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   28-JAN-2026, entry version 318.
DE   RecName: Full=Amyloid-beta precursor protein {ECO:0000312|HGNC:HGNC:620};
DE            Short=APP {ECO:0000312|HGNC:HGNC:620};
DE   AltName: Full=ABPP;
DE   AltName: Full=APPI;
DE   AltName: Full=Alzheimer disease amyloid A4 protein homolog;
DE   AltName: Full=Alzheimer disease amyloid protein;
DE   AltName: Full=Amyloid precursor protein {ECO:0000305};
DE   AltName: Full=Amyloid-beta (A4) precursor protein {ECO:0000250|UniProtKB:P12023};
DE   AltName: Full=Amyloid-beta A4 protein;
DE   AltName: Full=Cerebral vascular amyloid peptide;
DE            Short=CVAP;
DE   AltName: Full=PreA4;
DE   AltName: Full=Protease nexin-II;
DE            Short=PN-II;
DE   Contains:
DE     RecName: Full=N-APP;
DE   Contains:
DE     RecName: Full=Soluble APP-alpha {ECO:0000303|PubMed:10656250};
DE              Short=S-APP-alpha {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=Soluble APP-beta {ECO:0000303|PubMed:10656250};
DE              Short=S-APP-beta {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=C99;
DE     AltName: Full=Beta-secretase C-terminal fragment {ECO:0000303|PubMed:10656250};
DE              Short=Beta-CTF {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=Amyloid-beta protein 42 {ECO:0000303|PubMed:8886002};
DE              Short=Abeta42;
DE     AltName: Full=Beta-APP42;
DE   Contains:
DE     RecName: Full=Amyloid-beta protein 40 {ECO:0000303|PubMed:8886002};
DE              Short=Abeta40;
DE     AltName: Full=Beta-APP40;
DE   Contains:
DE     RecName: Full=C83;
DE     AltName: Full=Alpha-secretase C-terminal fragment {ECO:0000303|PubMed:10656250};
DE              Short=Alpha-CTF {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=P3(42);
DE   Contains:
DE     RecName: Full=P3(40);
DE   Contains:
DE     RecName: Full=C80;
DE   Contains:
DE     RecName: Full=Gamma-secretase C-terminal fragment 59;
DE     AltName: Full=Amyloid intracellular domain 59;
DE              Short=AICD-59;
DE              Short=AID(59);
DE     AltName: Full=Gamma-CTF(59);
DE   Contains:
DE     RecName: Full=Gamma-secretase C-terminal fragment 57;
DE     AltName: Full=Amyloid intracellular domain 57;
DE              Short=AICD-57;
DE              Short=AID(57);
DE     AltName: Full=Gamma-CTF(57);
DE   Contains:
DE     RecName: Full=Gamma-secretase C-terminal fragment 50;
DE     AltName: Full=Amyloid intracellular domain 50;
DE              Short=AICD-50;
DE              Short=AID(50);
DE     AltName: Full=Gamma-CTF(50);
DE   Contains:
DE     RecName: Full=C31;
DE   Flags: Precursor;
GN   Name=APP {ECO:0000312|HGNC:HGNC:620};
GN   Synonyms=A4 {ECO:0000303|PubMed:2881207}, AD1 {ECO:0000312|HGNC:HGNC:620};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
RC   TISSUE=Brain;
RX   PubMed=2881207; DOI=10.1038/325733a0;
RA   Kang J., Lemaire H.-G., Unterbeck A., Salbaum J.M., Masters C.L.,
RA   Grzeschik K.-H., Multhaup G., Beyreuther K., Mueller-Hill B.;
RT   "The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-
RT   surface receptor.";
RL   Nature 325:733-736(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
RC   TISSUE=Brain;
RX   PubMed=2893289; DOI=10.1038/331525a0;
RA   Ponte P., Gonzalez-Dewhitt P., Schilling J., Miller J., Hsu D.,
RA   Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F., Cordell B.;
RT   "A new A4 amyloid mRNA contains a domain homologous to serine proteinase
RT   inhibitors.";
RL   Nature 331:525-527(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP695).
RX   PubMed=2783775; DOI=10.1093/nar/17.2.517;
RA   Lemaire H.-G., Salbaum J.M., Multhaup G., Kang J., Bayney R.M.,
RA   Unterbeck A., Beyreuther K., Mueller-Hill B.;
RT   "The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is
RT   encoded by 16 exons.";
RL   Nucleic Acids Res. 17:517-522(1989).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
RX   PubMed=2110105; DOI=10.1016/0378-1119(90)90310-n;
RA   Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.;
RT   "Genomic organization of the human amyloid beta-protein precursor gene.";
RL   Gene 87:257-263(1990).
RN   [5]
RP   ERRATUM OF PUBMED:2110105.
RX   PubMed=1908403; DOI=10.1016/0378-1119(91)90093-q;
RA   Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.;
RL   Gene 102:291-292(1991).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L-APP733).
RC   TISSUE=Leukocyte;
RX   PubMed=1587857; DOI=10.1016/s0021-9258(19)50090-4;
RA   Koenig G., Moenning U., Czech C., Prior R., Banati R., Schreiter-Gasser U.,
RA   Bauer J., Masters C.L., Beyreuther K.;
RT   "Identification and differential expression of a novel alternative splice
RT   isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes
RT   and brain microglial cells.";
RL   J. Biol. Chem. 267:10804-10809(1992).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
RX   PubMed=9108164; DOI=10.1093/nar/25.9.1802;
RA   Hattori M., Tsukahara F., Furuhata Y., Tanahashi H., Hirose M., Saito M.,
RA   Tsukuni S., Sakaki Y.;
RT   "A novel method for making nested deletions and its application for
RT   sequencing of a 300 kb region of human APP locus.";
RL   Nucleic Acids Res. 25:1802-1808(1997).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP639), AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=12859342; DOI=10.1046/j.1460-9568.2003.02731.x;
RA   Tang K., Wang C., Shen C., Sheng S., Ravid R., Jing N.;
RT   "Identification of a novel alternative splicing isoform of human amyloid
RT   precursor protein gene, APP639.";
RL   Eur. J. Neurosci. 18:102-108(2003).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP770 AND 11).
RC   TISSUE=Cerebellum, and Hippocampus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-501.
RG   NIEHS SNPs program;
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [13]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP305 AND APP751).
RC   TISSUE=Eye, and Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [14]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-10.
RC   TISSUE=Liver;
RX   PubMed=3140222; DOI=10.1093/nar/16.19.9351;
RA   Schon E.A., Mita S., Sadlock J., Herbert J.;
RT   "A cDNA specifying the human amyloid beta precursor protein (ABPP) encodes
RT   a 95-kDa polypeptide.";
RL   Nucleic Acids Res. 16:9351-9351(1988).
RN   [15]
RP   ERRATUM OF PUBMED:3140222, AND SEQUENCE REVISION.
RA   Schon E.A., Mita S., Sadlock J., Herbert J.;
RL   Nucleic Acids Res. 16:11402-11402(1988).
RN   [16]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75.
RX   PubMed=2538123; DOI=10.1016/0006-291x(89)92437-6;
RA   La Fauci G., Lahiri D.K., Salton S.R., Robakis N.K.;
RT   "Characterization of the 5'-end region and the first two exons of the beta-
RT   protein precursor gene.";
RL   Biochem. Biophys. Res. Commun. 159:297-304(1989).
RN   [17]
RP   PROTEIN SEQUENCE OF 18-50.
RC   TISSUE=Fibroblast;
RX   PubMed=3597385; DOI=10.1016/s0021-9258(18)47443-1;
RA   van Nostrand W.E., Cunningham D.D.;
RT   "Purification of protease nexin II from human fibroblasts.";
RL   J. Biol. Chem. 262:8508-8514(1987).
RN   [18]
RP   PROTEIN SEQUENCE OF 18-40.
RC   TISSUE=Platelet;
RX   PubMed=12665801; DOI=10.1038/nbt810;
RA   Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA   Vandekerckhove J.;
RT   "Exploring proteomes and analyzing protein processing by mass spectrometric
RT   identification of sorted N-terminal peptides.";
RL   Nat. Biotechnol. 21:566-569(2003).
RN   [19]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 286-366.
RX   PubMed=2893290; DOI=10.1038/331528a0;
RA   Tanzi R.E., McClatchey A.I., Lamperti E.D., Villa-Komaroff L.,
RA   Gusella J.F., Neve R.L.;
RT   "Protease inhibitor domain encoded by an amyloid protein precursor mRNA
RT   associated with Alzheimer's disease.";
RL   Nature 331:528-530(1988).
RN   [20]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 287-367.
RX   PubMed=2893291; DOI=10.1038/331530a0;
RA   Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H.;
RT   "Novel precursor of Alzheimer's disease amyloid protein shows protease
RT   inhibitory activity.";
RL   Nature 331:530-532(1988).
RN   [21]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 507-770.
RC   TISSUE=Brain cortex;
RX   PubMed=2893379; DOI=10.1073/pnas.85.3.929;
RA   Zain S.B., Salim M., Chou W.G., Sajdel-Sulkowska E.M., Majocha R.E.,
RA   Marotta C.A.;
RT   "Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer
RT   disease brain: coding and noncoding regions of the fetal precursor mRNA are
RT   expressed in the cortex.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:929-933(1988).
RN   [22]
RP   PROTEIN SEQUENCE OF 523-555, AND DOMAIN COLLAGEN-BINDING.
RX   PubMed=8576160; DOI=10.1074/jbc.271.3.1613;
RA   Beher D., Hesse L., Masters C.L., Multhaup G.;
RT   "Regulation of amyloid protein precursor (APP) binding to collagen and
RT   mapping of the binding sites on APP and collagen type I.";
RL   J. Biol. Chem. 271:1613-1620(1996).
RN   [23]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 655-737, AND VARIANTS AD1 GLY-717; ILE-717
RP   AND PHE-717.
RX   PubMed=8476439; DOI=10.1006/bbrc.1993.1386;
RA   Denman R.B., Rosenzcwaig R., Miller D.L.;
RT   "A system for studying the effect(s) of familial Alzheimer disease
RT   mutations on the processing of the beta-amyloid peptide precursor.";
RL   Biochem. Biophys. Res. Commun. 192:96-103(1993).
RN   [24]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 656-737.
RX   PubMed=2675837; DOI=10.1016/0006-291x(89)91112-1;
RA   Johnstone E.M., Chaney M.O., Moore R.E., Ward K.E., Norris F.H.,
RA   Little S.P.;
RT   "Alzheimer's disease amyloid peptide is encoded by two exons and shows
RT   similarity to soybean trypsin inhibitor.";
RL   Biochem. Biophys. Res. Commun. 163:1248-1255(1989).
RN   [25]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 672-723, AND VARIANT AD1 ASN-678.
RX   PubMed=15201367; DOI=10.1136/jnnp.2003.010611;
RA   Wakutani Y., Watanabe K., Adachi Y., Wada-Isoe K., Urakami K., Ninomiya H.,
RA   Saido T.C., Hashimoto T., Iwatsubo T., Nakashima K.;
RT   "Novel amyloid precursor protein gene missense mutation (D678N) in probable
RT   familial Alzheimer's disease.";
RL   J. Neurol. Neurosurg. Psych. 75:1039-1042(2004).
