A4_HUMAN
ID A4_HUMAN Reviewed; 770 AA.
AC P05067; B2R5V1; B4DII8; D3DSD1; D3DSD2; D3DSD3; P09000; P78438; Q13764;
AC Q13778; Q13793; Q16011; Q16014; Q16019; Q16020; Q6GSC0; Q8WZ99; Q9BT38;
AC Q9UC33; Q9UCA9; Q9UCB6; Q9UCC8; Q9UCD1; Q9UQ58;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 3.
DT 03-AUG-2022, entry version 301.
DE RecName: Full=Amyloid-beta precursor protein {ECO:0000312|HGNC:HGNC:620};
DE Short=APP {ECO:0000312|HGNC:HGNC:620};
DE AltName: Full=ABPP;
DE AltName: Full=APPI;
DE AltName: Full=Alzheimer disease amyloid A4 protein homolog;
DE AltName: Full=Alzheimer disease amyloid protein;
DE AltName: Full=Amyloid precursor protein {ECO:0000305};
DE AltName: Full=Amyloid-beta (A4) precursor protein {ECO:0000250|UniProtKB:P12023};
DE AltName: Full=Amyloid-beta A4 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 {ECO:0000303|PubMed:10656250};
DE Short=S-APP-alpha {ECO:0000303|PubMed:10656250};
DE Contains:
DE RecName: Full=Soluble APP-beta {ECO:0000303|PubMed:10656250};
DE Short=S-APP-beta {ECO:0000303|PubMed:10656250};
DE Contains:
DE RecName: Full=C99;
DE AltName: Full=Beta-secretase C-terminal fragment {ECO:0000303|PubMed:10656250};
DE Short=Beta-CTF {ECO:0000303|PubMed:10656250};
DE Contains:
DE RecName: Full=Amyloid-beta protein 42 {ECO:0000303|PubMed:8886002};
DE Short=Abeta42;
DE AltName: Full=Beta-APP42;
DE Contains:
DE RecName: Full=Amyloid-beta protein 40 {ECO:0000303|PubMed:8886002};
DE Short=Abeta40;
DE AltName: Full=Beta-APP40;
DE Contains:
DE RecName: Full=C83;
DE AltName: Full=Alpha-secretase C-terminal fragment {ECO:0000303|PubMed:10656250};
DE Short=Alpha-CTF {ECO:0000303|PubMed:10656250};
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 {ECO:0000312|HGNC:HGNC:620};
GN Synonyms=A4 {ECO:0000303|PubMed:2881207}, AD1 {ECO:0000312|HGNC:HGNC:620};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 cell-
RT 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., Cordell B.;
RT "A new A4 amyloid mRNA contains a domain homologous to serine proteinase
RT 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 gene.";
RL Gene 87:257-263(1990).
RN [5]
RP ERRATUM OF PUBMED:2110105.
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; DOI=10.1016/s0021-9258(19)50090-4;
RA Koenig G., Moenning U., Czech C., Prior R., Banati R., Schreiter-Gasser U.,
RA Bauer J., Masters C.L., Beyreuther K.;
RT "Identification and differential expression of a novel alternative splice
RT isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes
RT 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., Saito M.,
RA 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 amyloid
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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) encodes
RT a 95-kDa polypeptide.";
RL Nucleic Acids Res. 16:9351-9351(1988).
RN [15]
RP ERRATUM OF PUBMED:3140222, 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 beta-
RT 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; DOI=10.1016/s0021-9258(18)47443-1;
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., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT 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 mRNA
RT 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 mRNA are
RT 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; ILE-717
RP 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., Ninomiya H.,
RA Saido T.C., Hashimoto T., Iwatsubo T., Nakashima K.;
RT "Novel amyloid precursor protein gene missense mutation (D678N) in probable
RT familial Alzheimer's disease.";
RL J. Neurol. Neurosurg. Psych. 75:1039-1042(2004).
RN [26]
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 [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., Sinha S.,
RA 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.
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 fluid.";
RL J. Neurochem. 61:1965-1968(1993).
RN [29]
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., Gowing E.,
RA 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 [30]
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 [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 brain
RT 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., St George-Hyslop P.H.,
RA Van Keuren M.L., Patterson D., Pagan S., Kurnit D.M., Neve R.L.;
RT "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage
RT near the Alzheimer locus.";
RL Science 235:880-884(1987).
RN [33]
RP PROTEIN SEQUENCE OF 609-713, AND GLYCOSYLATION AT THR-633; THR-651;
RP THR-652; THR-659; THR-663; SER-667 AND TYR-681.
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., Halim A.,
RA Larson G., Ruetschi U., Zetterberg H., Blennow K., Brinkmalm A.;
RT "An online nano-LC-ESI-FTICR-MS method for comprehensive characterization
RT of endogenous fragments from amyloid beta and amyloid precursor protein in
RT human and cat cerebrospinal fluid.";
RL J. Mass Spectrom. 47:591-603(2012).
RN [34]
RP PROTEIN SEQUENCE OF 691-698, AND PROTEOLYTIC CLEAVAGE AT PHE-690 BY
RP 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 SUBCELLULAR LOCATION, SIGNAL SEQUENCE CLEAVAGE SITE, AND TOPOLOGY.
RX PubMed=2900137; DOI=10.1002/j.1460-2075.1988.tb02900.x;
RA Dyrks T., Weidemann A., Multhaup G., Salbaum J.M., Lemaire H.-G., Kang J.,
RA Mueller-Hill B., Masters C.L., Beyreuther K.;
RT "Identification, transmembrane orientation and biogenesis of the amyloid A4
RT precursor of Alzheimer's disease.";
RL EMBO J. 7:949-957(1988).
RN [38]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, SULFATION, AND
RP OX-2 MOTIF.
RX PubMed=2649245; DOI=10.1016/0092-8674(89)90177-3;
RA Weidemann A., Koenig G., Bunke D., Fischer P., Salbaum J.M., Masters C.L.,
RA Beyreuther K.;
RT "Identification, biogenesis, and localization of precursors of Alzheimer's
RT disease A4 amyloid protein.";
RL Cell 57:115-126(1989).
RN [39]
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., Johnson-Wood K.L.,
RA Beattie E.C., Ward P.J., Blacher R.W., Dovey H.F., Sinha S.;
RT "The secreted form of the Alzheimer's amyloid precursor protein with the
RT Kunitz domain is protease nexin-II.";
RL Nature 341:144-147(1989).
RN [40]
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 disease
RT amyloid protein precursor.";
RL Biochem. Biophys. Res. Commun. 167:716-721(1990).
RN [41]
RP EXTRACELLULAR ZINC-BINDING DOMAIN.
RX PubMed=8344894; DOI=10.1016/s0021-9258(19)85394-2;
RA Bush A.I., Multhaup G., Moir R.D., Williamson T.G., Small D.H., Rumble B.,
RA 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 [42]
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 [43]
RP PHOSPHORYLATION AT THR-743.
RX PubMed=8131745; DOI=10.1002/j.1460-2075.1994.tb06360.x;
RA Suzuki T., Oishi M., Marshak D.R., Czernik A.J., Nairn A.C., Greengard P.;
RT "Cell cycle-dependent regulation of the phosphorylation and metabolism of
RT the Alzheimer amyloid precursor protein.";
RL EMBO J. 13:1114-1122(1994).
RN [44]
RP EXTRACELLULAR COPPER-BINDING DOMAIN, AND MUTAGENESIS OF HIS-137; MET-141;
RP 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; DOI=10.1523/jneurosci.14-04-02117.1994;
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 Alzheimer's
RT disease is involved in the regulation of neurite outgrowth.";
RL J. Neurosci. 14:2117-2127(1994).
RN [46]
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 splicing
RT out exon 15 of the amyloid precursor gene.";
RL J. Biol. Chem. 270:10388-10391(1995).
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 of the
RT 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; DOI=10.1128/mcb.16.11.6229;
RA Borg J.-P., Ooi J., Levy E., Margolis B.;
RT "The phosphotyrosine interaction domains of X11 and FE65 bind to distinct
RT 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 domain
RT of the amyloid-beta precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10832-10837(1996).
RN [50]
RP FUNCTION OF AMYLOID-BETA 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 peroxidation
RT as a result of its membrane interactions.";
RL Biochem. Biophys. Res. Commun. 233:760-764(1997).
RN [51]
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., Clarris H.J.,
RA 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 [52]
RP INTERACTION OF AMYLOID-BETA 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., Collinson K.,
RA Zhu A., Stern E., Saido T., Tohyama M., Ogawa S., 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 [53]
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., Pipkorn R.,
RA 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 [54]
RP INTERACTION WITH APPBP2, MUTAGENESIS OF TYR-728, AND DOMAIN.
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 [55]
RP AMYLOID-BETA ZINC-BINDING, AND MUTAGENESIS OF ARG-676; TYR-681 AND 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 of
RT the A beta peptide of Alzheimer's disease.";
RL Biochemistry 38:9373-9378(1999).
RN [56]
RP PROTEOLYTIC CLEAVAGE AT ASP-197; ASP-219 AND ASP-739 BY CASPASES, AND
RP 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., Huang J.,
RA LeBlanc A., Smith D., Rigby M., Shearman M.S., Clarke E.E., Zheng H.,
RA van der Ploeg L.H.T., Ruffolo S.C., Thornberry N.A., Xanthoudakis S.,
RA Zamboni R.J., Roy S., Nicholson D.W.;
RT "Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-
RT beta precursor protein and amyloidogenic A beta peptide formation.";
RL Cell 97:395-406(1999).
RN [57]
RP IMPORTANCE OF MET-706 IN FREE RADICAL OXIDATIVE STRESS, AND MUTAGENESIS OF
RP 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 free
RT radical oxidative stress.";
RL Brain Res. Bull. 50:133-141(1999).
RN [58]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF THR-743.
RX PubMed=10341243; DOI=10.1523/jneurosci.19-11-04421.1999;
RA Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C., Kirino Y.,
RA Greengard P., Suzuki T.;
RT "Role of phosphorylation of Alzheimer's amyloid precursor protein during
RT neuronal differentiation.";
RL J. Neurosci. 19:4421-4427(1999).
RN [59]
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., Sakiyama S.,
RA 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 [60]
RP SUBCELLULAR LOCATION, ENDOCYTOSIS SIGNAL, AND MUTAGENESIS OF TYR-728;
RP GLY-756; TYR-757; 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., Selkoe D.J.,
RA 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, including
RT Abeta42.";
RL J. Biol. Chem. 274:18851-18856(1999).
RN [61]
RP IMPORTANCE OF CYS-144 IN COPPER REDUCTION, AND MUTAGENESIS OF CYS-144 AND
RP 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-amyloid
RT precursor protein.";
RL J. Neurochem. 73:1288-1292(1999).
RN [62]
RP CLEAVAGE BY BACE1, SUBCELLULAR LOCATION (SOLUBLE APP-BETA), AND
RP CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX PubMed=10656250; DOI=10.1006/mcne.1999.0811;
RA Hussain I., Powell D.J., Howlett D.R., Tew D.G., Meek T.D., Chapman C.,
RA Gloger I.S., Murphy K.E., Southan C.D., Ryan D.M., Smith T.S.,
RA Simmons D.L., Walsh F.S., Dingwall C., Christie G.;
RT "Identification of a novel aspartic proteinase (Asp 2) as beta-secretase.";
RL Mol. Cell. Neurosci. 14:419-427(1999).
RN [63]
RP INTERACTION WITH APBB3.
RX PubMed=10081969; DOI=10.1016/s0304-3940(98)00995-1;
RA Tanahashi H.;
RT "Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's
RT beta-amyloid precursor protein.";
RL Neurosci. Lett. 261:143-146(1999).
RN [64]
RP INTERACTION OF AMYLOID-BETA WITH APOE.
RX PubMed=10816430; DOI=10.1042/bj3480359;
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., Ghiso J.;
RT "Lipidation of apolipoprotein E influences its isoform-specific interaction
RT with Alzheimer's amyloid beta peptides.";
RL Biochem. J. 348:359-365(2000).
RN [65]
RP INTERACTION OF APP42-BETA 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 with
RT high affinity. Implications for Alzheimer's disease pathology.";
RL J. Biol. Chem. 275:5626-5632(2000).
RN [66]
RP IDENTIFICATION OF GAMMA-CTFS BY MASS SPECTROMETRY, MUTAGENESIS OF ASP-739,
RP AND PROTEOLYTIC CLEAVAGE.
RX PubMed=12214090; DOI=10.3233/jad-2000-23-408;
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 [67]
RP REVIEW ON FUNCTION OF AMYLOID-BETA 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 [68]
RP INTERACTION WITH FPR2 (AMYLOID-BETA PROTEIN 42), AND SUBCELLULAR LOCATION
RP (AMYLOID-BETA PROTEIN 42).
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-coupled
RT receptor FPRL1 and forms fibrillar aggregates in macrophages.";
RL FASEB J. 15:2454-2462(2001).
RN [69]
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., Edris W.,
RA Chanda P., Wagner E., Vile S., Ryan K., McHendry-Rinde B., Smith S.C.,
RA Wood A., Rhodes K.J., Kennedy J.D., Bard J., Jacobsen J.S.,
RA 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 [70]
RP AMYLOID-BETA COPPER AND ZINC-BINDING SITES.
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 [71]
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 the
RT amyloidogenic pathway of Alzheimer's disease.";
RL J. Biol. Chem. 276:33923-33929(2001).
RN [72]
RP INTERACTION WITH APBB1, FUNCTION, AND SUBCELLULAR LOCATION (GAMMA-SECRETASE
RP C-TERMINAL FRAGMENT 59).
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 [73]
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 protein
RT and modulates its physiological function.";
RL J. Neurochem. 76:1411-1420(2001).
RN [74]
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., Fleck T.J.,
RA Johnston J.A., Sharma S.K.;
RT "Direct interaction of soluble human recombinant tau protein with Abeta 1-
RT 42 results in tau aggregation and hyperphosphorylation by tau protein
RT kinase II.";
RL FEBS Lett. 514:263-268(2002).
RN [75]
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 [76]
RP COPPER-MEDIATED LIPID PEROXIDATION, AND MUTAGENESIS OF HIS-147 AND HIS-151.
RX PubMed=11784781; DOI=10.1523/jneurosci.22-02-00365.2002;
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 neurotoxicity
RT by the Alzheimer's disease amyloid precursor protein.";
RL J. Neurosci. 22:365-376(2002).
RN [77]
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 [78]
RP PHOSPHORYLATION AT SER-198 AND SER-206 BY CASEIN KINASES, AND MUTAGENESIS
RP 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., Thinakaran G.,
RA 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 [79]
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 surface
RT by ectocasein kinases 1 and 2.";
RL J. Biol. Chem. 275:23523-23529(2000).
RN [80]
RP PROTEOLYTIC 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-protein
RT precursor.";
RL Nat. Med. 6:397-404(2000).
RN [81]
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 [82]
RP PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42).
RX PubMed=11604391; DOI=10.1074/jbc.m104068200;
RA Hu J., Igarashi A., Kamata M., Nakagawa H.;
RT "Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A
RT beta); retards A beta aggregation, deposition, fibril formation; and
RT inhibits cytotoxicity.";
RL J. Biol. Chem. 276:47863-47868(2001).
RN [83]
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 Alzheimer's
RT disease amyloid precursor protein by stress-activated protein kinase 1b
RT (Jun N-terminal kinase-3).";
RL J. Neurochem. 76:316-320(2001).
RN [84]
RP PROTEOLYTIC CLEAVAGE AT MET-671; LYS-687; VAL-711; ALA-713 AND LEU-720.
RX PubMed=11851430; DOI=10.1021/bi015794o;
RA Weidemann A., Eggert S., Reinhard F.B.M., Vogel M., Paliga K., Baier G.,
RA Masters C.L., Beyreuther K., Evin G.;
RT "A novel epsilon-cleavage within the transmembrane domain of the Alzheimer
RT amyloid precursor protein demonstrates homology with Notch processing.";
RL Biochemistry 41:2825-2835(2002).
RN [85]
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 cytoplasmic
RT tail promotes interaction with Shc.";
RL J. Biol. Chem. 277:16798-16804(2002).
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 APBB2.
RX PubMed=14527950; DOI=10.1074/jbc.m309561200;
RA Chang Y., Tesco G., Jeong W.J., Lindsley L., Eckman E.A., Eckman C.B.,
RA Tanzi R.E., Guenette S.Y.;
RT "Generation of the beta-amyloid peptide and the amyloid precursor protein
RT C-terminal fragment gamma are potentiated by FE65L1.";
RL J. Biol. Chem. 278:51100-51107(2003).
RN [88]
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 localization
RT in DIG domains and possible roles in the pathogenesis of Alzheimer's
RT disease.";
RL FASEB J. 18:1013-1015(2004).
RN [89]
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-associated
RT protein-1 proteins bind to AbetaPP and modulate its processing in an
RT isoform-specific manner.";
RL J. Biol. Chem. 279:49105-49112(2004).
RN [90]
RP PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42),
RP AND SUBCELLULAR LOCATION (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN
RP 42).
RX PubMed=16154999; DOI=10.1074/jbc.m508460200;
RA Hemming M.L., Selkoe D.J.;
RT "Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme
RT (ACE) and elevated by an ACE inhibitor.";
RL J. Biol. Chem. 280:37644-37650(2005).
RN [91]
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., Moore R.J.,
RA 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 [92]
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., Behlke J.,
RA von Arnim C.A., Breiderhoff T., Jansen P., Wu X., Bales K.R., Cappai R.,
RA Masters C.L., Gliemann J., Mufson E.J., Hyman B.T., Paul S.M., Nykjaer A.,
RA Willnow T.E.;
RT "Neuronal sorting protein-related receptor sorLA/LR11 regulates processing
RT of the amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005).
RN [93]
RP INTERACTION WITH SORL1, AND MUTAGENESIS OF 757-TYR--TYR-762.
RX PubMed=16407538; DOI=10.1523/jneurosci.3882-05.2006;
RA Spoelgen R., von Arnim C.A., Thomas A.V., Peltan I.D., Koker M., Deng A.,
RA Irizarry M.C., Andersen O.M., Willnow T.E., Hyman B.T.;
RT "Interaction of the cytosolic domains of sorLA/LR11 with the amyloid
RT precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme.";
RL J. Neurosci. 26:418-428(2006).
RN [94]
RP FUNCTION.
RX PubMed=17062754; DOI=10.1073/pnas.0607527103;
RA Satpute-Krishnan P., DeGiorgis J.A., Conley M.P., Jang M., Bearer E.L.;
RT "A peptide zipcode sufficient for anterograde transport within amyloid
RT precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16532-16537(2006).
RN [95]
RP INTERACTION WITH SORL1.
RX PubMed=17855360; DOI=10.1074/jbc.m705073200;
RA Schmidt V., Sporbert A., Rohe M., Reimer T., Rehm A., Andersen O.M.,
RA Willnow T.E.;
RT "SorLA/LR11 regulates processing of amyloid precursor protein via
RT interaction with adaptors GGA and PACS-1.";
RL J. Biol. Chem. 282:32956-32964(2007).
RN [96]
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 beta-
RT protein precursor in osmotically stressed cells.";
RL J. Biol. Chem. 283:19119-19131(2008).
RN [97]
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 mechanistically
RT distinct manner from its homologue dementia gene BRI2.";
RL J. Biol. Chem. 284:15815-15825(2009).
RN [98]
RP FUNCTION, PROTEOLYTIC 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 [99]
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 [100]
RP SUBCELLULAR LOCATION.
RX PubMed=20580937; DOI=10.1016/j.bbalip.2010.05.010;
RA Cossec J.C., Simon A., Marquer C., Moldrich R.X., Leterrier C., Rossier J.,
RA Duyckaerts C., Lenkei Z., Potier M.C.;
RT "Clathrin-dependent APP endocytosis and Abeta secretion are highly
RT sensitive to the level of plasma membrane cholesterol.";
RL Biochim. Biophys. Acta 1801:846-852(2010).
RN [101]
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., Bettayeb K.,
RA Flajolet M., Gorelick F., Wennogle L.P., Greengard P.;
RT "Gamma-secretase activating protein is a therapeutic target for Alzheimer's
RT disease.";
RL Nature 467:95-98(2010).
RN [102]
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., Buerckstuemmer T.,
RA 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 [103]
RP GLYCOSYLATION AT THR-633; THR-651; THR-652; SER-656; THR-663 AND SER-667
RP PROTEOLYTIC PROCESSING, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=21712440; DOI=10.1073/pnas.1102664108;
RA Halim A., Brinkmalm G., Ruetschi U., Westman-Brinkmalm A., Portelius E.,
RA 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 human
RT cerebrospinal fluid.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11848-11853(2011).
RN [104]
RP FUNCTION, AND INTERACTION WITH KIF5B.
RX PubMed=23011729; DOI=10.1088/1478-3975/9/5/055005;
RA Seamster P.E., Loewenberg M., Pascal J., Chauviere A., Gonzales A.,
RA Cristini V., Bearer E.L.;
RT "Quantitative measurements and modeling of cargo-motor interactions during
RT fast transport in the living axon.";
RL Phys. Biol. 9:055005-055005(2012).
