MASCOT Search Results
Protein View: A4_HUMAN
Amyloid beta A4 protein OS=Homo sapiens GN=APP PE=1 SV=3
ID A4_HUMAN Reviewed; 770 AA.
AC P05067; B2R5V1; B4DII8; D3DSD1; D3DSD2; D3DSD3; P09000; P78438;
AC Q13764; Q13778; Q13793; Q16011; Q16014; Q16019; Q16020; Q6GSC0;
AC Q8WZ99; Q9BT38; Q9UC33; Q9UCA9; Q9UCB6; Q9UCC8; Q9UCD1; Q9UQ58;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 3.
DT 09-JUL-2014, entry version 229.
DE RecName: Full=Amyloid beta A4 protein;
DE AltName: Full=ABPP;
DE AltName: Full=APPI;
DE Short=APP;
DE AltName: Full=Alzheimer disease amyloid protein;
DE AltName: Full=Cerebral vascular amyloid peptide;
DE Short=CVAP;
DE AltName: Full=PreA4;
DE AltName: Full=Protease nexin-II;
DE Short=PN-II;
DE Contains:
DE RecName: Full=N-APP;
DE Contains:
DE RecName: Full=Soluble APP-alpha;
DE Short=S-APP-alpha;
DE Contains:
DE RecName: Full=Soluble APP-beta;
DE Short=S-APP-beta;
DE Contains:
DE RecName: Full=C99;
DE Contains:
DE RecName: Full=Beta-amyloid protein 42;
DE AltName: Full=Beta-APP42;
DE Contains:
DE RecName: Full=Beta-amyloid protein 40;
DE AltName: Full=Beta-APP40;
DE Contains:
DE RecName: Full=C83;
DE Contains:
DE RecName: Full=P3(42);
DE Contains:
DE RecName: Full=P3(40);
DE Contains:
DE RecName: Full=C80;
DE Contains:
DE RecName: Full=Gamma-secretase C-terminal fragment 59;
DE AltName: Full=Amyloid intracellular domain 59;
DE Short=AICD-59;
DE Short=AID(59);
DE AltName: Full=Gamma-CTF(59);
DE Contains:
DE RecName: Full=Gamma-secretase C-terminal fragment 57;
DE AltName: Full=Amyloid intracellular domain 57;
DE Short=AICD-57;
DE Short=AID(57);
DE AltName: Full=Gamma-CTF(57);
DE Contains:
DE RecName: Full=Gamma-secretase C-terminal fragment 50;
DE AltName: Full=Amyloid intracellular domain 50;
DE Short=AICD-50;
DE Short=AID(50);
DE AltName: Full=Gamma-CTF(50);
DE Contains:
DE RecName: Full=C31;
DE Flags: Precursor;
GN Name=APP; Synonyms=A4, AD1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
RC TISSUE=Brain;
RX PubMed=2881207; DOI=10.1038/325733a0;
RA Kang J., Lemaire H.-G., Unterbeck A., Salbaum J.M., Masters C.L.,
RA Grzeschik K.-H., Multhaup G., Beyreuther K., Mueller-Hill B.;
RT "The precursor of Alzheimer's disease amyloid A4 protein resembles a
RT cell-surface receptor.";
RL Nature 325:733-736(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
RC TISSUE=Brain;
RX PubMed=2893289; DOI=10.1038/331525a0;
RA Ponte P., Gonzalez-Dewhitt P., Schilling J., Miller J., Hsu D.,
RA Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F.,
RA Cordell B.;
RT "A new A4 amyloid mRNA contains a domain homologous to serine
RT proteinase inhibitors.";
RL Nature 331:525-527(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP695).
RX PubMed=2783775; DOI=10.1093/nar/17.2.517;
RA Lemaire H.-G., Salbaum J.M., Multhaup G., Kang J., Bayney R.M.,
RA Unterbeck A., Beyreuther K., Mueller-Hill B.;
RT "The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is
RT encoded by 16 exons.";
RL Nucleic Acids Res. 17:517-522(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
RX PubMed=2110105; DOI=10.1016/0378-1119(90)90310-N;
RA Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.;
RT "Genomic organization of the human amyloid beta-protein precursor
RT gene.";
RL Gene 87:257-263(1990).
RN [5]
RP ERRATUM.
RX PubMed=1908403; DOI=10.1016/0378-1119(91)90093-Q;
RA Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.;
RL Gene 102:291-292(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L-APP733).
RC TISSUE=Leukocyte;
RX PubMed=1587857;
RA Koenig G., Moenning U., Czech C., Prior R., Banati R.,
RA Schreiter-Gasser U., Bauer J., Masters C.L., Beyreuther K.;
RT "Identification and differential expression of a novel alternative
RT splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in
RT leukocytes and brain microglial cells.";
RL J. Biol. Chem. 267:10804-10809(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
RX PubMed=9108164; DOI=10.1093/nar/25.9.1802;
RA Hattori M., Tsukahara F., Furuhata Y., Tanahashi H., Hirose M.,
RA Saito M., Tsukuni S., Sakaki Y.;
RT "A novel method for making nested deletions and its application for
RT sequencing of a 300 kb region of human APP locus.";
RL Nucleic Acids Res. 25:1802-1808(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP639), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12859342; DOI=10.1046/j.1460-9568.2003.02731.x;
RA Tang K., Wang C., Shen C., Sheng S., Ravid R., Jing N.;
RT "Identification of a novel alternative splicing isoform of human
RT amyloid precursor protein gene, APP639.";
RL Eur. J. Neurosci. 18:102-108(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP770 AND 11).
RC TISSUE=Cerebellum, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-501.
RG NIEHS SNPs program;
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T.,
RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP305 AND APP751).
RC TISSUE=Eye, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-10.
RC TISSUE=Liver;
RX PubMed=3140222; DOI=10.1093/nar/16.19.9351;
RA Schon E.A., Mita S., Sadlock J., Herbert J.;
RT "A cDNA specifying the human amyloid beta precursor protein (ABPP)
RT encodes a 95-kDa polypeptide.";
RL Nucleic Acids Res. 16:9351-9351(1988).
RN [15]
RP ERRATUM, AND SEQUENCE REVISION.
RA Schon E.A., Mita S., Sadlock J., Herbert J.;
RL Nucleic Acids Res. 16:11402-11402(1988).
RN [16]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75.
RX PubMed=2538123; DOI=10.1016/0006-291X(89)92437-6;
RA La Fauci G., Lahiri D.K., Salton S.R., Robakis N.K.;
RT "Characterization of the 5'-end region and the first two exons of the
RT beta-protein precursor gene.";
RL Biochem. Biophys. Res. Commun. 159:297-304(1989).
RN [17]
RP PROTEIN SEQUENCE OF 18-50.
RC TISSUE=Fibroblast;
RX PubMed=3597385;
RA van Nostrand W.E., Cunningham D.D.;
RT "Purification of protease nexin II from human fibroblasts.";
RL J. Biol. Chem. 262:8508-8514(1987).
RN [18]
RP PROTEIN SEQUENCE OF 18-40.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [19]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 286-366.
RX PubMed=2893290; DOI=10.1038/331528a0;
RA Tanzi R.E., McClatchey A.I., Lamperti E.D., Villa-Komaroff L.,
RA Gusella J.F., Neve R.L.;
RT "Protease inhibitor domain encoded by an amyloid protein precursor
RT mRNA associated with Alzheimer's disease.";
RL Nature 331:528-530(1988).
RN [20]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 287-367.
RX PubMed=2893291; DOI=10.1038/331530a0;
RA Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H.;
RT "Novel precursor of Alzheimer's disease amyloid protein shows protease
RT inhibitory activity.";
RL Nature 331:530-532(1988).
RN [21]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 507-770.
RC TISSUE=Brain cortex;
RX PubMed=2893379; DOI=10.1073/pnas.85.3.929;
RA Zain S.B., Salim M., Chou W.G., Sajdel-Sulkowska E.M., Majocha R.E.,
RA Marotta C.A.;
RT "Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer
RT disease brain: coding and noncoding regions of the fetal precursor
RT mRNA are expressed in the cortex.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:929-933(1988).
RN [22]
RP PROTEIN SEQUENCE OF 523-555, AND DOMAIN COLLAGEN-BINDING.
RX PubMed=8576160; DOI=10.1074/jbc.271.3.1613;
RA Beher D., Hesse L., Masters C.L., Multhaup G.;
RT "Regulation of amyloid protein precursor (APP) binding to collagen and
RT mapping of the binding sites on APP and collagen type I.";
RL J. Biol. Chem. 271:1613-1620(1996).
RN [23]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 655-737, AND VARIANTS AD1 GLY-717;
RP ILE-717 AND PHE-717.
RX PubMed=8476439; DOI=10.1006/bbrc.1993.1386;
RA Denman R.B., Rosenzcwaig R., Miller D.L.;
RT "A system for studying the effect(s) of familial Alzheimer disease
RT mutations on the processing of the beta-amyloid peptide precursor.";
RL Biochem. Biophys. Res. Commun. 192:96-103(1993).
RN [24]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 656-737.
RX PubMed=2675837; DOI=10.1016/0006-291X(89)91112-1;
RA Johnstone E.M., Chaney M.O., Moore R.E., Ward K.E., Norris F.H.,
RA Little S.P.;
RT "Alzheimer's disease amyloid peptide is encoded by two exons and shows
RT similarity to soybean trypsin inhibitor.";
RL Biochem. Biophys. Res. Commun. 163:1248-1255(1989).
RN [25]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 672-723, AND VARIANT AD1 ASN-678.
RX PubMed=15201367; DOI=10.1136/jnnp.2003.010611;
RA Wakutani Y., Watanabe K., Adachi Y., Wada-Isoe K., Urakami K.,
RA Ninomiya H., Saido T.C., Hashimoto T., Iwatsubo T., Nakashima K.;
RT "Novel amyloid precursor protein gene missense mutation (D678N) in
RT probable familial Alzheimer's disease.";
RL J. Neurol. Neurosurg. Psych. 75:1039-1042(2004).
RN [26]
RP PROTEIN SEQUENCE OF 672-713.
RC TISSUE=Blood vessel;
RX PubMed=8248178; DOI=10.1073/pnas.90.22.10836;
RA Roher A.E., Lowenson J.D., Clarke S., Woods A.S., Cotter R.J.,
RA Gowing E., Ball M.J.;
RT "Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid
RT deposits: implications for the pathology of Alzheimer disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10836-10840(1993).
RN [27]
RP PROTEIN SEQUENCE OF 672-704, AND TISSUE SPECIFICITY.
RX PubMed=1406936; DOI=10.1038/359325a0;
RA Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D.,
RA Sinha S., Schlossmacher M., Whaley J., Swindlehurst C.;
RT "Isolation and quantification of soluble Alzheimer's beta-peptide from
RT biological fluids.";
RL Nature 359:325-327(1992).
RN [28]
RP PROTEIN SEQUENCE OF 672-701 AND 707-713.
RX PubMed=8109908; DOI=10.1002/ana.410350223;
RA Wisniewski T., Lalowski M., Levy E., Marques M.R.F., Frangione B.;
RT "The amino acid sequence of neuritic plaque amyloid from a familial
RT Alzheimer's disease patient.";
RL Ann. Neurol. 35:245-246(1994).
RN [29]
RP PROTEIN SEQUENCE OF 672-701.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=8229004; DOI=10.1111/j.1471-4159.1993.tb09841.x;
RA Vigo-Pelfrey C., Lee D., Keim P., Lieberburg I., Schenk D.B.;
RT "Characterization of beta-amyloid peptide from human cerebrospinal
RT fluid.";
RL J. Neurochem. 61:1965-1968(1993).
RN [30]
RP PROTEIN SEQUENCE OF 672-681.
RC TISSUE=Brain cortex;
RX PubMed=3312495; DOI=10.1111/j.1471-4159.1987.tb01005.x;
RA Pardridge W.M., Vinters H.V., Yang J., Eisenberg J., Choi T.B.,
RA Tourtellotte W.W., Huebner V., Shively J.E.;
RT "Amyloid angiopathy of Alzheimer's disease: amino acid composition and
RT partial sequence of a 4,200-dalton peptide isolated from cortical
RT microvessels.";
RL J. Neurochem. 49:1394-1401(1987).
RN [31]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 674-770.
RC TISSUE=Brain;
RX PubMed=3810169; DOI=10.1126/science.3810169;
RA Goldgaber D., Lerman M.I., McBride O.W., Saffiotti U., Gajdusek D.C.;
RT "Characterization and chromosomal localization of a cDNA encoding
RT brain amyloid of Alzheimer's disease.";
RL Science 235:877-880(1987).
RN [32]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 674-703.
RC TISSUE=Fetal brain;
RX PubMed=2949367; DOI=10.1126/science.2949367;
RA Tanzi R.E., Gusella J.F., Watkins P.C., Bruns G.A.,
RA St George-Hyslop P.H., Van Keuren M.L., Patterson D., Pagan S.,
RA Kurnit D.M., Neve R.L.;
RT "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic
RT linkage near the Alzheimer locus.";
RL Science 235:880-884(1987).
RN [33]
RP PROTEIN SEQUENCE OF 609-713, AND GLYCOSYLATION AT SER-614; SER-623;
RP SER-628; SER-679 AND SER-697.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=22576872; DOI=10.1002/jms.2987;
RA Brinkmalm G., Portelius E., Ohrfelt A., Mattsson N., Persson R.,
RA Gustavsson M.K., Vite C.H., Gobom J., Mansson J.E., Nilsson J.,
RA Halim A., Larson G., Ruetschi U., Zetterberg H., Blennow K.,
RA Brinkmalm A.;
RT "An online nano-LC-ESI-FTICR-MS method for comprehensive
RT characterization of endogenous fragments from amyloid beta and amyloid
RT precursor protein in human and cat cerebrospinal fluid.";
RL J. Mass Spectrom. 47:591-603(2012).
RN [34]
RP PROTEIN SEQUENCE OF 691-698, AND CLEAVAGE BY THETA-SECRETASE.
RX PubMed=16816112; DOI=10.1096/fj.05-5632com;
RA Sun X., He G., Song W.;
RT "BACE2, as a novel APP theta-secretase, is not responsible for the
RT pathogenesis of Alzheimer's disease in Down syndrome.";
RL FASEB J. 20:1369-1376(2006).
RN [35]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
RC TISSUE=Brain;
RX PubMed=2569763; DOI=10.1126/science.2569763;
RA de Sauvage F., Octave J.-N.;
RT "A novel mRNA of the A4 amyloid precursor gene coding for a possibly
RT secreted protein.";
RL Science 245:651-653(1989).
RN [36]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
RC TISSUE=Brain;
RX PubMed=3035574; DOI=10.1073/pnas.84.12.4190;
RA Robakis N.K., Ramakrishna N., Wolfe G., Wisniewski H.M.;
RT "Molecular cloning and characterization of a cDNA encoding the
RT cerebrovascular and the neuritic plaque amyloid peptides.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:4190-4194(1987).
RN [37]
RP CHARACTERIZATION OF L-APP733, AND MUTAGENESIS OF SER-656.
RX PubMed=7737970; DOI=10.1074/jbc.270.18.10388;
RA Pangalos M.N., Efthimiopoulos S., Shioi J., Robakis N.K.;
RT "The chondroitin sulfate attachment site of appican is formed by
RT splicing out exon 15 of the amyloid precursor gene.";
RL J. Biol. Chem. 270:10388-10391(1995).
