressure;response to ethanol;response to extracellular stimulus;response to lithium ion;response to mechanical stimulus;response to steroid hormone;response to virus;skeletal muscle fiber adaptation;skeletal muscle fiber development;skeletal muscle thin filament assembly;vascular smooth muscle contraction ADP binding;ATP binding;ATPase activity;myosin binding;protein kinase binding;structural constituent of cytoskeleton actin cytoskeleton;actin filament;actomyosin, actin portion;blood microparticle;cell body;cell periphery;cytoplasm;cytosol;extracellular exosome;extracellular space;filopodium;focal adhesion;glutamatergic synapse;I band;lamellipodium;membrane;myosin filament;protein-containing complex;sarcomere;smooth muscle contractile fiber;stress fiber;striated muscle thin filament Adrenergic signaling in cardiomyocytes;Apelin signaling pathway;Cardiac muscle contraction;Dilated cardiomyopathy (DCM);Hypertrophic cardiomyopathy (HCM);Relaxin signaling pathway;Vascular smooth muscle contraction Atrial septal defect;Cap myopathy;Congenital fiber type disproportion;Dilated cardiomyopathy;Familial thoracic aortic aneurysm and dissection;Hypertrophic cardiomyopathy;Left ventricular noncompaction;Megacystis microcolon intestinal hypoperistalsis syndrome;Moyamoya disease;Nemaline myopathy;Patent ductus arteriosus;Restrictive cardiomyopathy NOTCH4 Intracellular Domain Regulates Transcription;Smooth Muscle Contraction;Striated Muscle Contraction Nop56p-associated pre-rRNA complex;WIP-WASp-actin-myosin-IIa complex 0.786601662635803 -0.0406864546239376 -1.3626948595047 -1.18199670314789 -1.23997497558594 -1.77065432071686 -1.31229102611542 -0.832933604717255 0.786601662635803 0.320908755064011 0.763144135475159 -0.0211002379655838 1.10441863536835 0.763144135475159 0.985340595245361 1.17385792732239 0.539157390594482 0.539157390594482 + Cluster -671 13 13 13 78.6 78.6 78.6 21.057 0 323.31 84174000000 107 6.67979911211331 0 P30086 P30086 Phosphatidylethanolamine-binding protein 1;Hippocampal cholinergic neurostimulating peptide PEBP1 866 Binds ATP, opioids and phosphatidylethanolamine. Haslower affinity for phosphatidylinositol and phosphatidylcholine.Serine protease inhibitor which inhibits thrombin, neuropsin andchymotrypsin but not trypsin, tissue type plasminogen activatorand elastase (By similarity). Inhibits the kinase activity of RAF1by inhibiting its activation and by dissociating the RAF1/MEKcomplex and acting as a competitive inhibitor of MEKphosphorylation. Cytoplasm {ECO:0000250}. aging;hippocampus development;MAPK cascade;negative regulation of MAPK cascade;positive regulation of acetylcholine metabolic process;positive regulation of cAMP-mediated signaling;positive regulation of mitotic nuclear division;regulation of neurotransmitter levels;regulation of the force of heart contraction;response to activity;response to calcium ion;response to cAMP;response to corticosterone;response to ethanol;response to heat;response to organonitrogen compound;response to oxidative stress;response to toxic substance;response to wounding;sperm capacitation ATP binding;enzyme binding;mitogen-activated protein kinase binding;phosphatidylethanolamine binding;protein kinase binding;RNA binding;serine-type endopeptidase inhibitor activity;signaling receptor binding apical part of cell;axon terminus;cell surface;cytosol;extracellular exosome;extracellular space;Golgi apparatus;mitochondrial outer membrane;mitochondrion;myelin sheath;neuronal cell body;nucleus;synaptic vesicle MAP2K and MAPK activation;Negative regulation of MAPK pathway;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Signaling by RAS mutants 0.775887906551361 0.202974006533623 -1.67481780052185 -1.1584244966507 -1.4380669593811 -1.47962701320648 -1.19097018241882 -0.798598527908325 0.987648963928223 0.307727754116058 0.436300456523895 -0.124457627534866 1.18192267417908 0.766078352928162 0.901641190052032 0.956044793128967 0.674368262290955 0.674368262290955 + Cluster -671 7 7 7 55.2 55.2 55.2 23.31 0 155.93 219270000000 174 7.65451265705105 0 P43487;P43487-2 P43487;P43487-2 Ran-specific GTPase-activating protein RANBP1 1030 Plays a role in RAN-dependent nucleocytoplasmictransport. Alleviates the TNPO1-dependent inhibition of RAN GTPaseactivity and mediates the dissociation of RAN from proteinsinvolved in transport into the nucleus (By similarity). Induces aconformation change in the complex formed by XPO1 and RAN thattriggers the release of the nuclear export signal of cargoproteins (PubMed:20485264). Promotes the disassembly of thecomplex formed by RAN and importin beta. Promotes dissociation ofRAN from a complex with KPNA2 and CSE1L (By similarity). Requiredfor normal mitotic spindle assembly and normal progress throughmitosis via its effect on RAN (PubMed:17671426). Does not increasethe RAN GTPase activity by itself, but increases GTP hydrolysismediated by RANGAP1 (PubMed:7882974). Inhibits RCC1-dependentexchange of RAN-bound GDP by GTP (PubMed:7882974, PubMed:7616957) intracellular transport;positive regulation of mitotic centrosome separation;signal transduction;viral process cadherin binding;GDP-dissociation inhibitor activity;GTPase activator activity;Ran GTPase binding centrosome;cytoplasm;cytosol;nuclear envelope;nuclear pore;nucleus Human T-cell leukemia virus 1 infection;Viral carcinogenesis Rev-mediated nuclear export of HIV RNA RANBMP-CD39 complex;RANBP1-RAN-KPNB1 complex 1.41592276096344 -0.585701465606689 -1.05916047096252 -1.35312974452972 -1.13932621479034 -1.26411414146423 -1.28514325618744 -1.09561967849731 0.634941637516022 -0.031494602560997 0.417082726955414 0.0462378710508347 1.24818706512451 0.875288307666779 1.08960199356079 1.1974686384201 0.320617020130157 0.568341851234436 + Cluster -671 7 7 7 26.8 26.8 26.8 29.096 0 29.173 2055800000 23 4.9040409734879 2.05128205128205E-05 Q00059;Q00059-2 Q00059;Q00059-2 Transcription factor A, mitochondrial TFAM 1465 Binds to the mitochondrial light strand promoter andfunctions in mitochondrial transcription regulation(PubMed:29445193). Required for accurate and efficient promoterrecognition by the mitochondrial RNA polymerase. Promotestranscription initiation from the HSP1 and the light strandpromoter by binding immediately upstream of transcriptional startsites. Is able to unwind DNA. Bends the mitochondrial light strandpromoter DNA into a U-turn shape via its HMG boxes. Required formaintenance of normal levels of mitochondrial DNA. May play a rolein organizing and compacting mitochondrial DNA Mitochondrion {ECO:0000269|PubMed:1737790,ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:22841477,ECO:0000269|PubMed:29445193}. Mitochondrion matrix, mitochondrionnucleoid {ECO:0000269|PubMed:18063578}. mitochondrial respiratory chain complex assembly;mitochondrial transcription;mitochondrion organization;positive regulation of transcription, DNA-templated;transcription initiation from mitochondrial promoter chromatin binding;DNA binding, bending;DNA-binding transcription factor activity;heat shock protein binding;mitochondrial promoter sequence-specific DNA binding;RNA binding;sequence-specific DNA binding;transcription coactivator binding cytosol;mitochondrial matrix;mitochondrial nucleoid;mitochondrion;nucleus;protein-containing complex Apelin signaling pathway;Huntington disease Mitochondrial DNA depletion syndrome Mitochondrial transcription initiation;Transcriptional activation of mitochondrial biogenesis 2.21140933036804 -0.334680944681168 -1.21519660949707 -0.792110621929169 -1.17961585521698 -1.39570915699005 -1.28245770931244 -0.938279449939728 0.380200803279877 0.410012394189835 0.759986817836761 -0.223397672176361 1.22723031044006 0.51538211107254 0.927254796028137 0.461672514677048 -0.0251715034246445 0.493470340967178 + Cluster -671 2 2 2 14.4 14.4 14.4 15.35 0 4.0424 232750000 11 3.21219228415053 0.000722772277227723 Q9Y4Z0 Q9Y4Z0 U6 snRNA-associated Sm-like protein LSm4 LSM4 3298 Plays role in pre-mRNA splicing as component of theU4/U6-U5 tri-snRNP complex that is involved in spliceosomeassembly, and as component of the precatalytic spliceosome(spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8complex binds specifically to the 3'-terminal U-tract of U6 snRNA(PubMed:10523320). Nucleus {ECO:0000269|PubMed:10523320,ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28781166}. cytoplasmic mRNA processing body assembly;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;mRNA splicing, via spliceosome;RNA splicing;spliceosomal snRNP assembly PH domain binding;RNA binding;U6 snRNA binding cytosol;Lsm2-8 complex;membrane;neuron projection;nucleoplasm;nucleus;P-body;protein-containing complex;U2-type precatalytic spliceosome;U4/U6 x U5 tri-snRNP complex;U6 snRNP RNA degradation;Spliceosome mRNA decay by 5' to 3' exoribonuclease;mRNA Splicing - Major Pathway LSm1-7 complex;LSm2-8 complex;Spliceosome 1.40262794494629 -0.403678804636002 -1.07743275165558 -1.32309198379517 -1.32309198379517 -0.357004344463348 0.150126531720161 -1.23753094673157 0.978295564651489 -0.724848568439484 -1.23753094673157 -0.178831055760384 1.41841411590576 1.08356308937073 1.08356308937073 0.481951922178268 0.842481851577759 0.422017097473145 + Cluster -671 6 1 1 36.3 5.5 5.5 17.163 0.00033267 2.4741 765460000 3 3.30043812760467 0.00059375 P61326;P61326-2 P61326;P61326-2 Protein mago nashi homolog MAGOH 1309 the function is different from the established EJCassembly.;Core component of the splicing-dependent multiproteinexon junction complex (EJC) deposited at splice junctions onmRNAs. The EJC is a dynamic structure consisting of core proteinsand several peripheral nuclear and cytoplasmic associated factorsthat join the complex only transiently either during EJC assemblyor during subsequent mRNA metabolism. The EJC marks the positionof the exon-exon junction in the mature mRNA for the geneexpression machinery and the core components remain bound tospliced mRNAs throughout all stages of mRNA metabolism therebyinfluencing downstream processes including nuclear mRNA export,subcellular mRNA localization, translation efficiency andnonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimerinhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. TheMAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1leading to EJC disassembly in the cytoplasm and translationenhancement of EJC-bearing spliced mRNAs by recruiting them to theribosomal 48S preinitiation complex. Involved in the splicingmodulation of BCL2L1/Bcl-X (and probably other apoptotic genes);specifically inhibits formation of proapoptotic isoforms such asBcl-X(S) Nucleus {ECO:0000269|PubMed:19324961}.Nucleus speckle {ECO:0000269|PubMed:19324961}. Cytoplasm{ECO:0000269|PubMed:19324961}. Note=Detected in granule-likestructures in the dendroplasm (By similarity). Travels to thecytoplasm as part of the exon junction complex (EJC) bound tomRNA. Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and UAP56in the nucleus and nuclear speckles. {ECO:0000250}. mRNA 3'-end processing;mRNA export from nucleus;mRNA splicing, via spliceosome;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;regulation of alternative mRNA splicing, via spliceosome;regulation of translation;RNA export from nucleus;RNA splicing RNA binding catalytic step 2 spliceosome;cytoplasm;exon-exon junction complex;nuclear speck;nucleoplasm;nucleus mRNA surveillance pathway;RNA transport;Spliceosome Cleavage of Growing Transcript in the Termination Region;mRNA 3'-end processing;mRNA Splicing - Major Pathway;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Regulation of expression of SLITs and ROBOs;Transport of Mature mRNA derived from an Intron-Containing Transcript C complex spliceosome;Exon junction complex;Exon junction complex (EIF4A3, MLN51, MAGOH, Y14);Exon junction complex (EIF4A3, MLN51, UPF3B, MAGOH, Y14);Exon junction complex (EIF4A3, MLN51, UPF3B, MAGOH, Y14, PYM);IPO13-RBM8A-MAGOH complex;SMG1-UPF2-Y14-MAGOH-UPF3B-EIF4A3 complex;Spliceosome;Y14-Magoh complex 1.57921421527863 0.275717943906784 -1.02203273773193 -1.63230156898499 -1.22976791858673 -0.171380117535591 -0.592532753944397 -0.573380827903748 -0.749018430709839 -0.592532753944397 -0.542286038398743 -0.850306808948517 1.21119010448456 0.900007426738739 1.21119010448456 1.33713209629059 0.715209424495697 0.725878536701202 + Cluster -671 2 2 2 16.3 16.3 16.3 21.178 0 7.693 5464000000 8 3.57964155630042 0.000377969762419006 Q8N668;Q8N668-2 Q8N668;Q8N668-2 COMM domain-containing protein 1 COMMD1 2199 competes withARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNAbinding and impaired transcriptional activation by HIF-1(PubMed:20458141). Negatively regulates neuroblastoma G1/S phasecell cycle progression and cell proliferation by stimulatingubiquitination of NF-kappa-B subunit RELA and NF-kappa-Bdegradation in a FAM107A- and actin-dependent manner(PubMed:28604741).; in vitro promotes CRL E3activity and dissociates CAND1 from CUL1 and CUL2(PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunitRELA and its subsequent proteasomal degradation. Down-regulatesNF-kappa-B activity (PubMed:15799966, PubMed:17183367,PubMed:20048074). Involved in the regulation of membraneexpression and ubiquitination of SLC12A2 (PubMed:23515529).Modulates Na(+) transport in epithelial cells by regulation ofapical cell surface expression of amiloride-sensitive sodiumchannel (ENaC) subunits and by promoting their ubiquitinationpresumably involving NEDD4L. Promotes the localization of SCNN1Dto recycling endosomes (PubMed:14645214, PubMed:20237237,PubMed:21741370). Promotes CFTR cell surface expression throughregulation of its ubiquitination (PubMed:21483833). Down-regulatesSOD1 activity by interfering with its homodimerization(PubMed:20595380). Plays a role in copper ion homeostasis.Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function isproposed to depend on its association within the CCC complex andcooperation with the WASH complex on early endosomes(PubMed:25355947). Can bind one copper ion per monomer(PubMed:17309234). May function to facilitate biliary copperexcretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in theregulation of HIF1A-mediated transcription;Proposed scaffold protein that is implicated in diversephysiological processes and whose function may be in part linkedto its ability to regulate ubiquitination of specific cellularproteins. Can modulate activity of cullin-RING E3 ubiquitin ligase(CRL) complexes by displacing CAND1 Nucleus {ECO:0000269|PubMed:21778237,ECO:0000269|PubMed:28604741}. Cytoplasm{ECO:0000269|PubMed:21778237}. Endosome membrane{ECO:0000269|PubMed:18940794}. Cytoplasmic vesicle{ECO:0000269|PubMed:18940794}. Early endosome{ECO:0000269|PubMed:21483833, ECO:0000269|PubMed:25355947}.Recycling endosome {ECO:0000269|PubMed:21483833,ECO:0000269|PubMed:21741370}. Note=Shuttles between nucleus andcytosol. Detected in perinuclear foci that may be aggresomescontaining misfolded, ubiquitinated proteins. copper ion homeostasis;Golgi to plasma membrane transport;negative regulation of NF-kappaB transcription factor activity;negative regulation of protein localization to cell surface;negative regulation of sodium ion transmembrane transport;plasma membrane to endosome transport;positive regulation of protein ubiquitination;post-translational protein modification;protein transport;regulation of proteasomal ubiquitin-dependent protein catabolic process copper ion binding;identical protein binding;phosphatidic acid binding;phosphatidylinositol-3,4,5-trisphosphate binding;phosphatidylinositol-3,4-bisphosphate binding;phosphatidylinositol-3,5-bisphosphate binding;phosphatidylinositol-4,5-bisphosphate binding;protein homodimerization activity Cul2-RING ubiquitin ligase complex;cytoplasm;cytosol;early endosome;endosome;endosome membrane;nucleoplasm;nucleus;recycling endosome Neddylation CCC complex;CCC-Wash (WASH1, FAM21C) complex;CCDC22-COMMD1-CUL2 complex;CCDC93-COMMD1-COMMD6 complex;COMMD1-CCDC22-CCDC93-C16orf62 complex;COMMD1-CCDC93-C16orf62 complex;MURR1-NF(kappa)Bp65-IKBA complex 0.0804367288947105 -0.459376722574234 -0.0687351152300835 -1.05401682853699 -0.878007113933563 0.0624191835522652 -0.718772351741791 -0.410049974918365 -0.228815257549286 -1.71860873699188 -0.807902693748474 -0.924196839332581 1.95926249027252 1.11354804039001 1.44432127475739 1.25415408611298 0.536355018615723 0.817984819412231 + Cluster -671 6 6 6 11.7 11.7 11.7 85.956 0 104.74 4817700000 22 4.93774209974976 2.09424083769634E-05 Q01826;Q01826-2 Q01826;Q01826-2 DNA-binding protein SATB1 SATB1 1489 Crucial silencing factor contributing to the initiationof X inactivation mediated by Xist RNA that occurs duringembryogenesis and in lymphoma (By similarity). Binds to DNA atspecial AT-rich sequences, the consensus SATB1-binding sequence(CSBS), at nuclear matrix- or scaffold-associated regions. Thoughtto recognize the sugar-phosphate structure of double-stranded DNA.Transcriptional repressor controlling nuclear and viral geneexpression in a phosphorylated and acetylated status-dependentmanner, by binding to matrix attachment regions (MARs) of DNA andinducing a local chromatin-loop remodeling. Acts as a docking sitefor several chromatin remodeling enzymes (e.g. PML at the MHC-Ilocus) and also by recruiting corepressors (HDACs) or coactivators(HATs) directly to promoters and enhancers. Modulates genes thatare essential in the maturation of the immune T-cell CD8SP fromthymocytes. Required for the switching of fetal globin species,and beta- and gamma-globin genes regulation during erythroiddifferentiation. Plays a role in chromatin organization andnuclear architecture during apoptosis. Interacts with the uniqueregion (UR) of cytomegalovirus (CMV). Alu-like motifs and SATB1-binding sites provide a unique chromatin context which seemspreferentially targeted by the HIV-1 integration machinery.Moreover, HIV-1 Tat may overcome SATB1-mediated repression of IL2and IL2RA (interleukin) in T-cells by binding to the same domainthan HDAC1. Delineates specific epigenetic modifications at targetgene loci, directly up-regulating metastasis-associated geneswhile down-regulating tumor-suppressor genes. Reprograms chromatinorganization and the transcription profiles of breast tumors topromote growth and metastasis. Nucleus matrix. Nucleus, PML body.Note=Organized into a cage-like network anchoring loops ofheterochromatin and tethering specialized DNA sequences. Whensumoylated, localized in promyelocytic leukemia nuclear bodies(PML NBs). activated T cell proliferation;CD4-positive, alpha-beta T cell differentiation;CD8-positive, alpha-beta T cell differentiation;chromatin organization;chromatin remodeling;epidermis development;histone methylation;negative regulation of transcription by RNA polymerase II;reflex;viral process chromatin binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;double-stranded DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;sequence-specific DNA binding nuclear body;nuclear heterochromatin;nuclear matrix;nucleoplasm;nucleus;PML body Apoptotic cleavage of cellular proteins;SUMOylation of chromatin organization proteins 1.65921819210052 -0.1042126044631 -0.676844239234924 -1.21647357940674 -1.03466141223907 -0.187702223658562 -0.596594929695129 -0.858581483364105 -0.219538852572441 -0.858581483364105 -1.26971995830536 -0.397083967924118 2.06815361976624 0.891396045684814 1.20869290828705 0.843250751495361 0.275720238685608 0.473562926054001 + Cluster -671 9 9 9 23 23 23 78.365 0 217.95 9134200000 33 3.13407711395073 0.000844690966719493 Q14444;Q14444-2 Q14444;Q14444-2 Caprin-1 CAPRIN1 1709 May regulate the transport and translation of mRNAs ofproteins involved in synaptic plasticity in neurons and cellproliferation and migration in multiple cell types. Binds directlyand selectively to MYC and CCND2 RNAs. In neuronal cells, directlybinds to several mRNAs associated with RNA granules, includingBDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 andKPNB1 mRNAs, but not to rRNAs. Cytoplasm, cytosol. Cell projection,dendrite. Note=Associated with RNA granules. {ECO:0000250}. negative regulation of translation;positive regulation of dendrite morphogenesis;positive regulation of dendritic spine morphogenesis RNA binding cytoplasmic stress granule;cytosol;dendrite;membrane;P-body;synapse CF IIAm complex (Cleavage factor IIAm complex) 1.34436452388763 -0.0580333732068539 -1.20462954044342 -0.607657909393311 -1.56504118442535 -0.548242926597595 -1.04981899261475 0.129425942897797 0.44763970375061 -0.844074428081512 -0.916784882545471 -0.548242926597595 1.94820702075958 0.754455089569092 1.07501232624054 1.36821341514587 0.0481866672635078 0.227021485567093 + Cluster -671 7 7 7 17.6 17.6 17.6 51.596 0 20.079 3940400000 17 3.05534383562899 0.00097583081570997 P61201;P61201-2 P61201;P61201-2 COP9 signalosome complex subunit 2 COPS2 1300 Essential component of the COP9 signalosome complex(CSN), a complex involved in various cellular and developmentalprocesses. The CSN complex is an essential regulator of theubiquitin (Ubl) conjugation pathway by mediating the deneddylationof the cullin subunits of SCF-type E3 ligase complexes, leading todecrease the Ubl ligase activity of SCF-type complexes such asSCF, CSA or DDB2. The complex is also involved in phosphorylationof p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP,possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protectsdegradation by the Ubl system, respectively. Involved in earlystage of neuronal differentiation via its interaction with NIF3L1 Cytoplasm {ECO:0000269|PubMed:9535219}.Nucleus {ECO:0000269|PubMed:10207062}. cell proliferation;negative regulation of nucleic acid-templated transcription;negative regulation of transcription by RNA polymerase II;negative regulation of transcription, DNA-templated;neuron differentiation;nucleotide-excision repair, DNA damage recognition;post-translational protein modification;protein deneddylation;protein phosphorylation;signal transduction;skeletal muscle cell differentiation;transcription by RNA polymerase II;transcription-coupled nucleotide-excision repair transcription corepressor activity COP9 signalosome;cytoplasm;cytosol;nucleoplasm Cargo recognition for clathrin-mediated endocytosis;DNA Damage Recognition in GG-NER;Formation of