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 27-NOV-2024, entry version 314. 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 GN {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 RETRACTED PAPER. 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 CAUTION, AND RETRACTION NOTICE OF PUBMED:19225519. RX PubMed=38110576; DOI=10.1038/s41586-023-06943-3; RA Nikolaev A., McLaughlin T., O'Leary D.D.M., Tessier-Lavigne M.; RT "Retraction Note: APP binds DR6 to trigger axon pruning and neuron death RT via distinct caspases."; RL Nature 625:204-204(2024). RN [100] 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 [101] 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 [102] 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 [103] 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 [104] 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 [105] 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 [106] 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 [107] 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 [108] 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 [109] 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 [110] 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 [111] 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 [112] 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 [113] 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 [114] 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 [115] 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 [116] 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 [117] 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 [118] 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 [119] 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 [120] 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 [121] 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 [122] 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 [123] 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 [124] {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 [125] 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 [126] 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 [127] 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 [128] {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 [129] 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 [130] 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 [131] 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 [132] {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 [133] {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 [134] {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 [135] {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 [136] {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 [137] {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 [138] {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 [139] 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 [140] 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 [141] 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 [142] 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 [143] 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 [144] 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 [145] 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 [146] 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 [147] 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 [148] 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 [149] 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 [150] 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 [151] 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 [152] 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 [153] 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 [154] 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 [155] 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 [156] 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 [157] 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 [158] 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 [159] 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 [160] 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 [161] 