RN [38]
RP FUNCTION OF BETA-AMYLOID PEPTIDE AS LIPID PEROXIDATION INHIBITOR, AND
RP MUTAGENESIS OF MET-706.
RX PubMed=9168929; DOI=10.1006/bbrc.1997.6547;
RA Walter M.F., Mason P.E., Mason R.P.;
RT "Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid
RT peroxidation as a result of its membrane interactions.";
RL Biochem. Biophys. Res. Commun. 233:760-764(1997).
RN [39]
RP REVIEW ON FUNCTION OF BETA-AMYLOID AS ANTIOXIDANT.
RX PubMed=11775062; DOI=10.1023/A:1012629603390;
RA Kontush A.;
RT "Alzheimer's amyloid-beta as a preventive antioxidant for brain
RT lipoproteins.";
RL Cell. Mol. Neurobiol. 21:299-315(2001).
RN [40]
RP IDENTITY OF APP WITH NEXIN-II.
RX PubMed=2506449; DOI=10.1038/341144a0;
RA Oltersdorf T., Fritz L.C., Schenk D.B., Lieberburg I.,
RA Johnson-Wood K.L., Beattie E.C., Ward P.J., Blacher R.W., Dovey H.F.,
RA Sinha S.;
RT "The secreted form of the Alzheimer's amyloid precursor protein with
RT the Kunitz domain is protease nexin-II.";
RL Nature 341:144-147(1989).
RN [41]
RP PROTEASE-SPECIFICITY OF INHIBITOR DOMAIN.
RX PubMed=1969731; DOI=10.1016/0006-291X(90)92084-D;
RA Kido H., Fukutomi A., Schilling J., Wang Y., Cordell B., Katunuma N.;
RT "Protease-specificity of Kunitz inhibitor domain of Alzheimer's
RT disease amyloid protein precursor.";
RL Biochem. Biophys. Res. Commun. 167:716-721(1990).
RN [42]
RP EXTRACELLULAR ZINC-BINDING DOMAIN.
RX PubMed=8344894;
RA Bush A.I., Multhaup G., Moir R.D., Williamson T.G., Small D.H.,
RA Rumble B., Pollwein P., Beyreuther K., Masters C.L.;
RT "A novel zinc(II) binding site modulates the function of the beta A4
RT amyloid protein precursor of Alzheimer's disease.";
RL J. Biol. Chem. 268:16109-16112(1993).
RN [43]
RP INTERACTION WITH G(O).
RX PubMed=8446172; DOI=10.1038/362075a0;
RA Nishimoto I., Okamoto T., Matsuura Y., Takahashi S., Okamoto T.,
RA Murayama Y., Ogata E.;
RT "Alzheimer amyloid protein precursor complexes with brain GTP-binding
RT protein G(o).";
RL Nature 362:75-79(1993).
RN [44]
RP EXTRACELLULAR COPPER-BINDING DOMAIN, AND MUTAGENESIS OF HIS-137;
RP MET-141; CYS-144; HIS-147 AND HIS-151.
RX PubMed=7913895; DOI=10.1016/0014-5793(94)00658-X;
RA Hesse L., Beher D., Masters C.L., Multhaup G.;
RT "The beta A4 amyloid precursor protein binding to copper.";
RL FEBS Lett. 349:109-116(1994).
RN [45]
RP N-TERMINAL HEPARIN-BINDING DOMAIN, AND MUTAGENESIS OF 99-LYS--ARG-102.
RX PubMed=8158260;
RA Small D.H., Nurcombe V., Reed G., Clarris H., Moir R., Beyreuther K.,
RA Masters C.L.;
RT "A heparin-binding domain in the amyloid protein precursor of
RT Alzheimer's disease is involved in the regulation of neurite
RT outgrowth.";
RL J. Neurosci. 14:2117-2127(1994).
RN [46]
RP MUTAGENESIS OF VAL-717.
RX PubMed=8886002; DOI=10.1006/bbrc.1996.1577;
RA Maruyama K., Tomita T., Shinozaki K., Kume H., Asada H., Saido T.C.,
RA Ishiura S., Iwatsubo T., Obata K.;
RT "Familial Alzheimer's disease-linked mutations at Val717 of amyloid
RT precursor protein are specific for the increased secretion of A beta
RT 42(43).";
RL Biochem. Biophys. Res. Commun. 227:730-735(1996).
RN [47]
RP INTERACTION WITH APP-BP1.
RX PubMed=8626687; DOI=10.1074/jbc.271.19.11339;
RA Chow N., Korenberg J.R., Chen X.-N., Neve R.L.;
RT "APP-BP1, a novel protein that binds to the carboxyl-terminal region
RT of the amyloid precursor protein.";
RL J. Biol. Chem. 271:11339-11346(1996).
RN [48]
RP INTERACTION WITH APBA1 AND APBB1, AND MUTAGENESIS OF TYR-728; TYR-757;
RP ASN-759 AND TYR-762.
RX PubMed=8887653;
RA Borg J.-P., Ooi J., Levy E., Margolis B.;
RT "The phosphotyrosine interaction domains of X11 and FE65 bind to
RT distinct sites on the YENPTY motif of amyloid precursor protein.";
RL Mol. Cell. Biol. 16:6229-6241(1996).
RN [49]
RP INTERACTION WITH APBB2.
RX PubMed=8855266; DOI=10.1073/pnas.93.20.10832;
RA Guenette S.Y., Chen J., Jondro P.D., Tanzi R.E.;
RT "Association of a novel human FE65-like protein with the cytoplasmic
RT domain of the beta-amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10832-10837(1996).
RN [50]
RP HEPARIN-BINDING DOMAINS.
RX PubMed=9357988; DOI=10.1016/S0014-5793(97)01146-0;
RA Mok S.S., Sberna G., Heffernan D., Cappai R., Galatis D.,
RA Clarris H.J., Sawyer W.H., Beyreuther K., Masters C.L., Small D.H.;
RT "Expression and analysis of heparin-binding regions of the amyloid
RT precursor protein of Alzheimer's disease.";
RL FEBS Lett. 415:303-307(1997).
RN [51]
RP INTERACTION OF BETA-AMYLOID PEPTIDE WITH HADH2.
RC TISSUE=Brain;
RX PubMed=9338779; DOI=10.1038/39522;
RA Yan S.D., Fu J., Soto C., Chen X., Zhu H., Al-Mohanna F.,
RA Collinson K., Zhu A., Stern E., Saido T., Tohyama M., Ogawa S.,
RA Roher A., Stern D.;
RT "An intracellular protein that binds amyloid-beta peptide and mediates
RT neurotoxicity in Alzheimer's disease.";
RL Nature 389:689-695(1997).
RN [52]
RP INTERACTION WITH APPBP2, AND MUTAGENESIS OF TYR-728.
RX PubMed=9843960; DOI=10.1073/pnas.95.25.14745;
RA Zheng P., Eastman J., Vande Pol S., Pimplikar S.W.;
RT "PAT1, a microtubule-interacting protein, recognizes the basolateral
RT sorting signal of amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14745-14750(1998).
RN [53]
RP BETA-AMYLOID ZINC-BINDING, AND MUTAGENESIS OF ARG-676; TYR-681 AND
RP HIS-684.
RX PubMed=10413512; DOI=10.1021/bi990205o;
RA Liu S.T., Howlett G., Barrow C.J.;
RT "Histidine-13 is a crucial residue in the zinc ion-induced aggregation
RT of the A beta peptide of Alzheimer's disease.";
RL Biochemistry 38:9373-9378(1999).
RN [54]
RP IMPORTANCE OF MET-706 IN FREE RADICAL OXIDATIVE STRESS, AND
RP MUTAGENESIS OF MET-706.
RX PubMed=10535332; DOI=10.1016/S0361-9230(99)00093-3;
RA Varadarajan S., Yatin S., Kanski J., Jahanshahi F., Butterfield D.A.;
RT "Methionine residue 35 is important in amyloid beta-peptide-associated
RT free radical oxidative stress.";
RL Brain Res. Bull. 50:133-141(1999).
RN [55]
RP INTERACTION WITH APBA2.
RX PubMed=9890987; DOI=10.1074/jbc.274.4.2243;
RA Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y.,
RA Sakiyama S., Kirino Y., Suzuki T.;
RT "Interaction of a neuron-specific protein containing PDZ domains with
RT Alzheimer's amyloid precursor protein.";
RL J. Biol. Chem. 274:2243-2254(1999).
RN [56]
RP ENDOCYTOSIS SIGNAL, AND MUTAGENESIS OF TYR-728; GLY-756; TYR-757;
RP ASN-759; PRO-760 AND TYR-762.
RX PubMed=10383380; DOI=10.1074/jbc.274.27.18851;
RA Perez R.G., Soriano S., Hayes J.D., Ostaszewski B., Xia W.,
RA Selkoe D.J., Chen X., Stokin G.B., Koo E.H.;
RT "Mutagenesis identifies new signals for beta-amyloid precursor protein
RT endocytosis, turnover, and the generation of secreted fragments,
RT including Abeta42.";
RL J. Biol. Chem. 274:18851-18856(1999).
RN [57]
RP IMPORTANCE OF CYS-144 IN COPPER REDUCTION, AND MUTAGENESIS OF CYS-144
RP AND 147-HIS--HIS-149.
RX PubMed=10461923; DOI=10.1046/j.1471-4159.1999.0731288.x;
RA Ruiz F.H., Gonzalez M., Bodini M., Opazo C., Inestrosa N.C.;
RT "Cysteine 144 is a key residue in the copper reduction by the beta-
RT amyloid precursor protein.";
RL J. Neurochem. 73:1288-1292(1999).
RN [58]
RP INTERACTION OF BETA-AMYLOID WITH APOE.
RX PubMed=10816430; DOI=10.1042/0264-6021:3480359;
RA Tokuda T., Calero M., Matsubara E., Vidal R., Kumar A., Permanne B.,
RA Zlokovic B., Smith J.D., Ladu M.J., Rostagno A., Frangione B.,
RA Ghiso J.;
RT "Lipidation of apolipoprotein E influences its isoform-specific
RT interaction with Alzheimer's amyloid beta peptides.";
RL Biochem. J. 348:359-365(2000).
RN [59]
RP INTERACTION OF BETA-APP42 WITH CHRNA7.
RX PubMed=10681545; DOI=10.1074/jbc.275.8.5626;
RA Wang H.-Y., Lee D.H.S., D'Andrea M.R., Peterson P.A., Shank R.P.,
RA Reitz A.B.;
RT "Beta-amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor
RT with high affinity. Implications for Alzheimer's disease pathology.";
RL J. Biol. Chem. 275:5626-5632(2000).
RN [60]
RP IDENTIFICATION OF GAMMA-CTFS BY MASS SPECTROMETRY, AND MUTAGENESIS OF
RP ASP-739.
RX PubMed=12214090;
RA Passer B., Pellegrini L., Russo C., Siegel R.M., Lenardo M.J.,
RA Schettini G., Bachmann M., Tabaton M., D'Adamio L.;
RT "Generation of an apoptotic intracellular peptide by gamma-secretase
RT cleavage of Alzheimer's amyloid beta protein precursor.";
RL J. Alzheimers Dis. 2:289-301(2000).
RN [61]
RP INTERACTION WITH FPRL1.
RX PubMed=11689470; DOI=10.1096/fj.01-0251com;
RA Yazawa H., Yu Z.-X., Takeda K., Le Y., Gong W., Ferrans V.J.,
RA Oppenheim J.J., Li C.C.H., Wang J.M.;
RT "Beta amyloid peptide (Abeta42) is internalized via the G-protein-
RT coupled receptor FPRL1 and forms fibrillar aggregates in
RT macrophages.";
RL FASEB J. 15:2454-2462(2001).
RN [62]
RP INTERACTION WITH BBP.
RX PubMed=11278849; DOI=10.1074/jbc.M011161200;
RA Kajkowski E.M., Lo C.F., Ning X., Walker S., Sofia H.J., Wang W.,
RA Edris W., Chanda P., Wagner E., Vile S., Ryan K., McHendry-Rinde B.,
RA Smith S.C., Wood A., Rhodes K.J., Kennedy J.D., Bard J.,
RA Jacobsen J.S., Ozenberger B.A.;
RT "Beta-amyloid peptide-induced apoptosis regulated by a novel protein
RT containing a G protein activation module.";
RL J. Biol. Chem. 276:18748-18756(2001).
RN [63]
RP BETA-AMYLOID COPPER AND ZINC-BINDING.
RX PubMed=11274207; DOI=10.1074/jbc.M100175200;
RA Curtain C.C., Ali F., Volitakis I., Cherny R.A., Norton R.S.,
RA Beyreuther K., Barrow C.J., Masters C.L., Bush A.I., Barnham K.J.;
RT "Alzheimer's disease amyloid-beta binds copper and zinc to generate an
RT allosterically ordered structure containing superoxide dismutase-like
RT subunits.";
RL J. Biol. Chem. 276:20466-20473(2001).
RN [64]
RP SUBUNIT.
RX PubMed=11438549; DOI=10.1074/jbc.M105410200;
RA Scheuermann S., Hambsch B., Hesse L., Stumm J., Schmidt C., Beher D.,
RA Bayer T.A., Beyreuther K., Multhaup G.;
RT "Homodimerization of amyloid precursor protein and its implication in
RT the amyloidogenic pathway of Alzheimer's disease.";
RL J. Biol. Chem. 276:33923-33929(2001).
RN [65]
RP INTERACTION WITH APBB1, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11544248; DOI=10.1074/jbc.C100447200;
RA Kimberly W.T., Zheng J.B., Guenette S.Y., Selkoe D.J.;
RT "The intracellular domain of the beta-amyloid precursor protein is
RT stabilized by Fe65 and translocates to the nucleus in a notch-like
RT manner.";
RL J. Biol. Chem. 276:40288-40292(2001).
RN [66]
RP INTERACTION WITH FBLN1.
RX PubMed=11238726; DOI=10.1046/j.1471-4159.2001.00144.x;
RA Ohsawa I., Takamura C., Kohsaka S.;
RT "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor
RT protein and modulates its physiological function.";
RL J. Neurochem. 76:1411-1420(2001).
RN [67]
RP INTERACTION WITH MAPT, AND FUNCTION.
RX PubMed=11943163; DOI=10.1016/S0014-5793(02)02376-1;
RA Rank K.B., Pauley A.M., Bhattacharya K., Wang Z., Evans D.B.,
RA Fleck T.J., Johnston J.A., Sharma S.K.;
RT "Direct interaction of soluble human recombinant tau protein with
RT Abeta 1-42 results in tau aggregation and hyperphosphorylation by tau
RT protein kinase II.";
RL FEBS Lett. 514:263-268(2002).
RN [68]
RP INTERACTION WITH MAPK8IP1, AND MUTAGENESIS OF TYR-757.
RX PubMed=11724784; DOI=10.1074/jbc.M108357200;
RA Scheinfeld M.H., Roncarati R., Vito P., Lopez P.A., Abdallah M.,
RA D'Adamio L.;
RT "Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the
RT cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein
RT (APP).";
RL J. Biol. Chem. 277:3767-3775(2002).
RN [69]
RP COPPER-MEDIATED LIPID PEROXIDATION, AND MUTAGENESIS OF HIS-147 AND
RP HIS-151.
RX PubMed=11784781;
RA White A.R., Multhaup G., Galatis D., McKinstry W.J., Parker M.W.,
RA Pipkorn R., Beyreuther K., Masters C.L., Cappai R.;
RT "Contrasting species-dependent modulation of copper-mediated
RT neurotoxicity by the Alzheimer's disease amyloid precursor protein.";
RL J. Neurosci. 22:365-376(2002).