TC-NER Pre-Incision Complex;Neddylation CNS-P53 complex;COP9 signalosome complex;CSA complex;CSA-POLIIa complex;CUL4B-DDB1-DTL-CSN complex;DDB2 complex 1.57253205776215 0.0671866983175278 -1.81460416316986 -1.35868859291077 -1.01907765865326 -0.287481069564819 -0.0385769344866276 -0.693403542041779 0.821916878223419 -0.314281612634659 -0.729271173477173 -1.2194744348526 1.35505044460297 0.915311932563782 1.01213812828064 1.00472176074982 0.274445682764053 0.451555550098419 + Cluster -671 5 5 5 31.2 31.2 31.2 17.779 0 41.249 41170000000 54 3.56323585279663 0.000384778012684989 P83731 P83731 60S ribosomal protein L24 RPL24 1448 assembly of large subunit precursor of preribosome;cytoplasmic translation;exit from mitosis;mitotic cell cycle checkpoint;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;optic nerve development;retina development in camera-type eye;retinal ganglion cell axon guidance;ribosomal large subunit assembly;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation cadherin binding;RNA binding;structural constituent of ribosome cytoplasm;cytosol;cytosolic large ribosomal subunit;endoplasmic reticulum;extracellular exosome;membrane;polysomal ribosome;synapse Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic 2.18635559082031 -0.26306813955307 -1.06617081165314 -1.64389944076538 -1.02945077419281 -0.555896580219269 -0.857932686805725 -1.05838465690613 0.209175229072571 -0.165005892515182 -0.187653854489326 -0.40738970041275 1.34064197540283 0.931967675685883 0.959716975688934 0.957553267478943 0.10155788064003 0.547883987426758 + Cluster -671 12 12 12 12.7 12.7 12.7 148.66 0 159.26 10600000000 41 3.31313653688782 0.000585964912280702 P19174-2;P19174 P19174-2;P19174 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 PLCG1 728 Mediates the production of the second messengermolecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate(IP3). Plays an important role in the regulation of intracellularsignaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such asPDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role inactin reorganization and cell migration Cell projection, lamellipodium. Cellprojection, ruffle. Note=Rapidly redistributed to ruffles andlamellipodia structures in response to epidermal growth factor(EGF) treatment. activation of phospholipase C activity;axon guidance;calcium ion transport;calcium-mediated signaling;cell migration;cellular response to epidermal growth factor stimulus;epidermal growth factor receptor signaling pathway;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;in utero embryonic development;inositol phosphate metabolic process;leukocyte migration;modulation of chemical synaptic transmission;phospholipid catabolic process;positive regulation of angiogenesis;positive regulation of blood vessel endothelial cell migration;positive regulation of endothelial cell apoptotic process;positive regulation of epithelial cell migration;positive regulation of phospholipase C activity;positive regulation of release of sequestered calcium ion into cytosol;positive regulation of vascular endothelial cell proliferation;signal transduction;T cell receptor signaling pathway;viral process calcium ion binding;glutamate receptor binding;neurotrophin TRKA receptor binding;phosphatidylinositol phospholipase C activity;phospholipase C activity;protein kinase binding;receptor tyrosine kinase binding cell projection;cell-cell junction;COP9 signalosome;cytoplasm;cytosol;glutamatergic synapse;lamellipodium;plasma membrane;ruffle;Schaffer collateral - CA1 synapse AGE-RAGE signaling pathway in diabetic complications;Axon guidance;Calcium signaling pathway;Choline metabolism in cancer;EGFR tyrosine kinase inhibitor resistance;Epithelial cell signaling in Helicobacter pylori infection;ErbB signaling pathway;Fc epsilon RI signaling pathway;Fc gamma R-mediated phagocytosis;Glioma;Hepatocellular carcinoma;HIF-1 signaling pathway;Human immunodeficiency virus 1 infection;Inflammatory mediator regulation of TRP channels;Inositol phosphate metabolism;Kaposi sarcoma-associated herpesvirus infection;Leukocyte transendothelial migration;Metabolic pathways;MicroRNAs in cancer;Natural killer cell mediated cytotoxicity;Neurotrophin signaling pathway;NF-kappa B signaling pathway;Non-small cell lung cancer;Pathways in cancer;PD-L1 expression and PD-1 checkpoint pathway in cancer;Phosphatidylinositol signaling system;Phospholipase D signaling pathway;Proteoglycans in cancer;Rap1 signaling pathway;Ras signaling pathway;T cell receptor signaling pathway;Th1 and Th2 cell differentiation;Th17 cell differentiation;Thyroid hormone signaling pathway;VEGF signaling pathway;Vibrio cholerae infection;Yersinia infection Activated NTRK2 signals through PLCG1;Activated NTRK3 signals through PLCG1;Constitutive Signaling by EGFRvIII;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;DAG and IP3 signaling;DAP12 signaling;Downstream signal transduction;EGFR interacts with phospholipase C-gamma;Erythropoietin activates Phospholipase C gamma (PLCG);FCERI mediated Ca+2 mobilization;FCERI mediated MAPK activation;Generation of second messenger molecules;ISG15 antiviral mechanism;PECAM1 interactions;Phospholipase C-mediated cascade, FGFR2;Phospholipase C-mediated cascade, FGFR3;Phospholipase C-mediated cascade, FGFR4;Phospholipase C-mediated cascade: FGFR1;PLCG1 events in ERBB2 signaling;PLC-gamma1 signalling;RET signaling;Role of phospholipids in phagocytosis;Role of second messengers in netrin-1 signaling;Signaling by FGFR1 in disease;Signaling by FGFR2 in disease;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR4 in disease;Synthesis of IP3 and IP4 in the cytosol;VEGFR2 mediated cell proliferation FYN-KHDRBS1-PLCG1 complex;LAT-PLC-gamma-1-p85-GRB2-CBL-VAV-SLP-76 signaling complex, C305 activated;LAT-PLC-gamma-1-p85-GRB2-SOS signaling complex, C305 activated;LCK-SLP76-PLC-gamma-1-LAT complex, pervanadate-activated;PDGFRA-PLC-gamma-1-PI3K-SHP-2 complex, PDGF stimulated;PLC-gamma-1-LAT-c-CBL complex, OKT3 stimulated;PLC-gamma-1-SLP-76-SOS1-LAT complex;SLP-76-PLC-gamma-1-ITK complex, alpha-TCR stimulated;SLP-76-PLC-gamma-1-VAV complex, alpha-TCR stimulated 1.86612141132355 0.0140315582975745 -1.48298680782318 -1.48298680782318 -1.45922517776489 -0.0223565418273211 -0.734104752540588 -0.704137325286865 0.619813203811646 -0.48630166053772 -0.218313857913017 -0.734104752540588 1.45654988288879 0.538088440895081 0.90471214056015 1.02775430679321 0.27763357758522 0.619813203811646 + Cluster -671 10 10 8 63.4 63.4 48.1 20.811 0 155.09 104940000000 127 3.55248120242925 0.000387966804979253 Q13185 Q13185 Chromobox protein homolog 3 CBX3 1607 Seems to be involved in transcriptional silencing inheterochromatin-like complexes. Recognizes and binds histone H3tails methylated at 'Lys-9', leading to epigenetic repression. Maycontribute to the association of the heterochromatin with theinner nuclear membrane through its interaction with lamin Breceptor (LBR). Involved in the formation of functionalkinetochore through interaction with MIS12 complex proteins.Contributes to the conversion of local chromatin to aheterochromatin-like repressive state through H3 'Lys-9'trimethylation, mediates the recruitment of the methyltransferasesSUV39H1 and/or SUV39H2 by the PER complex to the E-box elements ofthe circadian target genes such as PER2 itself or PER1. Mediatesthe recruitement of NIPBL to sites of DNA damage at double-strandbreaks (DSBs) (PubMed:28167679). Nucleus {ECO:0000305}. Note=Associates witheuchromatin and is largely excluded from constitutiveheterochromatin. May be associated with microtubules and mitoticpoles during mitosis (Potential). {ECO:0000305}. cellular response to DNA damage stimulus;chromatin remodeling;negative regulation of G0 to G1 transition;negative regulation of transcription, DNA-templated;rhythmic process enzyme binding;histone methyltransferase binding;identical protein binding;protein domain specific binding chromatin;chromosome, centromeric region;condensed chromosome, centromeric region;nuclear chromosome, telomeric region;nuclear envelope;nuclear euchromatin;nuclear heterochromatin;nuclear inner membrane;nuclear pericentric heterochromatin;nucleoplasm;nucleus;site of DNA damage;spindle ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;RNA Polymerase I Chain Elongation;Transcriptional Regulation by E2F6 CBX3-EHMT1-NR3C1 complex;CBX3-EHMT2-NR3C1 complex;CEN complex 1.51252460479736 0.169213861227036 -1.34349381923676 -1.25639188289642 -1.15281653404236 -0.741431772708893 -0.833970844745636 -0.355522245168686 0.512166500091553 -0.965145826339722 -0.572610974311829 -0.656526267528534 1.59391939640045 1.29883861541748 1.23245894908905 0.765010595321655 0.396888762712479 0.396888762712479 + Cluster -671 22 22 16 69.2 69.2 47.9 29.597 0 296.73 157110000000 218 4.79055733942644 2.73972602739726E-05 P62701;Q8TD47 P62701 40S ribosomal protein S4, X isoform RPS4X 1362 Cytoplasm {ECO:0000269|PubMed:17289661}.Note=Localized in cytoplasmic mRNP granules containinguntranslated mRNAs. multicellular organism development;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;positive regulation of cell proliferation;positive regulation of translation;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;rRNA binding;structural constituent of ribosome cytoplasmic ribonucleoprotein granule;cytosol;cytosolic small ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleoplasm;polysome;ribonucleoprotein complex;ribosome;small ribosomal subunit;synapse Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic 1.38773608207703 0.108335986733437 -1.16284608840942 -1.20312929153442 -0.979412078857422 -0.237810730934143 -1.00641882419586 -0.929331123828888 0.279384255409241 -0.657028555870056 -0.550329267978668 -0.797255218029022 2.12012791633606 0.792142570018768 1.26589488983154 0.996012330055237 0.144653081893921 0.429274171590805 + Cluster -671 12 12 12 31.2 31.2 31.2 48.227 0 86.374 73344000000 100 3.93191054658898 0.000168044077134986 Q07666;Q07666-2;Q07666-3;Q5VWX1;O75525;O75525-2;Q9UBC1;Q9H6N6;Q9UBC1-2;Q9UBC1-3 Q07666;Q07666-2;Q07666-3 KH domain-containing, RNA-binding, signal transduction-associated protein 1 KHDRBS1 1538 Has most probably lost the function in masticatorymuscles contraction suspected for its homologs in dog (AC F1PT61)and apes.;Involved in the regulation of innate immune response.Acts as negative regulator of Toll-like receptor and interferon-regulatory factor (IRF) signaling pathways. Contributes to thenegative regulation of transcriptional activation of NF-kappa-Btarget genes in response to endogenous proinflammatory stimuli;Recruited and tyrosine phosphorylated by severalreceptor systems, for example the T-cell, leptin and insulinreceptors. Once phosphorylated, functions as an adapter protein insignal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle.Represses CBP-dependent transcriptional activation apparently bycompeting with other nuclear factors for binding to CBP. Also actsas a putative regulator of mRNA stability and/or translation ratesand mediates mRNA nuclear export. Positively regulates theassociation of constitutive transport