RN   [26]
RP   PROTEIN SEQUENCE OF 672-681.
RC   TISSUE=Brain cortex;
RX   PubMed=3312495; DOI=10.1111/j.1471-4159.1987.tb01005.x;
RA   Pardridge W.M., Vinters H.V., Yang J., Eisenberg J., Choi T.B.,
RA   Tourtellotte W.W., Huebner V., Shively J.E.;
RT   "Amyloid angiopathy of Alzheimer's disease: amino acid composition and
RT   partial sequence of a 4,200-dalton peptide isolated from cortical
RT   microvessels.";
RL   J. Neurochem. 49:1394-1401(1987).
RN   [27]
RP   PROTEIN SEQUENCE OF 672-704, AND TISSUE SPECIFICITY.
RX   PubMed=1406936; DOI=10.1038/359325a0;
RA   Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D., Sinha S.,
RA   Schlossmacher M., Whaley J., Swindlehurst C.;
RT   "Isolation and quantification of soluble Alzheimer's beta-peptide from
RT   biological fluids.";
RL   Nature 359:325-327(1992).
RN   [28]
RP   PROTEIN SEQUENCE OF 672-701.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=8229004; DOI=10.1111/j.1471-4159.1993.tb09841.x;
RA   Vigo-Pelfrey C., Lee D., Keim P., Lieberburg I., Schenk D.B.;
RT   "Characterization of beta-amyloid peptide from human cerebrospinal fluid.";
RL   J. Neurochem. 61:1965-1968(1993).
RN   [29]
RP   PROTEIN SEQUENCE OF 672-713.
RC   TISSUE=Blood vessel;
RX   PubMed=8248178; DOI=10.1073/pnas.90.22.10836;
RA   Roher A.E., Lowenson J.D., Clarke S., Woods A.S., Cotter R.J., Gowing E.,
RA   Ball M.J.;
RT   "Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid
RT   deposits: implications for the pathology of Alzheimer disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:10836-10840(1993).
RN   [30]
RP   PROTEIN SEQUENCE OF 672-701 AND 707-713.
RX   PubMed=8109908; DOI=10.1002/ana.410350223;
RA   Wisniewski T., Lalowski M., Levy E., Marques M.R.F., Frangione B.;
RT   "The amino acid sequence of neuritic plaque amyloid from a familial
RT   Alzheimer's disease patient.";
RL   Ann. Neurol. 35:245-246(1994).
RN   [31]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 674-770.
RC   TISSUE=Brain;
RX   PubMed=3810169; DOI=10.1126/science.3810169;
RA   Goldgaber D., Lerman M.I., McBride O.W., Saffiotti U., Gajdusek D.C.;
RT   "Characterization and chromosomal localization of a cDNA encoding brain
RT   amyloid of Alzheimer's disease.";
RL   Science 235:877-880(1987).
RN   [32]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 674-703.
RC   TISSUE=Fetal brain;
RX   PubMed=2949367; DOI=10.1126/science.2949367;
RA   Tanzi R.E., Gusella J.F., Watkins P.C., Bruns G.A., St George-Hyslop P.H.,
RA   Van Keuren M.L., Patterson D., Pagan S., Kurnit D.M., Neve R.L.;
RT   "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage
RT   near the Alzheimer locus.";
RL   Science 235:880-884(1987).
RN   [33]
RP   PROTEIN SEQUENCE OF 609-713, AND GLYCOSYLATION AT THR-633; THR-651;
RP   THR-652; THR-659; THR-663; SER-667 AND TYR-681.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=22576872; DOI=10.1002/jms.2987;
RA   Brinkmalm G., Portelius E., Ohrfelt A., Mattsson N., Persson R.,
RA   Gustavsson M.K., Vite C.H., Gobom J., Mansson J.E., Nilsson J., Halim A.,
RA   Larson G., Ruetschi U., Zetterberg H., Blennow K., Brinkmalm A.;
RT   "An online nano-LC-ESI-FTICR-MS method for comprehensive characterization
RT   of endogenous fragments from amyloid beta and amyloid precursor protein in
RT   human and cat cerebrospinal fluid.";
RL   J. Mass Spectrom. 47:591-603(2012).
RN   [34]
RP   PROTEIN SEQUENCE OF 691-698, AND PROTEOLYTIC CLEAVAGE AT PHE-690 BY
RP   THETA-SECRETASE.
RX   PubMed=16816112; DOI=10.1096/fj.05-5632com;
RA   Sun X., He G., Song W.;
RT   "BACE2, as a novel APP theta-secretase, is not responsible for the
RT   pathogenesis of Alzheimer's disease in Down syndrome.";
RL   FASEB J. 20:1369-1376(2006).
RN   [35]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
RC   TISSUE=Brain;
RX   PubMed=2569763; DOI=10.1126/science.2569763;
RA   de Sauvage F., Octave J.-N.;
RT   "A novel mRNA of the A4 amyloid precursor gene coding for a possibly
RT   secreted protein.";
RL   Science 245:651-653(1989).
RN   [36]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
RC   TISSUE=Brain;
RX   PubMed=3035574; DOI=10.1073/pnas.84.12.4190;
RA   Robakis N.K., Ramakrishna N., Wolfe G., Wisniewski H.M.;
RT   "Molecular cloning and characterization of a cDNA encoding the
RT   cerebrovascular and the neuritic plaque amyloid peptides.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:4190-4194(1987).
RN   [37]
RP   SUBCELLULAR LOCATION, SIGNAL SEQUENCE CLEAVAGE SITE, AND TOPOLOGY.
RX   PubMed=2900137; DOI=10.1002/j.1460-2075.1988.tb02900.x;
RA   Dyrks T., Weidemann A., Multhaup G., Salbaum J.M., Lemaire H.-G., Kang J.,
RA   Mueller-Hill B., Masters C.L., Beyreuther K.;
RT   "Identification, transmembrane orientation and biogenesis of the amyloid A4
RT   precursor of Alzheimer's disease.";
RL   EMBO J. 7:949-957(1988).
RN   [38]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, SULFATION, AND
RP   OX-2 MOTIF.
RX   PubMed=2649245; DOI=10.1016/0092-8674(89)90177-3;
RA   Weidemann A., Koenig G., Bunke D., Fischer P., Salbaum J.M., Masters C.L.,
RA   Beyreuther K.;
RT   "Identification, biogenesis, and localization of precursors of Alzheimer's
RT   disease A4 amyloid protein.";
RL   Cell 57:115-126(1989).
RN   [39]
RP   IDENTITY OF APP WITH NEXIN-II.
RX   PubMed=2506449; DOI=10.1038/341144a0;
RA   Oltersdorf T., Fritz L.C., Schenk D.B., Lieberburg I., Johnson-Wood K.L.,
RA   Beattie E.C., Ward P.J., Blacher R.W., Dovey H.F., Sinha S.;
RT   "The secreted form of the Alzheimer's amyloid precursor protein with the
RT   Kunitz domain is protease nexin-II.";
RL   Nature 341:144-147(1989).
RN   [40]
RP   PROTEASE-SPECIFICITY OF INHIBITOR DOMAIN.
RX   PubMed=1969731; DOI=10.1016/0006-291x(90)92084-d;
RA   Kido H., Fukutomi A., Schilling J., Wang Y., Cordell B., Katunuma N.;
RT   "Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease
RT   amyloid protein precursor.";
RL   Biochem. Biophys. Res. Commun. 167:716-721(1990).
RN   [41]
RP   EXTRACELLULAR ZINC-BINDING DOMAIN.
RX   PubMed=8344894; DOI=10.1016/s0021-9258(19)85394-2;
RA   Bush A.I., Multhaup G., Moir R.D., Williamson T.G., Small D.H., Rumble B.,
RA   Pollwein P., Beyreuther K., Masters C.L.;
RT   "A novel zinc(II) binding site modulates the function of the beta A4
RT   amyloid protein precursor of Alzheimer's disease.";
RL   J. Biol. Chem. 268:16109-16112(1993).
RN   [42]
RP   INTERACTION WITH G(O).
RX   PubMed=8446172; DOI=10.1038/362075a0;
RA   Nishimoto I., Okamoto T., Matsuura Y., Takahashi S., Okamoto T.,
RA   Murayama Y., Ogata E.;
RT   "Alzheimer amyloid protein precursor complexes with brain GTP-binding
RT   protein G(o).";
RL   Nature 362:75-79(1993).
RN   [43]
RP   PHOSPHORYLATION AT THR-743.
RX   PubMed=8131745; DOI=10.1002/j.1460-2075.1994.tb06360.x;
RA   Suzuki T., Oishi M., Marshak D.R., Czernik A.J., Nairn A.C., Greengard P.;
RT   "Cell cycle-dependent regulation of the phosphorylation and metabolism of
RT   the Alzheimer amyloid precursor protein.";
RL   EMBO J. 13:1114-1122(1994).
RN   [44]
RP   EXTRACELLULAR COPPER-BINDING DOMAIN, AND MUTAGENESIS OF HIS-137; MET-141;
RP   CYS-144; HIS-147 AND HIS-151.
RX   PubMed=7913895; DOI=10.1016/0014-5793(94)00658-x;
RA   Hesse L., Beher D., Masters C.L., Multhaup G.;
RT   "The beta A4 amyloid precursor protein binding to copper.";
RL   FEBS Lett. 349:109-116(1994).
RN   [45]
RP   N-TERMINAL HEPARIN-BINDING DOMAIN, AND MUTAGENESIS OF 99-LYS--ARG-102.
RX   PubMed=8158260; DOI=10.1523/jneurosci.14-04-02117.1994;
RA   Small D.H., Nurcombe V., Reed G., Clarris H., Moir R., Beyreuther K.,
RA   Masters C.L.;
RT   "A heparin-binding domain in the amyloid protein precursor of Alzheimer's
RT   disease is involved in the regulation of neurite outgrowth.";
RL   J. Neurosci. 14:2117-2127(1994).
RN   [46]
RP   CHARACTERIZATION OF L-APP733, AND MUTAGENESIS OF SER-656.
RX   PubMed=7737970; DOI=10.1074/jbc.270.18.10388;
RA   Pangalos M.N., Efthimiopoulos S., Shioi J., Robakis N.K.;
RT   "The chondroitin sulfate attachment site of appican is formed by splicing
RT   out exon 15 of the amyloid precursor gene.";
RL   J. Biol. Chem. 270:10388-10391(1995).
RN   [47]
RP   INTERACTION WITH APP-BP1.
RX   PubMed=8626687; DOI=10.1074/jbc.271.19.11339;
RA   Chow N., Korenberg J.R., Chen X.-N., Neve R.L.;
RT   "APP-BP1, a novel protein that binds to the carboxyl-terminal region of the
RT   amyloid precursor protein.";
RL   J. Biol. Chem. 271:11339-11346(1996).
RN   [48]
RP   INTERACTION WITH APBA1 AND APBB1, AND MUTAGENESIS OF TYR-728; TYR-757;
RP   ASN-759 AND TYR-762.