RN [70]
RP REVIEW ON ZINC-BINDING.
RX PubMed=12032279; DOI=10.1073/pnas.122249699;
RA Bush A.I., Tanzi R.E.;
RT "The galvanization of beta-amyloid in Alzheimer's disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7317-7319(2002).
RN [71]
RP SUBCELLULAR LOCATION, AND ASSOCIATION OF AMYLOID FIBRILS WITH GCP1.
RX PubMed=15084524; DOI=10.1096/fj.03-1040fje;
RA Watanabe N., Araki W., Chui D.H., Makifuchi T., Ihara Y., Tabira T.;
RT "Glypican-1 as an Abeta binding HSPG in the human brain: its
RT localization in DIG domains and possible roles in the pathogenesis of
RT Alzheimer's disease.";
RL FASEB J. 18:1013-1015(2004).
RN [72]
RP INTERACTION WITH ANKS1B.
RX PubMed=15347684; DOI=10.1074/jbc.M405329200;
RA Ghersi E., Noviello C., D'Adamio L.;
RT "Amyloid-beta protein precursor (AbetaPP) intracellular domain-
RT associated protein-1 proteins bind to AbetaPP and modulate its
RT processing in an isoform-specific manner.";
RL J. Biol. Chem. 279:49105-49112(2004).
RN [73]
RP PHOSPHORYLATION AT THR-743.
RX PubMed=8131745;
RA Suzuki T., Oishi M., Marshak D.R., Czernik A.J., Nairn A.C.,
RA Greengard P.;
RT "Cell cycle-dependent regulation of the phosphorylation and metabolism
RT of the Alzheimer amyloid precursor protein.";
RL EMBO J. 13:1114-1122(1994).
RN [74]
RP PHOSPHORYLATION AT SER-198 AND SER-206 BY CASEIN KINASES, AND
RP MUTAGENESIS OF SER-198 AND SER-206.
RX PubMed=8999878; DOI=10.1074/jbc.272.3.1896;
RA Walter J., Capell A., Hung A.Y., Langen H., Schnoelzer M.,
RA Thinakaran G., Sisodia S.S., Selkoe D.J., Haass C.;
RT "Ectodomain phosphorylation of beta-amyloid precursor protein at two
RT distinct cellular locations.";
RL J. Biol. Chem. 272:1896-1903(1997).
RN [75]
RP COPPER-BINDING, AND DISULFIDE BOND FORMATION.
RX PubMed=9585534; DOI=10.1021/bi980022m;
RA Multhaup G., Ruppert T., Schlicksupp A., Hesse L., Bill E.,
RA Pipkorn R., Masters C.L., Beyreuther K.;
RT "Copper-binding amyloid precursor protein undergoes a site-specific
RT fragmentation in the reduction of hydrogen peroxide.";
RL Biochemistry 37:7224-7230(1998).
RN [76]
RP CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-739.
RX PubMed=10319819; DOI=10.1016/S0092-8674(00)80748-5;
RA Gervais F.G., Xu D., Robertson G.S., Vaillancourt J.P., Zhu Y.,
RA Huang J., LeBlanc A., Smith D., Rigby M., Shearman M.S., Clarke E.E.,
RA Zheng H., van der Ploeg L.H.T., Ruffolo S.C., Thornberry N.A.,
RA Xanthoudakis S., Zamboni R.J., Roy S., Nicholson D.W.;
RT "Involvement of caspases in proteolytic cleavage of Alzheimer's
RT amyloid-beta precursor protein and amyloidogenic A beta peptide
RT formation.";
RL Cell 97:395-406(1999).
RN [77]
RP PHOSPHORYLATION, AND MUTAGENESIS OF THR-743.
RX PubMed=10341243;
RA Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C.,
RA Kirino Y., Greengard P., Suzuki T.;
RT "Role of phosphorylation of Alzheimer's amyloid precursor protein
RT during neuronal differentiation.";
RL J. Neurosci. 19:4421-4427(1999).
RN [78]
RP CHARACTERIZATION OF CASEIN KINASE PHOSPHORYLATION, AND MUTAGENESIS OF
RP SER-198 AND SER-206.
RX PubMed=10806211; DOI=10.1074/jbc.M002850200;
RA Walter J., Schindzielorz A., Hartung B., Haass C.;
RT "Phosphorylation of the beta-amyloid precursor protein at the cell
RT surface by ectocasein kinases 1 and 2.";
RL J. Biol. Chem. 275:23523-23529(2000).
RN [79]
RP CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-739.
RX PubMed=10742146; DOI=10.1038/74656;
RA Lu D.C., Rabizadeh S., Chandra S., Shayya R.F., Ellerby L.M., Ye X.,
RA Salvesen G.S., Koo E.H., Bredesen D.E.;
RT "A second cytotoxic proteolytic peptide derived from amyloid beta-
RT protein precursor.";
RL Nat. Med. 6:397-404(2000).
RN [80]
RP PHOSPHORYLATION, INTERACTION WITH APBB1, AND MUTAGENESIS OF THR-743.
RX PubMed=11517218; DOI=10.1074/jbc.M104059200;
RA Ando K., Iijima K., Elliott J.I., Kirino Y., Suzuki T.;
RT "Phosphorylation-dependent regulation of the interaction of amyloid
RT precursor protein with Fe65 affects the production of beta-amyloid.";
RL J. Biol. Chem. 276:40353-40361(2001).
RN [81]
RP PHOSPHORYLATION BY MAPK10, AND MUTAGENESIS OF THR-743.
RX PubMed=11146006; DOI=10.1046/j.1471-4159.2001.00102.x;
RA Standen C.L., Brownlees J., Grierson A.J., Kesavapany S., Lau K.-F.,
RA McLoughlin D.M., Miller C.C.J.;
RT "Phosphorylation of thr(668) in the cytoplasmic domain of the
RT Alzheimer's disease amyloid precursor protein by stress-activated
RT protein kinase 1b (Jun N-terminal kinase-3).";
RL J. Neurochem. 76:316-320(2001).
RN [82]
RP CLEAVAGE AT LEU-720.
RX PubMed=11851430; DOI=10.1021/bi015794o;
RA Weidemann A., Eggert S., Reinhard F.B.M., Vogel M., Paliga K.,
RA Baier G., Masters C.L., Beyreuther K., Evin G.;
RT "A novel epsilon-cleavage within the transmembrane domain of the
RT Alzheimer amyloid precursor protein demonstrates homology with Notch
RT processing.";
RL Biochemistry 41:2825-2835(2002).
RN [83]
RP PHOSPHORYLATION AT TYR-757, INTERACTION WITH SHC1, AND MUTAGENESIS OF
RP THR-743 AND TYR-757.
RX PubMed=11877420; DOI=10.1074/jbc.M110286200;
RA Tarr P.E., Roncarati R., Pelicci G., Pelicci P.G., D'Adamio L.;
RT "Tyrosine phosphorylation of the beta-amyloid precursor protein
RT cytoplasmic tail promotes interaction with Shc.";
RL J. Biol. Chem. 277:16798-16804(2002).
RN [84]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-542.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [85]
RP SIGNAL SEQUENCE CLEAVAGE SITE, AND TOPOLOGY.
RX PubMed=2900137;
RA Dyrks T., Weidemann A., Multhaup G., Salbaum J.M., Lemaire H.-G.,
RA Kang J., Mueller-Hill B., Masters C.L., Beyreuther K.;
RT "Identification, transmembrane orientation and biogenesis of the
RT amyloid A4 precursor of Alzheimer's disease.";
RL EMBO J. 7:949-957(1988).
RN [86]
RP REVIEW.
RX PubMed=12142279; DOI=10.1146/annurev.cellbio.18.020402.142302;
RA Annaert W., De Strooper B.;
RT "A cell biological perspective on Alzheimer's disease.";
RL Annu. Rev. Cell Dev. Biol. 18:25-51(2002).
RN [87]
RP INTERACTION WITH SORL1, AND SUBCELLULAR LOCATION.
RX PubMed=16174740; DOI=10.1073/pnas.0503689102;
RA Andersen O.M., Reiche J., Schmidt V., Gotthardt M., Spoelgen R.,
RA Behlke J., von Arnim C.A., Breiderhoff T., Jansen P., Wu X.,
RA Bales K.R., Cappai R., Masters C.L., Gliemann J., Mufson E.J.,
RA Hyman B.T., Paul S.M., Nykjaer A., Willnow T.E.;
RT "Neuronal sorting protein-related receptor sorLA/LR11 regulates
RT processing of the amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005).
RN [88]
RP INTERACTION WITH APBB1.
RX PubMed=18468999; DOI=10.1074/jbc.M801827200;
RA Nakaya T., Kawai T., Suzuki T.;
RT "Regulation of FE65 nuclear translocation and function by amyloid
RT beta-protein precursor in osmotically stressed cells.";
RL J. Biol. Chem. 283:19119-19131(2008).
RN [89]
RP INTERACTION WITH ITM2C.
RX PubMed=19366692; DOI=10.1074/jbc.M109.006403;
RA Matsuda S., Matsuda Y., D'Adamio L.;
RT "BRI3 inhibits amyloid precursor protein processing in a
RT mechanistically distinct manner from its homologue dementia gene
RT BRI2.";
RL J. Biol. Chem. 284:15815-15825(2009).
RN [90]
RP FUNCTION, CLEAVAGE, AND INTERACTION WITH TNFRSF21.
RX PubMed=19225519; DOI=10.1038/nature07767;
RA Nikolaev A., McLaughlin T., O'Leary D.D.M., Tessier-Lavigne M.;
RT "APP binds DR6 to trigger axon pruning and neuron death via distinct
RT caspases.";
RL Nature 457:981-989(2009).
RN [91]
RP FUNCTION, AND INTERACTION WITH AGER.
RX PubMed=19901339; DOI=10.1073/pnas.0905686106;
RA Takuma K., Fang F., Zhang W., Yan S., Fukuzaki E., Du H., Sosunov A.,
RA McKhann G., Funatsu Y., Nakamichi N., Nagai T., Mizoguchi H., Ibi D.,
RA Hori O., Ogawa S., Stern D.M., Yamada K., Yan S.S.;
RT "RAGE-mediated signaling contributes to intraneuronal transport of
RT amyloid-{beta} and neuronal dysfunction.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:20021-20026(2009).
RN [92]
RP INTERACTION WITH GSAP.
RX PubMed=20811458; DOI=10.1038/nature09325;
RA He G., Luo W., Li P., Remmers C., Netzer W.J., Hendrick J.,
RA Bettayeb K., Flajolet M., Gorelick F., Wennogle L.P., Greengard P.;
RT "Gamma-secretase activating protein is a therapeutic target for
RT Alzheimer's disease.";
RL Nature 467:95-98(2010).
RN [93]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [94]
RP GLYCOSYLATION AT THR-633; THR-651; THR-652; SER-656; THR-663 AND
RP SER-667 PROTEOLYTIC PROCESSING, STRUCTURE OF CARBOHYDRATES, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21712440; DOI=10.1073/pnas.1102664108;
RA Halim A., Brinkmalm G., Ruetschi U., Westman-Brinkmalm A.,
RA Portelius E., Zetterberg H., Blennow K., Larson G., Nilsson J.;
RT "Site-specific characterization of threonine, serine, and tyrosine
RT glycosylations of amyloid precursor protein/amyloid beta-peptides in
RT human cerebrospinal fluid.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11848-11853(2011).
RN [95]
RP INTERACTION WITH S100A9.
RX PubMed=22457725; DOI=10.1371/journal.pone.0032953;
RA Zhang C., Liu Y., Gilthorpe J., van der Maarel J.R.;
RT "MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide
RT and induces its fibrillization.";
RL PLoS ONE 7:E32953-E32953(2012).
RN [96]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 287-344.
RX PubMed=2125487; DOI=10.1021/bi00495a002;
RA Hynes T.R., Randal M., Kennedy L.A., Eigenbrot C., Kossiakof A.A.;
RT "X-ray crystal structure of the protease inhibitor domain of
RT Alzheimer's amyloid beta-protein precursor.";
RL Biochemistry 29:10018-10022(1990).
RN [97]
RP STRUCTURE BY NMR OF 289-344.
RX PubMed=1718421; DOI=10.1021/bi00107a015;
RA Heald S.L., Tilton R.F. Jr., Hammond L.S., Lee A., Bayney R.M.,
RA Kamarck M.E., Ramabhadran T.V., Dreyer R.N., Davis G., Unterbeck A.,
RA Tamburini P.P.;
RT "Sequential NMR resonance assignment and structure determination of
RT the Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid
RT precursor protein.";
RL Biochemistry 30:10467-10478(1991).
RN [98]
RP STRUCTURE BY NMR OF 672-699.
RX PubMed=7516706; DOI=10.1021/bi00191a006;
RA Talafous J., Marcinowski K.J., Klopman G., Zagorski M.G.;
RT "Solution structure of residues 1-28 of the amyloid beta-peptide.";
RL Biochemistry 33:7788-7796(1994).
RN [99]
RP STRUCTURE BY NMR OF 672-711.
RX PubMed=7588758; DOI=10.1111/j.1432-1033.1995.293_1.x;
RA Sticht H., Bayer P., Willbold D., Dames S., Hilbich C., Beyreuther K.,
RA Frank R.W., Rosch P.;
RT "Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease.";
RL Eur. J. Biochem. 233:293-298(1995).
RN [100]
RP STRUCTURE BY NMR OF 696-706.
RX PubMed=8973180; DOI=10.1021/bi961598j;
RA Kohno T., Kobayashi K., Maeda T., Sato K., Takashima A.;
RT "Three-dimensional structures of the amyloid beta peptide (25-35) in
RT membrane-mimicking environment.";
RL Biochemistry 35:16094-16104(1996).
RN [101]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF KUNITZ DOMAIN IN COMPLEX WITH
RP CHYMOTRYPSIN; TRYPSIN AND BASIC PANCREATIC TRYPSIN INHIBITOR.
RX PubMed=9300481; DOI=10.1002/pro.5560060902;
RA Scheidig A.J., Hynes T.R., Pelletier L.A., Wells J.A.,
RA Kossiakoff A.A.;
RT "Crystal structures of bovine chymotrypsin and trypsin complexed to
RT the inhibitor domain of Alzheimer's amyloid beta-protein precursor
RT (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of
RT inhibitors with altered specificities.";
RL Protein Sci. 6:1806-1824(1997).
RN [102]
RP STRUCTURE BY NMR OF 672-711.
RX PubMed=9693002; DOI=10.1021/bi972979f;
RA Coles M., Bicknell W., Watson A.A., Fairlie D.P., Craik D.J.;
RT "Solution structure of amyloid beta-peptide(1-40) in a water-micelle
RT environment. Is the membrane-spanning domain where we think it is?";
RL Biochemistry 37:11064-11077(1998).
RN [103]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 28-123.
RX PubMed=10201399; DOI=10.1038/7562;
RA Rossjohn J., Cappai R., Feil S.C., Henry A., McKinstry W.J.,
RA Galatis D., Hesse L., Multhaup G., Beyreuther K., Masters C.L.,
RA Parker M.W.;
RT "Crystal structure of the N-terminal, growth factor-like domain of
RT Alzheimer amyloid precursor protein.";
RL Nat. Struct. Biol. 6:327-331(1999).
RN [104]
RP STRUCTURE OF CAA-APP VARIANTS.