element (CTE)-containingmRNA with large polyribosomes and translation initiation.According to some authors, is not involved in thenucleocytoplasmic export of unspliced (CTE)-containing RNA speciesaccording to (PubMed:22253824). RNA-binding protein that plays arole in the regulation of alternative splicing and influences mRNAsplice site selection and exon inclusion. Binds to RNA containing5'-[AU]UAA-3' as a bipartite motif spaced by more than 15nucleotides. Binds poly(A). Can regulate CD44 alternative splicingin a Ras pathway-dependent manner (By similarity). In cooperationwith HNRNPA1 modulates alternative splicing of BCL2L1 by promotingsplicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836,PubMed:20186123). Can regulate alternative splicing of NRXN1 andNRXN3 in the laminin G-like domain 6 containing the evolutionaryconserved neurexin alternative spliced segment 4 (AS4) involved inneurexin selective targeting to postsynaptic partners. In aneuronal activity-dependent manner cooperates synergistically withKHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. Thecooperation with KHDRBS2/SLIM-1 is antagonistic for regulation ofNXRN3 alternative splicing at AS4 (By similarity);RNA-binding protein that plays a role in the regulationof alternative splicing and influences mRNA splice site selectionand exon inclusion. Binds both poly(A) and poly(U) homopolymers.Phosphorylation by PTK6 inhibits its RNA-binding ability (Bysimilarity). Induces an increased concentration-dependentincorporation of exon in CD44 pre-mRNA by direct binding topurine-rich exonic enhancer. Can regulate alternative splicing ofNRXN1 in the laminin G-like domain 6 containing the evolutionaryconserved neurexin alternative spliced segment 4 (AS4) involved inneurexin selective targeting to postsynaptic partners. Regulatescell-type specific alternative splicing of NRXN1 at AS4 and actssynergystically with SAM68 in exon skipping. In contrast actsantagonistically with SAM68 in NRXN3 exon skipping at AS4. Itsphosphorylation by FYN inhibits its ability to regulate splicesite selection. May function as an adapter protein for Src kinasesduring mitosis.;RNA-binding protein that plays a role in the regulationof alternative splicing and influences mRNA splice site selectionand exon inclusion. Binds preferentially to the 5'-[AU]UAAA-3'motif in vitro. Binds optimally to RNA containing 5'-[AU]UAA-3' asa bipartite motif spaced by more than 15 nucleotides. Bindspoly(A). RNA-binding abilities are down-regulated by tyrosinekinase PTK6 (PubMed:10564820, PubMed:19561594, PubMed:26758068).Involved in splice site selection of vascular endothelial growthfactor (PubMed:15901763). In vitro regulates CD44 alternativesplicing by direct binding to purine-rich exonic enhancer (Bysimilarity). Can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionaryconserved neurexin alternative spliced segment 4 (AS4) involved inneurexin selective targeting to postsynaptic partners such asneuroligins and LRRTM family members (PubMed:26758068). Targeted,cell-type specific splicing regulation of NRXN1 at AS4 is involvedin neuronal glutamatergic synapse function and plasticity (Bysimilarity). May regulate expression of KHDRBS2/SLIM-1 in definedbrain neuron populations by modifying its alternative splicing (Bysimilarity). Can bind FABP9 mRNA (By similarity). May play a roleas a negative regulator of cell growth. Inhibits cellproliferation. Nucleus {ECO:0000250|UniProtKB:Q9WU01}.;Nucleus {ECO:0000269|PubMed:10332027,ECO:0000269|PubMed:15901763}. Note=Localized in a compartmentadjacent to the nucleolus, but distinct from the peri-nucleolarone.;Nucleus {ECO:0000269|PubMed:1374686,ECO:0000269|PubMed:29496907}. Cytoplasm{ECO:0000269|PubMed:29496907}. Membrane{ECO:0000269|PubMed:1374686}. Note=Predominantly located in thenucleus but also located partially in the cytoplasm.{ECO:0000269|PubMed:29496907}.;Nucleus {ECO:0000269|PubMed:20829348}.Note=Nuclear localization with a speckled expression pattern insome cells. Colocalizes with CACTIN in the nucleus. cell cycle arrest;cell proliferation;cell surface receptor signaling pathway;cellular response to lipopolysaccharide;cytoplasmic sequestering of transcription factor;G2/M transition of mitotic cell cycle;I-kappaB kinase/NF-kappaB signaling;mRNA processing;negative regulation of lipopolysaccharide-mediated signaling pathway;negative regulation of NF-kappaB transcription factor activity;negative regulation of toll-like receptor signaling pathway;negative regulation of transcription, DNA-templated;negative regulation of tumor necrosis factor production;positive regulation of RNA export from nucleus;positive regulation of translational initiation;protein complex oligomerization;regulation of alternative mRNA splicing, via spliceosome;regulation of mRNA splicing, via spliceosome;regulation of RNA export from nucleus;signal transduction;spermatogenesis DNA binding;identical protein binding;motor activity;poly(A) binding;poly(U) RNA binding;protein domain specific binding;protein heterodimerization activity;protein-containing complex binding;RNA binding;SH2 domain binding;SH3 domain binding;SH3/SH2 adaptor activity cytoplasm;cytosol;Grb2-Sos complex;membrane;myosin complex;nucleoplasm;nucleus PTK6 Regulates Proteins Involved in RNA Processing ASPP1-SAM68 complex;FYN-KHDRBS1-PLCG1 complex;Sam68-p120GAP complex;Sam68-p85 P13K-IRS-1-IR signaling complex 1.30361270904541 0.930375397205353 -1.56468200683594 -1.50036549568176 -1.25544798374176 -0.987913548946381 -0.691453337669373 -0.463403612375259 0.485685080289841 -0.33349534869194 -0.823195993900299 -0.169941127300262 1.55163979530334 0.989390015602112 0.928294837474823 0.89091295003891 0.622461259365082 0.087526448071003 + Cluster -671 13 13 13 33.6 33.6 33.6 71.428 0 323.31 79217000000 134 5.12780466135083 1.77514792899408E-05 Q16643;Q16643-3;Q16643-2 Q16643;Q16643-3;Q16643-2 Drebrin DBN1 1858 Actin cytoskeleton-organizing protein that plays a rolein the formation of cell projections (PubMed:20215400). Requiredfor actin polymerization at immunological synapses (IS) and forthe recruitment of the chemokine receptor CXCR4 to IS(PubMed:20215400). Plays a role in dendritic spine morphogenesisand organization, including the localization of the dopaminereceptor DRD1 to the dendritic spines (By similarity). Involved inmemory-related synaptic plasticity in the hippocampus (Bysimilarity). Cytoplasm {ECO:0000269|PubMed:20215400,ECO:0000269|PubMed:28966017, ECO:0000269|PubMed:8838578}. Cellprojection, dendrite {ECO:0000269|PubMed:8838578}. Cytoplasm, cellcortex {ECO:0000269|PubMed:20215400}. Cell junction{ECO:0000269|PubMed:20215400}. Cell projection, growth cone{ECO:0000250|UniProtKB:Q9QXS6}. Note=In the absence of antigen,evenly distributed throughout subcortical regions of the T-cellmembrane and cytoplasm (PubMed:20215400). In the presence ofantigen, distributes to the immunological synapse forming at theT-cell-APC contact area, where it localizes at the peripheral anddistal supramolecular activation clusters (SMAC)(PubMed:20215400). Colocalized with RUFY3 and F-actin at thetransitional domain of the axonal growth cone (By similarity).{ECO:0000250|UniProtKB:Q9QXS6, ECO:0000269|PubMed:20215400}. actin filament organization;cell communication by chemical coupling;cell communication by electrical coupling;cytoplasmic sequestering of protein;maintenance of protein location in cell;neural precursor cell proliferation;positive regulation of dendritic spine morphogenesis;positive regulation of receptor localization to synapse;positive regulation of synaptic plasticity;regulation of dendrite development;regulation of neuronal synaptic plasticity actin binding;cadherin binding;profilin binding actin cytoskeleton;actomyosin;cortical cytoskeleton;cytoplasm;cytoskeleton;dendrite;gap junction;glutamatergic synapse;growth cone;postsynaptic cytosol;postsynaptic density;postsynaptic membrane 0.82230281829834 0.0564301311969757 -1.78930997848511 -1.12277150154114 -1.38314628601074 -1.24946677684784 -0.602893769741058 -0.266737073659897 0.955686211585999 -0.35304057598114 -0.538349211215973 -0.538349211215973 1.40525257587433 1.16982853412628 0.973743200302124 0.913665592670441 0.840080142021179 0.707075178623199 + Cluster -671 4 4 4 39.3 39.3 39.3 9.461 0 37.143 27803000000 54 5.58468261623994 8.33333333333333E-06 P42677;Q71UM5 P42677;Q71UM5 40S ribosomal protein S27;40S ribosomal protein S27-like RPS27;RPS27L 1015 Component of the small ribosomal subunit(PubMed:8706699). Required for proper rRNA processing andmaturation of 18S rRNAs (PubMed:25424902) activation of cysteine-type endopeptidase activity involved in apoptotic process;cell proliferation;DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;mitotic G1 DNA damage checkpoint;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;positive regulation of translation;ribosomal small subunit assembly;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation cysteine-type endopeptidase activator activity involved in apoptotic process;DNA binding;metal ion binding;RNA binding;structural constituent of ribosome;translation activator activity;zinc ion binding cytosol;cytosolic small ribosomal subunit;GABA-ergic synapse;glutamatergic synapse;nucleoplasm;nucleus;postsynaptic density;presynapse;ribosome Ribosome Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Mitotic Prometaphase;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Resolution of Sister Chromatid Cohesion;RHO GTPases Activate Formins;Ribosomal scanning and start codon recognition;Selenocysteine synthesis;Separation of Sister Chromatids;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Ribosome, cytoplasmic 1.56978821754456 -0.184180721640587 -1.38017427921295 -0.981832087039948 -1.44984102249146 -1.25954258441925 -1.0847395658493 -0.440519124269485 0.877052187919617 -0.370368748903275 0.00260653207078576 -0.504130661487579 1.4229382276535 1.17371678352356 1.06002342700958 0.756588697433472 0.378188937902451 0.414425760507584 + Cluster -671 5 5 5 34.6 34.6 34.6 25.097 0 48.128 6576900000 20 4.55362861103769 4.7808764940239E-05 P06730;P06730-2;P06730-3 P06730;P06730-2;P06730-3 Eukaryotic translation initiation factor 4E EIF4E 518 Recognizes and binds the 7-methylguanosine-containingmRNA cap during an early step in the initiation of proteinsynthesis and facilitates ribosome binding by inducing theunwinding of the mRNAs secondary structures. Component of theCYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediatestranslational repression. In the CYFIP1-EIF4E-FMR1 complex thissubunit mediates the binding to the mRNA cap Cytoplasm, P-body{ECO:0000269|PubMed:20616046}. Cytoplasm {ECO:0000250}. behavioral fear response;cellular response to dexamethasone stimulus;G1/S transition of mitotic cell cycle;lung development;mRNA export from nucleus;negative regulation of neuron differentiation;negative regulation of translation;positive regulation of mitotic cell cycle;regulation of translation;regulation of translation at postsynapse, modulating synaptic transmission;RNA export from nucleus;stem cell population maintenance;translational initiation;viral process