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 [162] 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 [163] 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 [164] 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 [165] 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 [166] 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 [167] 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 [168] 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 [169] 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 [170] 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 [171] 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 [172] 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 [173] 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 [174] 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 synapses in axons (PubMed:17062754, PubMed:23011729). Involved in CC copper homeostasis/oxidative stress through copper ion reduction. In CC vitro, copper-metallated APP induces neuronal death directly or is CC potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. CC Can regulate neurite outgrowth through binding to components of the CC extracellular matrix such as heparin and collagen I and IV. The splice CC isoforms that contain the BPTI domain possess protease inhibitor CC activity. Induces a AGER-dependent pathway that involves activation of CC p38 MAPK, resulting in internalization of amyloid-beta peptide and CC leading to mitochondrial dysfunction in cultured cortical neurons. CC Provides Cu(2+) ions for GPC1 which are required for release of nitric CC oxide (NO) and subsequent degradation of the heparan sulfate chains on CC GPC1. {ECO:0000250, ECO:0000250|UniProtKB:P12023, CC ECO:0000269|PubMed:17062754, ECO:0000269|PubMed:23011729, CC 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 -!- 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. Interacts with ITM2B. Interacts CC with ITM2C. Interacts with IDE. Can form homodimers; dimerization is CC enhanced in the presence of Cu(2+) ions (PubMed:25122912). Can form CC homodimers; this is promoted by heparin binding. Amyloid-beta protein CC 40 interacts with S100A9. CTF-alpha product of APP interacts with GSAP. CC Isoform APP695 interacts with SORL1 (via N-terminal ectodomain); this CC interaction retains APP in the trans-Golgi network and reduces CC processing into soluble APP-alpha and amyloid-beta peptides CC (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). CC The C99 fragment also interacts with SORL1 (PubMed:16407538). Isoform CC APP751 interacts with SORL1 (PubMed:16174740). Isoform APP770 interacts CC with SORL1 (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:19366692, CC ECO:0000269|PubMed:19901339, ECO:0000269|PubMed:20212142, CC ECO:0000269|PubMed:20811458, ECO:0000269|PubMed:22457725, CC ECO:0000269|PubMed:23011729, ECO:0000269|PubMed:24336208, CC ECO:0000269|PubMed:24523320, ECO:0000269|PubMed:25122912, CC ECO:0000269|PubMed:25168729, ECO:0000269|PubMed:28720718, CC ECO:0000269|PubMed:30630874, ECO:0000269|PubMed:8446172, CC ECO:0000269|PubMed:8626687, ECO:0000269|PubMed:8855266, CC ECO:0000269|PubMed:8887653, ECO:0000269|PubMed:9300481, CC ECO:0000269|PubMed:9338779, ECO:0000269|PubMed:9843960, CC 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=5; IntAct=EBI-77613, EBI-368690; CC P05067; Q99767: APBA2; NbExp=2; IntAct=EBI-77613, EBI-81711; CC P05067; O96018: APBA3; NbExp=6; IntAct=EBI-77613, EBI-6115839; CC P05067; O00213: APBB1; NbExp=10; IntAct=EBI-77613, EBI-81694; CC P05067; O00213-2: APBB1; NbExp=6; IntAct=EBI-77613, EBI-13307975; CC P05067; Q92870: APBB2; NbExp=6; IntAct=EBI-77613, EBI-79277; CC P05067; Q92870-2: APBB2; NbExp=3; IntAct=EBI-77613, EBI-21535880; CC P05067; O95704: APBB3; NbExp=8; 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; P0DP25: 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=6; 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=6; 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; Q9UQF2: MAPK8IP1; NbExp=3; IntAct=EBI-77613, EBI-78404; CC P05067; P10636: MAPT; NbExp=8; IntAct=EBI-77613, EBI-366182; CC P05067; P10636-8: MAPT; NbExp=4; IntAct=EBI-77613, EBI-366233; 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; A0A6Q8PF08: PMP22; NbExp=3; IntAct=EBI-77613, EBI-50433196; 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; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-77613, EBI-358545; 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; Q9NV96: TMEM30A; NbExp=3; IntAct=EBI-77613, EBI-2836942; 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; 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; O60293: ZFC3H1; NbExp=3; IntAct=EBI-77613, EBI-746701; CC P05067; P17028: ZNF24; NbExp=3; IntAct=EBI-77613, EBI-707773; CC P05067; Q8N895: ZNF366; NbExp=3; IntAct=EBI-77613, EBI-2813661; CC P05067; Q03936: ZNF92; NbExp=4; IntAct=EBI-77613, EBI-12176441; 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; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-17264467, EBI-358545; 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 P05067-4; 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; O95411: MYO18A; NbExp=3; IntAct=EBI-821758, EBI-302378; 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; 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:11146006, PubMed:8131745). 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 form of Alzheimer CC disease, a neurodegenerative disorder characterized by progressive CC dementia, loss of cognitive abilities, and deposition of fibrillar CC amyloid proteins as intraneuronal neurofibrillary tangles, CC extracellular amyloid plaques and vascular amyloid deposits. The major CC constituents of these plaques are neurotoxic amyloid-beta protein 40 CC and amyloid-beta protein 42, that are produced by the proteolysis of CC the transmembrane APP protein. The cytotoxic C-terminal fragments CC (CTFs) and the caspase-cleaved products, such as C31, are also CC implicated in neuronal death. It can be associated with cerebral CC amyloid angiopathy. Alzheimer disease can be associated with cerebral CC amyloid angiopathy. {ECO:0000269|PubMed:10097173, CC ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10656250, CC ECO:0000269|PubMed:10665499, ECO:0000269|PubMed:10677483, CC ECO:0000269|PubMed:10867787, ECO:0000269|PubMed:11063718, CC ECO:0000269|PubMed:11311152, ECO:0000269|PubMed:11528419, CC ECO:0000269|PubMed:12034808, ECO:0000269|PubMed:1302033, CC ECO:0000269|PubMed:1303239, ECO:0000269|PubMed:1303275, CC ECO:0000269|PubMed:1415269, ECO:0000269|PubMed:1465129, CC ECO:0000269|PubMed:15201367, ECO:0000269|PubMed:15365148, CC ECO:0000269|PubMed:15668448, ECO:0000269|PubMed:1671712, CC ECO:0000269|PubMed:1678058, ECO:0000269|PubMed:1908231, CC ECO:0000269|PubMed:1925564, ECO:0000269|PubMed:1944558, CC ECO:0000269|PubMed:8267572, ECO:0000269|PubMed:8290042, CC ECO:0000269|PubMed:8476439, ECO:0000269|PubMed:8577393, CC ECO:0000269|PubMed:8886002, ECO:0000269|PubMed:9328472, CC ECO:0000269|PubMed:9754958}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cerebral amyloid angiopathy, APP-related (CAA-APP) CC [MIM:605714]: A hereditary localized amyloidosis due to amyloid-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 -!- CAUTION: Was reported to bind TNFRSF21 triggering caspase activation CC and degeneration of both neuronal cell bodies (via caspase-3) and axons CC (via caspase-6) (PubMed:19225519). This work was later retracted CC (PubMed:38110576). {ECO:0000305|PubMed:19225519, CC ECO:0000305|PubMed:38110576}. 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=Wikipedia; Note=Amyloid beta entry; CC URL="https://en.wikipedia.org/wiki/Amyloid_beta"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 7F29; EM; 3.10 A; A/B/C/D/E/F=677-713. 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; 7OW1; X-ray; 1.40 A; A=674-685. DR PDB; 7OXN; X-ray; 2.50 A; A=672-685. 