RX PubMed=10821838; DOI=10.1074/jbc.M003154200;
RA Miravalle L., Tokuda T., Chiarle R., Giaccone G., Bugiani O.,
RA Tagliavini F., Frangione B., Ghiso J.;
RT "Substitutions at codon 22 of Alzheimer's Abeta peptide induce diverse
RT conformational changes and apoptotic effects in human cerebral
RT endothelial cells.";
RL J. Biol. Chem. 275:27110-27116(2000).
RN [105]
RP STRUCTURE BY NMR OF 681-706.
RX PubMed=10940221; DOI=10.1006/jsbi.2000.4288;
RA Zhang S., Iwata K., Lachenmann M.J., Peng J.W., Li S., Stimson E.R.,
RA Lu Y., Felix A.M., Maggio J.E., Lee J.P.;
RT "The Alzheimer's peptide a beta adopts a collapsed coil structure in
RT water.";
RL J. Struct. Biol. 130:130-141(2000).
RN [106]
RP STRUCTURE BY NMR OF 672-699.
RX PubMed=10940222; DOI=10.1006/jsbi.2000.4267;
RA Poulsen S.-A., Watson A.A., Craik D.J.;
RT "Solution structures in aqueous SDS micelles of two amyloid beta
RT peptides of Abeta(1-28) mutated at the alpha-secretase cleavage
RT site.";
RL J. Struct. Biol. 130:142-152(2000).
RN [107]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 346-551, PARTIAL PROTEIN
RP SEQUENCE, MUTAGENESIS OF ARG-499 AND LYS-503, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=15304215; DOI=10.1016/j.molcel.2004.06.037;
RA Wang Y., Ha Y.;
RT "The X-ray structure of an antiparallel dimer of the human amyloid
RT precursor protein E2 domain.";
RL Mol. Cell 15:343-353(2004).
RN [108]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 672-711 IN COMPLEX WITH IDE.
RX PubMed=17051221; DOI=10.1038/nature05143;
RA Shen Y., Joachimiak A., Rosner M.R., Tang W.-J.;
RT "Structures of human insulin-degrading enzyme reveal a new substrate
RT recognition mechanism.";
RL Nature 443:870-874(2006).
RN [109]
RP X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 133-189, AND DISULFIDE
RP BONDS.
RX PubMed=17909280; DOI=10.1107/S1744309107041139;
RA Kong G.K., Adams J.J., Cappai R., Parker M.W.;
RT "Structure of Alzheimer's disease amyloid precursor protein copper-
RT binding domain at atomic resolution.";
RL Acta Crystallogr. F 63:819-824(2007).
RN [110]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 133-189 IN COMPLEXES WITH
RP COPPER IONS, AND DISULFIDE BONDS.
RX PubMed=17239395; DOI=10.1016/j.jmb.2006.12.041;
RA Kong G.K., Adams J.J., Harris H.H., Boas J.F., Curtain C.C.,
RA Galatis D., Masters C.L., Barnham K.J., McKinstry W.J., Cappai R.,
RA Parker M.W.;
RT "Structural studies of the Alzheimer's amyloid precursor protein
RT copper-binding domain reveal how it binds copper ions.";
RL J. Mol. Biol. 367:148-161(2007).
RN [111]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 672-679 IN COMPLEX WITH IGG.
RX PubMed=17895381; DOI=10.1073/pnas.0705888104;
RA Gardberg A.S., Dice L.T., Ou S., Rich R.L., Helmbrecht E., Ko J.,
RA Wetzel R., Myszka D.G., Patterson P.H., Dealwis C.;
RT "Molecular basis for passive immunotherapy of Alzheimer's disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:15659-15664(2007).
RN [112]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 672-678 IN COMPLEXES WITH
RP ANTIBODY FAB FRAGMENTS.
RX PubMed=19923222; DOI=10.1074/jbc.M109.045187;
RA Basi G.S., Feinberg H., Oshidari F., Anderson J., Barbour R.,
RA Baker J., Comery T.A., Diep L., Gill D., Johnson-Wood K., Goel A.,
RA Grantcharova K., Lee M., Li J., Partridge A., Griswold-Prenner I.,
RA Piot N., Walker D., Widom A., Pangalos M.N., Seubert P.,
RA Jacobsen J.S., Schenk D., Weis W.I.;
RT "Structural correlates of antibodies associated with acute reversal of
RT amyloid beta-related behavioral deficits in a mouse model of Alzheimer
RT disease.";
RL J. Biol. Chem. 285:3417-3427(2010).
RN [113]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 18-190, PARTIAL PROTEIN
RP SEQUENCE, SUBUNIT, DISULFIDE BONDS, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=20212142; DOI=10.1073/pnas.0911326107;
RA Dahms S.O., Hoefgen S., Roeser D., Schlott B., Guhrs K.H., Than M.E.;
RT "Structure and biochemical analysis of the heparin-induced E1 dimer of
RT the amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:5381-5386(2010).
RN [114]
RP REVIEW ON VARIANTS.
RX PubMed=1363811; DOI=10.1038/ng0792-233;
RA Hardy J.;
RT "Framing beta-amyloid.";
RL Nat. Genet. 1:233-234(1992).
RN [115]
RP VARIANT CAA-APP GLN-693.
RX PubMed=2111584; DOI=10.1126/science.2111584;
RA Levy E., Carman M.D., Fernandez-Madrid I.J., Power M.D.,
RA Lieberburg I., van Duinen S.G., Bots G.T.A.M., Luyendijk W.,
RA Frangione B.;
RT "Mutation of the Alzheimer's disease amyloid gene in hereditary
RT cerebral hemorrhage, Dutch type.";
RL Science 248:1124-1126(1990).
RN [116]
RP VARIANT AD1 ILE-717.
RX PubMed=1671712; DOI=10.1038/349704a0;
RA Goate A., Chartier-Harlin M.-C., Mullan M., Brown J., Crawford F.,
RA Fidani L., Giuffra L., Haynes A., Irving N., James L., Mant R.,
RA Newton P., Rooke K., Roques P., Talbot C., Pericak-Vance M.,
RA Roses A.D., Williamson R., Rossor M., Owen M., Hardy J.;
RT "Segregation of a missense mutation in the amyloid precursor protein
RT gene with familial Alzheimer's disease.";
RL Nature 349:704-706(1991).
RN [117]
RP VARIANT AD1 ILE-717.
RX PubMed=1908231; DOI=10.1016/0006-291X(91)91011-Z;
RA Yoshioka K., Miki T., Katsuya T., Ogihara T., Sakaki Y.;
RT "The 717Val-->Ile substitution in amyloid precursor protein is
RT associated with familial Alzheimer's disease regardless of ethnic
RT groups.";
RL Biochem. Biophys. Res. Commun. 178:1141-1146(1991).
RN [118]
RP VARIANT AD1 ILE-717.
RX PubMed=1678058; DOI=10.1016/0140-6736(91)91612-X;
RA Naruse S., Igarashi S., Kobayashi H., Aoki K., Inuzuka T., Kaneko K.,
RA Shimizu T., Iihara K., Kojima T., Miyatake T., Tsuji S.;
RT "Mis-sense mutation Val->Ile in exon 17 of amyloid precursor protein
RT gene in Japanese familial Alzheimer's disease.";
RL Lancet 337:978-979(1991).
RN [119]
RP VARIANT AD1 GLY-717.
RX PubMed=1944558; DOI=10.1038/353844a0;
RA Chartier-Harlin M.-C., Crawford F., Houlden H., Warren A., Hughes D.,
RA Fidani L., Goate A., Rossor M., Roques P., Hardy J., Mullan M.;
RT "Early-onset Alzheimer's disease caused by mutations at codon 717 of
RT the beta-amyloid precursor protein gene.";
RL Nature 353:844-846(1991).
RN [120]
RP VARIANT AD1 PHE-717.
RX PubMed=1925564; DOI=10.1126/science.1925564;
RA Murrell J.R., Farlow M., Ghetti B., Benson M.D.;
RT "A mutation in the amyloid precursor protein associated with
RT hereditary Alzheimer's disease.";
RL Science 254:97-99(1991).
RN [121]
RP VARIANT AD1 GLY-693.
RX PubMed=1415269;
RA Kamino K., Orr H.T., Payami H., Wijsman E.M., Alonso M.E., Pulst S.M.,
RA Anderson L., O'Dahl S., Nemens E., White J.A., Sadovnick A.D.,
RA Ball M.J., Kaye J., Warren A., McInnis M.G., Antonarakis S.E.,
RA Korenberg J.R., Sharma V., Kukull W., Larson E., Heston L.L.,
RA Martin G.M., Bird T.D., Schellenberg G.D.;
RT "Linkage and mutational analysis of familial Alzheimer disease
RT kindreds for the APP gene region.";
RL Am. J. Hum. Genet. 51:998-1014(1992).
RN [122]
RP VARIANT AD1 GLY-692.
RX PubMed=1303239; DOI=10.1038/ng0692-218;
RA Hendriks L., van Duijn C.M., Cras P., Cruts M., Van Hul W.,
RA van Harskamp F., Warren A., McInnis M.G., Antonarakis S.E.,
RA Martin J.J., Hofman A., Van Broeckhoven C.;
RT "Presenile dementia and cerebral haemorrhage linked to a mutation at
RT codon 692 of the beta-amyloid precursor protein gene.";
RL Nat. Genet. 1:218-221(1992).
RN [123]
RP VARIANT AD1 670-ASN-LEU-671.
RX PubMed=1302033; DOI=10.1038/ng0892-345;
RA Mullan M., Crawford F., Axelman K., Houlden H., Lilius L., Winblad B.,
RA Lannfelt L.;
RT "A pathogenic mutation for probable Alzheimer's disease in the APP
RT gene at the N-terminus of beta-amyloid.";
RL Nat. Genet. 1:345-347(1992).
RN [124]
RP VARIANT VAL-713.
RX PubMed=1307241; DOI=10.1038/ng0792-306;
RA Jones C.T., Morris S., Yates C.M., Moffoot A., Sharpe C.,
RA Brock D.J.H., St Clair D.;
RT "Mutation in codon 713 of the beta amyloid precursor protein gene
RT presenting with schizophrenia.";
RL Nat. Genet. 1:306-309(1992).
RN [125]
RP VARIANT AD1 THR-713.
RX PubMed=1303275; DOI=10.1038/ng1292-255;
RA Carter D.A., Desmarais E., Bellis M., Campion D., Clerget-Darpoux F.,
RA Brice A., Agid Y., Jaillard-Serradt A., Mallet J.;
RT "More missense in amyloid gene.";
RL Nat. Genet. 2:255-256(1992).
RN [126]
RP VARIANTS AD1 ILE-717 AND PHE-717.
RX PubMed=8267572; DOI=10.1006/bbrc.1993.2491;
RA Liepnieks J.J., Ghetti B., Farlow M., Roses A.D., Benson M.D.;
RT "Characterization of amyloid fibril beta-peptide in familial
RT Alzheimer's disease with APP717 mutations.";
RL Biochem. Biophys. Res. Commun. 197:386-392(1993).
RN [127]
RP VARIANT ASP-665.
RX PubMed=8154870; DOI=10.1002/ana.410350410;
RA Peacock M.L., Murman D.L., Sima A.A.F., Warren J.T. Jr., Roses A.D.,
RA Fink J.K.;
RT "Novel amyloid precursor protein gene mutation (codon 665Asp) in a
RT patient with late-onset Alzheimer's disease.";
RL Ann. Neurol. 35:432-438(1994).
RN [128]
RP VARIANT AD1 PHE-717.
RX PubMed=8290042; DOI=10.1212/WNL.44.1.105;
RA Farlow M., Murrell J., Ghetti B., Unverzagt F., Zeldenrust S.,
RA Benson M.D.;
RT "Clinical characteristics in a kindred with early-onset Alzheimer's
RT disease and their linkage to a G-->T change at position 2149 of the
RT amyloid precursor protein gene.";
RL Neurology 44:105-111(1994).
RN [129]
RP VARIANT AD1 ILE-717.
RX PubMed=8577393; DOI=10.1016/0304-3940(95)12046-7;
RA Brooks W.S., Martins R.N., De Voecht J., Nicholson G.A.,
RA Schofield P.R., Kwok J.B.J., Fisher C., Yeung L.U.,
RA Van Broeckhoven C.;
RT "A mutation in codon 717 of the amyloid precursor protein gene in an
RT Australian family with Alzheimer's disease.";
RL Neurosci. Lett. 199:183-186(1995).
RN [130]
RP VARIANT AD1 VAL-716.
RX PubMed=9328472; DOI=10.1093/hmg/6.12.2087;
RA Eckman C.B., Mehta N.D., Crook R., Perez-Tur J., Prihar G.,
RA Pfeiffer E., Graff-Radford N., Hinder P., Yager D., Zenk B.,
RA Refolo L.M., Prada C.M., Younkin S.G., Hutton M., Hardy J.;
RT "A new pathogenic mutation in the APP gene (I716V) increases the
RT relative proportion of A beta 42(43).";
RL Hum. Mol. Genet. 6:2087-2089(1997).
RN [131]
RP VARIANT AD1 GLY-692, AND CHARACTERIZATION OF PHENOTYPE.
RX PubMed=9754958; DOI=10.1007/s004010050892;
RA Cras P., van Harskamp F., Hendriks L., Ceuterick C., van Duijn C.M.,
RA Stefanko S.Z., Hofman A., Kros J.M., Van Broeckhoven C., Martin J.J.;
RT "Presenile Alzheimer dementia characterized by amyloid angiopathy and
RT large amyloid core type senile plaques in the APP 692Ala-->Gly
RT mutation.";
RL Acta Neuropathol. 96:253-260(1998).
RN [132]
RP VARIANT AD1 MET-715, AND CHARACTERIZATION OF VARIANT AD1 MET-715.
RX PubMed=10097173; DOI=10.1073/pnas.96.7.4119;
RA Ancolio K., Dumanchin C., Barelli H., Warter J.-M., Brice A.,
RA Campion D., Frebourg T., Checler F.;
RT "Unusual phenotypic alteration of beta amyloid precursor protein
RT (betaAPP) maturation by a new Val-715 --> Met betaAPP-770 mutation
RT responsible for probable early-onset Alzheimer's disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4119-4124(1999).
RN [133]
RP VARIANT AD1 ILE-717.
RX PubMed=10631141; DOI=10.1086/302702;
RA Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J.,
RA Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.;
RT "High prevalence of pathogenic mutations in patients with early-onset
RT dementia detected by sequence analyses of four different genes.";
RL Am. J. Hum. Genet. 66:110-117(2000).
RN [134]
RP VARIANT AD1 PRO-723.
RX PubMed=10665499;
RX DOI=10.1002/1531-8249(200002)47:2<249::AID-ANA18>3.0.CO;2-8;
RA Kwok J.B.J., Li Q.X., Hallupp M., Whyte S., Ames D., Beyreuther K.,
RA Masters C.L., Schofield P.R.;
RT "Novel Leu723Pro amyloid precursor protein mutation increases amyloid
RT beta42(43) peptide levels and induces apoptosis.";
RL Ann. Neurol. 47:249-253(2000).
RN [135]
RP VARIANT AD1 LEU-717.
RX PubMed=10867787; DOI=10.1001/archneur.57.6.885;
RA Murrell J.R., Hake A.M., Quaid K.A., Farlow M.R., Ghetti B.;
RT "Early-onset Alzheimer disease caused by a new mutation (V717L) in the
RT amyloid precursor protein gene.";
RL Arch. Neurol. 57:885-887(2000).