enzyme binding;eukaryotic initiation factor 4G binding;repressing transcription factor binding;RNA 7-methylguanosine cap binding;RNA binding;RNA cap binding;translation initiation factor activity;translation regulator activity chromatoid body;cytoplasm;cytoplasmic ribonucleoprotein granule;cytoplasmic stress granule;cytosol;eukaryotic translation initiation factor 4F complex;extracellular exosome;glutamatergic synapse;mRNA cap binding complex;P-body;perinuclear region of cytoplasm;postsynaptic cytosol;RISC complex EGFR tyrosine kinase inhibitor resistance;HIF-1 signaling pathway;Insulin signaling pathway;Longevity regulating pathway;mTOR signaling pathway;PI3K-Akt signaling pathway;RNA transport Autism Briciclib Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;Deadenylation of mRNA;GTP hydrolysis and joining of the 60S ribosomal subunit;ISG15 antiviral mechanism;L13a-mediated translational silencing of Ceruloplasmin expression;mTORC1-mediated signalling;Ribosomal scanning and start codon recognition;Translation initiation complex formation;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of the SLBP Dependant Mature mRNA;Transport of the SLBP independent Mature mRNA MNK1-eIF4F complex 0.725433588027954 0.0553014725446701 -1.71529304981232 -1.23116195201874 -1.50577461719513 -0.781011700630188 -0.514447867870331 0.00625453284010291 0.882182538509369 -0.890424132347107 -0.114426091313362 -0.995359420776367 1.09280776977539 1.22659265995026 0.970064640045166 1.03191411495209 1.03191411495209 0.725433588027954 + Cluster -671 14 14 14 47.1 47.1 47.1 31.324 0 232.43 136900000000 162 4.72179785170516 3.05676855895197E-05 P15880 P15880 40S ribosomal protein S2 RPS2 687 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;positive regulation of ubiquitin-protein transferase activity;rRNA processing;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation cadherin binding;enzyme binding;fibroblast growth factor binding;mRNA binding;RNA binding;structural constituent of ribosome cytosol;cytosolic small ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleoplasm;nucleus Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;Formation of the ternary complex, and subsequently, the 43S complex;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Protein methylation;Regulation of expression of SLITs and ROBOs;Ribosomal scanning and start codon recognition;RMTs methylate histone arginines;rRNA modification in the nucleus and cytosol;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Translation initiation complex formation;Viral mRNA Translation 40S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic 0.35987776517868 -0.591267585754395 -0.618359446525574 -0.867357492446899 -1.43273711204529 -1.41738545894623 -1.45421671867371 -0.729230761528015 0.35987776517868 -0.78276002407074 0.65925931930542 0.288429886102676 1.29825115203857 1.23028874397278 0.907363951206207 1.60069036483765 0.343481749296188 0.845793902873993 + Cluster -671 13 3 1 37.1 15.9 4.9 28.385 0 47.982 1359300000 5 4.40091664559841 6.02836879432624E-05 P09493-5 P09493-5 Tropomyosin alpha-1 chain TPM1 578 Binds to actin filaments in muscle and non-muscle cells(PubMed:23170982). Plays a central role, in association with thetroponin complex, in the calcium dependent regulation ofvertebrate striated muscle contraction (PubMed:23170982). Smoothmuscle contraction is regulated by interaction with caldesmon. Innon-muscle cells is implicated in stabilizing cytoskeleton actinfilaments. Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:P04692}. Note=Associates with F-actinstress fibers. {ECO:0000250|UniProtKB:P04692}. actin filament organization;cardiac muscle contraction;cellular response to reactive oxygen species;cytoskeleton organization;in utero embryonic development;muscle contraction;muscle filament sliding;negative regulation of cell migration;negative regulation of vascular associated smooth muscle cell migration;negative regulation of vascular smooth muscle cell proliferation;positive regulation of ATPase activity;positive regulation of cell adhesion;positive regulation of heart rate by epinephrine;positive regulation of stress fiber assembly;regulation of cell shape;regulation of heart contraction;regulation of muscle contraction;ruffle organization;sarcomere organization;ventricular cardiac muscle tissue morphogenesis;wound healing actin binding;actin filament binding;cytoskeletal protein binding;identical protein binding;protein heterodimerization activity;protein homodimerization activity;structural constituent of cytoskeleton;structural constituent of muscle actin cytoskeleton;actin filament;bleb;cytoskeleton;cytosol;muscle thin filament tropomyosin;ruffle membrane;sarcomere;stress fiber Adrenergic signaling in cardiomyocytes;Cardiac muscle contraction;Dilated cardiomyopathy (DCM);Hypertrophic cardiomyopathy (HCM);MicroRNAs in cancer Dilated cardiomyopathy;Hypertrophic cardiomyopathy Smooth Muscle Contraction;Striated Muscle Contraction -0.0496911071240902 -0.197784662246704 -1.26128399372101 -0.983458876609802 -1.40759229660034 -0.900168716907501 -1.04240679740906 -0.606275677680969 0.678834438323975 -1.27302730083466 0.43158170580864 0.0109449680894613 1.51081132888794 0.747925341129303 1.12062215805054 1.43923211097717 0.635561287403107 1.14617621898651 + Cluster -671 8 8 8 10.5 10.5 10.5 120.21 0 38.793 21684000000 18 4.77453974982116 2.69058295964126E-05 Q8IX01;Q8IX01-4;Q8IX01-3 Q8IX01;Q8IX01-4;Q8IX01-3 SURP and G-patch domain-containing protein 2 SUGP2 2151 May play a role in mRNA splicing. Nucleus {ECO:0000305}. mRNA processing;RNA splicing RNA binding nuclear body;nucleoplasm 0.156253889203072 0.020950959995389 -1.07237339019775 -1.03597104549408 -2.08167505264282 -0.151917025446892 -0.739916622638702 -0.258058488368988 0.156253889203072 -1.27931809425354 -0.419867038726807 0.157931968569756 1.21562039852142 0.680632054805756 0.794912815093994 1.77955877780914 0.932501614093781 1.14448058605194 + Cluster -671 11 8 8 48.8 38.1 38.1 38.58 0 205.71 62257000000 74 3.75461168286222 0.000263285024154589 Q15366;Q15366-6;Q15366-3;Q15366-2;Q15366-4;Q15366-5;Q15366-7;Q15366-8;P57721;P57721-2;P57721-3;P57721-5;P57721-4 Q15366;Q15366-6;Q15366-3;Q15366-2;Q15366-4;Q15366-5;Q15366-7;Q15366-8 Poly(rC)-binding protein 2 PCBP2 1792 Single-stranded nucleic acid binding protein that bindspreferentially to oligo dC.;Single-stranded nucleic acid binding protein that bindspreferentially to oligo dC. Major cellular poly(rC)-bindingprotein. Binds also poly(rU). Negatively regulates cellularantiviral responses mediated by MAVS signaling (PubMed:19881509).It acts as an adapter between MAVS and the E3 ubiquitin ligaseITCH, therefore triggering MAVS ubiquitination and degradation(PubMed:19881509). Cytoplasm {ECO:0000269|PubMed:14612387}.;Nucleus {ECO:0000269|PubMed:19029303}.Cytoplasm {ECO:0000269|PubMed:19029303}. Note=Loosely bound in thenucleus. May shuttle between the nucleus and the cytoplasm. defense response to virus;innate immune response;IRES-dependent viral translational initiation;mRNA metabolic process;mRNA splicing, via spliceosome;negative regulation of defense response to virus;negative regulation of type I interferon production;proteasome-mediated ubiquitin-dependent protein catabolic process;RNA metabolic process;viral RNA genome replication C-rich single-stranded DNA binding;DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;double-stranded DNA binding;enzyme binding;RNA binding;ubiquitin protein ligase binding cytoplasm;cytosol;extracellular exosome;focal adhesion;membrane;nucleoplasm;nucleus Ferroptosis mRNA Splicing - Major Pathway;Negative regulators of DDX58/IFIH1 signaling;Processing of Capped Intron-Containing Pre-mRNA 0.357803255319595 -0.199910849332809 -0.719607770442963 -1.20356810092926 -1.86523377895355 -0.247661381959915 -1.17033624649048 -0.857728004455566 -0.199910849332809 -0.0882825031876564 -0.526528596878052 -0.247661381959915 1.14317238330841 1.29017066955566 0.704905867576599 1.63059437274933 1.47858679294586 0.721196055412292 + Cluster -671 28 28 28 25.4 25.4 25.4 177.44 0 323.31 30271000000 107 5.32572986863391 1.36986301369863E-05 P48681 P48681 Nestin NES 1080 Required for brain and eye development. Promotes thedisassembly of phosphorylated vimentin intermediate filaments (IF)during mitosis and may play a role in the trafficking anddistribution of IF proteins and other cellular factors to daughtercells during progenitor cell division. Required for survival,renewal and mitogen-stimulated proliferation of neural progenitorcells (By similarity). brain development;central nervous system development;embryonic camera-type eye development;G2/M transition of mitotic cell cycle;negative regulation of catalytic activity;negative regulation of protein binding;positive regulation of intermediate filament depolymerization;positive regulation of neural precursor cell proliferation;stem cell proliferation intermediate filament binding;structural molecule activity cytoplasm;intermediate filament;intermediate filament cytoskeleton 0.430270791053772 0.0272207502275705 -0.988851308822632 -1.10512149333954 -1.91422116756439 -0.241081058979034 -1.32670223712921 -0.163247302174568 0.461825013160706 -0.476361334323883 -0.772088050842285 -0.476361334323883 1.50585436820984 1.00737547874451 0.942591965198517 1.59688115119934 0.811752319335938 0.68026340007782 + Cluster -671 11 11 6 44.9 44.9 23.4 42.613 0 178.46 37638000000 68 4.71614791599247 3.03030303030303E-05 P61163 P61163 Alpha-centractin ACTR1A 1298 Component of a multi-subunit complex involved inmicrotubule based vesicle motility. It is associated with thecentrosome. Cytoplasm, cytoskeleton{ECO:0000250|UniProtKB:P85515}. Cytoplasm, cytoskeleton,microtubule organizing center, centrosome{ECO:0000269|PubMed:14654843}. Cytoplasm, cell cortex{ECO:0000269|PubMed:22327364}. antigen processing and presentation of exogenous peptide antigen via MHC class II;ciliary basal body-plasma membrane docking;endoplasmic reticulum to Golgi vesicle-mediated transport;G2/M transition of mitotic cell cycle;regulation of G2/M transition of mitotic cell cycle;spermatogenesis;vesicle-mediated transport ATP binding cell cortex region;centriole;centrosome;COPI-coated vesicle;cytoplasm;cytosol;dynactin complex;extracellular exosome;manchette;microtubule associated complex;microtubule cytoskeleton;myelin sheath Anchoring of the basal body to the plasma membrane;AURKA Activation by TPX2;COPI-independent Golgi-to-ER retrograde traffic;COPI-mediated anterograde transport;HSP90 chaperone cycle for steroid hormone receptors (SHR);Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;MHC class II antigen presentation;Recruitment of mitotic centrosome proteins and complexes;Recruitment of NuMA to mitotic centrosomes;Regulation of PLK1 Activity at G2/M Transition 0.567343950271606 -0.601375639438629 -1.38662469387054 -1.04372346401215 -1.90809679031372 -0.323559373617172 -0.323559373617172 -0.793104648590088 0.199373349547386 -0.454975634813309 0.326445579528809 -0.607381701469421 1.3258992433548 0.243443191051483 0.606792747974396 1.60133564472198 1.43783664703369 