RN [105]
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 and
RT induces its fibrillization.";
RL PLoS ONE 7:E32953-E32953(2012).
RN [106]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-743, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [107]
RP INTERACTION WITH PLD3.
RX PubMed=24336208; DOI=10.1038/nature12825;
RG UK Brain Expression Consortium;
RA Cruchaga C., Karch C.M., Jin S.C., Benitez B.A., Cai Y., Guerreiro R.,
RA Harari O., Norton J., Budde J., Bertelsen S., Jeng A.T., Cooper B.,
RA Skorupa T., Carrell D., Levitch D., Hsu S., Choi J., Ryten M., Hardy J.,
RA Ryten M., Trabzuni D., Weale M.E., Ramasamy A., Smith C., Sassi C.,
RA Bras J., Gibbs J.R., Hernandez D.G., Lupton M.K., Powell J., Forabosco P.,
RA Ridge P.G., Corcoran C.D., Tschanz J.T., Norton M.C., Munger R.G.,
RA Schmutz C., Leary M., Demirci F.Y., Bamne M.N., Wang X., Lopez O.L.,
RA Ganguli M., Medway C., Turton J., Lord J., Braae A., Barber I., Brown K.,
RA Passmore P., Craig D., Johnston J., McGuinness B., Todd S., Heun R.,
RA Kolsch H., Kehoe P.G., Hooper N.M., Vardy E.R., Mann D.M.,
RA Pickering-Brown S., Brown K., Kalsheker N., Lowe J., Morgan K.,
RA David Smith A., Wilcock G., Warden D., Holmes C., Pastor P.,
RA Lorenzo-Betancor O., Brkanac Z., Scott E., Topol E., Morgan K., Rogaeva E.,
RA Singleton A.B., Hardy J., Kamboh M.I., St George-Hyslop P., Cairns N.,
RA Morris J.C., Kauwe J.S., Goate A.M.;
RT "Rare coding variants in the phospholipase D3 gene confer risk for
RT Alzheimer's disease.";
RL Nature 505:550-554(2014).
RN [108]
RP INTERACTION WITH VDAC1.
RX PubMed=25168729; DOI=10.1016/j.neuroscience.2014.07.079;
RA Fernandez-Echevarria C., Diaz M., Ferrer I., Canerina-Amaro A., Marin R.;
RT "Abeta promotes VDAC1 channel dephosphorylation in neuronal lipid rafts.
RT Relevance to the mechanisms of neurotoxicity in Alzheimer's disease.";
RL Neuroscience 278:354-366(2014).
RN [109]
RP INTERACTION WITH SORL1.
RX PubMed=24523320; DOI=10.1126/scitranslmed.3007747;
RA Caglayan S., Takagi-Niidome S., Liao F., Carlo A.S., Schmidt V.,
RA Burgert T., Kitago Y., Fuechtbauer E.M., Fuechtbauer A., Holtzman D.M.,
RA Takagi J., Willnow T.E.;
RT "Lysosomal sorting of amyloid-beta by the SORLA receptor is impaired by a
RT familial Alzheimer's disease mutation.";
RL Sci. Transl. Med. 6:223RA20-223RA20(2014).
RN [110]
RP PHOSPHORYLATION AT SER-441 AND TYR-497.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [111]
RP INTERACTION WITH LRRK2, PHOSPHORYLATION AT THR-743, AND MUTAGENESIS OF
RP THR-743.
RX PubMed=28720718; DOI=10.1126/scisignal.aam6790;
RA Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z.,
RA Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L.,
RA Tan E.K.;
RT "Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD
RT activity and neurotoxicity in Parkinson's disease.";
RL Sci. Signal. 10:0-0(2017).
RN [112]
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 Alzheimer's
RT amyloid beta-protein precursor.";
RL Biochemistry 29:10018-10022(1990).
RN [113]
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 the
RT Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor
RT protein.";
RL Biochemistry 30:10467-10478(1991).
RN [114]
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 [115]
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 [116]
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 [117]
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., Kossiakoff A.A.;
RT "Crystal structures of bovine chymotrypsin and trypsin complexed to the
RT inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and
RT basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with
RT altered specificities.";
RL Protein Sci. 6:1806-1824(1997).
RN [118]
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 [119]
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., Galatis D.,
RA Hesse L., Multhaup G., Beyreuther K., Masters C.L., 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 [120]
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 endothelial
RT cells.";
RL J. Biol. Chem. 275:27110-27116(2000).
RN [121]
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., Lu Y.,
RA 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 [122]
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 peptides
RT of Abeta(1-28) mutated at the alpha-secretase cleavage site.";
RL J. Struct. Biol. 130:142-152(2000).
RN [123] {ECO:0007744|PDB:1OWT}
RP STRUCTURE BY NMR OF 124-189, DISULFIDE BONDS, AND COPPER-BINDING SITES.
RX PubMed=12611883; DOI=10.1074/jbc.m300629200;
RA Barnham K.J., McKinstry W.J., Multhaup G., Galatis D., Morton C.J.,
RA Curtain C.C., Williamson N.A., White A.R., Hinds M.G., Norton R.S.,
RA Beyreuther K., Masters C.L., Parker M.W., Cappai R.;
RT "Structure of the Alzheimer's disease amyloid precursor protein copper
RT binding domain. A regulator of neuronal copper homeostasis.";
RL J. Biol. Chem. 278:17401-17407(2003).
RN [124]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 346-551, PARTIAL PROTEIN SEQUENCE,
RP MUTAGENESIS OF ARG-499 AND LYS-503, AND IDENTIFICATION BY MASS
RP 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 [125]
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 [126]
RP X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 133-189, AND DISULFIDE 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-binding
RT domain at atomic resolution.";
RL Acta Crystallogr. F 63:819-824(2007).
RN [127] {ECO:0007744|PDB:2FJZ, ECO:0007744|PDB:2FK1, ECO:0007744|PDB:2FK2, ECO:0007744|PDB:2FK3, ECO:0007744|PDB:2FKL}
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 133-189 IN COMPLEXES WITH COPPER
RP 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., Galatis D.,
RA Masters C.L., Barnham K.J., McKinstry W.J., Cappai R., Parker M.W.;
RT "Structural studies of the Alzheimer's amyloid precursor protein copper-
RT binding domain reveal how it binds copper ions.";
RL J. Mol. Biol. 367:148-161(2007).
RN [128]
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 [129]
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., Baker J.,
RA Comery T.A., Diep L., Gill D., Johnson-Wood K., Goel A., Grantcharova K.,
RA Lee M., Li J., Partridge A., Griswold-Prenner I., Piot N., Walker D.,
RA Widom A., Pangalos M.N., Seubert P., 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 [130]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 18-190, PARTIAL PROTEIN SEQUENCE,
RP SUBUNIT, DISULFIDE BONDS, AND IDENTIFICATION BY MASS 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 the
RT amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:5381-5386(2010).
RN [131] {ECO:0007744|PDB:2LOH}
RP STRUCTURE BY NMR OF 686-726, AND SUBCELLULAR LOCATION.
RX PubMed=22584060; DOI=10.1016/j.febslet.2012.04.062;
RA Nadezhdin K.D., Bocharova O.V., Bocharov E.V., Arseniev A.S.;
RT "Dimeric structure of transmembrane domain of amyloid precursor protein in
RT micellar environment.";
RL FEBS Lett. 586:1687-1692(2012).
RN [132] {ECO:0007744|PDB:2LP1}
RP STRUCTURE BY NMR OF 671-770, AND SUBCELLULAR LOCATION.
RX PubMed=22654059; DOI=10.1126/science.1219988;
RA Barrett P.J., Song Y., Van Horn W.D., Hustedt E.J., Schafer J.M.,
RA Hadziselimovic A., Beel A.J., Sanders C.R.;
RT "The amyloid precursor protein has a flexible transmembrane domain and
RT binds cholesterol.";
RL Science 336:1168-1171(2012).
RN [133] {ECO:0007744|PDB:4JFN}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 23-185 IN COMPLEX WITH COPPER,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, DISULFIDE BONDS, AND
RP MUTAGENESIS OF HIS-108; HIS-110; HIS-147 AND HIS-151.
RX PubMed=25122912; DOI=10.1523/jneurosci.0180-14.2014;
RA Baumkotter F., Schmidt N., Vargas C., Schilling S., Weber R., Wagner K.,
RA Fiedler S., Klug W., Radzimanowski J., Nickolaus S., Keller S., Eggert S.,
RA Wild K., Kins S.;
RT "Amyloid precursor protein dimerization and synaptogenic function depend on
RT copper binding to the growth factor-like domain.";
RL J. Neurosci. 34:11159-11172(2014).
RN [134] {ECO:0007744|PDB:2MGT}
RP STRUCTURE BY NMR OF 672-687, ZINC-BINDING SITES, AND DOMAIN.
RX PubMed=26898943; DOI=10.1038/srep21734;
RA Istrate A.N., Kozin S.A., Zhokhov S.S., Mantsyzov A.B., Kechko O.I.,
RA Pastore A., Makarov A.A., Polshakov V.I.;
RT "Interplay of histidine residues of the Alzheimer's disease Abeta peptide
RT governs its Zn-induced oligomerization.";
RL Sci. Rep. 6:21734-21734(2016).
RN [135] {ECO:0007744|PDB:5LFY}
RP STRUCTURE BY NMR OF 672-681, AND DOMAIN.
RX PubMed=28570778; DOI=10.1002/anie.201704615;
RA Polshakov V.I., Mantsyzov A.B., Kozin S.A., Adzhubei A.A., Zhokhov S.S.,
RA van Beek W., Kulikova A.A., Indeykina M.I., Mitkevich V.A., Makarov A.A.;
RT "A Binuclear Zinc Interaction Fold Discovered in the Homodimer of
RT Alzheimer's Amyloid-beta Fragment with Taiwanese Mutation D7H.";
RL Angew. Chem. Int. Ed. Engl. 56:11734-11739(2017).
RN [136] {ECO:0007744|PDB:5OQV}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS) OF 672-713.
RX PubMed=28882996; DOI=10.1126/science.aao2825;
RA Gremer L., Scholzel D., Schenk C., Reinartz E., Labahn J., Ravelli R.B.G.,
RA Tusche M., Lopez-Iglesias C., Hoyer W., Heise H., Willbold D.,
RA Schroder G.F.;
RT "Fibril structure of amyloid-beta(1-42) by cryo-electron microscopy.";
RL Science 358:116-119(2017).
RN [137] {ECO:0007744|PDB:5VOS}
RP STRUCTURE BY ELECTRON MICROSCOPY (1.42 ANGSTROMS) OF 695-705.
RX PubMed=29282295; DOI=10.1074/jbc.m117.806109;
RA Krotee P., Griner S.L., Sawaya M.R., Cascio D., Rodriguez J.A., Shi D.,
RA Philipp S., Murray K., Saelices L., Lee J., Seidler P., Glabe C.G.,
RA Jiang L., Gonen T., Eisenberg D.S.;
RT "Common fibrillar spines of amyloid-beta and human islet amyloid
RT polypeptide revealed by microelectron diffraction and structure-based
RT inhibitors.";
RL J. Biol. Chem. 293:2888-2902(2018).
RN [138]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 688-770 IN COMPLEX
RP WITH GAMMA-SECRETASE, INTERACTION WITH PSEN1, SUBUNIT, PROTEOLYTIC CLEAVAGE
RP BY PSEN1, TOPOLOGY, AND MUTAGENESIS OF VAL-695.
RX PubMed=30630874; DOI=10.1126/science.aaw0930;
RA Zhou R., Yang G., Guo X., Zhou Q., Lei J., Shi Y.;
RT "Recognition of the amyloid precursor protein by human gamma-secretase.";
RL Science 0:0-0(2019).
RN [139]
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 [140]
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., Lieberburg I.,
RA van Duinen S.G., Bots G.T.A.M., Luyendijk W., Frangione B.;
RT "Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral
RT hemorrhage, Dutch type.";
RL Science 248:1124-1126(1990).
RN [141]
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., Newton P.,
RA Rooke K., Roques P., Talbot C., Pericak-Vance M., Roses A.D.,
RA Williamson R., Rossor M., Owen M., Hardy J.;
RT "Segregation of a missense mutation in the amyloid precursor protein gene
RT with familial Alzheimer's disease.";
RL Nature 349:704-706(1991).
RN [142]
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 associated
RT with familial Alzheimer's disease regardless of ethnic groups.";
RL Biochem. Biophys. Res. Commun. 178:1141-1146(1991).
RN [143]
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 gene
RT in Japanese familial Alzheimer's disease.";
RL Lancet 337:978-979(1991).
RN [144]
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 the
RT beta-amyloid precursor protein gene.";
RL Nature 353:844-846(1991).
RN [145]
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 hereditary
RT Alzheimer's disease.";
RL Science 254:97-99(1991).
RN [146]
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., Ball M.J.,
RA Kaye J., Warren A., McInnis M.G., Antonarakis S.E., Korenberg J.R.,
RA Sharma V., Kukull W., Larson E., Heston L.L., Martin G.M., Bird T.D.,
RA Schellenberg G.D.;
RT "Linkage and mutational analysis of familial Alzheimer disease kindreds for
RT the APP gene region.";
RL Am. J. Hum. Genet. 51:998-1014(1992).
RN [147]
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., Martin J.J.,
RA Hofman A., Van Broeckhoven C.;
RT "Presenile dementia and cerebral haemorrhage linked to a mutation at codon
RT 692 of the beta-amyloid precursor protein gene.";
RL Nat. Genet. 1:218-221(1992).
RN [148]
RP VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
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 gene at
RT the N-terminus of beta-amyloid.";
RL Nat. Genet. 1:345-347(1992).
RN [149]
RP CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX PubMed=1465129; DOI=10.1038/360672a0;
RA Citron M., Oltersdorf T., Haass C., McConlogue L., Hung A.Y., Seubert P.,
RA Vigo-Pelfrey C., Lieberburg I., Selkoe D.J.;
RT "Mutation of the beta-amyloid precursor protein in familial Alzheimer's
RT disease increases beta-protein production.";
RL Nature 360:672-674(1992).
RN [150]
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., Brock D.J.H.,
RA 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 [151]
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 [152]
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 Alzheimer's
RT disease with APP717 mutations.";
RL Biochem. Biophys. Res. Commun. 197:386-392(1993).
RN [153]
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 patient
RT with late-onset Alzheimer's disease.";
RL Ann. Neurol. 35:432-438(1994).
RN [154]
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., Benson M.D.;
RT "Clinical characteristics in a kindred with early-onset Alzheimer's disease
RT and their linkage to a G-->T change at position 2149 of the amyloid
RT precursor protein gene.";
RL Neurology 44:105-111(1994).
RN [155]
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., Schofield P.R.,
RA Kwok J.B.J., Fisher C., Yeung L.U., 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 [156]
RP CHARACTERIZATION OF VARIANTS AD1 GLY-717; ILE-717 AND PHE-717, AND
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 [157]
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., Pfeiffer E.,
RA Graff-Radford N., Hinder P., Yager D., Zenk B., Refolo L.M., Prada C.M.,
RA Younkin S.G., Hutton M., Hardy J.;
RT "A new pathogenic mutation in the APP gene (I716V) increases the relative
RT proportion of A beta 42(43).";
RL Hum. Mol. Genet. 6:2087-2089(1997).
RN [158]
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 large
RT amyloid core type senile plaques in the APP 692Ala-->Gly mutation.";
RL Acta Neuropathol. 96:253-260(1998).
RN [159]
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., Campion D.,
RA Frebourg T., Checler F.;
RT "Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP)
RT maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for
RT probable early-onset Alzheimer's disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4119-4124(1999).
RN [160]
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 [161]
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 [162]
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 [163]
RP VARIANT AD1 ILE-714, AND CHARACTERIZATION OF VARIANTS AD1 ILE-714 AND
RP ILE-717.
RX PubMed=11063718; DOI=10.1093/hmg/9.18.2589;
RA Kumar-Singh S., De Jonghe C., Cruts M., Kleinert R., Wang R., Mercken M.,
RA De Strooper B., Vanderstichele H., Loefgren A., Vanderhoeven I.,
RA Backhovens H., Vanmechelen E., Kroisel P.M., Van Broeckhoven C.;
RT "Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site
RT mutation points to an essential role for N-truncated A beta(42) in
RT Alzheimer's disease.";
RL Hum. Mol. Genet. 9:2589-2598(2000).
RN [164]
RP CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX PubMed=10677483; DOI=10.1073/pnas.97.4.1456;
RA Lin X., Koelsch G., Wu S., Downs D., Dashti A., Tang J.;
RT "Human aspartic protease memapsin 2 cleaves the beta-secretase site of
RT beta-amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1456-1460(2000).
RN [165]
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., Greenberg S.M.;
RT "Novel amyloid precursor protein mutation in an Iowa family with dementia
RT and severe cerebral amyloid angiopathy.";
RL Ann. Neurol. 49:697-705(2001).
RN [166]
RP CHARACTERIZATION OF VARIANT AD1 GLY-692.
RX PubMed=11311152; DOI=10.1042/bj3550869;
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 [167]
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., Younkin S.G.,
RA Naeslund J., Lannfelt L.;
RT "The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced
RT Abeta protofibril formation.";
RL Nat. Neurosci. 4:887-893(2001).
RN [168]
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 mutation
RT (Thr714Ala).";
RL Neurology 58:1574-1575(2002).
RN [169]
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 [170]
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., Mangieri M.,
RA Giovagnoli A.R., Bizzi A., Tomaino C., Perri M., Di Natale M.,
RA Tagliavini F., Bugiani O., Bruni A.C.;
RT "A family with Alzheimer disease and strokes associated with A713T mutation
RT of the APP gene.";
RL Neurology 63:910-912(2004).
RN [171]
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., Donadei S.,
RA Arbustini E., Palladini G., Diegoli M., Genovese E., Ferrari G.,
RA Coverlizza S., Merlini G.;
RT "A novel AbetaPP mutation exclusively associated with cerebral amyloid
RT angiopathy.";
RL Ann. Neurol. 58:639-644(2005).
RN [172]
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., Rogaeva E.,
RA Hardy J.;
RT "An African American family with early-onset Alzheimer disease and an APP
RT (T714I) mutation.";
RL Neurology 64:377-379(2005).
RN [173]
RP VARIANT CAA-APP LYS-693.
RX PubMed=20697050; DOI=10.1001/archneurol.2010.178;
RA Bugiani O., Giaccone G., Rossi G., Mangieri M., Capobianco R., Morbin M.,
RA Mazzoleni G., Cupidi C., Marcon G., Giovagnoli A., Bizzi A., Di Fede G.,
RA Puoti G., Carella F., Salmaggi A., Romorini A., Patruno G.M., Magoni M.,
RA Padovani A., Tagliavini F.;
RT "Hereditary cerebral hemorrhage with amyloidosis associated with the E693K
RT mutation of APP.";
RL Arch. Neurol. 67:987-995(2010).
CC -!- FUNCTION: Functions as a cell surface receptor and performs
CC physiological functions on the surface of neurons relevant to neurite
CC growth, neuronal adhesion and axonogenesis. Interaction between APP
CC molecules on neighboring cells promotes synaptogenesis
CC (PubMed:25122912). Involved in cell mobility and transcription
CC regulation through protein-protein interactions. Can promote
CC transcription activation through binding to APBB1-KAT5 and inhibits
CC Notch signaling through interaction with Numb. Couples to apoptosis-
CC inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o)
CC alpha ATPase activity (By similarity). Acts as a kinesin I membrane
CC receptor, mediating the axonal transport of beta-secretase and
CC presenilin 1 (By similarity). By acting as a kinesin I membrane
CC receptor, plays a role in axonal anterograde transport of cargo towards
CC synapes in axons (PubMed:17062754, PubMed:23011729). Involved in copper
CC homeostasis/oxidative stress through copper ion reduction. In vitro,
CC copper-metallated APP induces neuronal death directly or is potentiated
CC through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate
CC neurite outgrowth through binding to components of the extracellular
CC matrix such as heparin and collagen I and IV. The splice isoforms that
CC contain the BPTI domain possess protease inhibitor activity. Induces a
CC AGER-dependent pathway that involves activation of p38 MAPK, resulting
CC in internalization of amyloid-beta peptide and leading to mitochondrial
CC dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1
CC which are required for release of nitric oxide (NO) and subsequent
CC degradation of the heparan sulfate chains on GPC1. {ECO:0000250,
CC ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:17062754,
CC ECO:0000269|PubMed:23011729, ECO:0000269|PubMed:25122912}.
CC -!- FUNCTION: Amyloid-beta peptides are lipophilic metal chelators with
CC metal-reducing activity. Bind transient metals such as copper, zinc and
CC iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+),
CC respectively. Amyloid-beta protein 42 is a more effective reductant
CC than amyloid-beta protein 40. Amyloid-beta peptides bind to
CC lipoproteins and apolipoproteins E and J in the CSF and to HDL
CC particles in plasma, inhibiting metal-catalyzed oxidation of
CC lipoproteins. APP42-beta may activate mononuclear phagocytes in the
CC brain and elicit inflammatory responses. Promotes both tau aggregation
CC and TPK II-mediated phosphorylation. Interaction with overexpressed
CC HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in
CC lipid rafts.