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 PDB; 7RTZ; X-ray; 2.10 A; A/B=682-711. DR PDB; 7U4P; X-ray; 1.80 A; A/B/C=687-707. DR PDB; 7WFY; X-ray; 2.45 A; A=754-761. DR PDB; 7WVY; EM; 3.00 A; L=672-713. DR PDB; 7Y3J; X-ray; 2.60 A; A=687-697. DR PDB; 7Y8Q; NMR; -; A/B/C/D/E/F/G/H=672-711. DR PDB; 8AZS; EM; 2.90 A; H=672-713. DR PDB; 8AZT; EM; 3.70 A; B=672-713. DR PDB; 8B9Q; NMR; -; A=672-711. DR PDB; 8B9R; NMR; -; A=672-711. DR PDB; 8BFA; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8BFB; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8BFZ; EM; 2.79 A; A/B=672-713. DR PDB; 8BG0; EM; 1.90 A; A/B/C/D=672-711. DR PDB; 8C3H; X-ray; 1.71 A; D/E=763-770. DR PDB; 8EZD; EM; 2.83 A; A/B/C/D/E/F/G/H=672-713. DR PDB; 8EZE; EM; 2.76 A; A/B/C/D/E/F/G/H=672-713. DR PDB; 8FF2; EM; 2.87 A; A/B/C/D/E/F/G/I/J/K=672-711. DR PDB; 8FF3; EM; 3.09 A; A/B/C/a/b/c=672-711. DR PDB; 8H8Q; X-ray; 2.50 A; A=686-700. DR PDB; 8I4O; X-ray; 3.10 A; B/D/F/H/J/L=681-700. DR PDB; 8KEW; EM; 3.30 A; A/B/C/D/F/G=1-770. DR PDB; 8KF1; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-770. DR PDB; 8KF3; EM; 3.50 A; A/B/C/D/E/F/G/H/I=1-770. DR PDB; 8KF4; EM; 3.00 A; A/B/C/D/E/F=1-770. DR PDB; 8KF5; EM; 3.40 A; A/B/C/D/E/F=1-770. DR PDB; 8KF6; EM; 3.70 A; A/B/C/D/E/F/G/H/I=1-770. DR PDB; 8OL2; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OL3; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OL5; EM; 3.40 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OL6; EM; 3.80 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OL7; EM; 3.00 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OLG; EM; 4.20 A; A/B/C/D/E=672-713. DR PDB; 8OLN; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OLO; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=672-713. DR PDB; 8OLQ; EM; 4.00 A; A/B/C/D/E=672-713. DR PDB; 8OT1; EM; 2.59 A; A/B/C/D/E/F/G/H/I/J/K/L=672-711. DR PDB; 8OT3; EM; 2.73 A; A/B/C/D/E/F/G/H/I/J/K/L=672-711. DR PDB; 8OT4; EM; 2.97 A; A/B/C/D/E/F/G/H/I/J/K/L=672-711. DR PDB; 8OTF; EM; 3.30 A; A/B/C/D/E/F=1-770. DR PDB; 8OVK; EM; 2.88 A; A/B/C/D/E/F/G/H/I/J=672-711. DR PDB; 8OVM; EM; 3.24 A; A/B/C/D/E=672-711. DR PDB; 8OWD; EM; 3.28 A; A/B/C/D/E=672-711. DR PDB; 8OWE; EM; 3.75 A; A/B/C/D/E/F/G/H/I/J=672-711. DR PDB; 8OWJ; EM; 3.75 A; A/B/C/D/E/F/G/H/I/J=672-711. DR PDB; 8OWK; EM; 3.86 A; A/B/C/D/E/F/G/H/I/J=672-711. DR PDB; 8QN6; EM; 2.40 A; A/F=672-711. DR PDB; 8QN7; EM; 2.70 A; A=672-711. DR PDB; 8SEJ; EM; 3.17 A; A/B/C/D/E/F/G/H/I/J=680-713. DR PDB; 8SEK; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=672-711. DR PDB; 8SEL; EM; 3.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=672-711. DR PDB; 8T82; X-ray; 1.10 A; A=706-711. DR PDB; 8T89; X-ray; 1.50 A; A=687-692. DR PDB; 8X52; EM; 2.90 A; E=671-770. DR PDB; 8X53; EM; 3.00 A; E=672-717. DR PDB; 8X54; EM; 2.90 A; E=671-770. 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; 7F29; -. DR PDBsum; 7JXN; -. DR PDBsum; 7JXO; -. DR PDBsum; 7O1Q; -. DR PDBsum; 7OW1; -. DR PDBsum; 7OXN; -. DR PDBsum; 7Q4B; -. DR PDBsum; 7Q4M; -. DR PDBsum; 7RTZ; -. DR PDBsum; 7U4P; -. DR PDBsum; 7WFY; -. DR PDBsum; 7WVY; -. DR PDBsum; 7Y3J; -. DR PDBsum; 7Y8Q; -. DR PDBsum; 8AZS; -. DR PDBsum; 8AZT; -. DR PDBsum; 8B9Q; -. DR PDBsum; 8B9R; -. DR PDBsum; 8BFA; -. DR PDBsum; 8BFB; -. DR PDBsum; 8BFZ; -. DR PDBsum; 8BG0; -. DR PDBsum; 8C3H; -. DR PDBsum; 8EZD; -. DR PDBsum; 8EZE; -. DR PDBsum; 8FF2; -. DR PDBsum; 8FF3; -. DR PDBsum; 8H8Q; -. DR PDBsum; 8I4O; -. DR PDBsum; 8KEW; -. DR PDBsum; 8KF1; -. DR PDBsum; 8KF3; -. DR PDBsum; 8KF4; -. DR PDBsum; 8KF5; -. DR PDBsum; 8KF6; -. DR PDBsum; 8OL2; -. DR PDBsum; 8OL3; -. DR PDBsum; 8OL5; -. DR PDBsum; 8OL6; -. DR PDBsum; 8OL7; -. DR PDBsum; 8OLG; -. DR PDBsum; 8OLN; -. DR PDBsum; 8OLO; -. DR PDBsum; 8OLQ; -. DR PDBsum; 8OT1; -. DR PDBsum; 8OT3; -. DR PDBsum; 8OT4; -. DR PDBsum; 8OTF; -. DR PDBsum; 8OVK; -. DR PDBsum; 8OVM; -. DR PDBsum; 8OWD; -. DR PDBsum; 8OWE; -. DR PDBsum; 8OWJ; -. DR PDBsum; 8OWK; -. DR PDBsum; 8QN6; -. DR PDBsum; 8QN7; -. DR PDBsum; 8SEJ; -. DR PDBsum; 8SEK; -. DR PDBsum; 8SEL; -. DR PDBsum; 8T82; -. DR PDBsum; 8T89; -. DR PDBsum; 8X52; -. DR PDBsum; 8X53; -. DR PDBsum; 8X54; -. DR AlphaFoldDB; P05067; -. DR BMRB; P05067; -. DR EMDB; EMD-0405; -. DR EMDB; EMD-0619; -. DR EMDB; EMD-10204; -. DR EMDB; EMD-13800; -. DR EMDB; EMD-13809; -. DR EMDB; EMD-15770; -. DR EMDB; EMD-15771; -. DR EMDB; EMD-16018; -. DR EMDB; EMD-16019; -. DR EMDB; EMD-16022; -. DR EMDB; EMD-16023; -. DR EMDB; EMD-16942; -. DR EMDB; EMD-16944; -. DR EMDB; EMD-16949; -. DR EMDB; EMD-16952; -. DR EMDB; EMD-16953; -. DR EMDB; EMD-16957; -. DR EMDB; EMD-16959; -. DR EMDB; EMD-16960; -. DR EMDB; EMD-16961; -. DR EMDB; EMD-17177; -. DR EMDB; EMD-18226; -. DR EMDB; EMD-21501; -. DR EMDB; EMD-22281; -. DR EMDB; EMD-28740; -. DR EMDB; EMD-28741; -. DR EMDB; EMD-29036; -. DR EMDB; EMD-29037; -. DR EMDB; EMD-29038; -. DR EMDB; EMD-32862; -. DR EMDB; EMD-37170; -. DR EMDB; EMD-38059; -. DR EMDB; EMD-38060; -. DR EMDB; EMD-38061; -. DR EMDB; EMD-3851; -. DR EMDB; EMD-40416; -. DR EMDB; EMD-40419; -. DR EMDB; EMD-40421; -. DR EMDB; EMD-9751; -. DR PCDDB; P05067; -. DR SASBDB; P05067; -. DR SMR; P05067; -. DR BioGRID; 106848; 2362. 