1.13393092155457 + Cluster -671 2 2 2 14.6 14.6 14.6 24.211 0 11.182 596980000 4 3.58355030505938 0.000379609544468547 Q9BYN8 Q9BYN8 28S ribosomal protein S26, mitochondrial MRPS26 2721 Mitochondrion {ECO:0000269|PubMed:25838379}. DNA damage response, detection of DNA damage;mitochondrial translational elongation;mitochondrial translational termination RNA binding mitochondrial inner membrane;mitochondrial small ribosomal subunit;mitochondrion;nucleoplasm Mitochondrial translation elongation;Mitochondrial translation initiation;Mitochondrial translation termination 28S ribosomal subunit, mitochondrial;55S ribosome, mitochondrial 0.578106939792633 -0.617948353290558 -1.35495448112488 -1.11717510223389 -1.6134340763092 -0.27217561006546 0.0948925390839577 0.0529866218566895 -0.299512296915054 -0.87365597486496 -0.4767726957798 -0.761618793010712 1.09058213233948 0.720994710922241 0.424734532833099 1.02734816074371 1.44030904769897 1.95729279518127 + Cluster -671 2 2 2 11 11 11 23.423 0 29.138 293920000 3 3.21439653773927 0.000722314049586777 Q8TEA8 Q8TEA8 D-tyrosyl-tRNA(Tyr) deacylase 1 DTD1 2275 Possible ATPase (PubMed:15653697) involved in DNAreplication, may facilitate loading of CDC45 onto pre-replicationcomplexes (PubMed:20065034). Nucleus {ECO:0000269|PubMed:15653697,ECO:0000269|PubMed:20065034}. Cytoplasm{ECO:0000250|UniProtKB:Q8IIS0}. Note=Associated with chromatin atsome replication origins containing functional DNA-unwindingelements (PubMed:20065034). DNA replication;tRNA metabolic process aminoacyl-tRNA editing activity;DNA binding;D-tyrosyl-tRNA(Tyr) deacylase activity;metal ion binding;tRNA binding cytoplasm;cytosol;nucleolus 0.467846632003784 -0.556467473506927 -1.01708400249481 -1.67559552192688 -1.58969044685364 -0.275851041078568 -0.703861653804779 -0.601140141487122 0.467846632003784 -0.49451619386673 -0.155388802289963 -0.38291147351265 1.23606300354004 0.518064916133881 0.859528601169586 2.0752420425415 0.806973993778229 1.02094078063965 + Cluster -671 18 18 18 71.6 71.6 71.6 32.66 0 198.46 91000000000 133 4.11357794592572 0.000118181818181818 Q15181 Q15181 Inorganic pyrophosphatase PPA1 1777 Cytoplasm {ECO:0000250}. diphosphate metabolic process;phosphate-containing compound metabolic process;tRNA aminoacylation for protein translation inorganic diphosphatase activity;magnesium ion binding cytoplasm;cytosol;extracellular exosome Oxidative phosphorylation Cytosolic tRNA aminoacylation;Pyrophosphate hydrolysis -0.465312272310257 -0.749226093292236 -0.616497278213501 -0.585174977779388 -1.31611359119415 -0.699784934520721 -0.773977339267731 -0.924763739109039 -0.160080909729004 -0.746630370616913 0.397333204746246 -0.559698164463043 2.05597352981567 0.325859099626541 0.92566305398941 1.79574823379517 0.768581509590149 1.32810080051422 + Cluster -671 4 4 4 32.1 32.1 32.1 24.579 0 29.063 8078300000 17 4.41410535218419 6.18181818181818E-05 P00492 P00492 Hypoxanthine-guanine phosphoribosyltransferase HPRT1 469 Converts guanine to guanosine monophosphate, andhypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto thepurine. Plays a central role in the generation of purinenucleotides through the purine salvage pathway. Cytoplasm. adenine salvage;central nervous system neuron development;cerebral cortex neuron differentiation;dendrite morphogenesis;dopamine metabolic process;GMP catabolic process;GMP salvage;grooming behavior;guanine salvage;hypoxanthine metabolic process;hypoxanthine salvage;IMP metabolic process;IMP salvage;locomotory behavior;lymphocyte proliferation;positive regulation of dopamine metabolic process;protein homotetramerization;purine nucleotide biosynthetic process;purine ribonucleoside salvage;purine-containing compound salvage;response to amphetamine;striatum development;T cell mediated cytotoxicity guanine phosphoribosyltransferase activity;hypoxanthine phosphoribosyltransferase activity;identical protein binding;magnesium ion binding;nucleotide binding;protein homodimerization activity cytoplasm;cytosol;extracellular exosome Drug metabolism - other enzymes;Metabolic pathways;Purine metabolism Lesch-Nyhan syndrome Mercaptopurine;Tioguanine Purine salvage 1.0119149684906 -0.337474405765533 -1.15838646888733 -1.3609014749527 -1.53603804111481 -0.371673703193665 -0.833727359771729 -0.725394487380981 0.0858598351478577 -0.584932327270508 0.145896941423416 -0.6575728058815 1.70087575912476 0.532317101955414 0.794231235980988 1.78073060512543 0.653429746627808 0.860844850540161 + Cluster -671 17 12 11 66.5 58 55.1 27.764 0 323.31 63289000000 112 4.12683995819127 0.000113496932515337 P27348 P27348 14-3-3 protein theta YWHAQ 825 Adapter protein implicated in the regulation of a largespectrum of both general and specialized signaling pathways. Bindsto a large number of partners, usually by recognition of aphosphoserine or phosphothreonine motif. Binding generally resultsin the modulation of the activity of the binding partner.Negatively regulates the kinase activity of PDPK1 Cytoplasm. Note=In neurons, axonallytransported to the nerve terminals. membrane organization;negative regulation of ion transmembrane transport;negative regulation of transcription, DNA-templated;positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway;substantia nigra development 14-3-3 protein binding;identical protein binding;ion channel binding;protein C-terminus binding;protein domain specific binding;protein N-terminus binding cytoplasm;cytosol;extracellular exosome;focal adhesion;membrane;mitochondrion;protein-containing complex;synapse Cell cycle;Hepatitis B;Hepatitis C;Hippo signaling pathway;Oocyte meiosis;Pathogenic Escherichia coli infection;PI3K-Akt signaling pathway;Viral carcinogenesis Activation of BAD and translocation to mitochondria;Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex;RHO GTPases activate PKNs;TP53 Regulates Metabolic Genes;Translocation of SLC2A4 (GLUT4) to the plasma membrane 14-3-3q-SGK1-tau complex;Emerin complex 52;Kinase maturation complex 1;WWTR1-YWHAQ complex;YWHAQ-CALM1-CABIN1 complex 0.961192429065704 -0.488499253988266 -1.05593490600586 -1.27985417842865 -0.724596202373505 -0.933559119701385 -0.691851854324341 -1.14560627937317 -0.206609398126602 0.547966241836548 -0.479379236698151 -1.08119451999664 1.48623204231262 1.09177768230438 1.20561838150024 1.61136639118195 0.543918073177338 0.639013648033142 + Cluster -671 2 2 2 5.4 5.4 5.4 44.877 0 22.857 916670000 6 4.13990399115494 0.000105590062111801 P31350;P31350-2 P31350;P31350-2 Ribonucleoside-diphosphate reductase subunit M2 RRM2 887 Provides the precursors necessary for DNA synthesis.Catalyzes the biosynthesis of deoxyribonucleotides from thecorresponding ribonucleotides. Inhibits Wnt signaling. Cytoplasm. deoxyribonucleotide biosynthetic process;DNA replication;negative regulation of G0 to G1 transition;regulation of transcription involved in G1/S transition of mitotic cell cycle metal ion binding;ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor cytosol Drug metabolism - other enzymes;Glutathione metabolism;Metabolic pathways;p53 signaling pathway;Purine metabolism;Pyrimidine metabolism Hydroxycarbamide Activation of E2F1 target genes at G1/S;Interconversion of nucleotide di- and triphosphates;Transcriptional Regulation by E2F6 1.12257838249207 -0.554284334182739 -1.48500061035156 -1.61218726634979 -0.819769978523254 -1.16989600658417 -0.820167064666748 -1.03575992584229 1.00978374481201 0.288847386837006 -0.168096020817757 -0.319239675998688 1.41741633415222 0.804858326911926 1.00206053256989 0.990078628063202 0.504173159599304 0.844604134559631 + Cluster -671 3 3 3 17.3 17.3 17.3 17.49 0 102.78 6742900000 25 4.84786434100615 2.39234449760766E-05 P30049 P30049 ATP synthase subunit delta, mitochondrial ATP5D 862 Mitochondrial membrane ATP synthase (F(1)F(0) ATPsynthase or Complex V) produces ATP from ADP in the presence of aproton gradient across the membrane which is generated by electrontransport complexes of the respiratory chain. F-type ATPasesconsist of two structural domains, F(1) - containing theextramembraneous catalytic core, and F(0) - containing themembrane proton channel, linked together by a central stalk and aperipheral stalk. During catalysis, ATP turnover in the catalyticdomain of F(1) is coupled via a rotary mechanism of the centralstalk subunits to proton translocation. Part of the complex F(1)domain and of the central stalk which is part of the complexrotary element. Rotation of the central stalk against thesurrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP inthree separate catalytic sites on the beta subunits. Mitochondrion. Mitochondrion inner membrane. ATP biosynthetic process;ATP synthesis coupled proton transport;cristae formation;mitochondrial ATP synthesis coupled proton transport;oxidative phosphorylation;response to copper ion ATPase activity;proton-transporting ATP synthase activity, rotational mechanism;transmembrane transporter activity;transporter activity mitochondrial inner membrane;mitochondrial matrix;mitochondrial proton-transporting ATP synthase complex;mitochondrial proton-transporting ATP synthase complex, catalytic core F(1);mitochondrion Alzheimer disease;Huntington disease;Metabolic pathways;Oxidative phosphorylation;Parkinson disease;Thermogenesis Cristae formation;Formation of ATP by chemiosmotic coupling F1F0-ATP synthase, mitochondrial 0.434368938207626 -0.527719557285309 -1.04031431674957 -1.8142124414444 -0.867414116859436 -0.734019994735718 -1.25740313529968 -0.880349934101105 0.325164765119553 0.821124017238617 -0.734019994735718 -0.140472918748856 1.28893494606018 0.937054812908173 0.699165105819702 1.22042679786682 0.934829831123352 1.3348571062088 + Cluster -671 12 12 5 27.8 27.8 15.3 47.655 0 193.63 143380000000 120 4.93954702722723 2.10526315789474E-05 Q09028;Q09028-3;Q09028-2;Q09028-4 Q09028;Q09028-3;Q09028-2;Q09028-4 Histone-binding protein RBBP4 RBBP4 1554 and the NURF (nucleosome remodeling factor) complex; the corehistone deacetylase (HDAC) complex, which promotes histonedeacetylation and consequent transcriptional repression; the PRC2/EED-EZH2complex, which promotes repression of homeotic genes duringdevelopment; thenucleosome remodeling and histone deacetylase complex (the NuRDcomplex), which promotes transcriptional repression by histonedeacetylation and nucleosome remodeling;Core histone-binding subunit that may target chromatinassembly factors, chromatin remodeling factors and histonedeacetylases to their histone substrates in a manner that isregulated by nucleosomal DNA. Component of several complexes whichregulate chromatin metabolism. These include the chromatinassembly factor 1 (CAF-1) complex, which is required for chromatinassembly following DNA replication and DNA repair Nucleus. ATP-dependent chromatin remodeling;cell cycle;CENP-A containing nucleosome assembly;chromatin assembly;chromatin remodeling;DNA replication;DNA replication-dependent nucleosome assembly;DNA replication-independent nucleosome assembly;negative regulation of cell proliferation;negative regulation of G0 to G1 transition;negative regulation of gene expression, epigenetic;regulation of cell