CC -!- FUNCTION: Appicans elicit adhesion of neural cells to the extracellular
CC matrix and may regulate neurite outgrowth in the brain. {ECO:0000250}.
CC -!- FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved
CC peptides, including C31, are potent enhancers of neuronal apoptosis.
CC -!- FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and
CC degeneration of both neuronal cell bodies (via caspase-3) and axons
CC (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 family,
CC MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1
CC inhibits its serine phosphorylation (By similarity). Interacts (via
CC NPXY motif) with DAB2 (via PID domain); the interaction is impaired by
CC tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-
CC like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via
CC BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By
CC similarity). Associates with microtubules in the presence of ATP and in
CC a kinesin-dependent manner (By similarity). Interacts, through a C-
CC terminal domain, with GNAO1. Amyloid-beta protein 42 binds CHRNA7 in
CC hippocampal neurons. Amyloid-beta associates with HADH2. Soluble APP
CC binds, via its N-terminal head, to FBLN1. Interacts with CPEB1 and AGER
CC (By similarity). Interacts with ANKS1B and TNFRSF21. Interacts with
CC ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers;
CC dimerization is enhanced in the presence of Cu(2+) ions
CC (PubMed:25122912). Can form homodimers; this is promoted by heparin
CC binding. Amyloid-beta protein 40 interacts with S100A9. CTF-alpha
CC product of APP interacts with GSAP. Isoform APP695 interacts with SORL1
CC (via N-terminal ectodomain); this interaction retains APP in the trans-
CC Golgi network and reduces processing into soluble APP-alpha and
CC amyloid-beta peptides (PubMed:16174740, PubMed:16407538,
CC PubMed:17855360, PubMed:24523320). The C99 fragment also interacts with
CC SORL1 (PubMed:16407538). Isoform APP751 interacts with SORL1
CC (PubMed:16174740). Isoform APP770 interacts with SORL1
CC (PubMed:16174740). Interacts with PLD3. Interacts with VDAC1
CC (PubMed:25168729). Interacts with NSG1; could regulate APP processing
CC (By similarity). Amyloid-beta protein 42 interacts with FPR2
CC (PubMed:11689470). Interacts with SYT7 (By similarity). Interacts (via
CC transmembrane region) with PSEN1; the interaction is direct
CC (PubMed:30630874). Interacts with LRRK2 (PubMed:28720718). Interacts
CC (via cytoplasmic domain) with KIF5B (PubMed:23011729). Interacts (via
CC C-terminus) with APBB2/FE65L1 (via C-terminus) (PubMed:14527950,
CC PubMed:8855266). Interacts (via intracellular domain) with APBB3
CC (PubMed:10081969). {ECO:0000250|UniProtKB:P08592,
CC ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:10081969,
CC ECO:0000269|PubMed:10681545, ECO:0000269|PubMed:10816430,
CC ECO:0000269|PubMed:11238726, ECO:0000269|PubMed:11278849,
CC ECO:0000269|PubMed:11438549, ECO:0000269|PubMed:11517218,
CC ECO:0000269|PubMed:11544248, ECO:0000269|PubMed:11689470,
CC ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420,
CC ECO:0000269|PubMed:11943163, ECO:0000269|PubMed:14527950,
CC ECO:0000269|PubMed:15347684, ECO:0000269|PubMed:16174740,
CC ECO:0000269|PubMed:16407538, ECO:0000269|PubMed:17051221,
CC ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:17895381,
CC ECO:0000269|PubMed:18468999, ECO:0000269|PubMed:19225519,
CC ECO:0000269|PubMed:19366692, ECO:0000269|PubMed:19901339,
CC ECO:0000269|PubMed:20212142, ECO:0000269|PubMed:20811458,
CC ECO:0000269|PubMed:22457725, ECO:0000269|PubMed:23011729,
CC ECO:0000269|PubMed:24336208, ECO:0000269|PubMed:24523320,
CC ECO:0000269|PubMed:25122912, ECO:0000269|PubMed:25168729,
CC ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:30630874,
CC ECO:0000269|PubMed:8446172, ECO:0000269|PubMed:8626687,
CC ECO:0000269|PubMed:8855266, ECO:0000269|PubMed:8887653,
CC ECO:0000269|PubMed:9300481, ECO:0000269|PubMed:9338779,
CC ECO:0000269|PubMed:9843960, ECO:0000269|PubMed:9890987}.
CC -!- INTERACTION:
CC P05067; Q9NY61: AATF; NbExp=3; IntAct=EBI-77613, EBI-372428;
CC P05067; P16112: ACAN; NbExp=3; IntAct=EBI-77613, EBI-9076211;
CC P05067; P60709: ACTB; NbExp=8; IntAct=EBI-77613, EBI-353944;
CC P05067; P61158: ACTR3; NbExp=3; IntAct=EBI-77613, EBI-351428;
CC P05067; O14672: ADAM10; NbExp=7; IntAct=EBI-77613, EBI-1536151;
CC P05067; A0AVL1: ADAM9; NbExp=3; IntAct=EBI-77613, EBI-25935864;
CC P05067; P18509: ADCYAP1; NbExp=3; IntAct=EBI-77613, EBI-8588930;
CC P05067; P41586-2: ADCYAP1R1; NbExp=3; IntAct=EBI-77613, EBI-17241711;
CC P05067; Q15109: AGER; NbExp=3; IntAct=EBI-77613, EBI-1646426;
CC P05067; Q13155: AIMP2; NbExp=3; IntAct=EBI-77613, EBI-745226;
CC P05067; P63010-2: AP2B1; NbExp=3; IntAct=EBI-77613, EBI-11529439;
CC P05067; Q02410: APBA1; NbExp=4; IntAct=EBI-77613, EBI-368690;
CC P05067; Q99767: APBA2; NbExp=2; IntAct=EBI-77613, EBI-81711;
CC P05067; O96018: APBA3; NbExp=3; IntAct=EBI-77613, EBI-6115839;
CC P05067; O00213: APBB1; NbExp=7; IntAct=EBI-77613, EBI-81694;
CC P05067; O00213-2: APBB1; NbExp=6; IntAct=EBI-77613, EBI-13307975;
CC P05067; Q92870: APBB2; NbExp=3; IntAct=EBI-77613, EBI-79277;
CC P05067; Q92870-2: APBB2; NbExp=3; IntAct=EBI-77613, EBI-21535880;
CC P05067; O95704: APBB3; NbExp=5; IntAct=EBI-77613, EBI-286427;
CC P05067; P02743: APCS; NbExp=3; IntAct=EBI-77613, EBI-2115799;
CC P05067; Q96BI3: APH1A; NbExp=3; IntAct=EBI-77613, EBI-2606935;
CC P05067; Q8WW43: APH1B; NbExp=3; IntAct=EBI-77613, EBI-2606497;
CC P05067; Q06481-5: APLP2; NbExp=3; IntAct=EBI-77613, EBI-25646567;
CC P05067; P02647: APOA1; NbExp=8; IntAct=EBI-77613, EBI-701692;
CC P05067; P05067: APP; NbExp=107; IntAct=EBI-77613, EBI-77613;
CC P05067; Q92624: APPBP2; NbExp=3; IntAct=EBI-77613, EBI-743771;
CC P05067; Q6P4J0: ARD1A; NbExp=3; IntAct=EBI-77613, EBI-10252815;
CC P05067; P61204: ARF3; NbExp=3; IntAct=EBI-77613, EBI-641535;
CC P05067; Q0P5N6: ARL16; NbExp=3; IntAct=EBI-77613, EBI-10186132;
CC P05067; P56211: ARPP19; NbExp=3; IntAct=EBI-77613, EBI-5773880;
CC P05067; P05026: ATP1B1; NbExp=3; IntAct=EBI-77613, EBI-714630;
CC P05067; P54253: ATXN1; NbExp=8; IntAct=EBI-77613, EBI-930964;
CC P05067; P56817: BACE1; NbExp=11; IntAct=EBI-77613, EBI-2433139;
CC P05067; Q9Y5Z0: BACE2; NbExp=3; IntAct=EBI-77613, EBI-11282723;
CC P05067; Q92934: BAD; NbExp=3; IntAct=EBI-77613, EBI-700771;
CC P05067; P46379-2: BAG6; NbExp=5; IntAct=EBI-77613, EBI-10988864;
CC P05067; Q96GW7: BCAN; NbExp=3; IntAct=EBI-77613, EBI-2690445;
CC P05067; P51572: BCAP31; NbExp=3; IntAct=EBI-77613, EBI-77683;
CC P05067; P10415: BCL2; NbExp=3; IntAct=EBI-77613, EBI-77694;
CC P05067; P23560-2: BDNF; NbExp=3; IntAct=EBI-77613, EBI-12275524;
CC P05067; O15392: BIRC5; NbExp=3; IntAct=EBI-77613, EBI-518823;
CC P05067; Q13867: BLMH; NbExp=3; IntAct=EBI-77613, EBI-718504;
CC P05067; P35613: BSG; NbExp=2; IntAct=EBI-77613, EBI-750709;
CC P05067; Q8IU99: CALHM1; NbExp=3; IntAct=EBI-77613, EBI-1790341;
CC P05067; P62158: CALM3; NbExp=3; IntAct=EBI-77613, EBI-397435;
CC P05067; P27797: CALR; NbExp=5; IntAct=EBI-77613, EBI-1049597;
CC P05067; O43852-3: CALU; NbExp=3; IntAct=EBI-77613, EBI-11536607;
CC P05067; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-77613, EBI-1383687;
CC P05067; P27824-2: CANX; NbExp=3; IntAct=EBI-77613, EBI-25890990;
CC P05067; P07384: CAPN1; NbExp=3; IntAct=EBI-77613, EBI-1542113;
CC P05067; P29466-3: CASP1; NbExp=3; IntAct=EBI-77613, EBI-12248206;
CC P05067; P42574: CASP3; NbExp=4; IntAct=EBI-77613, EBI-524064;
CC P05067; Q14790: CASP8; NbExp=3; IntAct=EBI-77613, EBI-78060;
CC P05067; Q03135: CAV1; NbExp=3; IntAct=EBI-77613, EBI-603614;
CC P05067; P83916: CBX1; NbExp=6; IntAct=EBI-77613, EBI-78129;
CC P05067; P40227: CCT6A; NbExp=3; IntAct=EBI-77613, EBI-356687;
CC P05067; P16671: CD36; NbExp=3; IntAct=EBI-77613, EBI-2808214;
CC P05067; Q08722-3: CD47; NbExp=3; IntAct=EBI-77613, EBI-17263290;
CC P05067; P06493: CDK1; NbExp=3; IntAct=EBI-77613, EBI-444308;
CC P05067; Q00535: CDK5; NbExp=3; IntAct=EBI-77613, EBI-1041567;
CC P05067; P42773: CDKN2C; NbExp=3; IntAct=EBI-77613, EBI-711290;
CC P05067; P43681: CHRNA4; NbExp=3; IntAct=EBI-77613, EBI-7132379;
CC P05067; P36544: CHRNA7; NbExp=4; IntAct=EBI-77613, EBI-79333;
CC P05067; Q16740: CLPP; NbExp=3; IntAct=EBI-77613, EBI-1056029;
CC P05067; O94985-2: CLSTN1; NbExp=3; IntAct=EBI-77613, EBI-16041593;
CC P05067; Q8IUW6: CLSTN3; NbExp=3; IntAct=EBI-77613, EBI-25832219;
CC P05067; P10909: CLU; NbExp=3; IntAct=EBI-77613, EBI-1104674;
CC P05067; P26441: CNTF; NbExp=3; IntAct=EBI-77613, EBI-1050897;
CC P05067; Q02246: CNTN2; NbExp=3; IntAct=EBI-77613, EBI-4397248;
CC P05067; Q8NE08: COL25A1; NbExp=3; IntAct=EBI-77613, EBI-25836642;
CC P05067; Q96A83-2: COL26A1; NbExp=3; IntAct=EBI-77613, EBI-21553822;
CC P05067; P29400-2: COL4A5; NbExp=3; IntAct=EBI-77613, EBI-12211159;
CC P05067; Q14031: COL4A6; NbExp=3; IntAct=EBI-77613, EBI-2432407;
CC P05067; P31146: CORO1A; NbExp=3; IntAct=EBI-77613, EBI-1046676;
CC P05067; P20674: COX5A; NbExp=3; IntAct=EBI-77613, EBI-715032;
CC P05067; P15086: CPB1; NbExp=3; IntAct=EBI-77613, EBI-25936844;
CC P05067; P02511: CRYAB; NbExp=7; IntAct=EBI-77613, EBI-739060;
CC P05067; P48730: CSNK1D; NbExp=3; IntAct=EBI-77613, EBI-751621;
CC P05067; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-77613, EBI-9087876;
CC P05067; P68400: CSNK2A1; NbExp=3; IntAct=EBI-77613, EBI-347804;
CC P05067; P01034: CST3; NbExp=3; IntAct=EBI-77613, EBI-948622;
CC P05067; P49711: CTCF; NbExp=3; IntAct=EBI-77613, EBI-932887;
CC P05067; P07339: CTSD; NbExp=2; IntAct=EBI-77613, EBI-2115097;
CC P05067; P99999: CYCS; NbExp=3; IntAct=EBI-77613, EBI-446479;
CC P05067; O75553-4: DAB1; NbExp=3; IntAct=EBI-77613, EBI-21246842;
CC P05067; P98082: DAB2; NbExp=3; IntAct=EBI-77613, EBI-1171238;
CC P05067; Q14203-5: DCTN1; NbExp=5; IntAct=EBI-77613, EBI-25840379;
CC P05067; Q13561: DCTN2; NbExp=3; IntAct=EBI-77613, EBI-715074;
CC P05067; Q6I9W9: DKFZP586N0721; NbExp=3; IntAct=EBI-77613, EBI-25927172;
CC P05067; O14645: DNALI1; NbExp=3; IntAct=EBI-77613, EBI-395638;
CC P05067; Q01658: DR1; NbExp=3; IntAct=EBI-77613, EBI-750300;
CC P05067; P21917: DRD4; NbExp=6; IntAct=EBI-77613, EBI-8592297;
CC P05067; Q16828: DUSP6; NbExp=3; IntAct=EBI-77613, EBI-746870;
CC P05067; Q92997: DVL3; NbExp=3; IntAct=EBI-77613, EBI-739789;
CC P05067; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-77613, EBI-25840445;
CC P05067; O14576-5: DYNC1I1; NbExp=3; IntAct=EBI-77613, EBI-25936079;
CC P05067; Q01094: E2F1; NbExp=3; IntAct=EBI-77613, EBI-448924;
CC P05067; Q3B7T1: EDRF1; NbExp=3; IntAct=EBI-77613, EBI-2870947;
CC P05067; P20042: EIF2S2; NbExp=6; IntAct=EBI-77613, EBI-711977;
CC P05067; P19419: ELK1; NbExp=3; IntAct=EBI-77613, EBI-726632;
CC P05067; P11171-2: EPB41; NbExp=3; IntAct=EBI-77613, EBI-10197451;
CC P05067; P11171-7: EPB41; NbExp=3; IntAct=EBI-77613, EBI-25852354;
CC P05067; Q9BS26: ERP44; NbExp=3; IntAct=EBI-77613, EBI-541644;
CC P05067; P00748: F12; NbExp=3; IntAct=EBI-77613, EBI-6378830;
CC P05067; P00734: F2; NbExp=3; IntAct=EBI-77613, EBI-297094;
CC P05067; P23142-4: FBLN1; NbExp=3; IntAct=EBI-77613, EBI-11956479;
CC P05067; Q92915: FGF14; NbExp=3; IntAct=EBI-77613, EBI-10489272;
CC P05067; P62942: FKBP1A; NbExp=3; IntAct=EBI-77613, EBI-1027571;
CC P05067; P21333-2: FLNA; NbExp=3; IntAct=EBI-77613, EBI-9641086;
CC P05067; O75955: FLOT1; NbExp=5; IntAct=EBI-77613, EBI-603643;
CC P05067; Q9BTI6: FLOT2; NbExp=3; IntAct=EBI-77613, EBI-23703366;
CC P05067; P01100: FOS; NbExp=3; IntAct=EBI-77613, EBI-852851;
CC P05067; P25090: FPR2; NbExp=3; IntAct=EBI-77613, EBI-17291771;
CC P05067; P09958: FURIN; NbExp=3; IntAct=EBI-77613, EBI-1056807;
CC P05067; P06241: FYN; NbExp=3; IntAct=EBI-77613, EBI-515315;
CC P05067; P04406: GAPDH; NbExp=3; IntAct=EBI-77613, EBI-354056;
CC P05067; Q9UJY5-4: GGA1; NbExp=3; IntAct=EBI-77613, EBI-12108696;
CC P05067; Q05586: GRIN1; NbExp=3; IntAct=EBI-77613, EBI-998542;
CC P05067; P25098: GRK2; NbExp=3; IntAct=EBI-77613, EBI-3904795;
CC P05067; P43250: GRK6; NbExp=3; IntAct=EBI-77613, EBI-722747;
CC P05067; P43250-2: GRK6; NbExp=3; IntAct=EBI-77613, EBI-6428342;
CC P05067; A4D1B5: GSAP; NbExp=3; IntAct=EBI-77613, EBI-15875313;
CC P05067; P49841-2: GSK3B; NbExp=3; IntAct=EBI-77613, EBI-15870655;
CC P05067; Q03013: GSTM4; NbExp=3; IntAct=EBI-77613, EBI-713363;
CC P05067; Q00403: GTF2B; NbExp=3; IntAct=EBI-77613, EBI-389564;
CC P05067; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-77613, EBI-1054873;
CC P05067; P09429: HMGB1; NbExp=3; IntAct=EBI-77613, EBI-389432;
CC P05067; P30519: HMOX2; NbExp=3; IntAct=EBI-77613, EBI-712096;
CC P05067; Q9UJC3: HOOK1; NbExp=3; IntAct=EBI-77613, EBI-746704;
CC P05067; Q99714: HSD17B10; NbExp=7; IntAct=EBI-77613, EBI-79964;
CC P05067; Q99714-2: HSD17B10; NbExp=3; IntAct=EBI-77613, EBI-25939412;
CC P05067; P07900: HSP90AA1; NbExp=5; IntAct=EBI-77613, EBI-296047;
CC P05067; P14625: HSP90B1; NbExp=3; IntAct=EBI-77613, EBI-359129;
CC P05067; P11021: HSPA5; NbExp=3; IntAct=EBI-77613, EBI-354921;
CC P05067; P11142: HSPA8; NbExp=8; IntAct=EBI-77613, EBI-351896;
CC P05067; P04792: HSPB1; NbExp=3; IntAct=EBI-77613, EBI-352682;
CC P05067; Q16082: HSPB2; NbExp=3; IntAct=EBI-77613, EBI-739395;
CC P05067; P10809: HSPD1; NbExp=6; IntAct=EBI-77613, EBI-352528;
CC P05067; P42858: HTT; NbExp=6; IntAct=EBI-77613, EBI-466029;
CC P05067; Q9UMF0: ICAM5; NbExp=3; IntAct=EBI-77613, EBI-6398041;
CC P05067; P14735: IDE; NbExp=3; IntAct=EBI-77613, EBI-2556886;
CC P05067; Q16352: INA; NbExp=3; IntAct=EBI-77613, EBI-366258;
CC P05067; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-77613, EBI-21911304;
CC P05067; P05556: ITGB1; NbExp=3; IntAct=EBI-77613, EBI-703066;
CC P05067; Q9Y287: ITM2B; NbExp=4; IntAct=EBI-77613, EBI-2866431;
CC P05067; P05412: JUN; NbExp=5; IntAct=EBI-77613, EBI-852823;
CC P05067; P17535: JUND; NbExp=3; IntAct=EBI-77613, EBI-2682803;
CC P05067; Q92993: KAT5; NbExp=3; IntAct=EBI-77613, EBI-399080;
CC P05067; Q92993-2: KAT5; NbExp=3; IntAct=EBI-77613, EBI-20795332;
CC P05067; Q13303: KCNAB2; NbExp=3; IntAct=EBI-77613, EBI-948729;
CC P05067; Q9Y2W7: KCNIP3; NbExp=3; IntAct=EBI-77613, EBI-751501;
CC P05067; O60333-2: KIF1B; NbExp=3; IntAct=EBI-77613, EBI-10975473;
CC P05067; Q07866-2: KLC1; NbExp=3; IntAct=EBI-77613, EBI-11979975;
CC P05067; O14901: KLF11; NbExp=3; IntAct=EBI-77613, EBI-948266;
CC P05067; Q92876: KLK6; NbExp=4; IntAct=EBI-77613, EBI-2432309;
CC P05067; P01116-2: KRAS; NbExp=3; IntAct=EBI-77613, EBI-367427;
CC P05067; Q16363-3: LAMA4; NbExp=3; IntAct=EBI-77613, EBI-17719490;
CC P05067; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-77613, EBI-1108377;
CC P05067; Q96FE5: LINGO1; NbExp=3; IntAct=EBI-77613, EBI-719955;
CC P05067; Q07954-2: LRP1; NbExp=3; IntAct=EBI-77613, EBI-25833471;
CC P05067; Q9NZR2: LRP1B; NbExp=3; IntAct=EBI-77613, EBI-1642131;
CC P05067; P30533: LRPAP1; NbExp=3; IntAct=EBI-77613, EBI-715927;
CC P05067; P42704: LRPPRC; NbExp=8; IntAct=EBI-77613, EBI-1050853;
CC P05067; P07948: LYN; NbExp=3; IntAct=EBI-77613, EBI-79452;
CC P05067; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-77613, EBI-373144;
CC P05067; P36507: MAP2K2; NbExp=3; IntAct=EBI-77613, EBI-1056930;
CC P05067; P28482: MAPK1; NbExp=3; IntAct=EBI-77613, EBI-959949;
CC P05067; P53778: MAPK12; NbExp=3; IntAct=EBI-77613, EBI-602406;
CC P05067; P10636: MAPT; NbExp=8; IntAct=EBI-77613, EBI-366182;