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; 896. 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 F-18. DR DrugBank; DB09149; Florbetapir (18F). DR DrugBank; DB09151; Flutemetamol (18F). DR DrugBank; DB12034; Gantenerumab. DR DrugBank; DB02235; L-methionine (R)-S-oxide. DR DrugBank; DB14580; Lecanemab. 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 GlyCosmos; P05067; 15 sites, 9 glycans. DR GlyGen; P05067; 26 sites, 13 N-linked glycans (2 sites), 6 O-linked glycans (22 sites). DR iPTMnet; P05067; -. DR MetOSite; P05067; -. DR PhosphoSitePlus; P05067; -. DR SwissPalm; P05067; -. DR BioMuta; APP; -. DR DMDM; 112927; -. DR jPOST; P05067; -. DR MassIVE; P05067; -. DR PaxDb; 9606-ENSP00000284981; -. DR PeptideAtlas; 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 Pumba; P05067; -. DR ABCD; P05067; 71 sequenced antibodies. DR Antibodypedia; 668; 4319 antibodies from 53 providers. DR DNASU; 351; -. DR Ensembl; ENST00000346798.8; ENSP00000284981.4; ENSG00000142192.22. [P05067-1] DR Ensembl; ENST00000348990.9; ENSP00000345463.5; ENSG00000142192.22. [P05067-4] DR Ensembl; ENST00000354192.7; ENSP00000346129.3; ENSG00000142192.22. [P05067-10] DR Ensembl; ENST00000357903.7; ENSP00000350578.3; ENSG00000142192.22. [P05067-8] DR Ensembl; ENST00000358918.7; ENSP00000351796.3; ENSG00000142192.22. [P05067-9] DR Ensembl; ENST00000440126.7; ENSP00000387483.2; ENSG00000142192.22. [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 AGR; HGNC:620; -. 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 OrthoDB; 2907766at2759; -. DR PhylomeDB; P05067; -. DR TreeFam; TF317274; -. DR BioCyc; MetaCyc:ENSG00000142192-MONOMER; -. 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 Reactome; R-HSA-9837999; Mitochondrial protein degradation. [P05067-4] DR SABIO-RK; P05067; -. DR SignaLink; P05067; -. DR SIGNOR; P05067; -. DR BioGRID-ORCS; 351; 12 hits in 1170 CRISPR screens. DR ChiTaRS; APP; human. DR EvolutionaryTrace; P05067; -. DR GeneWiki; Amyloid_precursor_protein; -. DR GenomeRNAi; 351; -. DR Pharos; P05067; Tclin. DR PRO; PR:P05067; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P05067; protein. DR Bgee; ENSG00000142192; Expressed in prefrontal cortex and 208 other cell types or tissues. DR ExpressionAtlas; P05067; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO: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:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; IDA:ARUK-UCL. 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:UniProtKB. 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:Reactome. 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:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:ParkinsonsUK-UCL. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. 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: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:UniProtKB. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0048786; C:presynaptic active zone; IEA:Ensembl. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB. 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:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI: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:0120283; F:protein serine/threonine kinase binding; IPI:ARUK-UCL. DR GO; GO:0051425; F:PTB domain binding; IPI:BHF-UCL. DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProt. 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; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL. DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro. DR GO; GO:0008344; P:adult locomotory behavior; ISS:UniProtKB. DR GO; GO:1990000; P:amyloid fibril formation; IMP:ParkinsonsUK-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:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:1904646; P:cellular response to amyloid-beta; IDA:UniProt. 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:0180011; P:cytosolic mRNA polyadenylation; IEA:Ensembl. 