cycle histone binding;histone deacetylase activity;histone deacetylase binding;RNA polymerase II proximal promoter sequence-specific DNA binding CAF-1 complex;cytosol;ESC/E(Z) complex;nuclear chromatin;nucleoplasm;nucleus;NuRD complex;NURF complex;protein-containing complex;Sin3 complex Cellular senescence Activation of anterior HOX genes in hindbrain development during early embryogenesis;Activation of E2F1 target genes at G1/S;Cyclin A:Cdk2-associated events at S phase entry;Cyclin E associated events during G1/S transition;Deposition of new CENPA-containing nucleosomes at the centromere;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;G0 and Early G1;HDACs deacetylate histones;Oxidative Stress Induced Senescence;PKMTs methylate histone lysines;Polo-like kinase mediated events;PRC2 methylates histones and DNA;Regulation of PTEN gene transcription;Regulation of TP53 Activity through Acetylation;RNA Polymerase I Transcription Initiation;Transcription of E2F targets under negative control by DREAM complex;Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1;Transcriptional Regulation by E2F6 ALL-1 supercomplex;Anti-HDAC2 complex;BRG1-SIN3A complex;BRMS1-SIN3-HDAC complex;BRM-SIN3A complex;Chromatin assembly complex (CAF-1 complex);EED-EZH2 complex;HCF-1 complex;HDAC1-associated core complex cII;HDAC1-associated protein complex;HDAC2-asscociated core complex;Histone H3.1 complex;Histone H3.3 complex;hNURF complex;ING2 complex;LARC complex (LCR-associated remodeling complex);LINC complex, quiescent cells;LINC complex, S-phase;LINC core complex;MeCP1 complex;Mi2/NuRD complex;mSin3A complex;MTA1 complex;MTA1-HDAC core complex;MTA2 complex;NK-3-Groucho-HIPK2-SIN3A-RbpA48-HDAC1 complex;NRD complex (Nucleosome remodeling and deacetylation complex);NuRD.1 complex;PID complex;Polycomb repressive complex 2 (PRC 2);SAP complex (Sin3-associated protein complex);Sin3 complex;SIN3 complex;SIN3-HDAC-SAP30-ARID4 complex;SIN3-ING1b complex I;SIN3-ING1b complex II;SIN3-SAP25 complex;SNF2h-cohesin-NuRD complex 0.556478679180145 -0.510701596736908 -0.948552906513214 -0.843504786491394 -1.65142381191254 -0.525289297103882 -0.867854237556458 -1.25695180892944 0.436678320169449 0.274129301309586 -0.585011303424835 -0.898537814617157 1.31578099727631 1.50128102302551 1.04248046875 1.01719868183136 0.78371274471283 1.16008722782135 + Cluster -671 15 15 15 59.7 59.7 59.7 38.438 0 323.31 82425000000 141 5.36878299594775 7.19424460431655E-06 Q9Y3F4;Q9Y3F4-2 Q9Y3F4;Q9Y3F4-2 Serine-threonine kinase receptor-associated protein STRAP 3274 The SMN complex plays a catalyst role in the assembly ofsmall nuclear ribonucleoproteins (snRNPs), the building blocks ofthe spliceosome. Thereby, plays an important role in the splicingof cellular pre-mRNAs. Most spliceosomal snRNPs contain a commonset of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF andSNRPG that assemble in a heptameric protein ring on the Sm site ofthe small nuclear RNA to form the core snRNP. In the cytosol, theSm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped inan inactive 6S pICln-Sm complex by the chaperone CLNS1A thatcontrols the assembly of the core snRNP. Dissociation by the SMNcomplex of CLNS1A from the trapped Sm proteins and their transferto an SMN-Sm complex triggers the assembly of core snRNPs andtheir transport to the nucleus. STRAP plays a role in the cellulardistribution of the SMN complex. Negatively regulates TGF-betasignaling but positively regulates the PDPK1 kinase activity byenhancing its autophosphorylation and by significantly reducingthe association of PDPK1 with 14-3-3 protein Cytoplasm. Nucleus. Note=Localizedpredominantly in the cytoplasm but also found in the nucleus. maintenance of gastrointestinal epithelium;negative regulation of epithelial cell migration;negative regulation of epithelial cell proliferation;negative regulation of epithelial to mesenchymal transition;negative regulation of pathway-restricted SMAD protein phosphorylation;negative regulation of transcription by RNA polymerase II;negative regulation of transforming growth factor beta receptor signaling pathway;spliceosomal snRNP assembly RNA binding;signaling receptor binding cytoplasm;cytosol;nucleoplasm;SMN complex;SMN-Sm protein complex RNA transport Downregulation of TGF-beta receptor signaling SMN complex;SMN complex (GEMIN6,7, UNRIP), SMN-independent intermediate 0.50369268655777 0.00384073588065803 -1.72573459148407 -0.968206882476807 -1.41103744506836 -1.21982669830322 -0.872661530971527 -0.79559862613678 0.829512357711792 -0.240628927946091 -0.240628927946091 -0.240628927946091 1.51481890678406 1.04755485057831 1.04755485057831 1.10895335674286 0.829512357711792 0.829512357711792 + Cluster -671 19 19 19 76 76 76 35.076 0 323.31 219920000000 211 7.33269913900674 0 P63244 P63244 Guanine nucleotide-binding protein subunit beta-2-like 1;Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed GNB2L1 1405 Scaffolding protein involved in the recruitment,assembly and/or regulation of a variety of signaling molecules.Interacts with a wide variety of proteins and plays a role in manycellular processes. Component of the 40S ribosomal subunitinvolved in translational repression (PubMed:23636399). Involvedin the initiation of the ribosome quality control (RQC), a pathwaythat takes place when a ribosome has stalled during translation,by promoting ubiquitination of a subset of 40S ribosomal subunits(PubMed:28132843). Binds to and stabilizes activated proteinkinase C (PKC), increasing PKC-mediated phosphorylation. Mayrecruit activated PKC to the ribosome, leading to phosphorylationof EIF6. Inhibits the activity of SRC kinases including SRC, LCKand YES1. Inhibits cell growth by prolonging the G0/G1 phase ofthe cell cycle. Enhances phosphorylation of BMAL1 by PRKCA andinhibits transcriptional activity of the BMAL1-CLOCK heterodimer.Facilitates ligand-independent nuclear translocation of ARfollowing PKC activation, represses AR transactivation activityand is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading andcontact with the extracellular matrix. Involved in PKC-dependenttranslocation of ADAM12 to the cell membrane. Promotes theubiquitination and proteasome-mediated degradation of proteinssuch as CLEC1B and HIF1A. Required for VANGL2 membranelocalization, inhibits Wnt signaling, and regulates cellularpolarization and oriented cell division during gastrulation.Required for PTK2/FAK1 phosphorylation and dephosphorylation.Regulates internalization of the muscarinic receptor CHRM2.Promotes apoptosis by increasing oligomerization of BAX anddisrupting the interaction of BAX with the anti-apoptotic factorBCL2L. Inhibits TRPM6 channel activity. Regulates cell surfaceexpression of some GPCRs such as TBXA2R. Plays a role inregulation of FLT1-mediated cell migration. Involved in thetransport of ABCB4 from the Golgi to the apical bile canalicularmembrane (PubMed:19674157). Promotes migration of breast carcinomacells by binding to and activating RHOA (PubMed:20499158) Peripheral membrane protein.Cytoplasm {ECO:0000269|PubMed:10849009,ECO:0000269|PubMed:11279199, ECO:0000269|PubMed:12958311,ECO:0000269|PubMed:19785988, ECO:0000269|PubMed:20499158,ECO:0000269|PubMed:20573744}. Cytoplasm, perinuclear region{ECO:0000269|PubMed:11279199, ECO:0000269|PubMed:12958311}.Nucleus {ECO:0000269|PubMed:10849009}. Perikaryon{ECO:0000250|UniProtKB:P68040}. Cell projection, dendrite{ECO:0000250|UniProtKB:P68040}. Cell projection, phagocytic cup{ECO:0000269|PubMed:21347310}. Note=Recruited to the plasmamembrane through interaction with KRT1 which binds to membrane-bound ITGB1 (PubMed:17956333). Also associated with the membranein oncogene-transformed cells (PubMed:11884618). PKC activationinduces translocation from the perinuclear region to the cellperiphery (PubMed:11279199). In the brain, detected mainly in cellbodies and dendrites with little expression in axonal fibers ornuclei (By similarity). Localized to phagocytic cups followinginfection by Y.pestis (PubMed:21347310).{ECO:0000250|UniProtKB:P68040, ECO:0000269|PubMed:11279199,ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:17956333,ECO:0000269|PubMed:21347310}.;Cell membrane {ECO:0000269|PubMed:11312657,ECO:0000269|PubMed:17956333} activation of cysteine-type endopeptidase activity involved in apoptotic process;cell cycle;cellular response to glucose stimulus;cellular response to growth factor stimulus;gastrulation;negative regulation of cell growth;negative regulation of endoplasmic reticulum unfolded protein response;negative regulation of gene expression;negative regulation of hydrogen peroxide-induced neuron death;negative regulation of peptidyl-serine phosphorylation;negative regulation of phagocytosis;negative regulation of protein kinase B signaling;negative regulation of translation;negative regulation of Wnt signaling pathway;pigmentation;positive regulation of apoptotic process;positive regulation of cell migration;positive regulation of ceramide biosynthetic process;positive regulation of cyclic-nucleotide phosphodiesterase activity;positive regulation of gastrulation;positive regulation of Golgi to plasma membrane protein transport;positive regulation of GTPase activity;positive regulation of intrinsic apoptotic signaling pathway;positive regulation of mitochondrial depolarization;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of protein homooligomerization;positive regulation of protein phosphorylation;protein ubiquitination;regulation of cell cycle;regulation of cell division;regulation of establishment of cell polarity;regulation of protein localization;regulation of tumor necrosis factor-mediated signaling pathway;rescue of stalled ribosome;rhythmic process;viral process cadherin binding;cyclin binding;cysteine-type endopeptidase activator activity involved in apoptotic process;enzyme binding;ion channel inhibitor activity;protein homodimerization activity;protein kinase C binding;protein phosphatase binding;protein tyrosine kinase inhibitor activity;protein-containing complex scaffold activity;receptor tyrosine kinase binding;ribosome binding;RNA binding;SH2 domain binding;signaling adaptor activity;signaling receptor binding cytoplasm;cytosol;cytosolic small ribosomal subunit;dendrite;extracellular exosome;IRE1-RACK1-PP2A complex;midbody;mitochondrion;neuronal cell body;nucleoplasm;nucleus;perikaryon;perinuclear region of cytoplasm;phagocytic cup;small ribosomal subunit Measles Regulation of TNFR1 signaling;TNFR1-induced NFkappaB signaling pathway;TNFR1-mediated ceramide production ABCB1-ANXA2-RACK1-SRC complex;FERMT3-RACK1 complex;G protein complex (GNG2, GNB2L1, RAF1);ITGB1-RACK1 complex;ITGB2-RACK1 complex 0.259999990463257 -0.152385801076889 -1.0413726568222 -0.982183396816254 -1.28000330924988 -1.15233206748962 -1.15233206748962 -0.831470131874084 0.00379080115817487 -0.550213575363159 -0.0782753676176071 -0.21174843609333 1.98613774776459 0.931417465209961 1.05881643295288 1.32147932052612 0.721514880657196 1.14916014671326 + Cluster -671 19 18 18 51.2 47.6 47.6 36.638 0 323.31 515280000000 554 7.37012846590946 0 P07195;P07864;Q6ZMR3 P07195 L-lactate