CC P05067; Q9P0L2: MARK1; NbExp=3; IntAct=EBI-77613, EBI-968587;
CC P05067; Q6IPE9: MARK4; NbExp=3; IntAct=EBI-77613, EBI-10250211;
CC P05067; Q96L34: MARK4; NbExp=3; IntAct=EBI-77613, EBI-302319;
CC P05067; Q00266: MAT1A; NbExp=3; IntAct=EBI-77613, EBI-967087;
CC P05067; P02686-2: MBP; NbExp=3; IntAct=EBI-77613, EBI-12159027;
CC P05067; Q93074: MED12; NbExp=2; IntAct=EBI-77613, EBI-394357;
CC P05067; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-77613, EBI-4397720;
CC P05067; O94851: MICAL2; NbExp=3; IntAct=EBI-77613, EBI-2804835;
CC P05067; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-77613, EBI-21250407;
CC P05067; P08473: MME; NbExp=3; IntAct=EBI-77613, EBI-353759;
CC P05067; P08253: MMP2; NbExp=3; IntAct=EBI-77613, EBI-1033518;
CC P05067; Q99547: MPHOSPH6; NbExp=3; IntAct=EBI-77613, EBI-373187;
CC P05067; Q8N594: MPND; NbExp=3; IntAct=EBI-77613, EBI-2512452;
CC P05067; P41227: NAA10; NbExp=3; IntAct=EBI-77613, EBI-747693;
CC P05067; Q13765: NACA; NbExp=3; IntAct=EBI-77613, EBI-712216;
CC P05067; Q13564: NAE1; NbExp=3; IntAct=EBI-77613, EBI-718631;
CC P05067; P41271-2: NBL1; NbExp=3; IntAct=EBI-77613, EBI-12135485;
CC P05067; P19404: NDUFV2; NbExp=3; IntAct=EBI-77613, EBI-713665;
CC P05067; O76041: NEBL; NbExp=3; IntAct=EBI-77613, EBI-2880203;
CC P05067; P12036: NEFH; NbExp=3; IntAct=EBI-77613, EBI-2880271;
CC P05067; I6L9F6: NEFL; NbExp=6; IntAct=EBI-77613, EBI-10178578;
CC P05067; P21359: NF1; NbExp=3; IntAct=EBI-77613, EBI-1172917;
CC P05067; P01138: NGF; NbExp=9; IntAct=EBI-77613, EBI-1028250;
CC P05067; P08138: NGFR; NbExp=2; IntAct=EBI-77613, EBI-1387782;
CC P05067; Q6IAD4: NOTCH1; NbExp=3; IntAct=EBI-77613, EBI-25860267;
CC P05067; Q99466: NOTCH4; NbExp=3; IntAct=EBI-77613, EBI-7970822;
CC P05067; P43354: NR4A2; NbExp=3; IntAct=EBI-77613, EBI-2681738;
CC P05067; Q6PK61: NRG1; NbExp=3; IntAct=EBI-77613, EBI-25938844;
CC P05067; Q02818: NUCB1; NbExp=3; IntAct=EBI-77613, EBI-2622179;
CC P05067; P49757-8: NUMB; NbExp=3; IntAct=EBI-77613, EBI-25937715;
CC P05067; P04181: OAT; NbExp=3; IntAct=EBI-77613, EBI-721662;
CC P05067; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-77613, EBI-1058491;
CC P05067; P11940: PABPC1; NbExp=3; IntAct=EBI-77613, EBI-81531;
CC P05067; O96013-2: PAK4; NbExp=3; IntAct=EBI-77613, EBI-21659863;
CC P05067; Q99497: PARK7; NbExp=3; IntAct=EBI-77613, EBI-1164361;
CC P05067; Q6ZW49: PAXIP1; NbExp=3; IntAct=EBI-77613, EBI-743225;
CC P05067; P61457: PCBD1; NbExp=2; IntAct=EBI-77613, EBI-740475;
CC P05067; P16234-2: PDGFRA; NbExp=3; IntAct=EBI-77613, EBI-13380852;
CC P05067; P09619: PDGFRB; NbExp=3; IntAct=EBI-77613, EBI-641237;
CC P05067; P30101: PDIA3; NbExp=6; IntAct=EBI-77613, EBI-979862;
CC P05067; Q15084: PDIA6; NbExp=3; IntAct=EBI-77613, EBI-1043087;
CC P05067; Q15118: PDK1; NbExp=3; IntAct=EBI-77613, EBI-7016221;
CC P05067; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-77613, EBI-716063;
CC P05067; P18669: PGAM1; NbExp=4; IntAct=EBI-77613, EBI-717905;
CC P05067; Q8WUB8-2: PHF10; NbExp=3; IntAct=EBI-77613, EBI-10276329;
CC P05067; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-77613, EBI-473160;
CC P05067; P42338: PIK3CB; NbExp=3; IntAct=EBI-77613, EBI-2609540;
CC P05067; P48736: PIK3CG; NbExp=3; IntAct=EBI-77613, EBI-1030384;
CC P05067; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-77613, EBI-9090282;
CC P05067; Q13526: PIN1; NbExp=4; IntAct=EBI-77613, EBI-714158;
CC P05067; Q9BXM7: PINK1; NbExp=3; IntAct=EBI-77613, EBI-2846068;
CC P05067; Q16512: PKN1; NbExp=3; IntAct=EBI-77613, EBI-602382;
CC P05067; P00749: PLAU; NbExp=3; IntAct=EBI-77613, EBI-3905042;
CC P05067; Q13393: PLD1; NbExp=3; IntAct=EBI-77613, EBI-2827556;
CC P05067; O14939: PLD2; NbExp=3; IntAct=EBI-77613, EBI-1053996;
CC P05067; P53350: PLK1; NbExp=3; IntAct=EBI-77613, EBI-476768;
CC P05067; O14494: PLPP1; NbExp=3; IntAct=EBI-77613, EBI-2865290;
CC P05067; O15162: PLSCR1; NbExp=3; IntAct=EBI-77613, EBI-740019;
CC P05067; Q8WVK1: PLSCR1; NbExp=3; IntAct=EBI-77613, EBI-10238872;
CC P05067; D3DTS7: PMP22; NbExp=3; IntAct=EBI-77613, EBI-25882629;
CC P05067; P00491: PNP; NbExp=9; IntAct=EBI-77613, EBI-712238;
CC P05067; P62937: PPIA; NbExp=4; IntAct=EBI-77613, EBI-437708;
CC P05067; P62136: PPP1CA; NbExp=3; IntAct=EBI-77613, EBI-357253;
CC P05067; P41236: PPP1R2; NbExp=3; IntAct=EBI-77613, EBI-1056517;
CC P05067; P67775: PPP2CA; NbExp=3; IntAct=EBI-77613, EBI-712311;
CC P05067; P63151: PPP2R2A; NbExp=3; IntAct=EBI-77613, EBI-1048931;
CC P05067; Q00005: PPP2R2B; NbExp=3; IntAct=EBI-77613, EBI-1052159;
CC P05067; Q15172: PPP2R5A; NbExp=3; IntAct=EBI-77613, EBI-641666;
CC P05067; P48454: PPP3CC; NbExp=3; IntAct=EBI-77613, EBI-2827192;
CC P05067; P17612: PRKACA; NbExp=3; IntAct=EBI-77613, EBI-476586;
CC P05067; P22694: PRKACB; NbExp=3; IntAct=EBI-77613, EBI-2679622;
CC P05067; P22694-8: PRKACB; NbExp=3; IntAct=EBI-77613, EBI-25937151;
CC P05067; P22612: PRKACG; NbExp=3; IntAct=EBI-77613, EBI-3907086;
CC P05067; Q9UGJ0-3: PRKAG2; NbExp=3; IntAct=EBI-77613, EBI-25939641;
CC P05067; Q05655: PRKCD; NbExp=3; IntAct=EBI-77613, EBI-704279;
CC P05067; Q02156: PRKCE; NbExp=3; IntAct=EBI-77613, EBI-706254;
CC P05067; O60260-5: PRKN; NbExp=5; IntAct=EBI-77613, EBI-21251460;
CC P05067; P04156: PRNP; NbExp=6; IntAct=EBI-77613, EBI-977302;
CC P05067; P60891: PRPS1; NbExp=3; IntAct=EBI-77613, EBI-749195;
CC P05067; P07602: PSAP; NbExp=3; IntAct=EBI-77613, EBI-716699;
CC P05067; P49768: PSEN1; NbExp=6; IntAct=EBI-77613, EBI-297277;
CC P05067; P49768-2: PSEN1; NbExp=6; IntAct=EBI-77613, EBI-11047108;
CC P05067; P49810: PSEN2; NbExp=4; IntAct=EBI-77613, EBI-2010251;
CC P05067; Q9NZ42: PSENEN; NbExp=3; IntAct=EBI-77613, EBI-998468;
CC P05067; P28062-2: PSMB8; NbExp=3; IntAct=EBI-77613, EBI-372312;
CC P05067; P17980: PSMC3; NbExp=6; IntAct=EBI-77613, EBI-359720;
CC P05067; Q14289: PTK2B; NbExp=3; IntAct=EBI-77613, EBI-298640;
CC P05067; P20340-2: RAB6A; NbExp=3; IntAct=EBI-77613, EBI-8840191;
CC P05067; P63000: RAC1; NbExp=3; IntAct=EBI-77613, EBI-413628;
CC P05067; P04049: RAF1; NbExp=3; IntAct=EBI-77613, EBI-365996;
CC P05067; Q96S59: RANBP9; NbExp=3; IntAct=EBI-77613, EBI-636085;
CC P05067; Q9Y272: RASD1; NbExp=3; IntAct=EBI-77613, EBI-740818;
CC P05067; P61586: RHOA; NbExp=3; IntAct=EBI-77613, EBI-446668;
CC P05067; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-77613, EBI-396669;
CC P05067; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-77613, EBI-21535400;
CC P05067; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-77613, EBI-25829984;
CC P05067; O75116: ROCK2; NbExp=6; IntAct=EBI-77613, EBI-366288;
CC P05067; P46779: RPL28; NbExp=3; IntAct=EBI-77613, EBI-366357;
CC P05067; Q15349: RPS6KA2; NbExp=3; IntAct=EBI-77613, EBI-1384149;
CC P05067; P23443-4: RPS6KB1; NbExp=3; IntAct=EBI-77613, EBI-25882353;
CC P05067; P04271: S100B; NbExp=3; IntAct=EBI-77613, EBI-458391;
CC P05067; P21673: SAT1; NbExp=3; IntAct=EBI-77613, EBI-711613;
CC P05067; Q6AZY7-2: SCARA3; NbExp=3; IntAct=EBI-77613, EBI-21598366;
CC P05067; Q8WTV0: SCARB1; NbExp=3; IntAct=EBI-77613, EBI-78657;
CC P05067; P18827: SDC1; NbExp=3; IntAct=EBI-77613, EBI-2855248;
CC P05067; Q15019-3: SEPTIN2; NbExp=3; IntAct=EBI-77613, EBI-11525407;
CC P05067; O43236: SEPTIN4; NbExp=3; IntAct=EBI-77613, EBI-1047513;
CC P05067; Q99719: SEPTIN5; NbExp=3; IntAct=EBI-77613, EBI-373345;
CC P05067; Q92599-3: SEPTIN8; NbExp=3; IntAct=EBI-77613, EBI-25891137;
CC P05067; P01011: SERPINA3; NbExp=3; IntAct=EBI-77613, EBI-296557;
CC P05067; P29353: SHC1; NbExp=5; IntAct=EBI-77613, EBI-78835;
CC P05067; Q92529: SHC3; NbExp=5; IntAct=EBI-77613, EBI-79084;
CC P05067; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-77613, EBI-11522811;
CC P05067; Q7Z2H8: SLC36A1; NbExp=3; IntAct=EBI-77613, EBI-9978258;
CC P05067; Q9NP59: SLC40A1; NbExp=5; IntAct=EBI-77613, EBI-725153;
CC P05067; P84022: SMAD3; NbExp=3; IntAct=EBI-77613, EBI-347161;
CC P05067; Q13485: SMAD4; NbExp=3; IntAct=EBI-77613, EBI-347263;
CC P05067; P37840: SNCA; NbExp=6; IntAct=EBI-77613, EBI-985879;
CC P05067; Q16143: SNCB; NbExp=3; IntAct=EBI-77613, EBI-727106;
CC P05067; Q15036: SNX17; NbExp=3; IntAct=EBI-77613, EBI-1752620;
CC P05067; O60749: SNX2; NbExp=3; IntAct=EBI-77613, EBI-1046690;
CC P05067; Q8WV41: SNX33; NbExp=3; IntAct=EBI-77613, EBI-2481535;
CC P05067; Q9UNH7: SNX6; NbExp=3; IntAct=EBI-77613, EBI-949294;
CC P05067; Q92673: SORL1; NbExp=5; IntAct=EBI-77613, EBI-1171329;
CC P05067; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-77613, EBI-11959123;
CC P05067; P11277: SPTB; NbExp=6; IntAct=EBI-77613, EBI-514908;
CC P05067; Q13501: SQSTM1; NbExp=6; IntAct=EBI-77613, EBI-307104;
CC P05067; P61278: SST; NbExp=3; IntAct=EBI-77613, EBI-20823968;
CC P05067; P32745: SSTR3; NbExp=3; IntAct=EBI-77613, EBI-6266935;
CC P05067; P40763-2: STAT3; NbExp=3; IntAct=EBI-77613, EBI-10692009;
CC P05067; Q8IWL8: STH; NbExp=3; IntAct=EBI-77613, EBI-12843506;
CC P05067; O14662-5: STX16; NbExp=3; IntAct=EBI-77613, EBI-9089968;
CC P05067; Q13190-4: STX5; NbExp=3; IntAct=EBI-77613, EBI-25938350;
CC P05067; O43752: STX6; NbExp=3; IntAct=EBI-77613, EBI-2695795;
CC P05067; P61764: STXBP1; NbExp=7; IntAct=EBI-77613, EBI-960169;
CC P05067; Q9Y5B9: SUPT16H; NbExp=3; IntAct=EBI-77613, EBI-1046849;
CC P05067; P43405: SYK; NbExp=3; IntAct=EBI-77613, EBI-78302;
CC P05067; P43405-2: SYK; NbExp=3; IntAct=EBI-77613, EBI-25892332;
CC P05067; P08247: SYP; NbExp=3; IntAct=EBI-77613, EBI-9071725;
CC P05067; Q13148: TARDBP; NbExp=6; IntAct=EBI-77613, EBI-372899;
CC P05067; P20226: TBP; NbExp=3; IntAct=EBI-77613, EBI-355371;
CC P05067; Q16650: TBR1; NbExp=3; IntAct=EBI-77613, EBI-1047158;
CC P05067; O43680: TCF21; NbExp=3; IntAct=EBI-77613, EBI-723267;
CC P05067; P01137: TGFB1; NbExp=3; IntAct=EBI-77613, EBI-779636;
CC P05067; P61812: TGFB2; NbExp=7; IntAct=EBI-77613, EBI-779581;
CC P05067; Q15583: TGIF1; NbExp=3; IntAct=EBI-77613, EBI-714215;
CC P05067; Q15583-2: TGIF1; NbExp=3; IntAct=EBI-77613, EBI-12691451;
CC P05067; P04216: THY1; NbExp=3; IntAct=EBI-77613, EBI-9071715;
CC P05067; P04183: TK1; NbExp=3; IntAct=EBI-77613, EBI-712550;
CC P05067; Q9BX74: TM2D1; NbExp=3; IntAct=EBI-77613, EBI-25832057;
CC P05067; P49755: TMED10; NbExp=3; IntAct=EBI-77613, EBI-998422;
CC P05067; Q9BTD3: TMEM121; NbExp=3; IntAct=EBI-77613, EBI-12155101;
CC P05067; P62328: TMSB4X; NbExp=3; IntAct=EBI-77613, EBI-712598;
CC P05067; P01375: TNF; NbExp=3; IntAct=EBI-77613, EBI-359977;
CC P05067; O43508: TNFSF12; NbExp=3; IntAct=EBI-77613, EBI-6932080;
CC P05067; O75888-3: TNFSF13; NbExp=3; IntAct=EBI-77613, EBI-12856452;
CC P05067; Q96GM8: TOE1; NbExp=3; IntAct=EBI-77613, EBI-717460;
CC P05067; O14656: TOR1A; NbExp=3; IntAct=EBI-77613, EBI-524257;
CC P05067; O14656-2: TOR1A; NbExp=3; IntAct=EBI-77613, EBI-25847109;
CC P05067; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-77613, EBI-11952721;
CC P05067; Q13625: TP53BP2; NbExp=3; IntAct=EBI-77613, EBI-77642;
CC P05067; Q9C026: TRIM9; NbExp=3; IntAct=EBI-77613, EBI-720828;
CC P05067; Q15714-2: TSC22D1; NbExp=3; IntAct=EBI-77613, EBI-12034704;
CC P05067; P02766: TTR; NbExp=3; IntAct=EBI-77613, EBI-711909;
CC P05067; Q71U36: TUBA1A; NbExp=3; IntAct=EBI-77613, EBI-302552;
CC P05067; P68363: TUBA1B; NbExp=3; IntAct=EBI-77613, EBI-487083;
CC P05067; P68366: TUBA4A; NbExp=3; IntAct=EBI-77613, EBI-351772;
CC P05067; P07437: TUBB; NbExp=5; IntAct=EBI-77613, EBI-350864;
CC P05067; Q8TBC4: UBA3; NbExp=3; IntAct=EBI-77613, EBI-717567;
CC P05067; P0CG47: UBB; NbExp=3; IntAct=EBI-77613, EBI-413034;
CC P05067; P62837: UBE2D2; NbExp=3; IntAct=EBI-77613, EBI-347677;
CC P05067; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-77613, EBI-741480;
CC P05067; P09936: UCHL1; NbExp=5; IntAct=EBI-77613, EBI-714860;
CC P05067; P13051-2: UNG; NbExp=3; IntAct=EBI-77613, EBI-25834258;
CC P05067; O75604-3: USP2; NbExp=3; IntAct=EBI-77613, EBI-10696113;
CC P05067; Q9BVJ6: UTP14A; NbExp=3; IntAct=EBI-77613, EBI-473284;
CC P05067; Q9H270: VPS11; NbExp=3; IntAct=EBI-77613, EBI-373380;
CC P05067; Q8N0S8: VPS29; NbExp=3; IntAct=EBI-77613, EBI-25892084;
CC P05067; Q96AX1: VPS33A; NbExp=3; IntAct=EBI-77613, EBI-2527283;
CC P05067; Q96QK1: VPS35; NbExp=3; IntAct=EBI-77613, EBI-1054634;
CC P05067; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-77613, EBI-358545;
CC P05067; O76024: WFS1; NbExp=3; IntAct=EBI-77613, EBI-720609;
CC P05067; O00744: WNT10B; NbExp=3; IntAct=EBI-77613, EBI-21797207;
CC P05067; P19544-6: WT1; NbExp=3; IntAct=EBI-77613, EBI-11745701;
CC P05067; P31946: YWHAB; NbExp=3; IntAct=EBI-77613, EBI-359815;
CC P05067; P17028: ZNF24; NbExp=3; IntAct=EBI-77613, EBI-707773;
CC P05067; Q8N895: ZNF366; NbExp=3; IntAct=EBI-77613, EBI-2813661;
CC P05067; Q8NHT4; NbExp=3; IntAct=EBI-77613, EBI-25939025;
CC P05067; O35431: Apba2; Xeno; NbExp=5; IntAct=EBI-77613, EBI-2028211;
CC P05067; P15253: CALR; Xeno; NbExp=3; IntAct=EBI-77613, EBI-9005200;
CC P05067; Q8BGY9: Slc5a7; Xeno; NbExp=2; IntAct=EBI-77613, EBI-2010752;
CC P05067; Q306T3; Xeno; NbExp=3; IntAct=EBI-77613, EBI-8294101;
CC P05067-2; Q9H7C9: AAMDC; NbExp=3; IntAct=EBI-17264467, EBI-10308705;
CC P05067-2; P63010-2: AP2B1; NbExp=3; IntAct=EBI-17264467, EBI-11529439;
CC P05067-2; Q0P5N6: ARL16; NbExp=3; IntAct=EBI-17264467, EBI-10186132;
CC P05067-2; O15392: BIRC5; NbExp=3; IntAct=EBI-17264467, EBI-518823;
CC P05067-2; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-17264467, EBI-396453;
CC P05067-2; P06241-3: FYN; NbExp=3; IntAct=EBI-17264467, EBI-10691738;
CC P05067-2; Q12891: HYAL2; NbExp=3; IntAct=EBI-17264467, EBI-2806068;
CC P05067-2; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-17264467, EBI-21911304;
CC P05067-2; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-17264467, EBI-1044640;
CC P05067-2; O95447: LCA5L; NbExp=3; IntAct=EBI-17264467, EBI-8473670;
CC P05067-2; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-17264467, EBI-1108377;
CC P05067-2; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-17264467, EBI-4397720;
CC P05067-2; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-17264467, EBI-21250407;
CC P05067-2; P15941-11: MUC1; NbExp=3; IntAct=EBI-17264467, EBI-17263240;
CC P05067-2; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-17264467, EBI-716063;
CC P05067-2; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-17264467, EBI-21535400;
CC P05067-2; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-17264467, EBI-25829984;
CC P05067-2; Q2NKQ1-4: SGSM1; NbExp=3; IntAct=EBI-17264467, EBI-10182463;
CC P05067-2; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-17264467, EBI-11522811;
CC P05067-2; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-17264467, EBI-11959123;
CC P05067-2; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-17264467, EBI-2510414;
CC P05067-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-17264467, EBI-372899;
CC P05067-2; Q16650: TBR1; NbExp=3; IntAct=EBI-17264467, EBI-1047158;
CC P05067-2; Q5HYA8: TMEM67; NbExp=3; IntAct=EBI-17264467, EBI-11334880;
CC P05067-2; P09936: UCHL1; NbExp=3; IntAct=EBI-17264467, EBI-714860;
CC P05067-2; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-17264467, EBI-358545;
CC P05067-4; O00213: APBB1; NbExp=5; IntAct=EBI-302641, EBI-81694;
CC P05067-4; P51693: APLP1; NbExp=2; IntAct=EBI-302641, EBI-74648;
CC P05067-4; Q06481: APLP2; NbExp=2; IntAct=EBI-302641, EBI-79306;
CC P05067-4; P05067-4: APP; NbExp=8; IntAct=EBI-302641, EBI-302641;
CC P05067-4; Q13867: BLMH; NbExp=2; IntAct=EBI-302641, EBI-718504;