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:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0006878; P:intracellular copper ion homeostasis; ISS: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:0007626; P:locomotory behavior; ISS:UniProtKB. DR GO; GO:0007617; P:mating behavior; ISS:UniProtKB. 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:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IGI:ARUK-UCL. DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IGI:ARUK-UCL. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0010466; P:negative regulation of peptidase activity; IEA:UniProtKB-KW. DR GO; GO:1905607; P:negative regulation of presynapse assembly; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. 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:0098989; P:NMDA selective glutamate receptor signaling pathway; TAS:ARUK-UCL. DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW. DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; IMP:ARUK-UCL. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IGI:ARUK-UCL. DR GO; GO:0032722; P:positive regulation of chemokine production; IGI:ARUK-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI: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; IMP:ARUK-UCL. DR GO; GO:0045821; P:positive regulation of glycolytic process; IGI:ARUK-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP: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:1900273; P:positive regulation of long-term synaptic potentiation; IGI:ARUK-UCL. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IMP: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: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:2000406; P:positive regulation of T cell migration; IMP: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: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:0040014; P:regulation of multicellular organism growth; ISS:UniProtKB. 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: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: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:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl. DR GO; GO: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; cd22607; Kunitz_ABPP-like; 1. DR DisProt; DP01280; -. DR FunFam; 3.30.1490.140:FF:000001; Amyloid beta (A4) protein b; 1. DR FunFam; 3.90.570.10:FF:000001; Amyloid beta A4 protein; 1. DR FunFam; 4.10.230.10:FF:000001; Amyloid beta A4 protein; 1. DR FunFam; 4.10.410.10:FF:000001; Amyloid beta A4 protein; 1. DR FunFam; 1.20.120.770:FF:000001; Amyloid beta A4 protein-like isoform 1; 1. DR Gene3D; 1.20.120.770; Amyloid precursor protein, E2 domain; 1. DR Gene3D; 4.10.230.10; Amyloidogenic glycoprotein, amyloid-beta peptide; 1. DR Gene3D; 3.30.1490.140; Amyloidogenic glycoprotein, copper-binding domain; 1. DR Gene3D; 3.90.570.10; Amyloidogenic glycoprotein, heparin-binding domain; 1. DR Gene3D; 4.10.410.10; Pancreatic trypsin inhibitor Kunitz domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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; 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; ALZHEIMER'S DISEASE BETA-AMYLOID RELATED; 1. DR PANTHER; PTHR23103:SF7; AMYLOID-BETA PRECURSOR PROTEIN; 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; SSF56491; A heparin-binding domain; 1. DR SUPFAM; SSF89811; Amyloid beta a4 protein copper binding domain (domain 2); 1. DR SUPFAM; SSF57362; BPTI-like; 1. DR SUPFAM; SSF109843; CAPPD, an extracellular domain of amyloid beta A4 protein; 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; KW Proteomics identification; Reference proteome; Secreted; KW 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 uncertain 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 FT 40/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 FT L-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 FT amyloid-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 FT amyloid-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..679 FT /evidence="ECO:0007829|PDB:7OW1" FT STRAND 682..684 FT /evidence="ECO:0007829|PDB:7OXN" 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 718..720 FT /evidence="ECO:0007829|PDB:8X52" 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 //