dehydrogenase B chain LDHB 530 Displays an lactate dehydrogenase activity.Significantly increases the transcriptional activity of JUN, whenoverexpressed.;Possible role in sperm motility. Cytoplasm {ECO:0000269|PubMed:18351441}.;Cytoplasm. ATP biosynthetic process;carbohydrate metabolic process;carboxylic acid metabolic process;flagellated sperm motility;lactate biosynthetic process from pyruvate;lactate oxidation;pyruvate metabolic process identical protein binding;L-lactate dehydrogenase activity cytoplasm;cytosol;extracellular exosome;membrane;membrane raft;motile cilium;nucleus Central carbon metabolism in cancer;Cysteine and methionine metabolism;Glucagon signaling pathway;Glycolysis / Gluconeogenesis;HIF-1 signaling pathway;Metabolic pathways;Propanoate metabolism;Pyruvate metabolism Pyruvate metabolism -0.0582918785512447 -0.243771314620972 -1.02202486991882 -0.727288722991943 -1.02202486991882 -1.16297614574432 -0.762721240520477 -1.16297614574432 0.166342422366142 -0.237058609724045 -0.762721240520477 -0.477485686540604 1.92063307762146 1.13231813907623 1.51298010349274 0.867625713348389 1.17181575298309 0.867625713348389 + Cluster -671 90 90 90 45.8 45.8 45.8 273.42 0 323.31 438440000000 748 7.48726095219934 0 P49327 P49327 Fatty acid synthase;[Acyl-carrier-protein] S-acetyltransferase;[Acyl-carrier-protein] S-malonyltransferase;3-oxoacyl-[acyl-carrier-protein] synthase;3-oxoacyl-[acyl-carrier-protein] reductase;3-hydroxyacyl-[acyl-carrier-protein] dehydratase;Enoyl-[acyl-carrier-protein] reductase;Oleoyl-[acyl-carrier-protein] hydrolase FASN 1091 Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. Thismultifunctional protein has 7 catalytic activities as an acylcarrier protein. Cytoplasm {ECO:0000269|PubMed:17081065}.Melanosome {ECO:0000269|PubMed:17081065}. Note=Identified by massspectrometry in melanosome fractions from stage I to stage IV. acetyl-CoA metabolic process;cellular response to interleukin-4;establishment of endothelial intestinal barrier;ether lipid biosynthetic process;fatty acid biosynthetic process;fatty acid metabolic process;fatty-acyl-CoA biosynthetic process;macromolecule metabolic process;mammary gland development;monocyte differentiation;neutrophil differentiation;osteoblast differentiation;positive regulation of cellular metabolic process;regulation of cholesterol biosynthetic process (3R)-hydroxymyristoyl-[acyl-carrier-protein] dehydratase activity;[acyl-carrier-protein] S-acetyltransferase activity;[acyl-carrier-protein] S-malonyltransferase activity;3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity;3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity;3-oxoacyl-[acyl-carrier-protein] synthase activity;3-oxo-glutaryl-[acp] methyl ester reductase activity;3-oxo-pimeloyl-[acp] methyl ester reductase activity;cadherin binding;drug binding;enoyl-[acyl-carrier-protein] reductase (NADPH, A-specific) activity;fatty acid synthase activity;myristoyl-[acyl-carrier-protein] hydrolase activity;NADPH binding;oleoyl-[acyl-carrier-protein] hydrolase activity;palmitoyl-[acyl-carrier-protein] hydrolase activity;phosphopantetheine binding;protein homodimerization activity;RNA binding cytosol;extracellular exosome;glycogen granule;Golgi apparatus;melanosome;membrane;plasma membrane AMPK signaling pathway;Fatty acid biosynthesis;Fatty acid metabolism;Insulin signaling pathway;Metabolic pathways Activation of gene expression by SREBF (SREBP);ChREBP activates metabolic gene expression;Fatty acyl-CoA biosynthesis;Vitamin B5 (pantothenate) metabolism 0.0564212016761303 -0.103317737579346 -1.01366674900055 -0.43482381105423 -0.615457534790039 -1.61440205574036 -0.720409154891968 -0.801613569259644 -0.0756360292434692 -0.14964596927166 -0.840480387210846 -0.801613569259644 2.14484477043152 1.31085240840912 1.47243213653564 1.05093944072723 0.497796982526779 0.637779355049133 + Cluster -671 6 6 6 43.5 43.5 43.5 12.784 0 133.05 78998000000 72 4.83137729542496 2.35849056603774E-05 P62888 P62888 60S ribosomal protein L30 RPL30 1378 antimicrobial humoral immune response mediated by antimicrobial peptide;cytoplasmic translation;defense response to Gram-negative bacterium;killing of cells of other organism;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;SRP-dependent cotranslational protein targeting to membrane;translation;translational initiation RNA binding;structural constituent of ribosome cytosol;cytosolic large ribosomal subunit;extracellular exosome;focal adhesion;membrane;nucleus;polysomal ribosome;postsynaptic density Ribosome Eukaryotic Translation Termination;Formation of a pool of free 40S subunits;GTP hydrolysis and joining of the 60S ribosomal subunit;L13a-mediated translational silencing of Ceruloplasmin expression;Major pathway of rRNA processing in the nucleolus and cytosol;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Peptide chain elongation;Regulation of expression of SLITs and ROBOs;Selenocysteine synthesis;SRP-dependent cotranslational protein targeting to membrane;Viral mRNA Translation 60S ribosomal subunit, cytoplasmic;Nop56p-associated pre-rRNA complex;Ribosome, cytoplasmic;TNF-alpha/Nf-kappa B signaling complex (RPL6, RPL30, RPS13, CHUK, DDX3X, NFKB2, NFKBIB, REL, IKBKG, NFKB1, MAP3K8, RELB, GLG1, NFKBIA, RELA, TNIP2, GTF2I);TNF-alpha/NF-kappa B signaling complex 6;TRBP containing complex (DICER, RPL7A, EIF6, MOV10 and subunits of the 60S ribosomal particle) 0.941935777664185 -0.286717295646667 -0.857076406478882 -1.15232384204865 -0.857076406478882 -0.634102761745453 -0.634102761745453 -1.43955934047699 0.546267032623291 -0.379383653402328 -0.634102761745453 -0.929350137710571 1.74284207820892 1.16490948200226 1.74284207820892 0.941935777664185 0.17679588496685 0.546267032623291 + Cluster -671 55 55 54 63.4 63.4 62.2 95.337 0 323.31 558650000000 598 4.40748423746326 6.09318996415771E-05 P13639 P13639 Elongation factor 2 EEF2 653 Catalyzes the GTP-dependent ribosomal translocation stepduring translation elongation. During this step, the ribosomechanges from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-boundpeptidyl-tRNA and P-site-bound deacylated tRNA move to the P and Esites, respectively. Catalyzes the coordinated movement of the twotRNA molecules, the mRNA and conformational changes in theribosome. Cytoplasm {ECO:0000269|PubMed:25064856}.Nucleus {ECO:0000269|PubMed:24648518}. Note=Phosphorylation by CSKpromotes cleavage and SUMOylation-dependent nuclear translocationof the C-terminal cleavage product. {ECO:0000269|PubMed:24648518}. aging;cellular response to brain-derived neurotrophic factor stimulus;glial cell proliferation;hematopoietic progenitor cell differentiation;neutrophil degranulation;positive regulation of cytoplasmic translation;positive regulation of translation;response to endoplasmic reticulum stress;response to estradiol;response to ethanol;response to folic acid;response to hydrogen peroxide;response to ischemia;skeletal muscle cell differentiation;skeletal muscle contraction;translational elongation 5S rRNA binding;actin filament binding;cadherin binding;GTP binding;GTPase activity;p53 binding;protein kinase binding;ribosome binding;RNA binding;translation elongation factor activity aggresome;cytoplasm;cytosol;extracellular exosome;extracellular region;ficolin-1-rich granule lumen;membrane;membrane raft;nucleus;plasma membrane;polysomal ribosome;ribonucleoprotein complex;secretory granule lumen;synapse AMPK signaling pathway;Oxytocin signaling pathway Spinocerebellar ataxia (SCA) Neutrophil degranulation;Peptide chain elongation;Protein methylation;Synthesis of diphthamide-EEF2;Uptake and function of diphtheria toxin Nop56p-associated pre-rRNA complex 0.661580622196198 -0.54472142457962 -0.54472142457962 -1.23884415626526 -0.54472142457962 -1.00171601772308 -1.16753137111664 -1.47713470458984 -0.130502790212631 -0.179642930626869 -0.368793278932571 -0.368793278932571 1.60163652896881 1.36032390594482 1.60163652896881 1.30769658088684 0.661580622196198 0.372667908668518 + Cluster -671 36 36 27 56 56 44 69.147 0 323.31 238830000000 325 4.99580605388179 2.18579234972678E-05 P17844;P17844-2 P17844;P17844-2 Probable ATP-dependent RNA helicase DDX5 DDX5 710 its RNA helicase activity is necessary for increasingtau exon 10 inclusion and occurs in a RBM4-dependent manner. Bindsto the tau pre-mRNA in the stem-loop region downstream of exon 10.The rate of ATP hydrolysis is highly stimulated by single-strandedRNA. Involved in transcriptional regulation; the function isindependent of the RNA helicase activity. Transcriptionalcoactivator for androgen receptor AR but probably not ESR1.Synergizes with DDX17 and SRA1 RNA to activate MYOD1transcriptional activity and involved in skeletal muscledifferentiation. Transcriptional coactivator for p53/TP53 andinvolved in p53/TP53 transcriptional response to DNA damage andp53/TP53-dependent apoptosis. Transcriptional coactivator forRUNX2 and involved in regulation of osteoblast differentiation.Acts as transcriptional repressor in a promoter-specific manner;Involved in the alternative regulation of pre-mRNAsplicing;the function probably involves association with histonedeacetylases, such as HDAC1. As component of a large PER complexis involved in the inhibition of 3' transcriptional termination ofcircadian target genes such as PER1 and NR1D1 and the control ofthe circadian rhythms. Nucleus, nucleolus{ECO:0000269|PubMed:10837141, ECO:0000269|PubMed:1996094}. alternative mRNA splicing, via spliceosome;androgen receptor signaling pathway;BMP signaling pathway;epithelial to mesenchymal transition;intracellular estrogen receptor signaling pathway;intrinsic apoptotic signaling pathway by p53 class mediator;mRNA splicing, via spliceosome;mRNA transcription;myoblast differentiation;negative regulation of transcription by RNA polymerase II;nuclear-transcribed mRNA catabolic process;positive regulation of DNA damage response, signal transduction by p53 class mediator;positive regulation of production of miRNAs involved in gene silencing by miRNA;pri-miRNA transcription by RNA polymerase II;regulation of alternative mRNA splicing, via spliceosome;regulation of androgen receptor signaling pathway;regulation of osteoblast differentiation;regulation of skeletal muscle cell differentiation;regulation of transcription by RNA polymerase II;regulation of viral genome replication;rhythmic process androgen receptor binding;ATP binding;ATP-dependent RNA helicase activity;calcium-dependent protein binding;calmodulin binding;enzyme binding;MH2 domain binding;mRNA 3'-UTR binding;pre-mRNA binding;primary miRNA binding;promoter-specific chromatin binding;ribonucleoprotein complex binding;RNA binding;RNA helicase activity;R-SMAD binding;SMAD binding catalytic step 2 spliceosome;extracellular exosome;membrane;nucleolus;nucleoplasm;nucleus;ribonucleoprotein complex Proteoglycans in cancer;Spliceosome;Transcriptional misregulation in cancer Estrogen-dependent gene expression;mRNA Splicing - Major Pathway;SUMOylation of transcription cofactors C complex spliceosome;CTNNB1-DDX5-HDGF complex;DGCR8 multiprotein complex;Large Drosha complex;snRNP-free U1A (SF-A) complex;Spliceosome