RN [136]
RP VARIANT AD1 ILE-714, CHARACTERIZATION OF VARIANT AD1 ILE-714, AND
RP MUTAGENESIS OF VAL-717.
RX PubMed=11063718; DOI=10.1093/hmg/9.18.2589;
RA Kumar-Singh S., De Jonghe C., Cruts M., Kleinert R., Wang R.,
RA Mercken M., De Strooper B., Vanderstichele H., Loefgren A.,
RA Vanderhoeven I., Backhovens H., Vanmechelen E., Kroisel P.M.,
RA Van Broeckhoven C.;
RT "Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase
RT site mutation points to an essential role for N-truncated A beta(42)
RT in Alzheimer's disease.";
RL Hum. Mol. Genet. 9:2589-2598(2000).
RN [137]
RP VARIANT CAA-APP ASN-694.
RX PubMed=11409420; DOI=10.1002/ana.1009;
RA Grabowski T.J., Cho H.S., Vonsattel J.P.G., Rebeck G.W.,
RA Greenberg S.M.;
RT "Novel amyloid precursor protein mutation in an Iowa family with
RT dementia and severe cerebral amyloid angiopathy.";
RL Ann. Neurol. 49:697-705(2001).
RN [138]
RP CHARACTERIZATION OF VARIANT AD1 GLY-692.
RX PubMed=11311152;
RA Walsh D.M., Hartley D.M., Condron M.M., Selkoe D.J., Teplow D.B.;
RT "In vitro studies of amyloid beta-protein fibril assembly and toxicity
RT provide clues to the aetiology of Flemish variant (Ala692-->Gly)
RT Alzheimer's disease.";
RL Biochem. J. 355:869-877(2001).
RN [139]
RP VARIANT AD1 GLY-693.
RX PubMed=11528419; DOI=10.1038/nn0901-887;
RA Nilsberth C., Westlind-Danielsson A., Eckman C.B., Condron M.M.,
RA Axelman K., Forsell C., Stenh C., Luthman J., Teplow D.B.,
RA Younkin S.G., Naeslund J., Lannfelt L.;
RT "The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by
RT enhanced Abeta protofibril formation.";
RL Nat. Neurosci. 4:887-893(2001).
RN [140]
RP VARIANT AD1 ALA-714.
RX PubMed=12034808; DOI=10.1212/WNL.58.10.1574;
RA Pasalar P., Najmabadi H., Noorian A.R., Moghimi B., Jannati A.,
RA Soltanzadeh A., Krefft T., Crook R., Hardy J.;
RT "An Iranian family with Alzheimer's disease caused by a novel APP
RT mutation (Thr714Ala).";
RL Neurology 58:1574-1575(2002).
RN [141]
RP VARIANT CAA-APP ASN-694.
RX PubMed=12654973; DOI=10.1212/01.WNL.0000050140.10044.A8;
RA Greenberg S.M., Shin Y., Grabowski T.J., Cooper G.E., Rebeck G.W.,
RA Iglesias S., Chapon F., Tournier-Lasserve E., Baron J.-C.;
RT "Hemorrhagic stroke associated with the Iowa amyloid precursor protein
RT mutation.";
RL Neurology 60:1020-1022(2003).
RN [142]
RP VARIANT AD1 THR-713.
RX PubMed=15365148; DOI=10.1212/01.WNL.0000137048.80666.86;
RA Rossi G., Giaccone G., Maletta R., Morbin M., Capobianco R.,
RA Mangieri M., Giovagnoli A.R., Bizzi A., Tomaino C., Perri M.,
RA Di Natale M., Tagliavini F., Bugiani O., Bruni A.C.;
RT "A family with Alzheimer disease and strokes associated with A713T
RT mutation of the APP gene.";
RL Neurology 63:910-912(2004).
RN [143]
RP VARIANT CAA-APP VAL-705.
RX PubMed=16178030; DOI=10.1002/ana.20571;
RA Obici L., Demarchi A., de Rosa G., Bellotti V., Marciano S.,
RA Donadei S., Arbustini E., Palladini G., Diegoli M., Genovese E.,
RA Ferrari G., Coverlizza S., Merlini G.;
RT "A novel AbetaPP mutation exclusively associated with cerebral amyloid
RT angiopathy.";
RL Ann. Neurol. 58:639-644(2005).
RN [144]
RP VARIANT AD1 ILE-714.
RX PubMed=15668448; DOI=10.1212/01.WNL.0000149761.70566.3E;
RA Edwards-Lee T., Ringman J.M., Chung J., Werner J., Morgan A.,
RA St George-Hyslop P.H., Thompson P., Dutton R., Mlikotic A.,
RA Rogaeva E., Hardy J.;
RT "An African American family with early-onset Alzheimer disease and an
RT APP (T714I) mutation.";
RL Neurology 64:377-379(2005).
CC -!- FUNCTION: Functions as a cell surface receptor and performs
CC physiological functions on the surface of neurons relevant to
CC neurite growth, neuronal adhesion and axonogenesis. Involved in
CC cell mobility and transcription regulation through protein-protein
CC interactions. Can promote transcription activation through binding
CC to APBB1-KAT5 and inhibits Notch signaling through interaction
CC with Numb. Couples to apoptosis-inducing pathways such as those
CC mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By
CC similarity). Acts as a kinesin I membrane receptor, mediating the
CC axonal transport of beta-secretase and presenilin 1. Involved in
CC copper homeostasis/oxidative stress through copper ion reduction.
CC In vitro, copper-metallated APP induces neuronal death directly or
CC is potentiated through Cu(2+)-mediated low-density lipoprotein
CC oxidation. Can regulate neurite outgrowth through binding to
CC components of the extracellular matrix such as heparin and
CC collagen I and IV. The splice isoforms that contain the BPTI
CC domain possess protease inhibitor activity. Induces a AGER-
CC dependent pathway that involves activation of p38 MAPK, resulting
CC in internalization of amyloid-beta peptide and leading to
CC mitochondrial dysfunction in cultured cortical neurons. Provides
CC Cu(2+) ions for GPC1 which are required for release of nitric
CC oxide (NO) and subsequent degradation of the heparan sulfate
CC chains on GPC1.
CC -!- FUNCTION: Beta-amyloid peptides are lipophilic metal chelators
CC with metal-reducing activity. Bind transient metals such as
CC copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to
CC Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more
CC effective reductant than beta-amyloid 40. Beta-amyloid peptides
CC bind to lipoproteins and apolipoproteins E and J in the CSF and to
CC HDL particles in plasma, inhibiting metal-catalyzed oxidation of
CC lipoproteins. Beta-APP42 may activate mononuclear phagocytes in
CC the brain and elicit inflammatory responses. Promotes both tau
CC aggregation and TPK II-mediated phosphorylation. Interaction with
CC Also bind GPC1 in lipid rafts.
CC -!- FUNCTION: Appicans elicit adhesion of neural cells to the
CC extracellular matrix and may regulate neurite outgrowth in the
CC brain (By similarity).
CC -!- FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved
CC peptides, including C31, are potent enhancers of neuronal
CC apoptosis.
CC -!- FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and
CC degeneration of both neuronal cell bodies (via caspase-3) and
CC axons (via caspase-6).
CC -!- SUBUNIT: Binds, via its C-terminus, to the PID domain of several
CC cytoplasmic proteins, including APBB family members, the APBA
CC family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding
CC to DAB1 inhibits its serine phosphorylation (By similarity).
CC Interacts (via NPXY motif) with DAB2 (via PID domain); the
CC interaction is impaired by tyrosine phosphorylation of the NPXY
CC motif. Also interacts with GPCR-like protein BPP, FPRL1, APPBP1,
CC IB1, KNS2 (via its TPR domains) (By similarity), APPBP2 (via BaSS)
CC and DDB1. In vitro, it binds MAPT via the MT-binding domains (By
CC similarity). Associates with microtubules in the presence of ATP
CC and in a kinesin-dependent manner (By similarity). Interacts,
CC through a C-terminal domain, with GNAO1. Amyloid beta-42 binds
CC CHRNA7 in hippocampal neurons. Beta-amyloid associates with HADH2.
CC Soluble APP binds, via its N-terminal head, to FBLN1. Interacts
CC with CPEB1 and AGER (By similarity). Interacts with ANKS1B and
CC TNFRSF21. Interacts with ITM2B. Interacts with ITM2C. Interacts
CC with IDE. Can form homodimers; this is promoted by heparin
CC binding. Beta-amyloid protein 40 interacts with S100A9. CTF-alpha
CC product of APP interacts with GSAP. Interacts with SORL1.
CC -!- INTERACTION:
CC Self; NbExp=79; IntAct=EBI-77613, EBI-77613;
CC Q306T3:- (xeno); NbExp=3; IntAct=EBI-77613, EBI-8294101;
CC P31696:AGRN (xeno); NbExp=3; IntAct=EBI-2431589, EBI-457650;
CC Q02410:APBA1; NbExp=3; IntAct=EBI-77613, EBI-368690;
CC O00213:APBB1; NbExp=5; IntAct=EBI-77613, EBI-81694;
CC Q92870:APBB2; NbExp=2; IntAct=EBI-77613, EBI-79277;
CC P51693:APLP1; NbExp=2; IntAct=EBI-302641, EBI-74648;
CC Q06481:APLP2; NbExp=2; IntAct=EBI-302641, EBI-79306;
CC P02647:APOA1; NbExp=5; IntAct=EBI-77613, EBI-701692;
CC Q13867:BLMH; NbExp=2; IntAct=EBI-302641, EBI-718504;
CC P15253:CALR (xeno); NbExp=3; IntAct=EBI-77613, EBI-9005200;
CC Q8K3H7:CALR (xeno); NbExp=2; IntAct=EBI-3894543, EBI-9005068;
CC P39060:COL18A1; NbExp=2; IntAct=EBI-821758, EBI-2566375;
CC P07339:CTSD; NbExp=2; IntAct=EBI-77613, EBI-2115097;
CC O75955:FLOT1; NbExp=5; IntAct=EBI-77613, EBI-603643;
CC P01100:FOS; NbExp=3; IntAct=EBI-77613, EBI-852851;
CC P46089:GPR3; NbExp=2; IntAct=EBI-302641, EBI-3909653;
CC Q9NSC5:HOMER3; NbExp=3; IntAct=EBI-302661, EBI-748420;
CC Q99714:HSD17B10; NbExp=4; IntAct=EBI-77613, EBI-79964;
CC O43736:ITM2A; NbExp=3; IntAct=EBI-302641, EBI-2431769;
CC P05412:JUN; NbExp=2; IntAct=EBI-77613, EBI-852823;
CC P10636:MAPT; NbExp=9; IntAct=EBI-77613, EBI-366182;
CC Q93074:MED12; NbExp=2; IntAct=EBI-77613, EBI-394357;
CC P03897:MT-ND3; NbExp=2; IntAct=EBI-821758, EBI-1246249;
CC P21359:NF1; NbExp=3; IntAct=EBI-77613, EBI-1172917;
CC P08138:NGFR; NbExp=2; IntAct=EBI-77613, EBI-1387782;
CC P07174:Ngfr (xeno); NbExp=2; IntAct=EBI-2431589, EBI-1038810;
CC P61457:PCBD1; NbExp=2; IntAct=EBI-77613, EBI-740475;
CC Q15113:PCOLCE; NbExp=3; IntAct=EBI-821758, EBI-8869614;
CC P30101:PDIA3; NbExp=3; IntAct=EBI-77613, EBI-979862;
CC Q13526:PIN1; NbExp=2; IntAct=EBI-302641, EBI-714158;
CC P04156:PRNP; NbExp=3; IntAct=EBI-77613, EBI-977302;
CC P49768:PSEN1; NbExp=6; IntAct=EBI-77613, EBI-297277;
CC P29353:SHC1; NbExp=5; IntAct=EBI-77613, EBI-78835;
CC Q92529:SHC3; NbExp=2; IntAct=EBI-77613, EBI-79084;
CC Q9NP59:SLC40A1; NbExp=4; IntAct=EBI-77613, EBI-725153;
CC Q8BGY9:Slc5a7 (xeno); NbExp=2; IntAct=EBI-77613, EBI-2010752;
CC Q9HCB6:SPON1; NbExp=3; IntAct=EBI-302641, EBI-2431846;
CC P01137:TGFB1; NbExp=2; IntAct=EBI-77613, EBI-779636;
CC P61812:TGFB2; NbExp=6; IntAct=EBI-77613, EBI-779581;
CC O75509:TNFRSF21; NbExp=3; IntAct=EBI-77613, EBI-2313231;
CC Q13625:TP53BP2; NbExp=3; IntAct=EBI-77613, EBI-77642;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein. Membrane, clathrin-coated pit. Note=Cell surface protein
CC that rapidly becomes internalized via clathrin-coated pits. During
CC maturation, the immature APP (N-glycosylated in the endoplasmic
CC reticulum) moves to the Golgi complex where complete maturation
CC occurs (O-glycosylated and sulfated). After alpha-secretase
CC cleavage, soluble APP is released into the extracellular space and
CC the C-terminal is internalized to endosomes and lysosomes. Some
CC APP accumulates in secretory transport vesicles leaving the late
CC Golgi compartment and returns to the cell surface. Gamma-CTF(59)
CC peptide is located to both the cytoplasm and nuclei of neurons. It
CC can be translocated to the nucleus through association with APBB1
CC (Fe65). Beta-APP42 associates with FRPL1 at the cell surface and
CC the complex is then rapidly internalized. APP sorts to the
CC basolateral surface in epithelial cells. During neuronal
CC differentiation, the Thr-743 phosphorylated form is located mainly
CC in growth cones, moderately in neurites and sparingly in the cell
CC body. Casein kinase phosphorylation can occur either at the cell
CC surface or within a post-Golgi compartment. Associates with GPC1
CC in perinuclear compartments. Colocalizes with SORL1 in a vesicular
CC pattern in cytoplasm and perinuclear regions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=11;
CC Comment=Additional isoforms seem to exist. Experimental
CC confirmation may be lacking for some isoforms;
CC Name=APP770; Synonyms=PreA4 770;
CC IsoId=P05067-1; Sequence=Displayed;
CC Note=A major isoform;
CC Name=APP305;
CC IsoId=P05067-2; Sequence=VSP_000005, VSP_000006;
CC Name=L-APP677;
CC IsoId=P05067-3; Sequence=VSP_000002, VSP_000004, VSP_000009;
CC Note=The L-isoforms are referred to as appicans;
CC Name=APP695; Synonyms=PreA4 695;
CC IsoId=P05067-4; Sequence=VSP_000002, VSP_000004;
CC Note=A major isoform;
CC Name=L-APP696;
CC IsoId=P05067-5; Sequence=VSP_000002, VSP_000003, VSP_000009;
CC Note=The L-isoforms are referred to as appicans;
CC Name=APP714;
CC IsoId=P05067-6; Sequence=VSP_000002, VSP_000003;
CC Name=L-APP733;
CC IsoId=P05067-7; Sequence=VSP_000007, VSP_000008, VSP_000009;
CC Note=The L-isoforms are referred to as appicans;
CC Name=APP751; Synonyms=PreA4 751;
CC IsoId=P05067-8; Sequence=VSP_000007, VSP_000008;
CC Note=A major isoform;
CC Name=L-APP752;
CC IsoId=P05067-9; Sequence=VSP_000009;
CC Name=APP639;
CC IsoId=P05067-10; Sequence=VSP_009116, VSP_009117, VSP_009118;
CC Name=11;
CC IsoId=P05067-11; Sequence=VSP_045446, VSP_045447;
CC -!- TISSUE SPECIFICITY: Expressed in all fetal tissues examined with
CC highest levels in brain, kidney, heart and spleen. Weak expression
CC in liver. In adult brain, highest expression found in the frontal
CC lobe of the cortex and in the anterior perisylvian cortex-
CC opercular gyri. Moderate expression in the cerebellar cortex, the
CC posterior perisylvian cortex-opercular gyri and the temporal
CC associated cortex. Weak expression found in the striate, extra-
CC striate and motor cortices. Expressed in cerebrospinal fluid, and
CC plasma. Isoform APP695 is the predominant form in neuronal tissue,
CC isoform APP751 and isoform APP770 are widely expressed in non-
CC neuronal cells. Isoform APP751 is the most abundant form in T-
CC lymphocytes. Appican is expressed in astrocytes.