RX   PubMed=8887653; DOI=10.1128/mcb.16.11.6229;
RA   Borg J.-P., Ooi J., Levy E., Margolis B.;
RT   "The phosphotyrosine interaction domains of X11 and FE65 bind to distinct
RT   sites on the YENPTY motif of amyloid precursor protein.";
RL   Mol. Cell. Biol. 16:6229-6241(1996).
RN   [49]
RP   INTERACTION WITH APBB2.
RX   PubMed=8855266; DOI=10.1073/pnas.93.20.10832;
RA   Guenette S.Y., Chen J., Jondro P.D., Tanzi R.E.;
RT   "Association of a novel human FE65-like protein with the cytoplasmic domain
RT   of the amyloid-beta precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:10832-10837(1996).
RN   [50]
RP   FUNCTION OF AMYLOID-BETA PEPTIDE AS LIPID PEROXIDATION INHIBITOR, AND
RP   MUTAGENESIS OF MET-706.
RX   PubMed=9168929; DOI=10.1006/bbrc.1997.6547;
RA   Walter M.F., Mason P.E., Mason R.P.;
RT   "Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation
RT   as a result of its membrane interactions.";
RL   Biochem. Biophys. Res. Commun. 233:760-764(1997).
RN   [51]
RP   HEPARIN-BINDING DOMAINS.
RX   PubMed=9357988; DOI=10.1016/s0014-5793(97)01146-0;
RA   Mok S.S., Sberna G., Heffernan D., Cappai R., Galatis D., Clarris H.J.,
RA   Sawyer W.H., Beyreuther K., Masters C.L., Small D.H.;
RT   "Expression and analysis of heparin-binding regions of the amyloid
RT   precursor protein of Alzheimer's disease.";
RL   FEBS Lett. 415:303-307(1997).
RN   [52]
RP   INTERACTION OF AMYLOID-BETA PEPTIDE WITH HADH2.
RC   TISSUE=Brain;
RX   PubMed=9338779; DOI=10.1038/39522;
RA   Yan S.D., Fu J., Soto C., Chen X., Zhu H., Al-Mohanna F., Collinson K.,
RA   Zhu A., Stern E., Saido T., Tohyama M., Ogawa S., Roher A., Stern D.;
RT   "An intracellular protein that binds amyloid-beta peptide and mediates
RT   neurotoxicity in Alzheimer's disease.";
RL   Nature 389:689-695(1997).
RN   [53]
RP   COPPER-BINDING, AND DISULFIDE BOND FORMATION.
RX   PubMed=9585534; DOI=10.1021/bi980022m;
RA   Multhaup G., Ruppert T., Schlicksupp A., Hesse L., Bill E., Pipkorn R.,
RA   Masters C.L., Beyreuther K.;
RT   "Copper-binding amyloid precursor protein undergoes a site-specific
RT   fragmentation in the reduction of hydrogen peroxide.";
RL   Biochemistry 37:7224-7230(1998).
RN   [54]
RP   INTERACTION WITH APPBP2, MUTAGENESIS OF TYR-728, AND DOMAIN.
RX   PubMed=9843960; DOI=10.1073/pnas.95.25.14745;
RA   Zheng P., Eastman J., Vande Pol S., Pimplikar S.W.;
RT   "PAT1, a microtubule-interacting protein, recognizes the basolateral
RT   sorting signal of amyloid precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:14745-14750(1998).
RN   [55]
RP   AMYLOID-BETA ZINC-BINDING, AND MUTAGENESIS OF ARG-676; TYR-681 AND HIS-684.
RX   PubMed=10413512; DOI=10.1021/bi990205o;
RA   Liu S.T., Howlett G., Barrow C.J.;
RT   "Histidine-13 is a crucial residue in the zinc ion-induced aggregation of
RT   the A beta peptide of Alzheimer's disease.";
RL   Biochemistry 38:9373-9378(1999).
RN   [56]
RP   PROTEOLYTIC CLEAVAGE AT ASP-197; ASP-219 AND ASP-739 BY CASPASES, AND
RP   MUTAGENESIS OF ASP-739.
RX   PubMed=10319819; DOI=10.1016/s0092-8674(00)80748-5;
RA   Gervais F.G., Xu D., Robertson G.S., Vaillancourt J.P., Zhu Y., Huang J.,
RA   LeBlanc A., Smith D., Rigby M., Shearman M.S., Clarke E.E., Zheng H.,
RA   van der Ploeg L.H.T., Ruffolo S.C., Thornberry N.A., Xanthoudakis S.,
RA   Zamboni R.J., Roy S., Nicholson D.W.;
RT   "Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-
RT   beta precursor protein and amyloidogenic A beta peptide formation.";
RL   Cell 97:395-406(1999).
RN   [57]
RP   IMPORTANCE OF MET-706 IN FREE RADICAL OXIDATIVE STRESS, AND MUTAGENESIS OF
RP   MET-706.
RX   PubMed=10535332; DOI=10.1016/s0361-9230(99)00093-3;
RA   Varadarajan S., Yatin S., Kanski J., Jahanshahi F., Butterfield D.A.;
RT   "Methionine residue 35 is important in amyloid beta-peptide-associated free
RT   radical oxidative stress.";
RL   Brain Res. Bull. 50:133-141(1999).
RN   [58]
RP   SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF THR-743.
RX   PubMed=10341243; DOI=10.1523/jneurosci.19-11-04421.1999;
RA   Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C., Kirino Y.,
RA   Greengard P., Suzuki T.;
RT   "Role of phosphorylation of Alzheimer's amyloid precursor protein during
RT   neuronal differentiation.";
RL   J. Neurosci. 19:4421-4427(1999).
RN   [59]
RP   INTERACTION WITH APBA2.
RX   PubMed=9890987; DOI=10.1074/jbc.274.4.2243;
RA   Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S.,
RA   Kirino Y., Suzuki T.;
RT   "Interaction of a neuron-specific protein containing PDZ domains with
RT   Alzheimer's amyloid precursor protein.";
RL   J. Biol. Chem. 274:2243-2254(1999).
RN   [60]
RP   SUBCELLULAR LOCATION, ENDOCYTOSIS SIGNAL, AND MUTAGENESIS OF TYR-728;
RP   GLY-756; TYR-757; ASN-759; PRO-760 AND TYR-762.
RX   PubMed=10383380; DOI=10.1074/jbc.274.27.18851;
RA   Perez R.G., Soriano S., Hayes J.D., Ostaszewski B., Xia W., Selkoe D.J.,
RA   Chen X., Stokin G.B., Koo E.H.;
RT   "Mutagenesis identifies new signals for beta-amyloid precursor protein
RT   endocytosis, turnover, and the generation of secreted fragments, including
RT   Abeta42.";
RL   J. Biol. Chem. 274:18851-18856(1999).
RN   [61]
RP   IMPORTANCE OF CYS-144 IN COPPER REDUCTION, AND MUTAGENESIS OF CYS-144 AND
RP   147-HIS--HIS-149.
RX   PubMed=10461923; DOI=10.1046/j.1471-4159.1999.0731288.x;
RA   Ruiz F.H., Gonzalez M., Bodini M., Opazo C., Inestrosa N.C.;
RT   "Cysteine 144 is a key residue in the copper reduction by the beta-amyloid
RT   precursor protein.";
RL   J. Neurochem. 73:1288-1292(1999).
RN   [62]
RP   CLEAVAGE BY BACE1, SUBCELLULAR LOCATION (SOLUBLE APP-BETA), AND
RP   CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX   PubMed=10656250; DOI=10.1006/mcne.1999.0811;
RA   Hussain I., Powell D.J., Howlett D.R., Tew D.G., Meek T.D., Chapman C.,
RA   Gloger I.S., Murphy K.E., Southan C.D., Ryan D.M., Smith T.S.,
RA   Simmons D.L., Walsh F.S., Dingwall C., Christie G.;
RT   "Identification of a novel aspartic proteinase (Asp 2) as beta-secretase.";
RL   Mol. Cell. Neurosci. 14:419-427(1999).
RN   [63]
RP   INTERACTION WITH APBB3.
RX   PubMed=10081969; DOI=10.1016/s0304-3940(98)00995-1;
RA   Tanahashi H.;
RT   "Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's
RT   beta-amyloid precursor protein.";
RL   Neurosci. Lett. 261:143-146(1999).
RN   [64]
RP   INTERACTION OF AMYLOID-BETA WITH APOE.
RX   PubMed=10816430; DOI=10.1042/bj3480359;
RA   Tokuda T., Calero M., Matsubara E., Vidal R., Kumar A., Permanne B.,
RA   Zlokovic B., Smith J.D., Ladu M.J., Rostagno A., Frangione B., Ghiso J.;
RT   "Lipidation of apolipoprotein E influences its isoform-specific interaction
RT   with Alzheimer's amyloid beta peptides.";
RL   Biochem. J. 348:359-365(2000).
RN   [65]
RP   INTERACTION OF APP42-BETA WITH CHRNA7.
RX   PubMed=10681545; DOI=10.1074/jbc.275.8.5626;
RA   Wang H.-Y., Lee D.H.S., D'Andrea M.R., Peterson P.A., Shank R.P.,
RA   Reitz A.B.;
RT   "Beta-amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with
RT   high affinity. Implications for Alzheimer's disease pathology.";
RL   J. Biol. Chem. 275:5626-5632(2000).
RN   [66]
RP   IDENTIFICATION OF GAMMA-CTFS BY MASS SPECTROMETRY, MUTAGENESIS OF ASP-739,
RP   AND PROTEOLYTIC CLEAVAGE.
RX   PubMed=12214090; DOI=10.3233/jad-2000-23-408;
RA   Passer B., Pellegrini L., Russo C., Siegel R.M., Lenardo M.J.,
RA   Schettini G., Bachmann M., Tabaton M., D'Adamio L.;
RT   "Generation of an apoptotic intracellular peptide by gamma-secretase
RT   cleavage of Alzheimer's amyloid beta protein precursor.";
RL   J. Alzheimers Dis. 2:289-301(2000).
RN   [67]
RP   REVIEW ON FUNCTION OF AMYLOID-BETA AS ANTIOXIDANT.
RX   PubMed=11775062; DOI=10.1023/a:1012629603390;
RA   Kontush A.;
RT   "Alzheimer's amyloid-beta as a preventive antioxidant for brain
RT   lipoproteins.";
RL   Cell. Mol. Neurobiol. 21:299-315(2001).
RN   [68]
RP   INTERACTION WITH FPR2 (AMYLOID-BETA PROTEIN 42), AND SUBCELLULAR LOCATION
RP   (AMYLOID-BETA PROTEIN 42).
RX   PubMed=11689470; DOI=10.1096/fj.01-0251com;
RA   Yazawa H., Yu Z.-X., Takeda K., Le Y., Gong W., Ferrans V.J.,
RA   Oppenheim J.J., Li C.C.H., Wang J.M.;
RT   "Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled
RT   receptor FPRL1 and forms fibrillar aggregates in macrophages.";
RL   FASEB J. 15:2454-2462(2001).
RN   [69]
RP   INTERACTION WITH BBP.