CC P05067-4; Q9NZU0: FLRT3; NbExp=3; IntAct=EBI-302641, EBI-1057092;
CC P05067-4; P46089: GPR3; NbExp=2; IntAct=EBI-302641, EBI-3909653;
CC P05067-4; O43736: ITM2A; NbExp=3; IntAct=EBI-302641, EBI-2431769;
CC P05067-4; Q68DU8: KCTD16; NbExp=3; IntAct=EBI-302641, EBI-20768174;
CC P05067-4; Q96FE5: LINGO1; NbExp=2; IntAct=EBI-302641, EBI-719955;
CC P05067-4; P04629: NTRK1; NbExp=7; IntAct=EBI-302641, EBI-1028226;
CC P05067-4; Q13526: PIN1; NbExp=2; IntAct=EBI-302641, EBI-714158;
CC P05067-4; P60201: PLP1; NbExp=5; IntAct=EBI-302641, EBI-8653150;
CC P05067-4; P04156: PRNP; NbExp=2; IntAct=EBI-302641, EBI-977302;
CC P05067-4; P49768: PSEN1; NbExp=4; IntAct=EBI-302641, EBI-297277;
CC P05067-4; Q92673: SORL1; NbExp=8; IntAct=EBI-302641, EBI-1171329;
CC P05067-4; PRO_0000033163 [Q99523]: SORT1; NbExp=4; IntAct=EBI-302641, EBI-21467118;
CC P05067-4; Q9HCB6: SPON1; NbExp=3; IntAct=EBI-302641, EBI-2431846;
CC P05067-4; O95793: STAU1; NbExp=2; IntAct=EBI-302641, EBI-358174;
CC P05067-4; Q8VEK0: Tmem30a; Xeno; NbExp=6; IntAct=EBI-302641, EBI-8381028;
CC P05067-8; P17677: GAP43; NbExp=3; IntAct=EBI-302661, EBI-1267511;
CC P05067-8; Q9NSC5: HOMER3; NbExp=3; IntAct=EBI-302661, EBI-748420;
CC P05067-8; Q9Y287: ITM2B; NbExp=4; IntAct=EBI-302661, EBI-2866431;
CC PRO_0000000089; O95631: NTN1; NbExp=3; IntAct=EBI-20829246, EBI-2678626;
CC PRO_0000000090; Q9UIK5: TMEFF2; NbExp=3; IntAct=EBI-21194918, EBI-11423693;
CC PRO_0000000091; Q92673: SORL1; NbExp=4; IntAct=EBI-3894543, EBI-1171329;
CC PRO_0000000091; Q8K3H7: CALR; Xeno; NbExp=2; IntAct=EBI-3894543, EBI-9005068;
CC PRO_0000000091; Q8VEK0: Tmem30a; Xeno; NbExp=3; IntAct=EBI-3894543, EBI-8381028;
CC PRO_0000000092; Q9BYF1: ACE2; NbExp=3; IntAct=EBI-821758, EBI-7730807;
CC PRO_0000000092; PRO_0000000092 [P05067]: APP; NbExp=77; IntAct=EBI-821758, EBI-821758;
CC PRO_0000000092; P48047: ATP5PO; NbExp=2; IntAct=EBI-821758, EBI-355815;
CC PRO_0000000092; P36544: CHRNA7; NbExp=7; IntAct=EBI-821758, EBI-79333;
CC PRO_0000000092; P10909-5: CLU; NbExp=2; IntAct=EBI-821758, EBI-10961636;
CC PRO_0000000092; PRO_0000005794 [P39060]: COL18A1; NbExp=2; IntAct=EBI-821758, EBI-2566375;
CC PRO_0000000092; PRO_0000033156 [O00230]: CORT; NbExp=4; IntAct=EBI-821758, EBI-20824092;
CC PRO_0000000092; Q99714: HSD17B10; NbExp=2; IntAct=EBI-821758, EBI-79964;
CC PRO_0000000092; Q8N423: LILRB2; NbExp=7; IntAct=EBI-821758, EBI-2816428;
CC PRO_0000000092; P10636: MAPT; NbExp=5; IntAct=EBI-821758, EBI-366182;
CC PRO_0000000092; P08253: MMP2; NbExp=4; IntAct=EBI-821758, EBI-1033518;
CC PRO_0000000092; Q9NZV6: MSRB1; NbExp=4; IntAct=EBI-821758, EBI-12330065;
CC PRO_0000000092; P03897: MT-ND3; NbExp=2; IntAct=EBI-821758, EBI-1246249;
CC PRO_0000000092; Q8IVG9: MT-RNR2; NbExp=4; IntAct=EBI-821758, EBI-8643752;
CC PRO_0000000092; O95631: NTN1; NbExp=6; IntAct=EBI-821758, EBI-2678626;
CC PRO_0000000092; Q15113: PCOLCE; NbExp=4; IntAct=EBI-821758, EBI-8869614;
CC PRO_0000000092; Q08752: PPID; NbExp=4; IntAct=EBI-821758, EBI-716596;
CC PRO_0000000092; P30405: PPIF; NbExp=2; IntAct=EBI-821758, EBI-5544229;
CC PRO_0000000092; P04156: PRNP; NbExp=3; IntAct=EBI-821758, EBI-977302;
CC PRO_0000000092; P11686-1: SFTPC; NbExp=5; IntAct=EBI-821758, EBI-16143688;
CC PRO_0000000092; PRO_0000033088 [P61278]: SST; NbExp=8; IntAct=EBI-821758, EBI-20824010;
CC PRO_0000000092; P21980: TGM2; NbExp=2; IntAct=EBI-821758, EBI-727668;
CC PRO_0000000092; O95411: TIAF1; NbExp=3; IntAct=EBI-821758, EBI-302378;
CC PRO_0000000092; O60602: TLR5; NbExp=3; IntAct=EBI-821758, EBI-3505951;
CC PRO_0000000092; Q9NZC2: TREM2; NbExp=4; IntAct=EBI-821758, EBI-14036387;
CC PRO_0000000092; P02766: TTR; NbExp=2; IntAct=EBI-821758, EBI-711909;
CC PRO_0000000092; P15253: CALR; Xeno; NbExp=2; IntAct=EBI-821758, EBI-9005200;
CC PRO_0000000092; Q05941: Chrna7; Xeno; NbExp=3; IntAct=EBI-821758, EBI-79422;
CC PRO_0000000092; P03452: HA; Xeno; NbExp=2; IntAct=EBI-821758, EBI-2548105;
CC PRO_0000000092; P97484: Lilrb3; Xeno; NbExp=8; IntAct=EBI-821758, EBI-15728641;
CC PRO_0000000092; K9N5Q8: S; Xeno; NbExp=2; IntAct=EBI-821758, EBI-25474996;
CC PRO_0000000092; PRO_0000449647 [P0DTC2]: S; Xeno; NbExp=3; IntAct=EBI-821758, EBI-25490323;
CC PRO_0000000092; Q99NH8: Trem2; Xeno; NbExp=2; IntAct=EBI-821758, EBI-15982016;
CC PRO_0000000093; P02649: APOE; NbExp=4; IntAct=EBI-2431589, EBI-1222467;
CC PRO_0000000093; PRO_0000000093 [P05067]: APP; NbExp=29; IntAct=EBI-2431589, EBI-2431589;
CC PRO_0000000093; P10909: CLU; NbExp=4; IntAct=EBI-2431589, EBI-1104674;
CC PRO_0000000093; P49840: GSK3A; NbExp=3; IntAct=EBI-2431589, EBI-1044067;
CC PRO_0000000093; P49841: GSK3B; NbExp=2; IntAct=EBI-2431589, EBI-373586;
CC PRO_0000000093; P14735-1: IDE; NbExp=3; IntAct=EBI-2431589, EBI-15607031;
CC PRO_0000000093; P08253: MMP2; NbExp=2; IntAct=EBI-2431589, EBI-1033518;
CC PRO_0000000093; P08138: NGFR; NbExp=2; IntAct=EBI-2431589, EBI-1387782;
CC PRO_0000000093; Q5JRX3-1: PITRM1; NbExp=3; IntAct=EBI-2431589, EBI-16109799;
CC PRO_0000000093; Q08752: PPID; NbExp=2; IntAct=EBI-2431589, EBI-716596;
CC PRO_0000000093; Q92673: SORL1; NbExp=3; IntAct=EBI-2431589, EBI-1171329;
CC PRO_0000000093; O60602: TLR5; NbExp=3; IntAct=EBI-2431589, EBI-3505951;
CC PRO_0000000093; P31696: AGRN; Xeno; NbExp=3; IntAct=EBI-2431589, EBI-457650;
CC PRO_0000000093; P15253: CALR; Xeno; NbExp=2; IntAct=EBI-2431589, EBI-9005200;
CC PRO_0000000093; P07174: Ngfr; Xeno; NbExp=2; IntAct=EBI-2431589, EBI-1038810;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10383380,
CC ECO:0000269|PubMed:20580937, ECO:0000269|PubMed:2649245,
CC ECO:0000305|PubMed:25122912}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:30630874, ECO:0000305|PubMed:10383380,
CC ECO:0000305|PubMed:25122912}. Membrane {ECO:0000269|PubMed:2900137,
CC ECO:0000305|PubMed:22584060}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:2900137, ECO:0000269|PubMed:30630874,
CC ECO:0000305|PubMed:22584060}. Perikaryon {ECO:0000269|PubMed:10341243}.
CC Cell projection, growth cone {ECO:0000269|PubMed:10341243}. Membrane,
CC clathrin-coated pit {ECO:0000269|PubMed:20580937}. Early endosome
CC {ECO:0000269|PubMed:20580937}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:20580937, ECO:0000269|PubMed:25122912}. Note=Cell
CC surface protein that rapidly becomes internalized via clathrin-coated
CC pits. Only a minor proportion is present at the cell membrane; most of
CC the protein is present in intracellular vesicles (PubMed:20580937).
CC During maturation, the immature APP (N-glycosylated in the endoplasmic
CC reticulum) moves to the Golgi complex where complete maturation occurs
CC (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble
CC APP is released into the extracellular space and the C-terminal is
CC internalized to endosomes and lysosomes. Some APP accumulates in
CC secretory transport vesicles leaving the late Golgi compartment and
CC returns to the cell surface. APP sorts to the basolateral surface in
CC epithelial cells. During neuronal differentiation, the Thr-743
CC phosphorylated form is located mainly in growth cones, moderately in
CC neurites and sparingly in the cell body (PubMed:10341243). Casein
CC kinase phosphorylation can occur either at the cell surface or within a
CC post-Golgi compartment. Associates with GPC1 in perinuclear
CC compartments. Colocalizes with SORL1 in a vesicular pattern in
CC cytoplasm and perinuclear regions. {ECO:0000269|PubMed:10341243,
CC ECO:0000269|PubMed:20580937}.
CC -!- SUBCELLULAR LOCATION: [C83]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:14527950}. Golgi apparatus
CC {ECO:0000269|PubMed:14527950}. Early endosome
CC {ECO:0000269|PubMed:14527950}.
CC -!- SUBCELLULAR LOCATION: [C99]: Early endosome
CC {ECO:0000269|PubMed:14527950}.
CC -!- SUBCELLULAR LOCATION: [Soluble APP-beta]: Secreted
CC {ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:2649245}.
CC -!- SUBCELLULAR LOCATION: [Amyloid-beta protein 40]: Cell surface
CC {ECO:0000269|PubMed:16154999}.
CC -!- SUBCELLULAR LOCATION: [Amyloid-beta protein 42]: Cell surface
CC {ECO:0000269|PubMed:11689470, ECO:0000269|PubMed:16154999}.
CC Note=Associates with FPR2 at the cell surface and the complex is then
CC rapidly internalized. {ECO:0000269|PubMed:11689470}.
CC -!- SUBCELLULAR LOCATION: [Gamma-secretase C-terminal fragment 59]: Nucleus
CC {ECO:0000269|PubMed:11544248}. Cytoplasm {ECO:0000269|PubMed:11544248}.
CC Note=Located to both the cytoplasm and nuclei of neurons. It can be
CC translocated to the nucleus through association with APBB1 (Fe65)
CC (PubMed:11544248). In dopaminergic neurons, the phosphorylated Thr-743
CC form is localized to the nucleus (By similarity).
CC {ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:11544248}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=11;
CC Comment=Additional isoforms seem to exist. Experimental confirmation
CC may be lacking for some isoforms.;
CC Name=APP770; Synonyms=PreA4 770;
CC IsoId=P05067-1; Sequence=Displayed;
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 Name=APP695; Synonyms=PreA4 695;
CC IsoId=P05067-4; Sequence=VSP_000002, VSP_000004;
CC Name=L-APP696;
CC IsoId=P05067-5; Sequence=VSP_000002, VSP_000003, VSP_000009;
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 Name=APP751; Synonyms=PreA4 751;
CC IsoId=P05067-8; Sequence=VSP_000007, VSP_000008;
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 the brain and in cerebrospinal fluid
CC (at protein level) (PubMed:2649245). Expressed in all fetal tissues
CC examined with highest levels in brain, kidney, heart and spleen. Weak
CC expression in liver. In adult brain, highest expression found in the
CC frontal 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 associated
CC cortex. Weak expression found in the striate, extra-striate and motor
CC cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695
CC is the predominant form in neuronal tissue, isoform APP751 and isoform
CC APP770 are widely expressed in non-neuronal cells. Isoform APP751 is
CC the most abundant form in T-lymphocytes. Appican is expressed in
CC astrocytes. {ECO:0000269|PubMed:12859342, ECO:0000269|PubMed:1406936,
CC ECO:0000269|PubMed:2649245}.
CC -!- INDUCTION: Increased levels during neuronal differentiation.
CC -!- DOMAIN: The transmembrane helix undergoes a conformation change and
CC unravels partially when bound to PSEN1, facilitating cleavage by PSEN1.
CC {ECO:0000269|PubMed:30630874}.
CC -!- DOMAIN: The basolateral sorting signal (BaSS) is required for sorting
CC of membrane proteins to the basolateral surface of epithelial cells.
CC {ECO:0000269|PubMed:9843960}.
CC -!- DOMAIN: The GFLD subdomain binds Cu(2+) ions; this promotes
CC homodimerization. {ECO:0000269|PubMed:25122912}.
CC -!- DOMAIN: The NPXY sequence motif found in many tyrosine-phosphorylated
CC proteins is required for the specific binding of the PID domain.
CC However, additional amino acids either N- or C-terminal to the NPXY
CC motif are often required for complete interaction. The PID domain-
CC containing proteins which bind APP require the YENPTY motif for full
CC interaction. These interactions are independent of phosphorylation on
CC the terminal tyrosine residue. The YENPXY site is also involved in
CC clathrin-mediated endocytosis. {ECO:0000269|PubMed:10383380}.
CC -!- DOMAIN: The C-terminal region can bind zinc ions; this favors
CC dimerization and formation of higher oligomers.
CC {ECO:0000269|PubMed:26898943, ECO:0000269|PubMed:28570778}.
CC -!- DOMAIN: The OX-2 motif shows some similarity to a region in the N-
CC terminus of CD200/MOX2. {ECO:0000269|PubMed:2649245}.
CC -!- PTM: Proteolytically processed under normal cellular conditions.
CC Cleavage either by alpha-secretase, beta-secretase or theta-secretase
CC leads to generation and extracellular release of soluble APP peptides,
CC S-APP-alpha and S-APP-beta, and the retention of corresponding
CC membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent
CC processing of C80 and C83 by gamma-secretase yields P3 peptides. This
CC is the major secretory pathway and is non-amyloidogenic. Alternatively,
CC presenilin/nicastrin-mediated gamma-secretase processing of C99
CC releases the amyloid-beta proteins, amyloid-beta protein 40 and
CC amyloid-beta protein 42, major components of amyloid plaques, and the
CC cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-
CC CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as
CC substrate (in vitro) (PubMed:30630874). Amyloid-beta protein 40 and
CC Amyloid-beta protein 42 are cleaved by ACE (PubMed:11604391,
CC PubMed:16154999). Many other minor amyloid-beta peptides, amyloid-beta
CC 1-X peptides, are found in cerebral spinal fluid (CSF) including the
CC amyloid-beta X-15 peptides, produced from the cleavage by alpha-
CC secretase and all terminating at Gln-686. {ECO:0000269|PubMed:10656250,
CC ECO:0000269|PubMed:11604391, ECO:0000269|PubMed:16154999,
CC ECO:0000269|PubMed:30630874}.
CC -!- PTM: Proteolytically cleaved by caspases during neuronal apoptosis.
CC Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the
CC production of the neurotoxic C31 peptide and the increased production
CC of amyloid-beta peptides. {ECO:0000269|PubMed:10319819}.
CC -!- PTM: N-glycosylated (PubMed:2900137). N- and O-glycosylated
CC (PubMed:2649245). O-glycosylation on Ser and Thr residues with core 1
CC or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is
CC found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-
CC 16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein
CC 38, amyloid-beta protein 40 nor on amyloid-beta protein 42.
CC Modification on a tyrosine is unusual and is more prevelant in AD
CC 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 2,8Neu5Ac
CC linked. O-glycosylations in the vicinity of the cleavage sites may
CC influence the proteolytic processing. Appicans are L-APP isoforms with
CC O-linked chondroitin sulfate. {ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:21712440, ECO:0000269|PubMed:22576872,
CC ECO:0000269|PubMed:2649245, ECO:0000269|PubMed:2900137}.
CC -!- PTM: Phosphorylation in the C-terminal on tyrosine, threonine and
CC serine residues is neuron-specific (PubMed:10341243). Phosphorylation
CC can affect APP processing, neuronal differentiation and interaction
CC with other proteins (PubMed:10341243). Phosphorylated on Thr-743 in
CC neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2
CC kinase in a cell-cycle dependent manner with maximal levels at the G2/M
CC phase and, in vitro, by GSK-3-beta (PubMed:8131745, PubMed:11146006).
CC The Thr-743 phosphorylated form causes a conformational change which
CC reduces binding of Fe65 family members (PubMed:11517218). In
CC dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes
CC the production and the nuclear translocation of the APP intracellular
CC domain (AICD) which induces DA neuron apoptosis (PubMed:28720718).
CC Phosphorylation on Tyr-757 is required for SHC binding
CC (PubMed:11877420). Phosphorylated in the extracellular domain by casein
CC kinases on both soluble and membrane-bound APP. This phosphorylation is
CC inhibited by heparin (PubMed:8999878). {ECO:0000269|PubMed:10341243,
CC ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218,
CC ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:28720718,
CC ECO:0000269|PubMed:8131745, ECO:0000269|PubMed:8999878}.