CC -!- INDUCTION: Increased levels during neuronal differentiation.
CC -!- DOMAIN: The basolateral sorting signal (BaSS) is required for
CC sorting of membrane proteins to the basolateral surface of
CC epithelial cells.
CC -!- DOMAIN: The NPXY sequence motif found in many tyrosine-
CC phosphorylated proteins is required for the specific binding of
CC the PID domain. However, additional amino acids either N- or C-
CC terminal to the NPXY motif are often required for complete
CC interaction. The PID domain-containing proteins which bind APP
CC require the YENPTY motif for full interaction. These interactions
CC are independent of phosphorylation on the terminal tyrosine
CC residue. The NPXY site is also involved in clathrin-mediated
CC endocytosis.
CC -!- PTM: Proteolytically processed under normal cellular conditions.
CC Cleavage either by alpha-secretase, beta-secretase or theta-
CC secretase leads to generation and extracellular release of soluble
CC APP peptides, S-APP-alpha and S-APP-beta, and the retention of
CC corresponding membrane-anchored C-terminal fragments, C80, C83 and
CC C99. Subsequent processing of C80 and C83 by gamma-secretase
CC yields P3 peptides. This is the major secretory pathway and is
CC non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated
CC gamma-secretase processing of C99 releases the amyloid beta
CC proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42),
CC major components of amyloid plaques, and the cytotoxic C-terminal
CC fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many
CC other minor beta-amyloid peptides, beta-amyloid 1-X peptides, are
CC found in cerebral spinal fluid (CSF) including the beta-amyloid X-
CC 15 peptides, produced from the cleavage by alpha-secretase and all
CC terminatiing at Gln-686.
CC -!- PTM: Proteolytically cleaved by caspases during neuronal
CC apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9
CC results in the production of the neurotoxic C31 peptide and the
CC increased production of beta-amyloid peptides.
CC -!- PTM: N- and O-glycosylated. O-glycosylation on Ser and Thr
CC residues with core 1 or possibly core 8 glycans. Partial tyrosine
CC glycosylation (Tyr-681) is found on some minor, short beta-amyloid
CC peptides (beta-amyloid 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but
CC not found on beta-amyloid 38, beta-amyloid 40 nor on beta-amyloid
CC 42. Modification on a tyrosine is unusual and is more prevelant in
CC AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr,
CC Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-
CC AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-
CC acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac
CC 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage
CC sites may influence the proteolytic processing. Appicans are L-APP
CC isoforms with O-linked chondroitin sulfate.
CC -!- PTM: Phosphorylation in the C-terminal on tyrosine, threonine and
CC serine residues is neuron-specific. Phosphorylation can affect APP
CC processing, neuronal differentiation and interaction with other
CC proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5
CC kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-
CC cycle dependent manner with maximal levels at the G2/M phase and,
CC in vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a
CC conformational change which reduces binding of Fe65 family
CC members. Phosphorylation on Tyr-757 is required for SHC binding.
CC Phosphorylated in the extracellular domain by casein kinases on
CC both soluble and membrane-bound APP. This phosphorylation is
CC inhibited by heparin.
CC -!- PTM: Extracellular binding and reduction of copper, results in a
CC corresponding oxidation of Cys-144 and Cys-158, and the formation
CC of a disulfide bond. In vitro, the APP-Cu(+) complex in the
CC presence of hydrogen peroxide results in an increased production
CC of beta-amyloid-containing peptides.
CC -!- PTM: Trophic-factor deprivation triggers the cleavage of surface
CC APP by beta-secretase to release sAPP-beta which is further
CC cleaved to release an N-terminal fragment of APP (N-APP).
CC -!- PTM: Beta-amyloid peptides are degraded by IDE.
CC -!- MASS SPECTROMETRY: Mass=6461.6; Method=MALDI; Range=712-767;
CC Source=PubMed:12214090;
CC -!- MASS SPECTROMETRY: Mass=6451.6; Method=MALDI; Range=714-770;
CC Source=PubMed:12214090;
CC -!- MASS SPECTROMETRY: Mass=6436.8; Method=MALDI; Range=715-769;
CC Source=PubMed:12214090;
CC -!- MASS SPECTROMETRY: Mass=5752.5; Method=MALDI; Range=719-767;
CC Source=PubMed:12214090;
CC -!- DISEASE: Alzheimer disease 1 (AD1) [MIM:104300]: A familial early-
CC onset form of Alzheimer disease. It can be associated with
CC cerebral amyloid angiopathy. Alzheimer disease is a
CC neurodegenerative disorder characterized by progressive dementia,
CC loss of cognitive abilities, and deposition of fibrillar amyloid
CC proteins as intraneuronal neurofibrillary tangles, extracellular
CC amyloid plaques and vascular amyloid deposits. The major
CC constituent of these plaques is the neurotoxic amyloid-beta-APP
CC 40-42 peptide (s), derived proteolytically from the transmembrane
CC precursor protein APP by sequential secretase processing. The
CC cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved
CC products such as C31 derived from APP, are also implicated in
CC neuronal death. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- DISEASE: Cerebral amyloid angiopathy, APP-related (CAA-APP)
CC [MIM:605714]: A hereditary localized amyloidosis due to amyloid-
CC beta A4 peptide(s) deposition in the cerebral vessels. The
CC principal clinical characteristics are recurrent cerebral and
CC cerebellar hemorrhages, recurrent strokes, cerebral ischemia,
CC cerebral infarction, and progressive mental deterioration.
CC Patients develop cerebral hemorrhage because of the severe
CC cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare
CC and largely in the form of pre-amyloid lesions or diffuse plaque-
CC like structures. They are Congo red negative and lack the dense
CC amyloid cores commonly present in Alzheimer disease. Some affected
CC individuals manifest progressive aphasic dementia,
CC leukoencephalopathy, and occipital calcifications. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- MISCELLANEOUS: Chelation of metal ions, notably copper, iron and
CC zinc, can induce histidine-bridging between beta-amyloid molecules
CC resulting in beta-amyloid-metal aggregates. The affinity for
CC copper is much higher than for other transient metals and is
CC increased under acidic conditions. Extracellular zinc-binding
CC increases binding of heparin to APP and inhibits collagen-binding.
CC -!- SIMILARITY: Belongs to the APP family.
CC -!- SIMILARITY: Contains 1 BPTI/Kunitz inhibitor domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA58727.1; Type=Miscellaneous discrepancy; Note=Contamination by an Alu repeat;
CC -!- WEB RESOURCE: Name=Alzheimer Research Forum; Note=APP mutations;
CC URL="http://www.alzforum.org/res/com/mut/app/default.asp";
CC -!- WEB RESOURCE: Name=AD mutations;
CC URL="http://www.molgen.ua.ac.be/ADmutations/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/app/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Amyloid beta entry;
CC URL="http://en.wikipedia.org/wiki/Amyloid_beta";
CC -----------------------------------------------------------------------
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DR EMBL; Y00264; CAA68374.1; -; mRNA.
DR EMBL; X13466; CAA31830.1; -; Genomic_DNA.
DR EMBL; X13467; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13468; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13469; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13470; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13471; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13472; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13473; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13474; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13475; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13476; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13477; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13478; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13479; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13487; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X13488; CAA31830.1; JOINED; Genomic_DNA.
DR EMBL; X06989; CAA30050.1; -; mRNA.
DR EMBL; M33112; AAB59502.1; -; Genomic_DNA.
DR EMBL; M34862; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34863; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34864; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34865; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34866; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34867; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34868; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34869; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34870; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34871; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34872; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34873; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34874; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34876; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34877; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34878; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34879; AAB59502.1; JOINED; Genomic_DNA.
DR EMBL; M34875; AAB59501.1; ALT_TERM; Genomic_DNA.
DR EMBL; M34862; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34863; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34864; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34865; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34866; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34867; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34868; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34869; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34870; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34871; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34872; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; M34873; AAB59501.1; JOINED; Genomic_DNA.
DR EMBL; D87675; BAA22264.1; -; Genomic_DNA.
DR EMBL; AK312326; BAG35248.1; -; mRNA.
DR EMBL; AK295621; BAG58500.1; -; mRNA.
DR EMBL; AY919674; AAW82435.1; -; Genomic_DNA.
DR EMBL; AP001439; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001440; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001441; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001442; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09958.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09959.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09960.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09961.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09963.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09965.1; -; Genomic_DNA.
DR EMBL; BC004369; AAH04369.1; -; mRNA.
DR EMBL; BC065529; AAH65529.1; -; mRNA.
DR EMBL; M35675; AAA60163.1; ALT_SEQ; mRNA.
DR EMBL; M24547; AAC13654.1; -; Genomic_DNA.
DR EMBL; M24546; AAC13654.1; JOINED; Genomic_DNA.
DR EMBL; M28373; AAA58727.1; ALT_SEQ; mRNA.
DR EMBL; X06982; CAA30042.1; -; mRNA.
DR EMBL; X06981; CAA30041.1; -; mRNA.
DR EMBL; M18734; AAA51726.1; -; mRNA.
DR EMBL; M29270; AAA51768.1; -; Genomic_DNA.
DR EMBL; M29269; AAA51768.1; JOINED; Genomic_DNA.
DR EMBL; AB066441; BAB71958.2; -; mRNA.
DR EMBL; M15533; AAA35540.1; -; mRNA.
DR EMBL; M15532; AAA51564.1; -; mRNA.
DR EMBL; M37896; AAA51727.1; -; Genomic_DNA.
DR EMBL; M37895; AAA51727.1; JOINED; Genomic_DNA.
DR EMBL; S45136; AAB23646.1; -; Genomic_DNA.
DR EMBL; S60317; AAC60601.2; -; Genomic_DNA.
DR EMBL; AF282245; AAQ14327.1; -; mRNA.
DR EMBL; S60721; AAB26263.2; -; mRNA.
DR EMBL; S61380; AAB26264.2; -; mRNA.
DR EMBL; S61383; AAB26265.2; -; mRNA.
DR EMBL; M16765; AAA51722.1; -; mRNA.
DR CCDS; CCDS13576.1; -. [P05067-1]
DR CCDS; CCDS13577.1; -. [P05067-4]
DR CCDS; CCDS33523.1; -. [P05067-8]
DR CCDS; CCDS46638.1; -. [P05067-10]
DR CCDS; CCDS56212.1; -. [P05067-11]
DR CCDS; CCDS56213.1; -. [P05067-9]
DR PIR; S01442; S01442.
DR PIR; S02260; QRHUA4.
DR RefSeq; NP_000475.1; NM_000484.3. [P05067-1]
DR RefSeq; NP_001129488.1; NM_001136016.3. [P05067-11]
DR RefSeq; NP_001129601.1; NM_001136129.2. [P05067-10]
DR RefSeq; NP_001129602.1; NM_001136130.2.
DR RefSeq; NP_001129603.1; NM_001136131.2.
DR RefSeq; NP_001191230.1; NM_001204301.1. [P05067-9]
DR RefSeq; NP_001191231.1; NM_001204302.1. [P05067-7]
DR RefSeq; NP_001191232.1; NM_001204303.1. [P05067-3]
DR RefSeq; NP_958816.1; NM_201413.2. [P05067-8]
DR RefSeq; NP_958817.1; NM_201414.2. [P05067-4]
DR UniGene; Hs.434980; -.
DR PDB; 1AAP; X-ray; 1.50 A; A/B=287-344.
DR PDB; 1AMB; NMR; -; A=672-699.
DR PDB; 1AMC; NMR; -; A=672-699.
DR PDB; 1AML; NMR; -; A=672-711.
DR PDB; 1BA4; NMR; -; A=672-711.
DR PDB; 1BA6; NMR; -; A=672-711.
DR PDB; 1BJB; NMR; -; A=672-699.
DR PDB; 1BJC; NMR; -; A=672-699.
DR PDB; 1BRC; X-ray; 2.50 A; I=287-342.
DR PDB; 1CA0; X-ray; 2.10 A; D/I=289-342.
DR PDB; 1HZ3; NMR; -; A=681-706.
DR PDB; 1IYT; NMR; -; A=672-713.
DR PDB; 1MWP; X-ray; 1.80 A; A=28-123.
DR PDB; 1OWT; NMR; -; A=124-189.
DR PDB; 1QCM; NMR; -; A=696-706.
DR PDB; 1QWP; NMR; -; A=696-706.
DR PDB; 1QXC; NMR; -; A=696-706.
DR PDB; 1QYT; NMR; -; A=696-706.
DR PDB; 1TAW; X-ray; 1.80 A; B=287-344.
DR PDB; 1TKN; NMR; -; A=460-569.
DR PDB; 1UO7; Model; -; A=672-713.
DR PDB; 1UO8; Model; -; A=672-713.
DR PDB; 1UOA; Model; -; A=672-713.
DR PDB; 1UOI; Model; -; A=672-713.
DR PDB; 1X11; X-ray; 2.50 A; C/D=754-766.
DR PDB; 1Z0Q; NMR; -; A=672-713.
DR PDB; 1ZE7; NMR; -; A=672-687.
DR PDB; 1ZE9; NMR; -; A=672-687.
DR PDB; 1ZJD; X-ray; 2.60 A; B=289-344.
DR PDB; 2BEG; NMR; -; A/B/C/D/E=672-713.
DR PDB; 2BOM; Model; -; A/B=681-713.
DR PDB; 2BP4; NMR; -; A=672-687.
DR PDB; 2FJZ; X-ray; 1.61 A; A=133-189.
DR PDB; 2FK1; X-ray; 1.60 A; A=133-189.
DR PDB; 2FK2; X-ray; 1.65 A; A=133-189.
DR PDB; 2FK3; X-ray; 2.40 A; A/B/C/D/E/F/G/H=133-189.
DR PDB; 2FKL; X-ray; 2.50 A; A/B=124-189.
DR PDB; 2FMA; X-ray; 0.85 A; A=133-189.
DR PDB; 2G47; X-ray; 2.10 A; C/D=672-711.
DR PDB; 2IPU; X-ray; 1.65 A; P/Q=672-679.
DR PDB; 2LFM; NMR; -; A=672-711.
DR PDB; 2LLM; NMR; -; A=686-726.
DR PDB; 2LMN; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L=672-711.
DR PDB; 2LMO; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L=672-711.
DR PDB; 2LMP; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=672-711.
DR PDB; 2LMQ; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=672-711.
DR PDB; 2LNQ; NMR; -; A/B/C/D/E/F/G/H=672-711.
DR PDB; 2LOH; NMR; -; A/B=686-726.
DR PDB; 2LP1; NMR; -; A=671-770.
DR PDB; 2LZ3; NMR; -; A/B=699-726.
DR PDB; 2LZ4; NMR; -; A/B=699-726.