RX   PubMed=11278849; DOI=10.1074/jbc.m011161200;
RA   Kajkowski E.M., Lo C.F., Ning X., Walker S., Sofia H.J., Wang W., Edris W.,
RA   Chanda P., Wagner E., Vile S., Ryan K., McHendry-Rinde B., Smith S.C.,
RA   Wood A., Rhodes K.J., Kennedy J.D., Bard J., Jacobsen J.S.,
RA   Ozenberger B.A.;
RT   "Beta-amyloid peptide-induced apoptosis regulated by a novel protein
RT   containing a G protein activation module.";
RL   J. Biol. Chem. 276:18748-18756(2001).
RN   [70]
RP   AMYLOID-BETA COPPER AND ZINC-BINDING SITES.
RX   PubMed=11274207; DOI=10.1074/jbc.m100175200;
RA   Curtain C.C., Ali F., Volitakis I., Cherny R.A., Norton R.S.,
RA   Beyreuther K., Barrow C.J., Masters C.L., Bush A.I., Barnham K.J.;
RT   "Alzheimer's disease amyloid-beta binds copper and zinc to generate an
RT   allosterically ordered structure containing superoxide dismutase-like
RT   subunits.";
RL   J. Biol. Chem. 276:20466-20473(2001).
RN   [71]
RP   SUBUNIT.
RX   PubMed=11438549; DOI=10.1074/jbc.m105410200;
RA   Scheuermann S., Hambsch B., Hesse L., Stumm J., Schmidt C., Beher D.,
RA   Bayer T.A., Beyreuther K., Multhaup G.;
RT   "Homodimerization of amyloid precursor protein and its implication in the
RT   amyloidogenic pathway of Alzheimer's disease.";
RL   J. Biol. Chem. 276:33923-33929(2001).
RN   [72]
RP   INTERACTION WITH APBB1, FUNCTION, AND SUBCELLULAR LOCATION (GAMMA-SECRETASE
RP   C-TERMINAL FRAGMENT 59).
RX   PubMed=11544248; DOI=10.1074/jbc.c100447200;
RA   Kimberly W.T., Zheng J.B., Guenette S.Y., Selkoe D.J.;
RT   "The intracellular domain of the beta-amyloid precursor protein is
RT   stabilized by Fe65 and translocates to the nucleus in a notch-like
RT   manner.";
RL   J. Biol. Chem. 276:40288-40292(2001).
RN   [73]
RP   INTERACTION WITH FBLN1.
RX   PubMed=11238726; DOI=10.1046/j.1471-4159.2001.00144.x;
RA   Ohsawa I., Takamura C., Kohsaka S.;
RT   "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein
RT   and modulates its physiological function.";
RL   J. Neurochem. 76:1411-1420(2001).
RN   [74]
RP   INTERACTION WITH MAPT, AND FUNCTION.
RX   PubMed=11943163; DOI=10.1016/s0014-5793(02)02376-1;
RA   Rank K.B., Pauley A.M., Bhattacharya K., Wang Z., Evans D.B., Fleck T.J.,
RA   Johnston J.A., Sharma S.K.;
RT   "Direct interaction of soluble human recombinant tau protein with Abeta 1-
RT   42 results in tau aggregation and hyperphosphorylation by tau protein
RT   kinase II.";
RL   FEBS Lett. 514:263-268(2002).
RN   [75]
RP   INTERACTION WITH MAPK8IP1, AND MUTAGENESIS OF TYR-757.
RX   PubMed=11724784; DOI=10.1074/jbc.m108357200;
RA   Scheinfeld M.H., Roncarati R., Vito P., Lopez P.A., Abdallah M.,
RA   D'Adamio L.;
RT   "Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the
RT   cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein
RT   (APP).";
RL   J. Biol. Chem. 277:3767-3775(2002).
RN   [76]
RP   COPPER-MEDIATED LIPID PEROXIDATION, AND MUTAGENESIS OF HIS-147 AND HIS-151.
RX   PubMed=11784781; DOI=10.1523/jneurosci.22-02-00365.2002;
RA   White A.R., Multhaup G., Galatis D., McKinstry W.J., Parker M.W.,
RA   Pipkorn R., Beyreuther K., Masters C.L., Cappai R.;
RT   "Contrasting species-dependent modulation of copper-mediated neurotoxicity
RT   by the Alzheimer's disease amyloid precursor protein.";
RL   J. Neurosci. 22:365-376(2002).
RN   [77]
RP   REVIEW ON ZINC-BINDING.
RX   PubMed=12032279; DOI=10.1073/pnas.122249699;
RA   Bush A.I., Tanzi R.E.;
RT   "The galvanization of beta-amyloid in Alzheimer's disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:7317-7319(2002).
RN   [78]
RP   PHOSPHORYLATION AT SER-198 AND SER-206 BY CASEIN KINASES, AND MUTAGENESIS
RP   OF SER-198 AND SER-206.
RX   PubMed=8999878; DOI=10.1074/jbc.272.3.1896;
RA   Walter J., Capell A., Hung A.Y., Langen H., Schnoelzer M., Thinakaran G.,
RA   Sisodia S.S., Selkoe D.J., Haass C.;
RT   "Ectodomain phosphorylation of beta-amyloid precursor protein at two
RT   distinct cellular locations.";
RL   J. Biol. Chem. 272:1896-1903(1997).
RN   [79]
RP   CHARACTERIZATION OF CASEIN KINASE PHOSPHORYLATION, AND MUTAGENESIS OF
RP   SER-198 AND SER-206.
RX   PubMed=10806211; DOI=10.1074/jbc.m002850200;
RA   Walter J., Schindzielorz A., Hartung B., Haass C.;
RT   "Phosphorylation of the beta-amyloid precursor protein at the cell surface
RT   by ectocasein kinases 1 and 2.";
RL   J. Biol. Chem. 275:23523-23529(2000).
RN   [80]
RP   PROTEOLYTIC CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-739.
RX   PubMed=10742146; DOI=10.1038/74656;
RA   Lu D.C., Rabizadeh S., Chandra S., Shayya R.F., Ellerby L.M., Ye X.,
RA   Salvesen G.S., Koo E.H., Bredesen D.E.;
RT   "A second cytotoxic proteolytic peptide derived from amyloid beta-protein
RT   precursor.";
RL   Nat. Med. 6:397-404(2000).
RN   [81]
RP   PHOSPHORYLATION, INTERACTION WITH APBB1, AND MUTAGENESIS OF THR-743.
RX   PubMed=11517218; DOI=10.1074/jbc.m104059200;
RA   Ando K., Iijima K., Elliott J.I., Kirino Y., Suzuki T.;
RT   "Phosphorylation-dependent regulation of the interaction of amyloid
RT   precursor protein with Fe65 affects the production of beta-amyloid.";
RL   J. Biol. Chem. 276:40353-40361(2001).
RN   [82]
RP   PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42).
RX   PubMed=11604391; DOI=10.1074/jbc.m104068200;
RA   Hu J., Igarashi A., Kamata M., Nakagawa H.;
RT   "Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A
RT   beta); retards A beta aggregation, deposition, fibril formation; and
RT   inhibits cytotoxicity.";
RL   J. Biol. Chem. 276:47863-47868(2001).
RN   [83]
RP   PHOSPHORYLATION BY MAPK10, AND MUTAGENESIS OF THR-743.
RX   PubMed=11146006; DOI=10.1046/j.1471-4159.2001.00102.x;
RA   Standen C.L., Brownlees J., Grierson A.J., Kesavapany S., Lau K.-F.,
RA   McLoughlin D.M., Miller C.C.J.;
RT   "Phosphorylation of thr(668) in the cytoplasmic domain of the Alzheimer's
RT   disease amyloid precursor protein by stress-activated protein kinase 1b
RT   (Jun N-terminal kinase-3).";
RL   J. Neurochem. 76:316-320(2001).
RN   [84]
RP   PROTEOLYTIC CLEAVAGE AT MET-671; LYS-687; VAL-711; ALA-713 AND LEU-720.
RX   PubMed=11851430; DOI=10.1021/bi015794o;
RA   Weidemann A., Eggert S., Reinhard F.B.M., Vogel M., Paliga K., Baier G.,
RA   Masters C.L., Beyreuther K., Evin G.;
RT   "A novel epsilon-cleavage within the transmembrane domain of the Alzheimer
RT   amyloid precursor protein demonstrates homology with Notch processing.";
RL   Biochemistry 41:2825-2835(2002).
RN   [85]
RP   PHOSPHORYLATION AT TYR-757, INTERACTION WITH SHC1, AND MUTAGENESIS OF
RP   THR-743 AND TYR-757.
RX   PubMed=11877420; DOI=10.1074/jbc.m110286200;
RA   Tarr P.E., Roncarati R., Pelicci G., Pelicci P.G., D'Adamio L.;
RT   "Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic
RT   tail promotes interaction with Shc.";
RL   J. Biol. Chem. 277:16798-16804(2002).
RN   [86]
RP   REVIEW.
RX   PubMed=12142279; DOI=10.1146/annurev.cellbio.18.020402.142302;
RA   Annaert W., De Strooper B.;
RT   "A cell biological perspective on Alzheimer's disease.";
RL   Annu. Rev. Cell Dev. Biol. 18:25-51(2002).
RN   [87]
RP   INTERACTION WITH APBB2.
RX   PubMed=14527950; DOI=10.1074/jbc.m309561200;
RA   Chang Y., Tesco G., Jeong W.J., Lindsley L., Eckman E.A., Eckman C.B.,
RA   Tanzi R.E., Guenette S.Y.;
RT   "Generation of the beta-amyloid peptide and the amyloid precursor protein
RT   C-terminal fragment gamma are potentiated by FE65L1.";
RL   J. Biol. Chem. 278:51100-51107(2003).
RN   [88]
RP   SUBCELLULAR LOCATION, AND ASSOCIATION OF AMYLOID FIBRILS WITH GCP1.
RX   PubMed=15084524; DOI=10.1096/fj.03-1040fje;
RA   Watanabe N., Araki W., Chui D.H., Makifuchi T., Ihara Y., Tabira T.;
RT   "Glypican-1 as an Abeta binding HSPG in the human brain: its localization
RT   in DIG domains and possible roles in the pathogenesis of Alzheimer's
RT   disease.";
RL   FASEB J. 18:1013-1015(2004).
RN   [89]
RP   INTERACTION WITH ANKS1B.
RX   PubMed=15347684; DOI=10.1074/jbc.m405329200;
RA   Ghersi E., Noviello C., D'Adamio L.;
RT   "Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated
RT   protein-1 proteins bind to AbetaPP and modulate its processing in an
RT   isoform-specific manner.";
RL   J. Biol. Chem. 279:49105-49112(2004).
RN   [90]
RP   PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42),
RP   AND SUBCELLULAR LOCATION (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN
RP   42).
RX   PubMed=16154999; DOI=10.1074/jbc.m508460200;
RA   Hemming M.L., Selkoe D.J.;
RT   "Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme
RT   (ACE) and elevated by an ACE inhibitor.";
RL   J. Biol. Chem. 280:37644-37650(2005).
RN   [91]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-542.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [92]
RP   INTERACTION WITH SORL1, AND SUBCELLULAR LOCATION.