CC -!- PTM: Extracellular binding and reduction of copper, results in a
CC corresponding oxidation of Cys-144 and Cys-158, and the formation of a
CC disulfide bond. In vitro, the APP-Cu(+) complex in the presence of
CC hydrogen peroxide results in an increased production of amyloid-beta-
CC containing peptides.
CC -!- PTM: Trophic-factor deprivation triggers the cleavage of surface APP by
CC beta-secretase to release sAPP-beta which is further cleaved to release
CC an N-terminal fragment of APP (N-APP).
CC -!- PTM: Amyloid-beta peptides are degraded by IDE.
CC {ECO:0000250|UniProtKB:P12023}.
CC -!- PTM: Sulfated on tyrosine residues. {ECO:0000269|PubMed:2649245}.
CC -!- MASS SPECTROMETRY: [Gamma-secretase C-terminal fragment 59]:
CC Mass=6461.6; Method=MALDI; Evidence={ECO:0000269|PubMed:12214090};
CC -!- MASS SPECTROMETRY: [Gamma-secretase C-terminal fragment 57]:
CC Mass=6451.6; Method=MALDI; Evidence={ECO:0000269|PubMed:12214090};
CC -!- DISEASE: Alzheimer disease 1 (AD1) [MIM:104300]: A familial early-onset
CC form of Alzheimer disease. It can be associated with cerebral amyloid
CC angiopathy. Alzheimer disease is a neurodegenerative disorder
CC characterized by progressive dementia, loss of cognitive abilities, and
CC deposition of fibrillar amyloid proteins as intraneuronal
CC neurofibrillary tangles, extracellular amyloid plaques and vascular
CC amyloid deposits. The major constituents of these plaques are
CC neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that
CC are produced by the proteolysis of the transmembrane APP protein. The
CC cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products,
CC such as C31, are also implicated in neuronal death.
CC {ECO:0000269|PubMed:10097173, ECO:0000269|PubMed:10631141,
CC ECO:0000269|PubMed:10656250, ECO:0000269|PubMed:10665499,
CC ECO:0000269|PubMed:10677483, ECO:0000269|PubMed:10867787,
CC ECO:0000269|PubMed:11063718, ECO:0000269|PubMed:11311152,
CC ECO:0000269|PubMed:11528419, ECO:0000269|PubMed:12034808,
CC ECO:0000269|PubMed:1302033, ECO:0000269|PubMed:1303239,
CC ECO:0000269|PubMed:1303275, ECO:0000269|PubMed:1415269,
CC ECO:0000269|PubMed:1465129, ECO:0000269|PubMed:15201367,
CC ECO:0000269|PubMed:15365148, ECO:0000269|PubMed:15668448,
CC ECO:0000269|PubMed:1671712, ECO:0000269|PubMed:1678058,
CC ECO:0000269|PubMed:1908231, ECO:0000269|PubMed:1925564,
CC ECO:0000269|PubMed:1944558, ECO:0000269|PubMed:8267572,
CC ECO:0000269|PubMed:8290042, ECO:0000269|PubMed:8476439,
CC ECO:0000269|PubMed:8577393, ECO:0000269|PubMed:8886002,
CC ECO:0000269|PubMed:9328472, ECO:0000269|PubMed:9754958}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cerebral amyloid angiopathy, APP-related (CAA-APP)
CC [MIM:605714]: A hereditary localized amyloidosis due to amyloid-beta A4
CC peptide(s) deposition in the cerebral vessels. The principal clinical
CC characteristics are recurrent cerebral and cerebellar hemorrhages,
CC recurrent strokes, cerebral ischemia, cerebral infarction, and
CC progressive mental deterioration. Patients develop cerebral hemorrhage
CC because of the severe cerebral amyloid angiopathy. Parenchymal amyloid
CC deposits are rare and largely in the form of pre-amyloid lesions or
CC diffuse plaque-like structures. They are Congo red negative and lack
CC the dense amyloid cores commonly present in Alzheimer disease. Some
CC affected individuals manifest progressive aphasic dementia,
CC leukoencephalopathy, and occipital calcifications.
CC {ECO:0000269|PubMed:11409420, ECO:0000269|PubMed:12654973,
CC ECO:0000269|PubMed:16178030, ECO:0000269|PubMed:20697050,
CC ECO:0000269|PubMed:2111584}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Chelation of metal ions, notably copper, iron and zinc,
CC can induce histidine-bridging between amyloid-beta molecules resulting
CC in amyloid-beta-metal aggregates. The affinity for copper is much
CC higher than for other transient metals and is increased under acidic
CC conditions. Extracellular zinc-binding increases binding of heparin to
CC APP and inhibits collagen-binding. {ECO:0000269|PubMed:26898943,
CC ECO:0000269|PubMed:28570778}.
CC -!- MISCELLANEOUS: [Isoform APP770]: A major isoform.
CC -!- MISCELLANEOUS: [Isoform L-APP677]: The L-isoforms are referred to as
CC appicans. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform APP695]: A major isoform. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform L-APP696]: The L-isoforms are referred to as
CC appicans. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform L-APP733]: The L-isoforms are referred to as
CC appicans. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform APP751]: A major isoform. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000255|PROSITE-
CC ProRule:PRU01217}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA58727.1; Type=Miscellaneous discrepancy; Note=Contamination by an Alu repeat.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Alzforum; Note=APP mutations;
CC URL="https://www.alzforum.org/mutations/search?genes%255B%255D=348";
CC -!- WEB RESOURCE: Name=AD mutations;
CC URL="https://uantwerpen.vib.be/CMTMutations";
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="https://en.wikipedia.org/wiki/Amyloid_beta";
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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 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; 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; 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; 2MGT; NMR; -; A/B=672-687.
DR PDB; 2MJ1; NMR; -; A=688-705.
DR PDB; 2MPZ; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a=686-711.
DR PDB; 2MVX; NMR; -; A/B/C/D/E/F/G/H/I/J=672-711.
DR PDB; 2MXU; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L=672-713.
DR PDB; 2NAO; NMR; -; A/B/C/D/E/F=672-713.
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; 3PZZ; X-ray; 1.29 A; A/B=700-705.
DR PDB; 3Q2X; X-ray; 1.45 A; A=698-703.
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; 4JFN; X-ray; 1.75 A; A=23-185.
DR PDB; 4M1C; X-ray; 3.50 A; G/H=672-711.
DR PDB; 4MDR; X-ray; 1.85 A; B=758-767.
DR PDB; 4MVI; X-ray; 1.70 A; B=672-711.
DR PDB; 4MVK; X-ray; 1.50 A; B=689-694.
DR PDB; 4MVL; X-ray; 2.30 A; E/F/G/H=672-711.
DR PDB; 4NGE; X-ray; 2.70 A; B/E=672-711.
DR PDB; 4OJF; X-ray; 2.00 A; A=672-679.
DR PDB; 4ONF; X-ray; 2.00 A; P=672-678.
DR PDB; 4ONG; X-ray; 2.20 A; P=672-711.
DR PDB; 4PQD; X-ray; 1.33 A; A=22-126.
DR PDB; 4PWQ; X-ray; 1.40 A; A/B=18-190.
DR PDB; 4XXD; X-ray; 2.41 A; C/F=683-699.
DR PDB; 5AEF; EM; 5.00 A; A/B=686-713.
DR PDB; 5AM8; X-ray; 1.90 A; P/Q/R/S=675-681.
DR PDB; 5AMB; X-ray; 1.55 A; P/Q=706-713.
DR PDB; 5BUO; X-ray; 2.31 A; A/B=370-710.
DR PDB; 5C67; X-ray; 1.83 A; C/E=294-344.
DR PDB; 5CSZ; X-ray; 1.80 A; D/E=672-682.
DR PDB; 5HOW; X-ray; 2.29 A; A/B/C/D/E/F=688-705.
DR PDB; 5HOX; X-ray; 1.90 A; A/B/C/D/E/F=688-707.
DR PDB; 5HOY; X-ray; 2.29 A; A/B/C/D/E/F=688-707.
DR PDB; 5KK3; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=672-713.
DR PDB; 5LFY; NMR; -; A/B=672-681.
DR PDB; 5LV0; X-ray; 2.70 A; C/D=706-711.
DR PDB; 5MY4; X-ray; 2.21 A; C=674-683.
DR PDB; 5MYO; X-ray; 1.59 A; E=674-683.
DR PDB; 5MYX; X-ray; 1.49 A; E/F=674-689.
DR PDB; 5ONP; X-ray; 1.34 A; B=700-704.
DR PDB; 5ONQ; X-ray; 1.17 A; B=700-704.
DR PDB; 5OQV; EM; 4.00 A; A/B/C/D/E/F/G/H/I=672-713.
DR PDB; 5TXD; X-ray; 1.45 A; Z=698-703.
DR PDB; 5VOS; EM; 1.42 A; A=695-705.
DR PDB; 5VZY; X-ray; 2.32 A; A=682-696.
DR PDB; 5W3P; X-ray; 1.92 A; P=672-687.
DR PDB; 6CO3; X-ray; 2.38 A; Q=672-682.
DR PDB; 6GFI; X-ray; 2.30 A; C/E=294-346.
DR PDB; 6ITU; X-ray; 2.17 A; B=755-766.
DR PDB; 6IYC; EM; 2.60 A; E=688-770.
DR PDB; 6NB9; EM; 1.05 A; A=691-705.
DR PDB; 6O4J; EM; 1.40 A; A/B=687-697.
DR PDB; 6OC9; NMR; -; A/B/C/D/E/F/G/H/I/J=672-711.
DR PDB; 6OIZ; EM; 1.10 A; A=691-705.
DR PDB; 6RHY; NMR; -; A/B/C/D=672-713.
DR PDB; 6SHS; EM; 4.40 A; A/B/C/D/E/F/G/H/I/J/K/L=672-711.
DR PDB; 6SZF; NMR; -; A=672-713.
DR PDB; 6TI5; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=672-711.
DR PDB; 6TI6; NMR; -; A/C/E/G/I/K/M/O=672-711, B/D/F/H/J/L/N/P=672-713.
DR PDB; 6TI7; NMR; -; A/C/E/G/J/L/N/P=672-711, B/D/F/H/I/K/M/O=672-713.
DR PDB; 6W0O; Other; 2.77 A; 1/2/3/4/5/6=672-711.
DR PDB; 6WXM; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J/K=685-706.
DR PDB; 6XOV; EM; 3.30 A; B=672-711.
DR PDB; 6YHF; NMR; -; A=697-726.
DR PDB; 6YHI; NMR; -; A=697-726.
DR PDB; 6YHO; NMR; -; A=697-726.
DR PDB; 6YHP; NMR; -; A=697-726.
DR PDB; 6YHX; NMR; -; A=697-726.
DR PDB; 7B3J; NMR; -; A=672-726.
DR PDB; 7B3K; NMR; -; A=672-726.
DR PDB; 7E6P; X-ray; 2.50 A; A=686-701.
DR PDB; 7JXN; X-ray; 2.00 A; A/B/C/D=686-706.
DR PDB; 7JXO; X-ray; 2.81 A; A/B/C=686-706.
DR PDB; 7O1Q; EM; 3.40 A; A/B/C/D/E/F/G=672-713.
DR PDB; 7Q4B; EM; 2.50 A; A/B/C/D/E/F/G/H/I/R=672-713.
DR PDB; 7Q4M; EM; 2.80 A; A/B/C/D/E/F/G/H/I/J=672-713.
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; 1X11; -.
DR PDBsum; 1Z0Q; -.
DR PDBsum; 1ZE7; -.
DR PDBsum; 1ZE9; -.
DR PDBsum; 1ZJD; -.
DR PDBsum; 2BEG; -.
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; 2MGT; -.
DR PDBsum; 2MJ1; -.
DR PDBsum; 2MPZ; -.
DR PDBsum; 2MVX; -.
DR PDBsum; 2MXU; -.
DR PDBsum; 2NAO; -.
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; 3PZZ; -.
DR PDBsum; 3Q2X; -.
DR PDBsum; 3SV1; -.
DR PDBsum; 3U0T; -.
DR PDBsum; 3UMH; -.
DR PDBsum; 3UMI; -.
DR PDBsum; 3UMK; -.
DR PDBsum; 4HIX; -.
DR PDBsum; 4JFN; -.
DR PDBsum; 4M1C; -.
DR PDBsum; 4MDR; -.
DR PDBsum; 4MVI; -.
DR PDBsum; 4MVK; -.
DR PDBsum; 4MVL; -.
DR PDBsum; 4NGE; -.
DR PDBsum; 4OJF; -.
DR PDBsum; 4ONF; -.
DR PDBsum; 4ONG; -.
DR PDBsum; 4PQD; -.
DR PDBsum; 4PWQ; -.
DR PDBsum; 4XXD; -.
DR PDBsum; 5AEF; -.
DR PDBsum; 5AM8; -.
DR PDBsum; 5AMB; -.
DR PDBsum; 5BUO; -.
DR PDBsum; 5C67; -.
DR PDBsum; 5CSZ; -.
DR PDBsum; 5HOW; -.
DR PDBsum; 5HOX; -.
DR PDBsum; 5HOY; -.
DR PDBsum; 5KK3; -.
DR PDBsum; 5LFY; -.
DR PDBsum; 5LV0; -.
DR PDBsum; 5MY4; -.
DR PDBsum; 5MYO; -.
DR PDBsum; 5MYX; -.
DR PDBsum; 5ONP; -.
DR PDBsum; 5ONQ; -.
DR PDBsum; 5OQV; -.
DR PDBsum; 5TXD; -.
DR PDBsum; 5VOS; -.
DR PDBsum; 5VZY; -.
DR PDBsum; 5W3P; -.
DR PDBsum; 6CO3; -.
DR PDBsum; 6GFI; -.
DR PDBsum; 6ITU; -.
DR PDBsum; 6IYC; -.
DR PDBsum; 6NB9; -.
DR PDBsum; 6O4J; -.
DR PDBsum; 6OC9; -.
DR PDBsum; 6OIZ; -.
DR PDBsum; 6RHY; -.
DR PDBsum; 6SHS; -.
DR PDBsum; 6SZF; -.
DR PDBsum; 6TI5; -.
DR PDBsum; 6TI6; -.
DR PDBsum; 6TI7; -.
DR PDBsum; 6W0O; -.
DR PDBsum; 6WXM; -.
DR PDBsum; 6XOV; -.
DR PDBsum; 6YHF; -.
DR PDBsum; 6YHI; -.
DR PDBsum; 6YHO; -.
DR PDBsum; 6YHP; -.
DR PDBsum; 6YHX; -.
DR PDBsum; 7B3J; -.
DR PDBsum; 7B3K; -.
DR PDBsum; 7E6P; -.
DR PDBsum; 7JXN; -.
DR PDBsum; 7JXO; -.
DR PDBsum; 7O1Q; -.
DR PDBsum; 7Q4B; -.
DR PDBsum; 7Q4M; -.
DR AlphaFoldDB; P05067; -.
DR BMRB; P05067; -.
DR PCDDB; P05067; -.
DR SASBDB; P05067; -.
DR SMR; P05067; -.
DR BioGRID; 106848; 2308.
DR ComplexPortal; CPX-1062; Amyloid-beta protein 40/42 complex.
DR ComplexPortal; CPX-1069; Amyloid-beta protein 40 complex.
DR ComplexPortal; CPX-1070; Amyloid-beta protein 42 complex.
DR ComplexPortal; CPX-1120; Amyloid-beta protein 40/42 oligomeric complex.
DR ComplexPortal; CPX-1134; Amyloid-beta protein 42 oligomeric complex.
DR ComplexPortal; CPX-1180; Amyloid-beta protein 40 oligomeric complex.
DR CORUM; P05067; -.
DR DIP; DIP-574N; -.
DR ELM; P05067; -.
DR IntAct; P05067; 867.
DR MINT; P05067; -.
DR STRING; 9606.ENSP00000284981; -.
DR BindingDB; P05067; -.
DR ChEMBL; CHEMBL2487; -.
DR DrugBank; DB12274; Aducanumab.
DR DrugBank; DB01370; Aluminium.
DR DrugBank; DB14517; Aluminium phosphate.
DR DrugBank; DB14518; Aluminum acetate.
DR DrugBank; DB05150; CAD106.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00746; Deferoxamine.
DR DrugBank; DB06782; Dimercaprol.
DR DrugBank; DB05938; Edonerpic.
DR DrugBank; DB09148; Florbetaben (18F).
DR DrugBank; DB09149; Florbetapir (18F).
DR DrugBank; DB09151; Flutemetamol (18F).
DR DrugBank; DB02235; L-methionine (R)-S-oxide.
DR DrugBank; DB05846; Mito-4509.
DR DrugBank; DB04892; Phenserine.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB05088; Tetrathiomolybdate.
DR DrugBank; DB03754; Tromethamine.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P05067; -.
DR MEROPS; I02.015; -.
DR TCDB; 1.C.50.1.2; the amyloid Beta-protein peptide (aBetapp) family.
DR GlyConnect; 49; 2 N-Linked glycans.
DR GlyGen; P05067; 17 sites, 4 N-linked glycans (1 site), 5 O-linked glycans (8 sites).
DR iPTMnet; P05067; -.
DR MetOSite; P05067; -.
DR PhosphoSitePlus; P05067; -.
DR SwissPalm; P05067; -.
DR BioMuta; APP; -.
DR DMDM; 112927; -.
DR SWISS-2DPAGE; P05067; -.
DR EPD; P05067; -.
DR jPOST; P05067; -.
DR MassIVE; P05067; -.
DR MaxQB; P05067; -.
DR PaxDb; P05067; -.
DR PeptideAtlas; P05067; -.
DR PRIDE; P05067; -.
DR ProteomicsDB; 4307; -.
DR ProteomicsDB; 51774; -. [P05067-1]
DR ProteomicsDB; 51775; -. [P05067-10]
DR ProteomicsDB; 51776; -. [P05067-2]
DR ProteomicsDB; 51777; -. [P05067-3]
DR ProteomicsDB; 51778; -. [P05067-4]
DR ProteomicsDB; 51779; -. [P05067-5]
DR ProteomicsDB; 51780; -. [P05067-6]
DR ProteomicsDB; 51781; -. [P05067-7]
DR ProteomicsDB; 51782; -. [P05067-8]
DR ProteomicsDB; 51783; -. [P05067-9]
DR ABCD; P05067; 52 sequenced antibodies.
DR Antibodypedia; 668; 3991 antibodies from 52 providers.
DR DNASU; 351; -.
DR Ensembl; ENST00000346798.8; ENSP00000284981.4; ENSG00000142192.21. [P05067-1]
DR Ensembl; ENST00000348990.9; ENSP00000345463.5; ENSG00000142192.21. [P05067-4]
DR Ensembl; ENST00000354192.7; ENSP00000346129.3; ENSG00000142192.21. [P05067-10]
DR Ensembl; ENST00000357903.7; ENSP00000350578.3; ENSG00000142192.21. [P05067-8]
DR Ensembl; ENST00000358918.7; ENSP00000351796.3; ENSG00000142192.21. [P05067-9]
DR Ensembl; ENST00000440126.7; ENSP00000387483.2; ENSG00000142192.21. [P05067-11]
DR GeneID; 351; -.
DR KEGG; hsa:351; -.
DR MANE-Select; ENST00000346798.8; ENSP00000284981.4; NM_000484.4; NP_000475.1.
DR UCSC; uc002ylz.4; human. [P05067-1]
DR CTD; 351; -.
DR DisGeNET; 351; -.
DR GeneCards; APP; -.
DR HGNC; HGNC:620; APP.
DR HPA; ENSG00000142192; Low tissue specificity.
DR MalaCards; APP; -.
DR MIM; 104300; phenotype.
DR MIM; 104760; gene.
DR MIM; 605714; phenotype.
DR neXtProt; NX_P05067; -.
DR NIAGADS; ENSG00000142192; -.
DR OpenTargets; ENSG00000142192; -.
DR Orphanet; 324723; ABeta amyloidosis, Arctic type.
DR Orphanet; 100006; ABeta amyloidosis, Dutch type.
DR Orphanet; 324708; ABeta amyloidosis, Iowa type.
DR Orphanet; 324713; ABeta amyloidosis, Italian type.
DR Orphanet; 324718; ABetaA21G amyloidosis.
DR Orphanet; 324703; ABetaL34V amyloidosis.
DR Orphanet; 1020; Early-onset autosomal dominant Alzheimer disease.
DR PharmGKB; PA24910; -.
DR VEuPathDB; HostDB:ENSG00000142192; -.
DR eggNOG; KOG3540; Eukaryota.
DR GeneTree; ENSGT00530000063252; -.
DR InParanoid; P05067; -.
DR OMA; RERMSQX; -.
DR PhylomeDB; P05067; -.
DR TreeFam; TF317274; -.
DR BioCyc; MetaCyc:ENSG00000142192-MON; -.
DR PathwayCommons; P05067; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-HSA-444473; Formyl peptide receptors bind formyl peptides and many other ligands.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-879415; Advanced glycosylation endproduct receptor signaling.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SABIO-RK; P05067; -.