DR PDB; 2M4J; NMR; -; A/B/C/D/E/F/G/H/I=672-711.
DR PDB; 2M9R; NMR; -; A=672-711.
DR PDB; 2M9S; NMR; -; A=672-711.
DR PDB; 2OTK; NMR; -; C=672-711.
DR PDB; 2R0W; X-ray; 2.50 A; Q=672-679.
DR PDB; 2WK3; X-ray; 2.59 A; C/D=672-713.
DR PDB; 2Y29; X-ray; 2.30 A; A=687-692.
DR PDB; 2Y2A; X-ray; 1.91 A; A=687-692.
DR PDB; 2Y3J; X-ray; 1.99 A; A/B/C/D/E/F/G/H=701-706.
DR PDB; 2Y3K; X-ray; 1.90 A; A/B/C/D/E/F/G/H=706-713.
DR PDB; 2Y3L; X-ray; 2.10 A; A/B/C/G=706-713.
DR PDB; 3AYU; X-ray; 2.00 A; B=586-595.
DR PDB; 3BAE; X-ray; 1.59 A; A=672-699.
DR PDB; 3BKJ; X-ray; 1.59 A; A=672-687.
DR PDB; 3DXC; X-ray; 2.10 A; B/D=739-770.
DR PDB; 3DXD; X-ray; 2.20 A; B/D=739-770.
DR PDB; 3DXE; X-ray; 2.00 A; B/D=739-770.
DR PDB; 3GCI; X-ray; 2.04 A; P=707-713.
DR PDB; 3IFL; X-ray; 1.50 A; P=672-678.
DR PDB; 3IFN; X-ray; 1.50 A; P=672-711.
DR PDB; 3IFO; X-ray; 2.15 A; P/Q=672-678.
DR PDB; 3IFP; X-ray; 2.95 A; P/Q/R/S=672-678.
DR PDB; 3JQ5; X-ray; 2.03 A; B=672-679.
DR PDB; 3JQL; X-ray; 1.20 A; B=687-692.
DR PDB; 3JTI; X-ray; 1.80 A; B=699-706.
DR PDB; 3KTM; X-ray; 2.70 A; A/B/C/D/E/F/G/H=18-190.
DR PDB; 3L33; X-ray; 2.48 A; E/F/G/H=290-341.
DR PDB; 3L81; X-ray; 1.60 A; B=761-767.
DR PDB; 3MOQ; X-ray; 2.05 A; A/B/C/D=689-712.
DR PDB; 3MXC; X-ray; 2.00 A; L=754-762.
DR PDB; 3MXY; X-ray; 2.30 A; L=754-762.
DR PDB; 3NYJ; X-ray; 3.20 A; A=365-567.
DR PDB; 3NYL; X-ray; 2.80 A; A=365-570.
DR PDB; 3OVJ; X-ray; 1.80 A; A/B/C/D=687-692.
DR PDB; 3OW9; X-ray; 1.80 A; A/B=687-692.
DR PDB; 3SV1; X-ray; 3.30 A; D/E/F=754-767.
DR PDB; 3U0T; X-ray; 2.50 A; E/F=701-711.
DR PDB; 3UMH; X-ray; 2.00 A; A=370-575.
DR PDB; 3UMI; X-ray; 2.40 A; A=370-575.
DR PDB; 3UMK; X-ray; 2.60 A; A=370-575.
DR PDB; 4HIX; X-ray; 2.20 A; A=672-699.
DR PDB; 4MDR; X-ray; 1.85 A; B=758-767.
DR PDB; 4NGE; X-ray; 2.70 A; B/E=672-711.
DR PDBsum; 1AAP; -.
DR PDBsum; 1AMB; -.
DR PDBsum; 1AMC; -.
DR PDBsum; 1AML; -.
DR PDBsum; 1BA4; -.
DR PDBsum; 1BA6; -.
DR PDBsum; 1BJB; -.
DR PDBsum; 1BJC; -.
DR PDBsum; 1BRC; -.
DR PDBsum; 1CA0; -.
DR PDBsum; 1HZ3; -.
DR PDBsum; 1IYT; -.
DR PDBsum; 1MWP; -.
DR PDBsum; 1OWT; -.
DR PDBsum; 1QCM; -.
DR PDBsum; 1QWP; -.
DR PDBsum; 1QXC; -.
DR PDBsum; 1QYT; -.
DR PDBsum; 1TAW; -.
DR PDBsum; 1TKN; -.
DR PDBsum; 1UO7; -.
DR PDBsum; 1UO8; -.
DR PDBsum; 1UOA; -.
DR PDBsum; 1UOI; -.
DR PDBsum; 1X11; -.
DR PDBsum; 1Z0Q; -.
DR PDBsum; 1ZE7; -.
DR PDBsum; 1ZE9; -.
DR PDBsum; 1ZJD; -.
DR PDBsum; 2BEG; -.
DR PDBsum; 2BOM; -.
DR PDBsum; 2BP4; -.
DR PDBsum; 2FJZ; -.
DR PDBsum; 2FK1; -.
DR PDBsum; 2FK2; -.
DR PDBsum; 2FK3; -.
DR PDBsum; 2FKL; -.
DR PDBsum; 2FMA; -.
DR PDBsum; 2G47; -.
DR PDBsum; 2IPU; -.
DR PDBsum; 2LFM; -.
DR PDBsum; 2LLM; -.
DR PDBsum; 2LMN; -.
DR PDBsum; 2LMO; -.
DR PDBsum; 2LMP; -.
DR PDBsum; 2LMQ; -.
DR PDBsum; 2LNQ; -.
DR PDBsum; 2LOH; -.
DR PDBsum; 2LP1; -.
DR PDBsum; 2LZ3; -.
DR PDBsum; 2LZ4; -.
DR PDBsum; 2M4J; -.
DR PDBsum; 2M9R; -.
DR PDBsum; 2M9S; -.
DR PDBsum; 2OTK; -.
DR PDBsum; 2R0W; -.
DR PDBsum; 2WK3; -.
DR PDBsum; 2Y29; -.
DR PDBsum; 2Y2A; -.
DR PDBsum; 2Y3J; -.
DR PDBsum; 2Y3K; -.
DR PDBsum; 2Y3L; -.
DR PDBsum; 3AYU; -.
DR PDBsum; 3BAE; -.
DR PDBsum; 3BKJ; -.
DR PDBsum; 3DXC; -.
DR PDBsum; 3DXD; -.
DR PDBsum; 3DXE; -.
DR PDBsum; 3GCI; -.
DR PDBsum; 3IFL; -.
DR PDBsum; 3IFN; -.
DR PDBsum; 3IFO; -.
DR PDBsum; 3IFP; -.
DR PDBsum; 3JQ5; -.
DR PDBsum; 3JQL; -.
DR PDBsum; 3JTI; -.
DR PDBsum; 3KTM; -.
DR PDBsum; 3L33; -.
DR PDBsum; 3L81; -.
DR PDBsum; 3MOQ; -.
DR PDBsum; 3MXC; -.
DR PDBsum; 3MXY; -.
DR PDBsum; 3NYJ; -.
DR PDBsum; 3NYL; -.
DR PDBsum; 3OVJ; -.
DR PDBsum; 3OW9; -.
DR PDBsum; 3SV1; -.
DR PDBsum; 3U0T; -.
DR PDBsum; 3UMH; -.
DR PDBsum; 3UMI; -.
DR PDBsum; 3UMK; -.
DR PDBsum; 4HIX; -.
DR PDBsum; 4MDR; -.
DR PDBsum; 4NGE; -.
DR ProteinModelPortal; P05067; -.
DR SMR; P05067; 26-192, 287-342, 385-567, 683-728, 741-768.
DR BioGrid; 106848; 1971.
DR DIP; DIP-574N; -.
DR IntAct; P05067; 113.
DR MINT; MINT-150767; -.
DR BindingDB; P05067; -.
DR ChEMBL; CHEMBL2487; -.
DR MEROPS; I02.015; -.
DR TCDB; 1.C.50.1.2; the amyloid -protein peptide (app) family.
DR PhosphoSite; P05067; -.
DR UniCarbKB; P05067; -.
DR DMDM; 112927; -.
DR SWISS-2DPAGE; P05067; -.
DR MaxQB; P05067; -.
DR PaxDb; P05067; -.
DR PRIDE; P05067; -.
DR DNASU; 351; -.
DR Ensembl; ENST00000346798; ENSP00000284981; ENSG00000142192. [P05067-1]
DR Ensembl; ENST00000348990; ENSP00000345463; ENSG00000142192. [P05067-4]
DR Ensembl; ENST00000354192; ENSP00000346129; ENSG00000142192. [P05067-10]
DR Ensembl; ENST00000357903; ENSP00000350578; ENSG00000142192. [P05067-8]
DR Ensembl; ENST00000358918; ENSP00000351796; ENSG00000142192. [P05067-9]
DR Ensembl; ENST00000359726; ENSP00000352760; ENSG00000142192. [P05067-6]
DR Ensembl; ENST00000440126; ENSP00000387483; ENSG00000142192. [P05067-11]
DR GeneID; 351; -.
DR KEGG; hsa:351; -.
DR UCSC; uc002ylz.3; human. [P05067-1]
DR UCSC; uc002yma.3; human. [P05067-8]
DR UCSC; uc002ymb.3; human. [P05067-4]
DR UCSC; uc010glj.3; human. [P05067-10]
DR UCSC; uc010glk.3; human.
DR UCSC; uc011acj.2; human. [P05067-2]
DR UCSC; uc021whz.1; human. [P05067-9]
DR UCSC; uc021wia.1; human. [P05067-7]
DR UCSC; uc021wib.1; human. [P05067-3]
DR CTD; 351; -.
DR GeneCards; GC21M027252; -.
DR GeneReviews; APP; -.
DR HGNC; HGNC:620; APP.
DR HPA; CAB000157; -.
DR HPA; HPA001462; -.
DR MIM; 104300; phenotype.
DR MIM; 104760; gene.
DR MIM; 605714; phenotype.
DR neXtProt; NX_P05067; -.
DR Orphanet; 1020; Early-onset autosomal dominant Alzheimer disease.
DR Orphanet; 324723; Hereditary cerebral hemorrhage with amyloidosis, Arctic type.
DR Orphanet; 100006; Hereditary cerebral hemorrhage with amyloidosis, Dutch type.
DR Orphanet; 324718; Hereditary cerebral hemorrhage with amyloidosis, Flemish type.
DR Orphanet; 324708; Hereditary cerebral hemorrhage with amyloidosis, Iowa type.
DR Orphanet; 324713; Hereditary cerebral hemorrhage with amyloidosis, Italian type.
DR Orphanet; 324703; Hereditary cerebral hemorrhage with amyloidosis, Piedmont type.
DR PharmGKB; PA24910; -.
DR eggNOG; NOG289770; -.
DR HOVERGEN; HBG000051; -.
DR InParanoid; P05067; -.
DR KO; K04520; -.
DR OMA; THAHIVI; -.
DR OrthoDB; EOG7RNJZP; -.
DR PhylomeDB; P05067; -.
DR TreeFam; TF317274; -.
DR BioCyc; MetaCyc:ENSG00000142192-MONOMER; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SABIO-RK; P05067; -.
DR ChiTaRS; app; human.
DR EvolutionaryTrace; P05067; -.
DR GeneWiki; Amyloid_precursor_protein; -.
DR GenomeRNAi; 351; -.
DR NextBio; 1445; -.
DR PMAP-CutDB; P05067; -.
DR PRO; PR:P05067; -.
DR ArrayExpress; P05067; -.
DR Bgee; P05067; -.
DR Genevestigator; P05067; -.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043198; C:dendritic shaft; IDA:MGI.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProt.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0045121; C:membrane raft; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0005641; C:nuclear envelope lumen; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProt.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0051233; C:spindle midzone; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0033130; F:acetylcholine receptor binding; IPI:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016504; F:peptidase activator activity; IEA:Ensembl.
DR GO; GO:0005515; F:protein binding; IPI:IntAct.
DR GO; GO:0051425; F:PTB domain binding; IPI:BHF-UCL.
DR GO; GO:0005102; F:receptor binding; IPI:BHF-UCL.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0008344; P:adult locomotory behavior; ISS:UniProtKB.
DR GO; GO:0008088; P:axon cargo transport; ISS:UniProtKB.
DR GO; GO:0016199; P:axon midline choice point recognition; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0006878; P:cellular copper ion homeostasis; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0048669; P:collateral sprouting in absence of injury; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; ISS:UniProtKB.
DR GO; GO:0007617; P:mating behavior; ISS:UniProtKB.
DR GO; GO:0000085; P:mitotic G2 phase; ISS:UniProtKB.
DR GO; GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:GOC.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0016322; P:neuron remodeling; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0050803; P:regulation of synapse structure and activity; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl.
DR GO; GO:0051124; P:synaptic growth at neuromuscular junction; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; ISS:UniProtKB.
DR Gene3D; 3.30.1490.140; -; 1.
DR Gene3D; 3.90.570.10; -; 1.
DR Gene3D; 4.10.230.10; -; 1.
DR Gene3D; 4.10.410.10; -; 1.
DR InterPro; IPR008155; Amyloid_glyco.
DR InterPro; IPR013803; Amyloid_glyco_Abeta.
DR InterPro; IPR011178; Amyloid_glyco_Cu-bd.
DR InterPro; IPR024329; Amyloid_glyco_E2_domain.
DR InterPro; IPR008154; Amyloid_glyco_extra.
DR InterPro; IPR019744; Amyloid_glyco_extracell_CS.
DR InterPro; IPR015849; Amyloid_glyco_heparin-bd.
DR InterPro; IPR019745; Amyloid_glyco_intracell_CS.
DR InterPro; IPR028866; APP.
DR InterPro; IPR019543; APP_amyloid_C.
DR InterPro; IPR002223; Prot_inh_Kunz-m.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR PANTHER; PTHR23103:SF7; PTHR23103:SF7; 1.
DR Pfam; PF10515; APP_amyloid; 1.
DR Pfam; PF12924; APP_Cu_bd; 1.
DR Pfam; PF12925; APP_E2; 1.
DR Pfam; PF02177; APP_N; 1.
DR Pfam; PF03494; Beta-APP; 1.
DR Pfam; PF00014; Kunitz_BPTI; 1.
DR PRINTS; PR00203; AMYLOIDA4.
DR PRINTS; PR00759; BASICPTASE.
DR PRINTS; PR00204; BETAAMYLOID.
DR SMART; SM00006; A4_EXTRA; 1.
DR SMART; SM00131; KU; 1.
DR SUPFAM; SSF109843; SSF109843; 1.
DR SUPFAM; SSF56491; SSF56491; 1.
DR SUPFAM; SSF57362; SSF57362; 1.
DR SUPFAM; SSF89811; SSF89811; 1.
DR PROSITE; PS00319; A4_EXTRA; 1.
DR PROSITE; PS00320; A4_INTRA; 1.
DR PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Alzheimer disease; Amyloid;
KW Amyloidosis; Apoptosis; Cell adhesion; Coated pit; Complete proteome;
KW Copper; Direct protein sequencing; Disease mutation; Disulfide bond;
KW Endocytosis; Glycoprotein; Heparin-binding; Iron; Membrane;
KW Metal-binding; Neurodegeneration; Notch signaling pathway;
KW Phosphoprotein; Polymorphism; Protease inhibitor; Proteoglycan;
KW Reference proteome; Serine protease inhibitor; Signal; Transmembrane;
KW Transmembrane helix; Zinc.