RX   PubMed=16174740; DOI=10.1073/pnas.0503689102;
RA   Andersen O.M., Reiche J., Schmidt V., Gotthardt M., Spoelgen R., Behlke J.,
RA   von Arnim C.A., Breiderhoff T., Jansen P., Wu X., Bales K.R., Cappai R.,
RA   Masters C.L., Gliemann J., Mufson E.J., Hyman B.T., Paul S.M., Nykjaer A.,
RA   Willnow T.E.;
RT   "Neuronal sorting protein-related receptor sorLA/LR11 regulates processing
RT   of the amyloid precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005).
RN   [93]
RP   INTERACTION WITH SORL1, AND MUTAGENESIS OF 757-TYR--TYR-762.
RX   PubMed=16407538; DOI=10.1523/jneurosci.3882-05.2006;
RA   Spoelgen R., von Arnim C.A., Thomas A.V., Peltan I.D., Koker M., Deng A.,
RA   Irizarry M.C., Andersen O.M., Willnow T.E., Hyman B.T.;
RT   "Interaction of the cytosolic domains of sorLA/LR11 with the amyloid
RT   precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme.";
RL   J. Neurosci. 26:418-428(2006).
RN   [94]
RP   FUNCTION.
RX   PubMed=17062754; DOI=10.1073/pnas.0607527103;
RA   Satpute-Krishnan P., DeGiorgis J.A., Conley M.P., Jang M., Bearer E.L.;
RT   "A peptide zipcode sufficient for anterograde transport within amyloid
RT   precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:16532-16537(2006).
RN   [95]
RP   INTERACTION WITH SORL1.
RX   PubMed=17855360; DOI=10.1074/jbc.m705073200;
RA   Schmidt V., Sporbert A., Rohe M., Reimer T., Rehm A., Andersen O.M.,
RA   Willnow T.E.;
RT   "SorLA/LR11 regulates processing of amyloid precursor protein via
RT   interaction with adaptors GGA and PACS-1.";
RL   J. Biol. Chem. 282:32956-32964(2007).
RN   [96]
RP   INTERACTION WITH APBB1.
RX   PubMed=18468999; DOI=10.1074/jbc.m801827200;
RA   Nakaya T., Kawai T., Suzuki T.;
RT   "Regulation of FE65 nuclear translocation and function by amyloid beta-
RT   protein precursor in osmotically stressed cells.";
RL   J. Biol. Chem. 283:19119-19131(2008).
RN   [97]
RP   INTERACTION WITH ITM2C.
RX   PubMed=19366692; DOI=10.1074/jbc.m109.006403;
RA   Matsuda S., Matsuda Y., D'Adamio L.;
RT   "BRI3 inhibits amyloid precursor protein processing in a mechanistically
RT   distinct manner from its homologue dementia gene BRI2.";
RL   J. Biol. Chem. 284:15815-15825(2009).
RN   [98]
RP   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 peptides bind to lipoproteins and
CC       apolipoproteins E and J in the CSF and to HDL particles in plasma,
CC       inhibiting metal-catalyzed oxidation of lipoproteins. Promotes both tau
CC       aggregation and TPK II-mediated phosphorylation. Interaction with
CC       overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also
CC       binds GPC1 in lipid rafts.
CC   -!- FUNCTION: [Amyloid-beta protein 42]: More effective reductant than
CC       amyloid-beta protein 40. May activate mononuclear phagocytes in the
CC       brain and elicit inflammatory responses.
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. Interacts with CPEB1 and AGER (By similarity).
CC       Interacts with ANKS1B. Interacts with ITM2B. Interacts with ITM2C.
CC       Interacts with IDE (PubMed:17051221). Homodimerizes; dimerization is
CC       enhanced in the presence of Cu(2+) ions and is promoted by heparin
CC       binding (PubMed:25122912, PubMed:20212142). Interacts with PLD3.
CC       Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could
CC       regulate APP processing (By similarity). Interacts with SYT7 (By
CC       similarity). Interacts (via transmembrane region) with PSEN1; the
CC       interaction is direct (PubMed:30630874). Interacts with LRRK2
CC       (PubMed:28720718). Interacts (via cytoplasmic domain) with KIF5B
CC       (PubMed:23011729). Interacts (via C-terminus) with APBB2/FE65L1 (via C-
CC       terminus) (PubMed:14527950, PubMed:8855266). Interacts (via
CC       intracellular domain) with APBB3 (PubMed:10081969). Amyloid-beta
CC       associates with HADH2 (PubMed:9338779). Soluble APP binds, via its N-
CC       terminal head, to FBLN1. {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   -!- SUBUNIT: [Amyloid-beta protein 40]: Interacts with S100A9.
CC   -!- SUBUNIT: [Amyloid-beta protein 42]: Interacts with FPR2.
CC       {ECO:0000269|PubMed:11689470}.
CC   -!- SUBUNIT: [C83]: Interacts with GSAP. {ECO:0000269|PubMed:20811458}.
CC   -!- SUBUNIT: [Isoform APP695]: Interacts with SORL1 (via N-terminal
CC       ectodomain); this interaction retains APP in the trans-Golgi network
CC       and reduces processing into soluble APP-alpha and amyloid-beta
CC       peptides. {ECO:0000269|PubMed:16174740, ECO:0000269|PubMed:16407538,
CC       ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:24523320}.
CC   -!- SUBUNIT: [C99]: Interacts with SORL1. {ECO:0000269|PubMed:16407538}.
CC   -!- SUBUNIT: [Isoform APP751]: Interacts with SORL1.
CC       {ECO:0000269|PubMed:16174740}.
CC   -!- SUBUNIT: [Isoform APP770]: Interacts with SORL1.
CC       {ECO:0000269|PubMed:16174740}.
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=3; IntAct=EBI-77613, EBI-81711;
CC       P05067; O96018: APBA3; NbExp=7; 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=7; 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; P62158: CALM3; NbExp=3; IntAct=EBI-77613, EBI-397435;
CC       P05067; P27797: CALR; NbExp=5; IntAct=EBI-77613, EBI-1049597;
CC       P05067; O43852-3: CALU; NbExp=3; IntAct=EBI-77613, EBI-11536607;
CC       P05067; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-77613, EBI-1383687;
CC       P05067; P27824-2: CANX; NbExp=3; IntAct=EBI-77613, EBI-25890990;
CC       P05067; P07384: CAPN1; NbExp=3; IntAct=EBI-77613, EBI-1542113;
CC       P05067; P29466-3: CASP1; NbExp=3; IntAct=EBI-77613, EBI-12248206;
CC       P05067; P42574: CASP3; NbExp=4; IntAct=EBI-77613, EBI-524064;
CC       P05067; Q14790: CASP8; NbExp=3; IntAct=EBI-77613, EBI-78060;
CC       P05067; Q03135: CAV1; NbExp=3; IntAct=EBI-77613, EBI-603614;
CC       P05067; P83916: CBX1; NbExp=6; IntAct=EBI-77613, EBI-78129;
CC       P05067; P40227: CCT6A; NbExp=3; IntAct=EBI-77613, EBI-356687;
CC       P05067; P16671: CD36; NbExp=3; IntAct=EBI-77613, EBI-2808214;
CC       P05067; Q08722-3: CD47; NbExp=3; IntAct=EBI-77613, EBI-17263290;
CC       P05067; P06493: CDK1; NbExp=3; IntAct=EBI-77613, EBI-444308;
CC       P05067; Q00535: CDK5; NbExp=3; IntAct=EBI-77613, EBI-1041567;
CC       P05067; P42773: CDKN2C; NbExp=3; IntAct=EBI-77613, EBI-711290;
CC       P05067; P43681: CHRNA4; NbExp=3; IntAct=EBI-77613, EBI-7132379;
CC       P05067; P36544: CHRNA7; NbExp=4; IntAct=EBI-77613, EBI-79333;
CC       P05067; Q16740: CLPP; NbExp=3; IntAct=EBI-77613, EBI-1056029;
CC       P05067; O94985-2: CLSTN1; NbExp=3; IntAct=EBI-77613, EBI-16041593;
CC       P05067; Q8IUW6: CLSTN3; NbExp=3; IntAct=EBI-77613, EBI-25832219;
CC       P05067; P10909: CLU; NbExp=3; IntAct=EBI-77613, EBI-1104674;
CC       P05067; P26441: CNTF; NbExp=3; IntAct=EBI-77613, EBI-1050897;
CC       P05067; Q02246: CNTN2; NbExp=3; IntAct=EBI-77613, EBI-4397248;
CC       P05067; Q8NE08: COL25A1; NbExp=3; IntAct=EBI-77613, EBI-25836642;
CC       P05067; Q96A83-2: COL26A1; NbExp=3; IntAct=EBI-77613, EBI-21553822;
CC       P05067; P29400-2: COL4A5; NbExp=3; IntAct=EBI-77613, EBI-12211159;
CC       P05067; Q14031: COL4A6; NbExp=3; IntAct=EBI-77613, EBI-2432407;
CC       P05067; P31146: CORO1A; NbExp=3; IntAct=EBI-77613, EBI-1046676;
CC       P05067; P20674: COX5A; NbExp=3; IntAct=EBI-77613, EBI-715032;
CC       P05067; P15086: CPB1; NbExp=3; IntAct=EBI-77613, EBI-25936844;
CC       P05067; P02511: CRYAB; NbExp=7; IntAct=EBI-77613, EBI-739060;
CC       P05067; P48730: CSNK1D; NbExp=3; IntAct=EBI-77613, EBI-751621;
CC       P05067; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-77613, EBI-9087876;
CC       P05067; P68400: CSNK2A1; NbExp=3; IntAct=EBI-77613, EBI-347804;
CC       P05067; P01034: CST3; NbExp=3; IntAct=EBI-77613, EBI-948622;
CC       P05067; P49711: CTCF; NbExp=3; IntAct=EBI-77613, EBI-932887;
CC       P05067; P07339: CTSD; NbExp=2; IntAct=EBI-77613, EBI-2115097;
CC       P05067; P99999: CYCS; NbExp=3; IntAct=EBI-77613, EBI-446479;