DR SignaLink; P05067; -.
DR SIGNOR; P05067; -.
DR BioGRID-ORCS; 351; 11 hits in 1084 CRISPR screens.
DR ChiTaRS; APP; human.
DR EvolutionaryTrace; P05067; -.
DR GeneWiki; Amyloid_precursor_protein; -.
DR GenomeRNAi; 351; -.
DR Pharos; P05067; Tchem.
DR PRO; PR:P05067; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P05067; protein.
DR Bgee; ENSG00000142192; Expressed in prefrontal cortex and 206 other tissues.
DR ExpressionAtlas; P05067; baseline and differential.
DR Genevisible; P05067; HS.
DR GO; GO:0106003; C:amyloid-beta complex; IMP:ARUK-UCL.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0097449; C:astrocyte projection; IEA:Ensembl.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
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:0005769; C:early endosome; IDA:ARUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0031904; C:endosome lumen; TAS:ARUK-UCL.
DR GO; GO:0070381; C:endosome to plasma membrane transport vesicle; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:ARUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005798; C:Golgi-associated vesicle; ISS:UniProtKB.
DR GO; GO:1990812; C:growth cone filopodium; IEA:Ensembl.
DR GO; GO:1990761; C:growth cone lamellipodium; IEA:Ensembl.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:ARUK-UCL.
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:0034363; C:intermediate-density lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:1990777; C:lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:0044304; C:main axon; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:ARUK-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:0005634; C:nucleus; IGI:ARUK-UCL.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0048786; C:presynaptic active zone; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:ARUK-UCL.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:GOC.
DR GO; GO:0051233; C:spindle midzone; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0030549; F:acetylcholine receptor activator activity; TAS:ARUK-UCL.
DR GO; GO:0033130; F:acetylcholine receptor binding; IPI:UniProtKB.
DR GO; GO:0097645; F:amylin binding; TAS:ARUK-UCL.
DR GO; GO:0034185; F:apolipoprotein binding; IPI:ARUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:ARUK-UCL.
DR GO; GO:0042056; F:chemoattractant activity; IGI:ARUK-UCL.
DR GO; GO:0003682; F:chromatin binding; IGI:ARUK-UCL.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:ARUK-UCL.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:ARUK-UCL.
DR GO; GO:0005109; F:frizzled binding; IPI:ARUK-UCL.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:ARUK-UCL.
DR GO; GO:0070851; F:growth factor receptor binding; IEA:Ensembl.
DR GO; GO:1904399; F:heparan sulfate binding; TAS:ARUK-UCL.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IMP:ARUK-UCL.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005158; F:insulin receptor binding; IPI:ARUK-UCL.
DR GO; GO:0005178; F:integrin binding; IDA:ARUK-UCL.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISS:ARUK-UCL.
DR GO; GO:0016504; F:peptidase activator activity; IEA:Ensembl.
DR GO; GO:0046983; F:protein dimerization activity; IDA:ARUK-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ARUK-UCL.
DR GO; GO:0051425; F:PTB domain binding; IPI:BHF-UCL.
DR GO; GO:0050786; F:RAGE receptor binding; IPI:ARUK-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030546; F:signaling receptor activator activity; IDA:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; ISS:UniProtKB.
DR GO; GO:1990000; P:amyloid fibril formation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0019732; P:antifungal humoral response; IMP:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IMP:UniProtKB.
DR GO; GO:0008306; P:associative learning; IGI:ARUK-UCL.
DR GO; GO:0048143; P:astrocyte activation; IGI:ARUK-UCL.
DR GO; GO:0002265; P:astrocyte activation involved in immune response; IGI:ARUK-UCL.
DR GO; GO:0008088; P:axo-dendritic 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:0019722; P:calcium-mediated signaling; IDA:ARUK-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0006878; P:cellular copper ion homeostasis; ISS:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071287; P:cellular response to manganese ion; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071874; P:cellular response to norepinephrine stimulus; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0050890; P:cognition; ISS:UniProtKB.
DR GO; GO:0048669; P:collateral sprouting in absence of injury; ISS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA: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:0007186; P:G protein-coupled receptor signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007612; P:learning; IMP:ARUK-UCL.
DR GO; GO:0007611; P:learning or memory; IMP:ARUK-UCL.
DR GO; GO:0042157; P:lipoprotein metabolic process; IC:ARUK-UCL.
DR GO; GO:0007626; P:locomotory behavior; ISS:UniProtKB.
DR GO; GO:0007617; P:mating behavior; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; IGI:ARUK-UCL.
DR GO; GO:0014005; P:microglia development; IGI:ARUK-UCL.
DR GO; GO:0001774; P:microglial cell activation; IGI:ARUK-UCL.
DR GO; GO:0098815; P:modulation of excitatory postsynaptic potential; IGI:ARUK-UCL.
DR GO; GO:0006378; P:mRNA polyadenylation; ISS:UniProtKB.
DR GO; GO:1903523; P:negative regulation of blood circulation; IGI:ARUK-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IDA:ComplexPortal.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IDA:ComplexPortal.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IDA:ARUK-UCL.
DR GO; GO:0010823; P:negative regulation of mitochondrion organization; TAS:ARUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:ARUK-UCL.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IGI:ARUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:ARUK-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:ComplexPortal.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:1990535; P:neuron projection maintenance; IGI:ARUK-UCL.
DR GO; GO:0016322; P:neuron remodeling; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0061903; P:positive regulation of 1-phosphatidylinositol-3-kinase activity; IGI:ARUK-UCL.
DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; IMP:ARUK-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ARUK-UCL.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IGI:ARUK-UCL.
DR GO; GO:0050867; P:positive regulation of cell activation; NAS:ARUK-UCL.
DR GO; GO:1905893; P:positive regulation of cellular response to thapsigargin; IDA:ARUK-UCL.
DR GO; GO:1905896; P:positive regulation of cellular response to tunicamycin; IDA:ARUK-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IGI:ARUK-UCL.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:ARUK-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; NAS:ARUK-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IGI:ARUK-UCL.
DR GO; GO:1904472; P:positive regulation of endothelin production; IGI:ARUK-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI:ARUK-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IGI:ARUK-UCL.
DR GO; GO:1904022; P:positive regulation of G protein-coupled receptor internalization; IDA:ARUK-UCL.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IGI:ARUK-UCL.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IGI:ARUK-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IGI:ARUK-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IGI:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IGI:ARUK-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IGI:ARUK-UCL.
DR GO; GO:1900454; P:positive regulation of long-term synaptic depression; IDA:ComplexPortal.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IGI:ARUK-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:ARUK-UCL.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:ARUK-UCL.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:ARUK-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:ARUK-UCL.
DR GO; GO:1901216; P:positive regulation of neuron death; IDA:ARUK-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IGI:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IGI:ARUK-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:ARUK-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IGI:ARUK-UCL.
DR GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; IGI:ARUK-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:ARUK-UCL.
DR GO; GO:1904591; P:positive regulation of protein import; IDA:ARUK-UCL.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; NAS:ARUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; NAS:ARUK-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:ARUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IGI:ARUK-UCL.
DR GO; GO:1900122; P:positive regulation of receptor binding; IDA:ARUK-UCL.
DR GO; GO:1905898; P:positive regulation of response to endoplasmic reticulum stress; IDA:ARUK-UCL.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IGI:ARUK-UCL.
DR GO; GO:2000406; P:positive regulation of T cell migration; IMP:ARUK-UCL.
DR GO; GO:1902949; P:positive regulation of tau-protein kinase activity; IGI:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:ARUK-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IGI:ARUK-UCL.
DR GO; GO:0051260; P:protein homooligomerization; IDA:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IMP:ARUK-UCL.
DR GO; GO:0070206; P:protein trimerization; IMP:ARUK-UCL.
DR GO; GO:1903048; P:regulation of acetylcholine-gated cation channel activity; IGI:ARUK-UCL.
DR GO; GO:1905906; P:regulation of amyloid fibril formation; IGI:ARUK-UCL.
DR GO; GO:1900221; P:regulation of amyloid-beta clearance; IMP:ARUK-UCL.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IEA:UniProt.
DR GO; GO:1902950; P:regulation of dendritic spine maintenance; IGI:ARUK-UCL.
DR GO; GO:0007176; P:regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IGI:ARUK-UCL.
DR GO; GO:0043408; P:regulation of MAPK cascade; IC:ComplexPortal.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; TAS:ARUK-UCL.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IGI:ARUK-UCL.
DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO.
DR GO; GO:0061097; P:regulation of protein tyrosine kinase activity; IC:ComplexPortal.
DR GO; GO:1905945; P:regulation of response to calcium ion; ISS:ARUK-UCL.
DR GO; GO:0010469; P:regulation of signaling receptor activity; IDA:ComplexPortal.
DR GO; GO:0150003; P:regulation of spontaneous synaptic transmission; IGI:ARUK-UCL.
DR GO; GO:0050803; P:regulation of synapse structure or activity; ISS:UniProtKB.
DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:ARUK-UCL.
DR GO; GO:0006417; P:regulation of translation; ISS:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IC:ARUK-UCL.
DR GO; GO:0070555; P:response to interleukin-1; ISS:ARUK-UCL.
DR GO; GO:0010288; P:response to lead ion; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0001878; P:response to yeast; IMP:UniProtKB.
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:0050808; P:synapse organization; IGI:ARUK-UCL.
DR GO; GO:0051124; P:synaptic assembly at neuromuscular junction; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; ISS:UniProtKB.
DR CDD; cd00109; KU; 1.
DR DisProt; DP01280; -.
DR Gene3D; 1.20.120.770; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
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 IDEAL; IID00294; -.
DR InterPro; IPR036669; Amyloid_Cu-bd_sf.
DR InterPro; IPR008155; Amyloid_glyco.
DR InterPro; IPR013803; Amyloid_glyco_Abeta.
DR InterPro; IPR037071; Amyloid_glyco_Abeta_sf.
DR InterPro; IPR011178; Amyloid_glyco_Cu-bd.
DR InterPro; IPR024329; Amyloid_glyco_E2_domain.
DR InterPro; IPR008154; Amyloid_glyco_extra.
DR InterPro; IPR015849; Amyloid_glyco_heparin-bd.
DR InterPro; IPR036454; Amyloid_glyco_heparin-bd_sf.
DR InterPro; IPR019745; Amyloid_glyco_intracell_CS.
DR InterPro; IPR028866; APP.
DR InterPro; IPR019543; APP_amyloid_C.
DR InterPro; IPR019744; APP_CUBD_CS.
DR InterPro; IPR036176; E2_sf.
DR InterPro; IPR002223; Kunitz_BPTI.
DR InterPro; IPR036880; Kunitz_BPTI_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR PANTHER; PTHR23103; PTHR23103; 1.
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; APP_CUBD; 1.
DR PROSITE; PS51869; APP_E1; 1.
DR PROSITE; PS51870; APP_E2; 1.
DR PROSITE; PS00320; APP_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; Cell membrane; Cell projection;
KW Coated pit; Copper; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Disease variant; Disulfide bond; Endocytosis;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus;
KW Heparin-binding; Iron; Isopeptide bond; Membrane; Metal-binding;
KW Neurodegeneration; Notch signaling pathway; Nucleus; Oxidation;
KW Phosphoprotein; Protease inhibitor; Proteoglycan; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal; Sulfation; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:2900137, ECO:0000269|PubMed:3597385"
FT CHAIN 18..770
FT /note="Amyloid-beta precursor protein"
FT /id="PRO_0000000088"
FT CHAIN 18..687
FT /note="Soluble APP-alpha"
FT /id="PRO_0000000089"
FT CHAIN 18..671
FT /note="Soluble APP-beta"
FT /id="PRO_0000000090"
FT CHAIN 18..286
FT /note="N-APP"
FT /id="PRO_0000381966"
FT CHAIN 672..770
FT /note="C99"
FT /id="PRO_0000000091"
FT CHAIN 672..713
FT /note="Amyloid-beta protein 42"
FT /evidence="ECO:0000305|PubMed:16154999"
FT /id="PRO_0000000092"
FT CHAIN 672..711
FT /note="Amyloid-beta protein 40"
FT /evidence="ECO:0000305|PubMed:11604391,
FT ECO:0000305|PubMed:16154999"
FT /id="PRO_0000000093"
FT CHAIN 688..770
FT /note="C83"
FT /id="PRO_0000000094"
FT PEPTIDE 688..713
FT /note="P3(42)"
FT /id="PRO_0000000095"
FT PEPTIDE 688..711
FT /note="P3(40)"
FT /id="PRO_0000000096"
FT CHAIN 691..770
FT /note="C80"
FT /id="PRO_0000384574"
FT CHAIN 712..770
FT /note="Gamma-secretase C-terminal fragment 59"
FT /id="PRO_0000000097"
FT CHAIN 714..770
FT /note="Gamma-secretase C-terminal fragment 57"
FT /id="PRO_0000000098"
FT CHAIN 721..770
FT /note="Gamma-secretase C-terminal fragment 50"
FT /evidence="ECO:0000250"
FT /id="PRO_0000000099"
FT CHAIN 740..770
FT /note="C31"
FT /id="PRO_0000000100"
FT TOPO_DOM 18..701
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 702..722
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:22584060,
FT ECO:0000305|PubMed:22654059, ECO:0000305|PubMed:30630874"
FT TOPO_DOM 723..770
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 28..189
FT /note="E1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT DOMAIN 291..341
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DOMAIN 374..565
FT /note="E2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01218"
FT REGION 28..123
FT /note="GFLD subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT REGION 131..189
FT /note="CuBD subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT REGION 194..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..423
FT /note="Heparin-binding"
FT REGION 491..522
FT /note="Heparin-binding"
FT REGION 523..540
FT /note="Collagen-binding"
FT /evidence="ECO:0000269|PubMed:8576160"
FT REGION 695..722
FT /note="Interaction with PSEN1"
FT /evidence="ECO:0000269|PubMed:30630874"
FT REGION 732..751
FT /note="Interaction with G(o)-alpha"
FT REGION 756..770
FT /note="Required for the interaction with KIF5B and for
FT anterograde transport in axons"
FT /evidence="ECO:0000269|PubMed:17062754"
FT MOTIF 344..365
FT /note="OX-2"
FT /evidence="ECO:0000269|PubMed:2649245"
FT MOTIF 724..734
FT /note="Basolateral sorting signal"
FT MOTIF 757..762
FT /note="YENPXY motif; contains endocytosis signal"
FT /evidence="ECO:0000269|PubMed:10383380"
FT COMPBIAS 195..210
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..263
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 96..110
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000269|PubMed:8158260"
FT BINDING 147
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0000269|PubMed:17239395, ECO:0000269|PubMed:25122912,
FT ECO:0007744|PDB:2FK1"
FT BINDING 151
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0000269|PubMed:17239395, ECO:0000269|PubMed:25122912,
FT ECO:0007744|PDB:2FK1"
FT BINDING 168
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0000269|PubMed:17239395, ECO:0007744|PDB:2FK1"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:8344894"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:8344894"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:8344894"
FT BINDING 677
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11274207"
FT BINDING 677
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11274207,
FT ECO:0000269|PubMed:26898943"
FT BINDING 681
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:11274207"
FT BINDING 681
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:10413512,
FT ECO:0000305|PubMed:11274207"
FT BINDING 684
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11274207"
FT BINDING 684
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10413512,
FT ECO:0000269|PubMed:11274207, ECO:0000269|PubMed:26898943"
FT BINDING 685
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11274207"
FT BINDING 685
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11274207,
FT ECO:0000269|PubMed:26898943"
FT SITE 170
FT /note="Required for Cu(2+) reduction"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217"
FT SITE 197..198
FT /note="Cleavage; by caspases"
FT /evidence="ECO:0000269|PubMed:10319819"
FT SITE 219..220
FT /note="Cleavage; by caspases"
FT /evidence="ECO:0000269|PubMed:10319819"
FT SITE 301..302
FT /note="Reactive bond"
FT SITE 671..672
FT /note="Cleavage; by beta-secretase"
FT /evidence="ECO:0000305|PubMed:11851430"
FT SITE 672..673
FT /note="Cleavage; by caspase-6; when associated with variant
FT 670-N-L-671"
FT SITE 678..679
FT /note="Cleavage; by ACE"
FT /evidence="ECO:0000269|PubMed:11604391,
FT ECO:0000269|PubMed:16154999"
FT SITE 687..688
FT /note="Cleavage; by alpha-secretase"
FT /evidence="ECO:0000305|PubMed:11851430"
FT SITE 690..691
FT /note="Cleavage; by theta-secretase"
FT /evidence="ECO:0000269|PubMed:16816112"
FT SITE 704
FT /note="Implicated in free radical propagation"
FT /evidence="ECO:0000250"
FT SITE 706
FT /note="Susceptible to oxidation"
FT /evidence="ECO:0000269|PubMed:10535332"
FT SITE 711..712
FT /note="Cleavage; by gamma-secretase; site 1"
FT /evidence="ECO:0000305|PubMed:11851430"
FT SITE 713..714
FT /note="Cleavage; by gamma-secretase; site 2"
FT /evidence="ECO:0000305|PubMed:11851430"
FT SITE 720..721
FT /note="Cleavage; by gamma-secretase; site 3"
FT /evidence="ECO:0000269|PubMed:11851430,
FT ECO:0000305|PubMed:30630874"
FT SITE 739..740
FT /note="Cleavage; by caspase-6, caspase-8 or caspase-9"
FT /evidence="ECO:0000269|PubMed:10319819"
FT MOD_RES 198
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8999878"
FT MOD_RES 206
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000269|PubMed:8999878"
FT MOD_RES 217
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 262
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 336
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 441
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 497