FT SIGNAL 1 17
FT CHAIN 18 770 Amyloid beta A4 protein.
FT /FTId=PRO_0000000088.
FT CHAIN 18 687 Soluble APP-alpha.
FT /FTId=PRO_0000000089.
FT CHAIN 18 671 Soluble APP-beta.
FT /FTId=PRO_0000000090.
FT CHAIN 18 286 N-APP.
FT /FTId=PRO_0000381966.
FT CHAIN 672 770 C99.
FT /FTId=PRO_0000000091.
FT CHAIN 672 713 Beta-amyloid protein 42.
FT /FTId=PRO_0000000092.
FT CHAIN 672 711 Beta-amyloid protein 40.
FT /FTId=PRO_0000000093.
FT CHAIN 688 770 C83.
FT /FTId=PRO_0000000094.
FT PEPTIDE 688 713 P3(42).
FT /FTId=PRO_0000000095.
FT PEPTIDE 688 711 P3(40).
FT /FTId=PRO_0000000096.
FT CHAIN 691 770 C80.
FT /FTId=PRO_0000384574.
FT CHAIN 712 770 Gamma-secretase C-terminal fragment 59.
FT /FTId=PRO_0000000097.
FT CHAIN 714 770 Gamma-secretase C-terminal fragment 57.
FT /FTId=PRO_0000000098.
FT CHAIN 721 770 Gamma-secretase C-terminal fragment 50
FT (By similarity).
FT /FTId=PRO_0000000099.
FT CHAIN 740 770 C31.
FT /FTId=PRO_0000000100.
FT TOPO_DOM 18 699 Extracellular (Potential).
FT TRANSMEM 700 723 Helical; (Potential).
FT TOPO_DOM 724 770 Cytoplasmic (Potential).
FT DOMAIN 291 341 BPTI/Kunitz inhibitor.
FT REGION 96 110 Heparin-binding.
FT REGION 181 188 Zinc-binding.
FT REGION 391 423 Heparin-binding.
FT REGION 491 522 Heparin-binding.
FT REGION 523 540 Collagen-binding.
FT REGION 732 751 Interaction with G(o)-alpha.
FT MOTIF 724 734 Basolateral sorting signal.
FT MOTIF 759 762 NPXY motif; contains endocytosis signal.
FT COMPBIAS 230 260 Asp/Glu-rich (acidic).
FT COMPBIAS 274 280 Poly-Thr.
FT METAL 147 147 Copper 1.
FT METAL 151 151 Copper 1.
FT METAL 168 168 Copper 1.
FT METAL 677 677 Copper or zinc 2.
FT METAL 681 681 Copper or zinc 2 (Probable).
FT METAL 684 684 Copper or zinc 2.
FT METAL 685 685 Copper or zinc 2.
FT SITE 144 144 Required for Cu(2+) reduction.
FT SITE 301 302 Reactive bond.
FT SITE 671 672 Cleavage; by beta-secretase.
FT SITE 672 673 Cleavage; by caspase-6; when associated
FT with variant 670-N-L-671.
FT SITE 687 688 Cleavage; by alpha-secretase.
FT SITE 690 691 Cleavage; by theta-secretase.
FT SITE 704 704 Implicated in free radical propagation
FT (By similarity).
FT SITE 706 706 Susceptible to oxidation.
FT SITE 711 712 Cleavage; by gamma-secretase; site 1.
FT SITE 713 714 Cleavage; by gamma-secretase; site 2.
FT SITE 720 721 Cleavage; by gamma-secretase; site 3.
FT SITE 739 740 Cleavage; by caspase-6, caspase-8 or
FT caspase-9.
FT MOD_RES 198 198 Phosphoserine; by CK2.
FT MOD_RES 206 206 Phosphoserine; by CK1.
FT MOD_RES 729 729 Phosphothreonine (By similarity).
FT MOD_RES 730 730 Phosphoserine; by APP-kinase I (By
FT similarity).
FT MOD_RES 743 743 Phosphothreonine; by CDK5 and MAPK10.
FT MOD_RES 757 757 Phosphotyrosine.
FT CARBOHYD 542 542 N-linked (GlcNAc...).
FT CARBOHYD 571 571 N-linked (GlcNAc...) (Probable).
FT CARBOHYD 614 614 O-linked (GalNAc...).
FT CARBOHYD 623 623 O-linked (GalNAc...).
FT CARBOHYD 628 628 O-linked (GalNAc...).
FT CARBOHYD 633 633 O-linked (GalNAc...).
FT CARBOHYD 651 651 O-linked (GalNAc...).
FT CARBOHYD 652 652 O-linked (GalNAc...).
FT CARBOHYD 656 656 O-linked (Xyl...) (chondroitin sulfate);
FT in L-APP isoforms.
FT CARBOHYD 659 659 O-linked (GalNAc...).
FT CARBOHYD 663 663 O-linked (GalNAc...) (Probable).
FT CARBOHYD 667 667 O-linked (GalNAc...) (Probable).
FT CARBOHYD 679 679 O-linked (GalNAc...).
FT CARBOHYD 697 697 O-linked (GalNAc...).
FT DISULFID 38 62
FT DISULFID 73 117
FT DISULFID 98 105
FT DISULFID 133 187
FT DISULFID 144 174
FT DISULFID 158 186
FT DISULFID 291 341
FT DISULFID 300 324
FT DISULFID 316 337
FT VAR_SEQ 1 19 MLPGLALLLLAAWTARALE -> MDQLEDLLVLFINY (in
FT isoform 11).
FT /FTId=VSP_045446.
FT VAR_SEQ 19 74 Missing (in isoform APP639).
FT /FTId=VSP_009116.
FT VAR_SEQ 289 363 Missing (in isoform APP639).
FT /FTId=VSP_009117.
FT VAR_SEQ 289 289 E -> V (in isoform APP695, isoform L-
FT APP696, isoform L-APP677 and isoform
FT APP714).
FT /FTId=VSP_000002.
FT VAR_SEQ 290 364 Missing (in isoform APP695 and isoform L-
FT APP677).
FT /FTId=VSP_000004.
FT VAR_SEQ 290 345 Missing (in isoform L-APP696 and isoform
FT APP714).
FT /FTId=VSP_000003.
FT VAR_SEQ 290 305 VCSEQAETGPCRAMIS -> KWYKEVHSGQARWLML (in
FT isoform APP305).
FT /FTId=VSP_000005.
FT VAR_SEQ 306 770 Missing (in isoform APP305).
FT /FTId=VSP_000006.
FT VAR_SEQ 345 364 MSQSLLKTTQEPLARDPVKL -> I (in isoform
FT 11).
FT /FTId=VSP_045447.
FT VAR_SEQ 345 345 M -> I (in isoform L-APP733 and isoform
FT APP751).
FT /FTId=VSP_000007.
FT VAR_SEQ 346 364 Missing (in isoform L-APP733 and isoform
FT APP751).
FT /FTId=VSP_000008.
FT VAR_SEQ 364 364 L -> V (in isoform APP639).
FT /FTId=VSP_009118.
FT VAR_SEQ 637 654 Missing (in isoform L-APP677, isoform L-
FT APP696, isoform L-APP733 and isoform L-
FT APP752).
FT /FTId=VSP_000009.
FT VARIANT 501 501 E -> K (in dbSNP:rs45588932).
FT /FTId=VAR_022315.
FT VARIANT 665 665 E -> D (in a patient with late onset
FT Alzheimer disease).
FT /FTId=VAR_010107.
FT VARIANT 670 671 KM -> NL (in AD1).
FT /FTId=VAR_000015.
FT VARIANT 678 678 D -> N (in AD1).
FT /FTId=VAR_044424.
FT VARIANT 692 692 A -> G (in AD1; Flemish mutation;
FT increases the solubility of processed
FT beta-amyloid peptides and increases the
FT stability of peptide oligomers).
FT /FTId=VAR_000016.
FT VARIANT 693 693 E -> G (in AD1).
FT /FTId=VAR_014215.
FT VARIANT 693 693 E -> K (in CAA-APP; Italian type).
FT /FTId=VAR_014216.
FT VARIANT 693 693 E -> Q (in CAA-APP; Dutch type).
FT /FTId=VAR_000017.
FT VARIANT 694 694 D -> N (in CAA-APP; Iowa type).
FT /FTId=VAR_014217.
FT VARIANT 705 705 L -> V (in CAA-APP; Italian type).
FT /FTId=VAR_032276.
FT VARIANT 713 713 A -> T (in AD1).
FT /FTId=VAR_000019.
FT VARIANT 713 713 A -> V (in one chronic schizophrenia
FT patient; unknown pathological
FT significance; dbSNP:rs1800557).
FT /FTId=VAR_000018.
FT VARIANT 714 714 T -> A (in AD1).
FT /FTId=VAR_032277.
FT VARIANT 714 714 T -> I (in AD1; increased beta-APP42/
FT beta-APP40 ratio).
FT /FTId=VAR_014218.
FT VARIANT 715 715 V -> M (in AD1; decreased beta-APP40/
FT total APP-beta).
FT /FTId=VAR_010108.
FT VARIANT 716 716 I -> V (in AD1).
FT /FTId=VAR_000020.
FT VARIANT 717 717 V -> F (in AD1).
FT /FTId=VAR_000023.
FT VARIANT 717 717 V -> G (in AD1).
FT /FTId=VAR_000022.
FT VARIANT 717 717 V -> I (in AD1).
FT /FTId=VAR_000021.
FT VARIANT 717 717 V -> L (in AD1).
FT /FTId=VAR_014219.
FT VARIANT 723 723 L -> P (in AD1).
FT /FTId=VAR_010109.
FT MUTAGEN 99 102 KRGR->NQGG: Reduced heparin-binding.
FT MUTAGEN 137 137 H->N: Binds copper. Forms dimer.
FT MUTAGEN 141 141 M->T: Binds copper. Forms dimer.
FT MUTAGEN 144 144 C->S: Binds copper. No dimer formation.
FT No copper reducing activity.
FT MUTAGEN 147 149 HLH->ALA: 50% decrease in copper reducing
FT activity.
FT MUTAGEN 147 147 H->A: Some decrease in copper reducing
FT activity.
FT MUTAGEN 147 147 H->N: Binds copper. Forms dimer.
FT MUTAGEN 147 147 H->Y: Greatly reduced copper-mediated
FT low-density lipoprotein oxidation.
FT MUTAGEN 151 151 H->K: Greatly reduced copper-mediated
FT low-density lipoprotein oxidation.
FT MUTAGEN 151 151 H->N: Binds copper. Forms dimer.
FT MUTAGEN 198 198 S->A: Greatly reduced casein kinase
FT phosphorylation.
FT MUTAGEN 206 206 S->A: Reduced casein kinase
FT phosphorylation.
FT MUTAGEN 499 499 R->A: Reduced affinity for heparin; when
FT associated with A-503.
FT MUTAGEN 503 503 K->A: Reduced affinity for heparin; when
FT associated with A-499.
FT MUTAGEN 656 656 S->A: Abolishes chondroitin sulfate
FT binding in L-APP733 isoform.
FT MUTAGEN 676 676 R->G: 60-70% zinc-induced beta-APP (28)
FT peptide aggregation.
FT MUTAGEN 681 681 Y->F: 60-70% zinc-induced beta-APP (28)
FT peptide aggregation.
FT MUTAGEN 684 684 H->R: Only 23% zinc-induced beta-APP (28)
FT peptide aggregation.
FT MUTAGEN 704 704 G->V: Reduced protein oxidation. No
FT hippocampal neuron toxicity.
FT MUTAGEN 706 706 M->L: Reduced lipid peroxidation
FT inhibition.
FT MUTAGEN 706 706 M->V: No free radical production. No
FT hippocampal neuron toxicity.
FT MUTAGEN 717 717 V->C,S: Unchanged beta-APP42/total APP-
FT beta ratio.
FT MUTAGEN 717 717 V->F,G,I: Increased beta-APP42/beta-APP40
FT ratio.
FT MUTAGEN 717 717 V->K: Decreased beta-APP42/total APP-beta
FT ratio.
FT MUTAGEN 717 717 V->M: Increased beta-APP42/beta-APP40
FT ratio. No change in apoptosis after
FT caspase cleavage.
FT MUTAGEN 728 728 Y->A: No effect on APBA1 nor APBB1
FT binding. Greatly reduces the binding to
FT APPBP2. APP internalization unchanged. No
FT change in beta-APP42 secretion.
FT MUTAGEN 739 739 D->A: No cleavage by caspases during
FT apoptosis.
FT MUTAGEN 739 739 D->N: No effect on FADD-induced
FT apoptosis.
FT MUTAGEN 743 743 T->A: Greatly reduces the binding to SHC1
FT and APBB family members; no effect on
FT NGF-stimulated neurite extension.
FT MUTAGEN 743 743 T->E: Reduced NGF-stimulated neurite
FT extension. No effect on APP maturation.
FT MUTAGEN 756 756 G->A: APP internalization unchanged. No
FT change in beta-APP42 secretion.
FT MUTAGEN 757 757 Y->A: Little APP internalization. Reduced
FT beta-APP42 secretion.
FT MUTAGEN 757 757 Y->G: Loss of binding to MAPK8IP1, APBA1,
FT APBB1, APPBP2 and SHC1.
FT MUTAGEN 759 759 N->A: No binding to APBA1, no effect on
FT APBB1 binding. Little APP
FT internalization. Reduced beta-APP42
FT secretion.
FT MUTAGEN 760 760 P->A: Little APP internalization. Reduced
FT beta-APP42 secretion.
FT MUTAGEN 762 762 Y->A: Loss of binding to APBA1 and APBB1.
FT APP internalization unchanged. No change
FT in beta-APP42 secretion.
FT CONFLICT 15 16 AR -> VW (in Ref. 3; CAA31830).
FT CONFLICT 647 647 D -> E (in Ref. 36; AAA51722).
FT CONFLICT 724 724 Missing (in Ref. 23; AAB26263/AAB26264).
FT CONFLICT 731 731 I -> N (in Ref. 23; AAB26263/AAB26264/
FT AAB26265).
FT CONFLICT 757 757 Y -> S (in Ref. 31; AAA35540).
FT STRAND 33 35
FT STRAND 43 45
FT TURN 47 49
FT STRAND 52 54
FT HELIX 66 76
FT STRAND 82 87
FT STRAND 92 94
FT STRAND 97 99
FT HELIX 100 102
FT STRAND 103 106
FT STRAND 110 112
FT STRAND 115 119
FT STRAND 134 139
FT HELIX 147 160
FT STRAND 163 174
FT TURN 175 177
FT STRAND 178 188
FT HELIX 288 292
FT STRAND 299 301
FT STRAND 304 310
FT TURN 311 314
FT STRAND 315 321
FT STRAND 323 325
FT STRAND 331 333
FT HELIX 334 341
FT HELIX 374 380
FT HELIX 389 418
FT STRAND 421 423
FT HELIX 425 480
FT STRAND 482 484
FT HELIX 487 518
FT HELIX 520 546
FT HELIX 547 550
FT HELIX 552 566
FT HELIX 673 675
FT STRAND 679 682
FT STRAND 683 685
FT STRAND 688 691
FT HELIX 695 697
FT STRAND 698 700
FT STRAND 702 705
FT STRAND 707 712
FT HELIX 744 754
FT STRAND 755 758
FT STRAND 763 765
SQ SEQUENCE 770 AA; 86943 MW; A12EE761403740F5 CRC64;
MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN
IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN
Score > 15 indicates identity