CC       P05067; O75553-4: DAB1; NbExp=3; IntAct=EBI-77613, EBI-21246842;
CC       P05067; P98082: DAB2; NbExp=3; IntAct=EBI-77613, EBI-1171238;
CC       P05067; Q14203-5: DCTN1; NbExp=5; IntAct=EBI-77613, EBI-25840379;
CC       P05067; Q13561: DCTN2; NbExp=3; IntAct=EBI-77613, EBI-715074;
CC       P05067; Q6I9W9: DKFZP586N0721; NbExp=3; IntAct=EBI-77613, EBI-25927172;
CC       P05067; O14645: DNALI1; NbExp=3; IntAct=EBI-77613, EBI-395638;
CC       P05067; Q01658: DR1; NbExp=3; IntAct=EBI-77613, EBI-750300;
CC       P05067; P21917: DRD4; NbExp=6; IntAct=EBI-77613, EBI-8592297;
CC       P05067; Q16828: DUSP6; NbExp=3; IntAct=EBI-77613, EBI-746870;
CC       P05067; Q92997: DVL3; NbExp=3; IntAct=EBI-77613, EBI-739789;
CC       P05067; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-77613, EBI-25840445;
CC       P05067; O14576-5: DYNC1I1; NbExp=3; IntAct=EBI-77613, EBI-25936079;
CC       P05067; Q01094: E2F1; NbExp=3; IntAct=EBI-77613, EBI-448924;
CC       P05067; Q3B7T1: EDRF1; NbExp=3; IntAct=EBI-77613, EBI-2870947;
CC       P05067; P20042: EIF2S2; NbExp=6; IntAct=EBI-77613, EBI-711977;
CC       P05067; P19419: ELK1; NbExp=3; IntAct=EBI-77613, EBI-726632;
CC       P05067; P11171-2: EPB41; NbExp=3; IntAct=EBI-77613, EBI-10197451;
CC       P05067; P11171-7: EPB41; NbExp=3; IntAct=EBI-77613, EBI-25852354;
CC       P05067; Q9BS26: ERP44; NbExp=3; IntAct=EBI-77613, EBI-541644;
CC       P05067; P00748: F12; NbExp=3; IntAct=EBI-77613, EBI-6378830;
CC       P05067; P00734: F2; NbExp=3; IntAct=EBI-77613, EBI-297094;
CC       P05067; P23142-4: FBLN1; NbExp=3; IntAct=EBI-77613, EBI-11956479;
CC       P05067; Q92915: FGF14; NbExp=3; IntAct=EBI-77613, EBI-10489272;
CC       P05067; P62942: FKBP1A; NbExp=3; IntAct=EBI-77613, EBI-1027571;
CC       P05067; P21333-2: FLNA; NbExp=3; IntAct=EBI-77613, EBI-9641086;
CC       P05067; O75955: FLOT1; NbExp=5; IntAct=EBI-77613, EBI-603643;
CC       P05067; Q9BTI6: FLOT2; NbExp=3; IntAct=EBI-77613, EBI-23703366;
CC       P05067; P01100: FOS; NbExp=3; IntAct=EBI-77613, EBI-852851;
CC       P05067; P25090: FPR2; NbExp=3; IntAct=EBI-77613, EBI-17291771;
CC       P05067; P09958: FURIN; NbExp=3; IntAct=EBI-77613, EBI-1056807;
CC       P05067; P06241: FYN; NbExp=3; IntAct=EBI-77613, EBI-515315;
CC       P05067; P04406: GAPDH; NbExp=3; IntAct=EBI-77613, EBI-354056;
CC       P05067; Q9UJY5-4: GGA1; NbExp=3; IntAct=EBI-77613, EBI-12108696;
CC       P05067; Q05586: GRIN1; NbExp=3; IntAct=EBI-77613, EBI-998542;
CC       P05067; P25098: GRK2; NbExp=3; IntAct=EBI-77613, EBI-3904795;
CC       P05067; P43250: GRK6; NbExp=3; IntAct=EBI-77613, EBI-722747;
CC       P05067; P43250-2: GRK6; NbExp=3; IntAct=EBI-77613, EBI-6428342;
CC       P05067; A4D1B5: GSAP; NbExp=3; IntAct=EBI-77613, EBI-15875313;
CC       P05067; P49841-2: GSK3B; NbExp=3; IntAct=EBI-77613, EBI-15870655;
CC       P05067; Q03013: GSTM4; NbExp=3; IntAct=EBI-77613, EBI-713363;
CC       P05067; Q00403: GTF2B; NbExp=3; IntAct=EBI-77613, EBI-389564;
CC       P05067; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-77613, EBI-1054873;
CC       P05067; P09429: HMGB1; NbExp=3; IntAct=EBI-77613, EBI-389432;
CC       P05067; P30519: HMOX2; NbExp=3; IntAct=EBI-77613, EBI-712096;
CC       P05067; Q9UJC3: HOOK1; NbExp=3; IntAct=EBI-77613, EBI-746704;
CC       P05067; Q99714: HSD17B10; NbExp=7; IntAct=EBI-77613, EBI-79964;
CC       P05067; Q99714-2: HSD17B10; NbExp=3; IntAct=EBI-77613, EBI-25939412;
CC       P05067; P07900: HSP90AA1; NbExp=5; IntAct=EBI-77613, EBI-296047;
CC       P05067; P14625: HSP90B1; NbExp=3; IntAct=EBI-77613, EBI-359129;
CC       P05067; P11021: HSPA5; NbExp=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=3; 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=6; 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; Q9HCM2: PLXNA4; NbExp=2; IntAct=EBI-77613, EBI-46257296;
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=6; 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; O75509: TNFRSF21; NbExp=2; IntAct=EBI-77613, EBI-2313231;
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; Q9WVI9-1: Mapk8ip1; Xeno; NbExp=2; IntAct=EBI-77613, EBI-288461;
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; O35430: Apba1; Xeno; NbExp=2; IntAct=EBI-302641, EBI-704760;
CC       P05067-4; O35431: Apba2; Xeno; NbExp=2; IntAct=EBI-302641, EBI-2028211;
CC       P05067-4; O70248: Apba3; Xeno; NbExp=2; IntAct=EBI-302641, EBI-8513381;
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: Pirb; 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/app";
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_000484.4. [P05067-1]
DR   RefSeq; NP_001129488.1; NM_001136016.3. [P05067-11]
DR   RefSeq; NP_001129601.1; NM_001136129.3. [P05067-10]
DR   RefSeq; NP_001129602.1; NM_001136130.2.
DR   RefSeq; NP_001129603.1; NM_001136131.2.
DR   RefSeq; NP_001191230.1; NM_001204301.2. [P05067-9]
DR   RefSeq; NP_001191231.1; NM_001204302.2. [P05067-7]
DR   RefSeq; NP_001191232.1; NM_001204303.2. [P05067-3]
DR   RefSeq; NP_001372182.1; NM_001385253.1. [P05067-6]
DR   RefSeq; NP_958816.1; NM_201413.3. [P05067-8]
DR   RefSeq; NP_958817.1; NM_201414.3. [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   PDB; 8Z9V; EM; 7.84 A; e=678-713.
DR   PDB; 9CZN; EM; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=680-713.
DR   PDB; 9CZP; EM; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=680-713.
DR   PDB; 9IIO; EM; 3.30 A; 2/3/4/5/6/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=672-711.
DR   PDB; 9JAZ; EM; 3.00 A; A/AA/B/BB/C/CC/D/DD/E/EE/F/FF=672-713.
DR   PDB; 9JB0; EM; 2.90 A; A/AA/B/BB/C/CC/D/DD/E/EE/F/FF=672-713.
DR   PDB; 9JB1; EM; 2.50 A; FF/FG/FH/FI/FJ/FK/FL/FM/FN/FO/FP/FQ=672-713.
DR   PDB; 9JB2; EM; 2.90 A; A/B/BA/BB/BC/BD/BE/C/CA/CB/CC/CD/CE/D/E=672-713.
DR   PDBsum; 1AAP; -.
DR   PDBsum; 1AMB; -.
DR   PDBsum; 1AMC; -.
DR   PDBsum; 1AML; -.
DR   PDBsum; 1BA4; -.
DR   PDBsum; 1BA6; -.
DR   PDBsum; 1BJB; -.
DR   PDBsum; 1BJC; -.
DR   PDBsum; 1BRC; -.
DR   PDBsum; 1CA0; -.
DR   PDBsum; 1HZ3; -.
DR   PDBsum; 1IYT; -.
DR   PDBsum; 1MWP; -.
DR   PDBsum; 1OWT; -.
DR   PDBsum; 1QCM; -.
DR   PDBsum; 1QWP; -.
DR   PDBsum; 1QXC; -.
DR   PDBsum; 1QYT; -.
DR   PDBsum; 1TAW; -.
DR   PDBsum; 1TKN; -.
DR   PDBsum; 1X11; -.
DR   PDBsum; 1Z0Q; -.
DR   PDBsum; 1ZE7; -.
DR   PDBsum; 1ZE9; -.
DR   PDBsum; 1ZJD; -.
DR   PDBsum; 2BEG; -.
DR   PDBsum; 2BP4; -.
DR   PDBsum; 2FJZ; -.
DR   PDBsum; 2FK1; -.
DR   PDBsum; 2FK2; -.
DR   PDBsum; 2FK3; -.
DR   PDBsum; 2FKL; -.
DR   PDBsum; 2FMA; -.
DR   PDBsum; 2G47; -.
DR   PDBsum; 2IPU; -.
DR   PDBsum; 2LFM; -.
DR   PDBsum; 2LLM; -.
DR   PDBsum; 2LMN; -.
DR   PDBsum; 2LMO; -.
DR   PDBsum; 2LMP; -.
DR   PDBsum; 2LMQ; -.
DR   PDBsum; 2LNQ; -.
DR   PDBsum; 2LOH; -.
DR   PDBsum; 2LP1; -.
DR   PDBsum; 2LZ3; -.
DR   PDBsum; 2LZ4; -.
DR   PDBsum; 2M4J; -.
DR   PDBsum; 2M9R; -.
DR   PDBsum; 2M9S; -.
DR   PDBsum; 2MGT; -.
DR   PDBsum; 2MJ1; -.
DR   PDBsum; 2MPZ; -.
DR   PDBsum; 2MVX; -.
DR   PDBsum; 2MXU; -.
DR   PDBsum; 2NAO; -.
DR   PDBsum; 2OTK; -.
DR   PDBsum; 2R0W; -.
DR   PDBsum; 2WK3; -.
DR   PDBsum; 2Y29; -.
DR   PDBsum; 2Y2A; -.
DR   PDBsum; 2Y3J; -.
DR   PDBsum; 2Y3K; -.
DR   PDBsum; 2Y3L; -.
DR   PDBsum; 3AYU; -.
DR   PDBsum; 3BAE; -.
DR   PDBsum; 3BKJ; -.
DR   PDBsum; 3DXC; -.
DR   PDBsum; 3DXD; -.
DR   PDBsum; 3DXE; -.
DR   PDBsum; 3GCI; -.
DR   PDBsum; 3IFL; -.
DR   PDBsum; 3IFN; -.
DR   PDBsum; 3IFO; -.
DR   PDBsum; 3IFP; -.
DR   PDBsum; 3JQ5; -.
DR   PDBsum; 3JQL; -.
DR   PDBsum; 3JTI; -.
DR   PDBsum; 3KTM; -.
DR   PDBsum; 3L33; -.
DR   PDBsum; 3L81; -.
DR   PDBsum; 3MOQ; -.
DR   PDBsum; 3MXC; -.
DR   PDBsum; 3MXY; -.
DR   PDBsum; 3NYJ; -.
DR   PDBsum; 3NYL; -.
DR   PDBsum; 3OVJ; -.
DR   PDBsum; 3OW9; -.
DR   PDBsum; 3PZZ; -.
DR   PDBsum; 3Q2X; -.
DR   PDBsum; 3SV1; -.
DR   PDBsum; 3U0T; -.
DR   PDBsum; 3UMH; -.
DR   PDBsum; 3UMI; -.
DR   PDBsum; 3UMK; -.
DR   PDBsum; 4HIX; -.
DR   PDBsum; 4JFN; -.
DR   PDBsum; 4M1C; -.
DR   PDBsum; 4MDR; -.
DR   PDBsum; 4MVI; -.
DR   PDBsum; 4MVK; -.
DR   PDBsum; 4MVL; -.
DR   PDBsum; 4NGE; -.
DR   PDBsum; 4OJF; -.
DR   PDBsum; 4ONF; -.