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 729
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08592"
FT MOD_RES 730
FT /note="Phosphoserine; by APP-kinase I"
FT /evidence="ECO:0000250|UniProtKB:P08592"
FT MOD_RES 743
FT /note="Phosphothreonine; by CDK5 and MAPK10"
FT /evidence="ECO:0000269|PubMed:28720718,
FT ECO:0000269|PubMed:8131745, ECO:0007744|PubMed:24275569"
FT MOD_RES 757
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11877420"
FT CARBOHYD 542
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 571
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 633
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:21712440,
FT ECO:0000269|PubMed:22576872"
FT CARBOHYD 651
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:21712440,
FT ECO:0000269|PubMed:22576872"
FT CARBOHYD 652
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:21712440,
FT ECO:0000269|PubMed:22576872"
FT CARBOHYD 656
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine; in
FT L-APP isoforms"
FT /evidence="ECO:0000269|PubMed:21712440"
FT CARBOHYD 659
FT /note="O-linked (HexNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:22576872"
FT CARBOHYD 663
FT /note="O-linked (GalNAc...) threonine; partial"
FT /evidence="ECO:0000269|PubMed:22576872,
FT ECO:0000305|PubMed:21712440"
FT CARBOHYD 667
FT /note="O-linked (GalNAc...) serine; partial"
FT /evidence="ECO:0000269|PubMed:22576872,
FT ECO:0000305|PubMed:21712440"
FT CARBOHYD 681
FT /note="O-linked (HexNAc...) tyrosine; partial"
FT /evidence="ECO:0000269|PubMed:22576872"
FT DISULFID 38..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0007744|PDB:1MWP, ECO:0007744|PDB:3KTM,
FT ECO:0007744|PDB:4JFN, ECO:0007744|PDB:4PQD,
FT ECO:0007744|PDB:4PWQ"
FT DISULFID 73..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0007744|PDB:1MWP, ECO:0007744|PDB:3KTM,
FT ECO:0007744|PDB:4JFN, ECO:0007744|PDB:4PQD,
FT ECO:0007744|PDB:4PWQ"
FT DISULFID 98..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0007744|PDB:1MWP, ECO:0007744|PDB:3KTM,
FT ECO:0007744|PDB:4PQD, ECO:0007744|PDB:4PWQ"
FT DISULFID 133..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0000269|PubMed:12611883, ECO:0000269|PubMed:17239395,
FT ECO:0000269|PubMed:17909280, ECO:0007744|PDB:1OWT,
FT ECO:0007744|PDB:2FJZ, ECO:0007744|PDB:2FK1,
FT ECO:0007744|PDB:2FK2, ECO:0007744|PDB:2FK3,
FT ECO:0007744|PDB:2FKL, ECO:0007744|PDB:2FMA,
FT ECO:0007744|PDB:3KTM, ECO:0007744|PDB:4PWQ"
FT DISULFID 144..174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0000269|PubMed:12611883, ECO:0000269|PubMed:17239395,
FT ECO:0000269|PubMed:17909280, ECO:0007744|PDB:1OWT,
FT ECO:0007744|PDB:2FJZ, ECO:0007744|PDB:2FK1,
FT ECO:0007744|PDB:2FK2, ECO:0007744|PDB:2FK3,
FT ECO:0007744|PDB:2FKL, ECO:0007744|PDB:2FMA,
FT ECO:0007744|PDB:3KTM, ECO:0007744|PDB:4PWQ"
FT DISULFID 158..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01217,
FT ECO:0000269|PubMed:12611883, ECO:0000269|PubMed:17239395,
FT ECO:0000269|PubMed:17909280, ECO:0007744|PDB:1OWT,
FT ECO:0007744|PDB:2FJZ, ECO:0007744|PDB:2FK1,
FT ECO:0007744|PDB:2FK2, ECO:0007744|PDB:2FK3,
FT ECO:0007744|PDB:2FKL, ECO:0007744|PDB:2FMA,
FT ECO:0007744|PDB:3KTM, ECO:0007744|PDB:4PWQ"
FT DISULFID 291..341
FT /evidence="ECO:0007744|PDB:1AAP, ECO:0007744|PDB:1BRC,
FT ECO:0007744|PDB:1CA0, ECO:0007744|PDB:1TAW,
FT ECO:0007744|PDB:1ZJD, ECO:0007744|PDB:3L33"
FT DISULFID 300..324
FT /evidence="ECO:0007744|PDB:1AAP, ECO:0007744|PDB:1BRC,
FT ECO:0007744|PDB:1CA0, ECO:0007744|PDB:1TAW,
FT ECO:0007744|PDB:1ZJD, ECO:0007744|PDB:3L33,
FT ECO:0007744|PDB:5C67"
FT DISULFID 316..337
FT /evidence="ECO:0007744|PDB:1AAP, ECO:0007744|PDB:1BRC,
FT ECO:0007744|PDB:1CA0, ECO:0007744|PDB:1TAW,
FT ECO:0007744|PDB:1ZJD, ECO:0007744|PDB:3L33,
FT ECO:0007744|PDB:5C67"
FT CROSSLNK 763
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P08592"
FT VAR_SEQ 1..19
FT /note="MLPGLALLLLAAWTARALE -> MDQLEDLLVLFINY (in isoform
FT 11)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045446"
FT VAR_SEQ 19..74
FT /note="Missing (in isoform APP639)"
FT /evidence="ECO:0000303|PubMed:12859342"
FT /id="VSP_009116"
FT VAR_SEQ 289..363
FT /note="Missing (in isoform APP639)"
FT /evidence="ECO:0000303|PubMed:12859342"
FT /id="VSP_009117"
FT VAR_SEQ 289
FT /note="E -> V (in isoform APP695, isoform L-APP696, isoform
FT L-APP677 and isoform APP714)"
FT /evidence="ECO:0000303|PubMed:2881207"
FT /id="VSP_000002"
FT VAR_SEQ 290..364
FT /note="Missing (in isoform APP695 and isoform L-APP677)"
FT /evidence="ECO:0000303|PubMed:2881207"
FT /id="VSP_000004"
FT VAR_SEQ 290..345
FT /note="Missing (in isoform L-APP696 and isoform APP714)"
FT /evidence="ECO:0000305"
FT /id="VSP_000003"
FT VAR_SEQ 290..305
FT /note="VCSEQAETGPCRAMIS -> KWYKEVHSGQARWLML (in isoform
FT APP305)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000005"
FT VAR_SEQ 306..770
FT /note="Missing (in isoform APP305)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000006"
FT VAR_SEQ 345..364
FT /note="MSQSLLKTTQEPLARDPVKL -> I (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045447"
FT VAR_SEQ 345
FT /note="M -> I (in isoform L-APP733 and isoform APP751)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1587857, ECO:0000303|PubMed:2893289"
FT /id="VSP_000007"
FT VAR_SEQ 346..364
FT /note="Missing (in isoform L-APP733 and isoform APP751)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1587857, ECO:0000303|PubMed:2893289"
FT /id="VSP_000008"
FT VAR_SEQ 364
FT /note="L -> V (in isoform APP639)"
FT /evidence="ECO:0000303|PubMed:12859342"
FT /id="VSP_009118"
FT VAR_SEQ 637..654
FT /note="Missing (in isoform L-APP677, isoform L-APP696,
FT isoform L-APP733 and isoform L-APP752)"
FT /evidence="ECO:0000303|PubMed:1587857"
FT /id="VSP_000009"
FT VARIANT 501
FT /note="E -> K (in dbSNP:rs45588932)"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_022315"
FT VARIANT 665
FT /note="E -> D (in a patient with late onset Alzheimer
FT disease; dbSNP:rs63750363)"
FT /evidence="ECO:0000269|PubMed:8154870"
FT /id="VAR_010107"
FT VARIANT 670..671
FT /note="KM -> NL (in AD1; Swedish mutation; highly increases
FT hydrolysis by BACE1 and amyloid-beta proteins production;
FT dbSNP:rs281865161)"
FT /evidence="ECO:0000269|PubMed:10656250,
FT ECO:0000269|PubMed:10677483, ECO:0000269|PubMed:1302033,
FT ECO:0000269|PubMed:1465129"
FT /id="VAR_000015"
FT VARIANT 678
FT /note="D -> N (in AD1; dbSNP:rs63750064)"
FT /evidence="ECO:0000269|PubMed:15201367"
FT /id="VAR_044424"
FT VARIANT 692
FT /note="A -> G (in AD1; Flemish mutation; increases the
FT solubility of processed amyloid-beta peptides and increases
FT the stability of peptide oligomers; dbSNP:rs63750671)"
FT /evidence="ECO:0000269|PubMed:11311152,
FT ECO:0000269|PubMed:1303239, ECO:0000269|PubMed:9754958"
FT /id="VAR_000016"
FT VARIANT 693
FT /note="E -> G (in AD1; dbSNP:rs63751039)"
FT /evidence="ECO:0000269|PubMed:11528419,
FT ECO:0000269|PubMed:1415269"
FT /id="VAR_014215"
FT VARIANT 693
FT /note="E -> K (in CAA-APP; Italian type; dbSNP:rs63750579)"
FT /evidence="ECO:0000269|PubMed:20697050"
FT /id="VAR_014216"
FT VARIANT 693
FT /note="E -> Q (in CAA-APP; Dutch type; dbSNP:rs63750579)"
FT /evidence="ECO:0000269|PubMed:2111584"
FT /id="VAR_000017"
FT VARIANT 694
FT /note="D -> N (in CAA-APP; Iowa type; dbSNP:rs63749810)"
FT /evidence="ECO:0000269|PubMed:11409420,
FT ECO:0000269|PubMed:12654973"
FT /id="VAR_014217"
FT VARIANT 705
FT /note="L -> V (in CAA-APP; Italian type; dbSNP:rs63750921)"
FT /evidence="ECO:0000269|PubMed:16178030"
FT /id="VAR_032276"
FT VARIANT 713
FT /note="A -> T (in AD1; dbSNP:rs63750066)"
FT /evidence="ECO:0000269|PubMed:1303275,
FT ECO:0000269|PubMed:15365148"
FT /id="VAR_000019"
FT VARIANT 713
FT /note="A -> V (in one chronic schizophrenia patient;
FT unknown pathological significance; dbSNP:rs1800557)"
FT /evidence="ECO:0000269|PubMed:1307241"
FT /id="VAR_000018"
FT VARIANT 714
FT /note="T -> A (in AD1; dbSNP:rs63750643)"
FT /evidence="ECO:0000269|PubMed:12034808"
FT /id="VAR_032277"
FT VARIANT 714
FT /note="T -> I (in AD1; increased amyloid-beta protein 42/40
FT ratio; dbSNP:rs63750973)"
FT /evidence="ECO:0000269|PubMed:11063718,
FT ECO:0000269|PubMed:15668448"
FT /id="VAR_014218"
FT VARIANT 715
FT /note="V -> M (in AD1; decreased amyloid-beta protein 40/
FT total amyloid-beta; dbSNP:rs63750734)"
FT /evidence="ECO:0000269|PubMed:10097173"
FT /id="VAR_010108"
FT VARIANT 716
FT /note="I -> V (in AD1; dbSNP:rs63750399)"
FT /evidence="ECO:0000269|PubMed:9328472"
FT /id="VAR_000020"
FT VARIANT 717
FT /note="V -> F (in AD1; increased amyloid-beta protein 42/40
FT ratio; dbSNP:rs63750264)"
FT /evidence="ECO:0000269|PubMed:1925564,
FT ECO:0000269|PubMed:8267572, ECO:0000269|PubMed:8290042,
FT ECO:0000269|PubMed:8476439, ECO:0000269|PubMed:8886002"
FT /id="VAR_000023"
FT VARIANT 717
FT /note="V -> G (in AD1; increased amyloid-beta protein 42/40
FT ratio; dbSNP:rs63749964)"
FT /evidence="ECO:0000269|PubMed:1944558,
FT ECO:0000269|PubMed:8476439, ECO:0000269|PubMed:8886002"
FT /id="VAR_000022"
FT VARIANT 717
FT /note="V -> I (in AD1; increased amyloid-beta protein 42/40
FT ratio; dbSNP:rs63750264)"
FT /evidence="ECO:0000269|PubMed:10631141,
FT ECO:0000269|PubMed:11063718, ECO:0000269|PubMed:1671712,
FT ECO:0000269|PubMed:1678058, ECO:0000269|PubMed:1908231,
FT ECO:0000269|PubMed:8267572, ECO:0000269|PubMed:8476439,
FT ECO:0000269|PubMed:8577393, ECO:0000269|PubMed:8886002"
FT /id="VAR_000021"
FT VARIANT 717
FT /note="V -> L (in AD1; dbSNP:rs63750264)"
FT /evidence="ECO:0000269|PubMed:10867787"
FT /id="VAR_014219"
FT VARIANT 723
FT /note="L -> P (in AD1; dbSNP:rs63751122)"
FT /evidence="ECO:0000269|PubMed:10665499"
FT /id="VAR_010109"
FT MUTAGEN 99..102
FT /note="KRGR->NQGG: Reduced heparin-binding."
FT /evidence="ECO:0000269|PubMed:8158260"
FT MUTAGEN 108
FT /note="H->A: Loss of the copper binding site in the GFLD
FT subdomain; when associated with A-110."
FT /evidence="ECO:0000269|PubMed:25122912"
FT MUTAGEN 110
FT /note="H->A: Loss of the copper binding site in the GFLD
FT subdomain; when associated with A-108."
FT /evidence="ECO:0000269|PubMed:25122912"
FT MUTAGEN 137
FT /note="H->N: Binds copper. Forms dimer."
FT /evidence="ECO:0000269|PubMed:7913895"
FT MUTAGEN 141
FT /note="M->T: Binds copper. Forms dimer."
FT /evidence="ECO:0000269|PubMed:7913895"
FT MUTAGEN 144
FT /note="C->S: Binds copper. No dimer formation. No copper
FT reducing activity."
FT /evidence="ECO:0000269|PubMed:10461923,
FT ECO:0000269|PubMed:7913895"
FT MUTAGEN 147..149
FT /note="HLH->ALA: 50% decrease in copper reducing activity."
FT /evidence="ECO:0000269|PubMed:10461923"
FT MUTAGEN 147
FT /note="H->A: Loss of a copper binding site; when associated
FT with A-151."
FT /evidence="ECO:0000269|PubMed:25122912"
FT MUTAGEN 147
FT /note="H->A: Some decrease in copper reducing activity."
FT /evidence="ECO:0000269|PubMed:11784781,
FT ECO:0000269|PubMed:7913895"
FT MUTAGEN 147
FT /note="H->N: Binds copper. Forms dimer."
FT /evidence="ECO:0000269|PubMed:11784781,
FT ECO:0000269|PubMed:7913895"
FT MUTAGEN 147
FT /note="H->Y: Greatly reduced copper-mediated low-density
FT lipoprotein oxidation."
FT /evidence="ECO:0000269|PubMed:11784781,
FT ECO:0000269|PubMed:7913895"
FT MUTAGEN 151
FT /note="H->A: Loss of a copper binding site; when associated
FT with A-147."
FT /evidence="ECO:0000269|PubMed:25122912"
FT MUTAGEN 151
FT /note="H->K: Greatly reduced copper-mediated low-density
FT lipoprotein oxidation."
FT /evidence="ECO:0000269|PubMed:11784781,
FT ECO:0000269|PubMed:7913895"
FT MUTAGEN 151
FT /note="H->N: Binds copper. Forms dimer."
FT /evidence="ECO:0000269|PubMed:11784781,
FT ECO:0000269|PubMed:7913895"
FT MUTAGEN 198
FT /note="S->A: Greatly reduced casein kinase
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10806211,
FT ECO:0000269|PubMed:8999878"
FT MUTAGEN 206
FT /note="S->A: Reduced casein kinase phosphorylation."
FT /evidence="ECO:0000269|PubMed:10806211,
FT ECO:0000269|PubMed:8999878"
FT MUTAGEN 499
FT /note="R->A: Reduced affinity for heparin; when associated
FT with A-503."
FT /evidence="ECO:0000269|PubMed:15304215"
FT MUTAGEN 503
FT /note="K->A: Reduced affinity for heparin; when associated
FT with A-499."
FT /evidence="ECO:0000269|PubMed:15304215"
FT MUTAGEN 656
FT /note="S->A: Abolishes chondroitin sulfate binding in L-
FT APP733 isoform."
FT /evidence="ECO:0000269|PubMed:7737970"
FT MUTAGEN 676
FT /note="R->G: 60-70% zinc-induced amyloid-beta protein 28
FT aggregation."
FT /evidence="ECO:0000269|PubMed:10413512"
FT MUTAGEN 681
FT /note="Y->F: 60-70% zinc-induced amyloid-beta protein 28
FT aggregation."
FT /evidence="ECO:0000269|PubMed:10413512"
FT MUTAGEN 684
FT /note="H->R: Only 23% zinc-induced amyloid-beta protein 28
FT aggregation."
FT /evidence="ECO:0000269|PubMed:10413512"
FT MUTAGEN 695
FT /note="V->C: Causes formation of an artifactual disulfide
FT bond with PSEN1."
FT /evidence="ECO:0000269|PubMed:30630874"
FT MUTAGEN 704
FT /note="G->V: Reduced protein oxidation. No hippocampal
FT neuron toxicity."
FT MUTAGEN 706
FT /note="M->L: Reduced lipid peroxidation inhibition."
FT /evidence="ECO:0000269|PubMed:10535332,
FT ECO:0000269|PubMed:9168929"
FT MUTAGEN 706
FT /note="M->V: No free radical production. No hippocampal
FT neuron toxicity."
FT /evidence="ECO:0000269|PubMed:10535332,
FT ECO:0000269|PubMed:9168929"
FT MUTAGEN 717
FT /note="V->C,S: Unchanged amyloid-beta protein 42/total
FT amyloid-beta ratio."
FT /evidence="ECO:0000269|PubMed:8886002"
FT MUTAGEN 717
FT /note="V->K: Decreased amyloid-beta protein 42/total
FT amyloid-beta ratio."
FT /evidence="ECO:0000269|PubMed:8886002"
FT MUTAGEN 717
FT /note="V->M: Increased amyloid-beta protein 42/40 ratio. No
FT change in apoptosis after caspase cleavage."
FT /evidence="ECO:0000269|PubMed:8886002"
FT MUTAGEN 728
FT /note="Y->A: No effect on APBA1 nor APBB1 binding. Greatly
FT reduces the binding to APPBP2. APP internalization
FT unchanged. No change in amyloid-beta protein 42 secretion."
FT /evidence="ECO:0000269|PubMed:10383380,
FT ECO:0000269|PubMed:8887653, ECO:0000269|PubMed:9843960"
FT MUTAGEN 739
FT /note="D->A: No cleavage by caspases during apoptosis."
FT /evidence="ECO:0000269|PubMed:10319819,
FT ECO:0000269|PubMed:10742146, ECO:0000269|PubMed:12214090"
FT MUTAGEN 739
FT /note="D->N: No effect on FADD-induced apoptosis."
FT /evidence="ECO:0000269|PubMed:10319819,
FT ECO:0000269|PubMed:10742146, ECO:0000269|PubMed:12214090"
FT MUTAGEN 743
FT /note="T->A: Greatly reduces the binding to SHC1 and APBB
FT family members; no effect on NGF-stimulated neurite
FT extension. Loss of phosphorylation by LRRK2."
FT /evidence="ECO:0000269|PubMed:10341243,
FT ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218,
FT ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:28720718"
FT MUTAGEN 743
FT /note="T->E: Reduced NGF-stimulated neurite extension. No
FT effect on APP maturation."
FT /evidence="ECO:0000269|PubMed:10341243,
FT ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218,
FT ECO:0000269|PubMed:11877420"
FT MUTAGEN 756
FT /note="G->A: APP internalization unchanged. No change in
FT amyloid-beta protein 42 secretion."
FT /evidence="ECO:0000269|PubMed:10383380"
FT MUTAGEN 757..762
FT /note="YENPTY->AENPTA: No effect on C99 interaction with
FT SORL1."
FT /evidence="ECO:0000269|PubMed:16407538"
FT MUTAGEN 757
FT /note="Y->A: Little APP internalization. Reduced amyloid-
FT beta protein 42 secretion."
FT /evidence="ECO:0000269|PubMed:10383380,
FT ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420,
FT ECO:0000269|PubMed:8887653"
FT MUTAGEN 757
FT /note="Y->G: Loss of binding to MAPK8IP1, APBA1, APBB1,
FT APPBP2 and SHC1."
FT /evidence="ECO:0000269|PubMed:10383380,
FT ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420,
FT ECO:0000269|PubMed:8887653"
FT MUTAGEN 759
FT /note="N->A: No binding to APBA1, no effect on APBB1
FT binding. Little APP internalization. Reduced amyloid-beta
FT protein 42 secretion."
FT /evidence="ECO:0000269|PubMed:10383380,
FT ECO:0000269|PubMed:8887653"
FT MUTAGEN 760
FT /note="P->A: Little APP internalization. Reduced amyloid-
FT beta protein 42 secretion."
FT /evidence="ECO:0000269|PubMed:10383380"
FT MUTAGEN 762
FT /note="Y->A: Loss of binding to APBA1 and APBB1. APP
FT internalization unchanged. No change in amyloid-beta
FT protein 42 secretion."
FT /evidence="ECO:0000269|PubMed:10383380,
FT ECO:0000269|PubMed:8887653"
FT CONFLICT 15..16
FT /note="AR -> VW (in Ref. 3; CAA31830)"
FT /evidence="ECO:0000305"
FT CONFLICT 647
FT /note="D -> E (in Ref. 36; AAA51722)"
FT /evidence="ECO:0000305"
FT CONFLICT 724
FT /note="Missing (in Ref. 23; AAB26263/AAB26264)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="I -> N (in Ref. 23; AAB26263/AAB26264/AAB26265)"
FT /evidence="ECO:0000305"
FT CONFLICT 757
FT /note="Y -> S (in Ref. 31; AAA35540)"
FT /evidence="ECO:0000305"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:4PQD"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:4PWQ"
FT HELIX 66..76
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:4PQD"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:4PQD"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:2FMA"
FT HELIX 147..160
FT /evidence="ECO:0007829|PDB:2FMA"
FT STRAND 163..174
FT /evidence="ECO:0007829|PDB:2FMA"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:2FMA"
FT STRAND 178..188
FT /evidence="ECO:0007829|PDB:2FMA"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:1AAP"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:1AAP"
FT STRAND 304..310
FT /evidence="ECO:0007829|PDB:1AAP"
FT TURN 311..314
FT /evidence="ECO:0007829|PDB:1AAP"
FT STRAND 315..321
FT /evidence="ECO:0007829|PDB:1AAP"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:1AAP"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:1AAP"
FT HELIX 334..341
FT /evidence="ECO:0007829|PDB:1AAP"
FT HELIX 374..380
FT /evidence="ECO:0007829|PDB:3NYL"
FT HELIX 389..418
FT /evidence="ECO:0007829|PDB:3UMH"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:3UMH"
FT HELIX 425..480
FT /evidence="ECO:0007829|PDB:3UMH"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:3NYJ"
FT HELIX 487..518
FT /evidence="ECO:0007829|PDB:3UMH"
FT HELIX 520..546
FT /evidence="ECO:0007829|PDB:3UMH"
FT HELIX 547..550
FT /evidence="ECO:0007829|PDB:3UMH"
FT HELIX 552..566
FT /evidence="ECO:0007829|PDB:3UMH"
FT HELIX 615..618
FT /evidence="ECO:0007829|PDB:5BUO"
FT STRAND 620..622
FT /evidence="ECO:0007829|PDB:5BUO"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:4OJF"
FT TURN 677..680
FT /evidence="ECO:0007829|PDB:5MYO"
FT STRAND 681..684
FT /evidence="ECO:0007829|PDB:7Q4B"
FT STRAND 688..691
FT /evidence="ECO:0007829|PDB:6O4J"
FT STRAND 692..694
FT /evidence="ECO:0007829|PDB:4MVI"
FT TURN 695..698
FT /evidence="ECO:0007829|PDB:4MVI"
FT STRAND 701..703
FT /evidence="ECO:0007829|PDB:3PZZ"
FT STRAND 707..712
FT /evidence="ECO:0007829|PDB:2Y3K"
FT HELIX 713..715
FT /evidence="ECO:0007829|PDB:6IYC"
FT STRAND 721..725
FT /evidence="ECO:0007829|PDB:6IYC"
FT HELIX 744..754
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 756..758
FT /evidence="ECO:0007829|PDB:6ITU"
FT STRAND 763..765
FT /evidence="ECO:0007829|PDB:3L81"
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