DR   PDBsum; 4ONG; -.
DR   PDBsum; 4PQD; -.
DR   PDBsum; 4PWQ; -.
DR   PDBsum; 4XXD; -.
DR   PDBsum; 5AEF; -.
DR   PDBsum; 5AM8; -.
DR   PDBsum; 5AMB; -.
DR   PDBsum; 5BUO; -.
DR   PDBsum; 5C67; -.
DR   PDBsum; 5CSZ; -.
DR   PDBsum; 5HOW; -.
DR   PDBsum; 5HOX; -.
DR   PDBsum; 5HOY; -.
DR   PDBsum; 5KK3; -.
DR   PDBsum; 5LFY; -.
DR   PDBsum; 5LV0; -.
DR   PDBsum; 5MY4; -.
DR   PDBsum; 5MYO; -.
DR   PDBsum; 5MYX; -.
DR   PDBsum; 5ONP; -.
DR   PDBsum; 5ONQ; -.
DR   PDBsum; 5OQV; -.
DR   PDBsum; 5TXD; -.
DR   PDBsum; 5VOS; -.
DR   PDBsum; 5VZY; -.
DR   PDBsum; 5W3P; -.
DR   PDBsum; 6CO3; -.
DR   PDBsum; 6GFI; -.
DR   PDBsum; 6ITU; -.
DR   PDBsum; 6IYC; -.
DR   PDBsum; 6NB9; -.
DR   PDBsum; 6O4J; -.
DR   PDBsum; 6OC9; -.
DR   PDBsum; 6OIZ; -.
DR   PDBsum; 6RHY; -.
DR   PDBsum; 6SHS; -.
DR   PDBsum; 6SZF; -.
DR   PDBsum; 6TI5; -.
DR   PDBsum; 6TI6; -.
DR   PDBsum; 6TI7; -.
DR   PDBsum; 6W0O; -.
DR   PDBsum; 6WXM; -.
DR   PDBsum; 6XOV; -.
DR   PDBsum; 6YHF; -.
DR   PDBsum; 6YHI; -.
DR   PDBsum; 6YHO; -.
DR   PDBsum; 6YHP; -.
DR   PDBsum; 6YHX; -.
DR   PDBsum; 7B3J; -.
DR   PDBsum; 7B3K; -.
DR   PDBsum; 7E6P; -.
DR   PDBsum; 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   PDBsum; 8Z9V; -.
DR   PDBsum; 9CZN; -.
DR   PDBsum; 9CZP; -.
DR   PDBsum; 9IIO; -.
DR   PDBsum; 9JAZ; -.
DR   PDBsum; 9JB0; -.
DR   PDBsum; 9JB1; -.
DR   PDBsum; 9JB2; -.
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-37170; -.
DR   EMDB; EMD-37195; -.
DR   EMDB; EMD-37197; -.
DR   EMDB; EMD-37198; -.
DR   EMDB; EMD-37199; -.
DR   EMDB; EMD-37200; -.
DR   EMDB; EMD-38059; -.
DR   EMDB; EMD-38060; -.
DR   EMDB; EMD-38061; -.
DR   EMDB; EMD-3851; -.
DR   EMDB; EMD-39869; -.
DR   EMDB; EMD-40416; -.
DR   EMDB; EMD-40419; -.
DR   EMDB; EMD-40421; -.
DR   EMDB; EMD-46422; -.
DR   EMDB; EMD-46424; -.
DR   EMDB; EMD-50437; -.
DR   EMDB; EMD-50438; -.
DR   EMDB; EMD-50439; -.
DR   EMDB; EMD-50440; -.
DR   EMDB; EMD-60603; -.
DR   EMDB; EMD-61302; -.
DR   EMDB; EMD-61303; -.
DR   EMDB; EMD-61304; -.
DR   EMDB; EMD-61305; -.
DR   EMDB; EMD-61944; -.
DR   EMDB; EMD-61945; -.
DR   EMDB; EMD-61946; -.
DR   EMDB; EMD-63646; -.
DR   EMDB; EMD-63647; -.
DR   EMDB; EMD-63648; -.
DR   EMDB; EMD-64274; -.
DR   EMDB; EMD-9751; -.
DR   PCDDB; P05067; -.
DR   SASBDB; P05067; -.
DR   SMR; P05067; -.
DR   BioGRID; 106848; 2408.
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   FunCoup; P05067; 1765.
DR   IntAct; P05067; 926.
DR   MINT; P05067; -.
DR   STRING; 9606.ENSP00000284981; -.
DR   BindingDB; P05067; -.
DR   ChEMBL; CHEMBL2487; -.
DR   DrugBank; DB12274; Aducanumab.
DR   DrugBank; DB06086; Affitope AD01.
DR   DrugBank; DB01370; Aluminium.
DR   DrugBank; DB14517; Aluminium phosphate.
DR   DrugBank; DB14518; Aluminum acetate.
DR   DrugBank; DB05150; CAD106.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB11672; Curcumin.
DR   DrugBank; DB00746; Deferoxamine.
DR   DrugBank; DB06782; Dimercaprol.
DR   DrugBank; DB05938; Edonerpic.
DR   DrugBank; DB09148; Florbetaben F-18.
DR   DrugBank; DB09149; Florbetapir F-18.
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; DB18298; PTI-110.
DR   DrugBank; DB02709; Resveratrol.
DR   DrugBank; DB05088; Tetrathiomolybdate.
DR   DrugBank; DB06527; Tramiprosate.
DR   DrugBank; DB03754; Tromethamine.
DR   DrugBank; DB19191; Valiltramiprosate.
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; 27 sites, 13 N-linked glycans (3 sites), 6 O-linked glycans (23 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; 142 sequenced antibodies.
DR   Antibodypedia; 668; 4422 antibodies from 55 providers.
DR   DNASU; 351; -.
DR   YCharOS; P05067; Tested 11 antibodies from 5 manufacturers.
DR   Ensembl; ENST00000346798.8; ENSP00000284981.4; ENSG00000142192.23. [P05067-1]
DR   Ensembl; ENST00000348990.9; ENSP00000345463.5; ENSG00000142192.23. [P05067-4]
DR   Ensembl; ENST00000354192.7; ENSP00000346129.3; ENSG00000142192.23. [P05067-10]
DR   Ensembl; ENST00000357903.7; ENSP00000350578.3; ENSG00000142192.23. [P05067-8]
DR   Ensembl; ENST00000358918.7; ENSP00000351796.3; ENSG00000142192.23. [P05067-9]
DR   Ensembl; ENST00000440126.7; ENSP00000387483.2; ENSG00000142192.23. [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   ClinPGx; PA24910; -.
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   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   VEuPathDB; HostDB:ENSG00000142192; -.
DR   eggNOG; KOG3540; Eukaryota.
DR   GeneTree; ENSGT00530000063252; -.
DR   InParanoid; P05067; -.
DR   OMA; THRVQKC; -.
DR   OrthoDB; 6147836at2759; -.
DR   PAN-GO; P05067; 9 GO annotations based on evolutionary models.
DR   PhylomeDB; P05067; -.
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   Agora; ENSG00000142192; Agora Nominated Target for Alzheimer's Disease.
DR   BioGRID-ORCS; 351; 12 hits in 1170 CRISPR screens.
DR   CD-CODE; 2C639066; Synthetic Condensate 000143.
DR   CD-CODE; 8C2F96ED; Centrosome.
DR   CD-CODE; 9F779CC8; Nuclear body.
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:0106003; C:amyloid-beta complex; IDA:UniProt.
DR   GO; GO:0097449; C:astrocyte projection; IEA:Ensembl.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
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:0031901; C:early endosome membrane; IDA:UniProt.
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:HPA.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0005798; C:Golgi-associated vesicle; ISS:UniProtKB.
DR   GO; GO:1990812; C:growth cone filopodium; IEA:Ensembl.
DR   GO; GO:1990761; C:growth cone lamellipodium; IEA:Ensembl.
DR   GO; GO:0044304; C:main axon; IEA:Ensembl.
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:0098992; C:neuronal dense core vesicle; 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:0043235; C:receptor complex; IDA:MGI.
DR   GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; IDA:MGI.
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:0070851; F:growth factor receptor binding; IEA:Ensembl.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0016504; F:peptidase activator activity; IEA:Ensembl.
DR   GO; GO: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: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:0006816; P:calcium ion transport; IEA:Ensembl.
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:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR   GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR   GO; GO:0071287; P:cellular response to manganese ion; IEA:Ensembl.
DR   GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0071874; P:cellular response to norepinephrine stimulus; IEA:Ensembl.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:0050890; P:cognition; ISS:UniProtKB.
DR   GO; GO:0048669; P:collateral sprouting in absence of injury; ISS:UniProtKB.
DR   GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR   GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR   GO; GO:0030198; P:extracellular matrix organization; ISS:UniProtKB.
DR   GO; GO:0110088; P:hippocampal neuron apoptotic process; 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: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: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:0051247; P:positive regulation of protein metabolic process; IMP: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:0043523; P:regulation of neuron apoptotic process; IEA:Ensembl.
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:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:1990418; P:response to insulin-like growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0070555; P:response to interleukin-1; ISS:ARUK-UCL.
DR   GO; GO:0010288; P:response to lead ion; IEA:Ensembl.
DR   GO; GO:0036269; P:swimming behavior; IEA:Ensembl.
DR   GO; GO:0050808; P:synapse organization; IGI:ARUK-UCL.
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        194..207
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        228..264
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        268..281
FT                   /note="Low complexity"
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 40/
FT                   total amyloid-beta; dbSNP:rs63750734)"
FT                   /evidence="ECO:0000269|PubMed:10097173"
FT                   /id="VAR_010108"
FT   VARIANT         716
FT                   /note="I -> V (in AD1; dbSNP:rs63750399)"
FT                   /evidence="ECO:0000269|PubMed:9328472"
FT                   /id="VAR_000020"
FT   VARIANT         717
FT                   /note="V -> F (in AD1; increased amyloid-beta protein 42/40
FT                   ratio; dbSNP:rs63750264)"
FT                   /evidence="ECO:0000269|PubMed:1925564,
FT                   ECO:0000269|PubMed:8267572, ECO:0000269|PubMed:8290042,
FT                   ECO:0000269|PubMed:8476439, ECO:0000269|PubMed:8886002"
FT                   /id="VAR_000023"
FT   VARIANT         717
FT                   /note="V -> G (in AD1; increased amyloid-beta protein 42/40
FT                   ratio; dbSNP:rs63749964)"
FT                   /evidence="ECO:0000269|PubMed:1944558,
FT                   ECO:0000269|PubMed:8476439, ECO:0000269|PubMed:8886002"
FT                   /id="VAR_000022"
FT   VARIANT         717
FT                   /note="V -> I (in AD1; increased amyloid-beta protein 42/40
FT                   ratio; dbSNP:rs63750264)"
FT                   /evidence="ECO:0000269|PubMed:10631141,
FT                   ECO:0000269|PubMed:11063718, ECO:0000269|PubMed:1671712,
FT                   ECO:0000269|PubMed:1678058, ECO:0000269|PubMed:1908231,
FT                   ECO:0000269|PubMed:8267572, ECO:0000269|PubMed:8476439,
FT                   ECO:0000269|PubMed:8577393, ECO:0000269|PubMed:8886002"
FT                   /id="VAR_000021"
FT   VARIANT         717
FT                   /note="V -> L (in AD1; dbSNP:rs63750264)"
FT                   /evidence="ECO:0000269|PubMed:10867787"
FT                   /id="VAR_014219"
FT   VARIANT         723
FT                   /note="L -> P (in AD1; dbSNP:rs63751122)"
FT                   /evidence="ECO:0000269|PubMed:10665499"
FT                   /id="VAR_010109"
FT   MUTAGEN         99..102
FT                   /note="KRGR->NQGG: Reduced heparin-binding."
FT                   /evidence="ECO:0000269|PubMed:8158260"
FT   MUTAGEN         108
FT                   /note="H->A: Loss of the copper binding site in the GFLD
FT                   subdomain; when associated with A-110."
FT                   /evidence="ECO:0000269|PubMed:25122912"
FT   MUTAGEN         110
FT                   /note="H->A: Loss of the copper binding site in the GFLD
FT                   subdomain; when associated with A-108."
FT                   /evidence="ECO:0000269|PubMed:25122912"
FT   MUTAGEN         137
FT                   /note="H->N: Binds copper. Forms dimer."
FT                   /evidence="ECO:0000269|PubMed:7913895"
FT   MUTAGEN         141
FT                   /note="M->T: Binds copper. Forms dimer."
FT                   /evidence="ECO:0000269|PubMed:7913895"
FT   MUTAGEN         144
FT                   /note="C->S: Binds copper. No dimer formation. No copper
FT                   reducing activity."
FT                   /evidence="ECO:0000269|PubMed:10461923,
FT                   ECO:0000269|PubMed:7913895"
FT   MUTAGEN         147..149
FT                   /note="HLH->ALA: 50% decrease in copper reducing activity."
FT                   /evidence="ECO:0000269|PubMed:10461923"
FT   MUTAGEN         147
FT                   /note="H->A: Loss of a copper binding site; when associated
FT                   with A-151."
FT                   /evidence="ECO:0000269|PubMed:25122912"
FT   MUTAGEN         147
FT                   /note="H->A: Some decrease in copper reducing activity."
FT                   /evidence="ECO:0000269|PubMed:11784781,
FT                   ECO:0000269|PubMed:7913895"
FT   MUTAGEN         147
FT                   /note="H->N: Binds copper. Forms dimer."
FT                   /evidence="ECO:0000269|PubMed:11784781,
FT                   ECO:0000269|PubMed:7913895"
FT   MUTAGEN         147
FT                   /note="H->Y: Greatly reduced copper-mediated low-density
FT                   lipoprotein oxidation."
FT                   /evidence="ECO:0000269|PubMed:11784781,
FT                   ECO:0000269|PubMed:7913895"
FT   MUTAGEN         151
FT                   /note="H->A: Loss of a copper binding site; when associated
FT                   with A-147."
FT                   /evidence="ECO:0000269|PubMed:25122912"
FT   MUTAGEN         151
FT                   /note="H->K: Greatly reduced copper-mediated low-density
FT                   lipoprotein oxidation."
FT                   /evidence="ECO:0000269|PubMed:11784781,
FT                   ECO:0000269|PubMed:7913895"
FT   MUTAGEN         151
FT                   /note="H->N: Binds copper. Forms dimer."
FT                   /evidence="ECO:0000269|PubMed:11784781,
FT                   ECO:0000269|PubMed:7913895"
FT   MUTAGEN         198
FT                   /note="S->A: Greatly reduced casein kinase
FT                   phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:10806211,
FT                   ECO:0000269|PubMed:8999878"
FT   MUTAGEN         206
FT                   /note="S->A: Reduced casein kinase phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:10806211,
FT                   ECO:0000269|PubMed:8999878"
FT   MUTAGEN         499
FT                   /note="R->A: Reduced affinity for heparin; when associated
FT                   with A-503."
FT                   /evidence="ECO:0000269|PubMed:15304215"
FT   MUTAGEN         503
FT                   /note="K->A: Reduced affinity for heparin; when associated
FT                   with A-499."
FT                   /evidence="ECO:0000269|PubMed:15304215"
FT   MUTAGEN         656
FT                   /note="S->A: Abolishes chondroitin sulfate binding in L-
FT                   APP733 isoform."
FT                   /evidence="ECO:0000269|PubMed:7737970"
FT   MUTAGEN         676
FT                   /note="R->G: 60-70% zinc-induced amyloid-beta protein 28
FT                   aggregation."
FT                   /evidence="ECO:0000269|PubMed:10413512"
FT   MUTAGEN         681
FT                   /note="Y->F: 60-70% zinc-induced amyloid-beta protein 28
FT                   aggregation."
FT                   /evidence="ECO:0000269|PubMed:10413512"
FT   MUTAGEN         684
FT                   /note="H->R: Only 23% zinc-induced amyloid-beta protein 28
FT                   aggregation."
FT                   /evidence="ECO:0000269|PubMed:10413512"
FT   MUTAGEN         695
FT                   /note="V->C: Causes formation of an artifactual disulfide
FT                   bond with PSEN1."
FT                   /evidence="ECO:0000269|PubMed:30630874"
FT   MUTAGEN         704
FT                   /note="G->V: Reduced protein oxidation. No hippocampal
FT                   neuron toxicity."
FT   MUTAGEN         706
FT                   /note="M->L: Reduced lipid peroxidation inhibition."
FT                   /evidence="ECO:0000269|PubMed:10535332,
FT                   ECO:0000269|PubMed:9168929"
FT   MUTAGEN         706
FT                   /note="M->V: No free radical production. No hippocampal
FT                   neuron toxicity."
FT                   /evidence="ECO:0000269|PubMed:10535332,
FT                   ECO:0000269|PubMed:9168929"
FT   MUTAGEN         717
FT                   /note="V->C,S: Unchanged amyloid-beta protein 42/total
FT                   amyloid-beta ratio."
FT                   /evidence="ECO:0000269|PubMed:8886002"
FT   MUTAGEN         717
FT                   /note="V->K: Decreased amyloid-beta protein 42/total
FT                   amyloid-beta ratio."
FT                   /evidence="ECO:0000269|PubMed:8886002"
FT   MUTAGEN         717
FT                   /note="V->M: Increased amyloid-beta protein 42/40 ratio. No
FT                   change in apoptosis after caspase cleavage."
FT                   /evidence="ECO:0000269|PubMed:8886002"
FT   MUTAGEN         728
FT                   /note="Y->A: No effect on APBA1 nor APBB1 binding. Greatly
FT                   reduces the binding to APPBP2. APP internalization
FT                   unchanged. No change in amyloid-beta protein 42 secretion."
FT                   /evidence="ECO:0000269|PubMed:10383380,
FT                   ECO:0000269|PubMed:8887653, ECO:0000269|PubMed:9843960"
FT   MUTAGEN         739
FT                   /note="D->A: No cleavage by caspases during apoptosis."
FT                   /evidence="ECO:0000269|PubMed:10319819,
FT                   ECO:0000269|PubMed:10742146, ECO:0000269|PubMed:12214090"
FT   MUTAGEN         739
FT                   /note="D->N: No effect on FADD-induced apoptosis."
FT                   /evidence="ECO:0000269|PubMed:10319819,
FT                   ECO:0000269|PubMed:10742146, ECO:0000269|PubMed:12214090"
FT   MUTAGEN         743
FT                   /note="T->A: Greatly reduces the binding to SHC1 and APBB
FT                   family members; no effect on NGF-stimulated neurite
FT                   extension. Loss of phosphorylation by LRRK2."
FT                   /evidence="ECO:0000269|PubMed:10341243,
FT                   ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218,
FT                   ECO:0000269|PubMed:11877420, ECO:0000269|PubMed:28720718"
FT   MUTAGEN         743
FT                   /note="T->E: Reduced NGF-stimulated neurite extension. No
FT                   effect on APP maturation."
FT                   /evidence="ECO:0000269|PubMed:10341243,
FT                   ECO:0000269|PubMed:11146006, ECO:0000269|PubMed:11517218,
FT                   ECO:0000269|PubMed:11877420"
FT   MUTAGEN         756
FT                   /note="G->A: APP internalization unchanged. No change in
FT                   amyloid-beta protein 42 secretion."
FT                   /evidence="ECO:0000269|PubMed:10383380"
FT   MUTAGEN         757..762
FT                   /note="YENPTY->AENPTA: No effect on C99 interaction with
FT                   SORL1."
FT                   /evidence="ECO:0000269|PubMed:16407538"
FT   MUTAGEN         757
FT                   /note="Y->A: Little APP internalization. Reduced amyloid-
FT                   beta protein 42 secretion."
FT                   /evidence="ECO:0000269|PubMed:10383380,
FT                   ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420,
FT                   ECO:0000269|PubMed:8887653"
FT   MUTAGEN         757
FT                   /note="Y->G: Loss of binding to MAPK8IP1, APBA1, APBB1,
FT                   APPBP2 and SHC1."
FT                   /evidence="ECO:0000269|PubMed:10383380,
FT                   ECO:0000269|PubMed:11724784, ECO:0000269|PubMed:11877420,
FT                   ECO:0000269|PubMed:8887653"
FT   MUTAGEN         759
FT                   /note="N->A: No binding to APBA1, no effect on APBB1
FT                   binding. Little APP internalization. Reduced amyloid-beta
FT                   protein 42 secretion."
FT                   /evidence="ECO:0000269|PubMed:10383380,
FT                   ECO:0000269|PubMed:8887653"
FT   MUTAGEN         760
FT                   /note="P->A: Little APP internalization. Reduced amyloid-
FT                   beta protein 42 secretion."
FT                   /evidence="ECO:0000269|PubMed:10383380"
FT   MUTAGEN         762
FT                   /note="Y->A: Loss of binding to APBA1 and APBB1. APP
FT                   internalization unchanged. No change in amyloid-beta
FT                   protein 42 secretion."
FT                   /evidence="ECO:0000269|PubMed:10383380,
FT                   ECO:0000269|PubMed:8887653"
FT   CONFLICT        15..16
FT                   /note="AR -> VW (in Ref. 3; CAA31830)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        647
FT                   /note="D -> E (in Ref. 36; AAA51722)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        724
FT                   /note="Missing (in Ref. 23; AAB26263/AAB26264)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        731
FT                   /note="I -> N (in Ref. 23; AAB26263/AAB26264/AAB26265)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        757
FT                   /note="Y -> S (in Ref. 31; AAA35540)"
FT                   /evidence="ECO:0000305"
FT   HELIX           26..28
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          33..35
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          43..45
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   TURN            47..49
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          52..54
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          56..58
FT                   /evidence="ECO:0007829|PDB:4PWQ"
FT   HELIX           66..76
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          82..87
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          92..94
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          97..99
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   TURN            100..102
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          103..106
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          110..112
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          115..119
FT                   /evidence="ECO:0007829|PDB:4PQD"
FT   STRAND          134..139
FT                   /evidence="ECO:0007829|PDB:2FMA"
FT   HELIX           147..160
FT                   /evidence="ECO:0007829|PDB:2FMA"
FT   STRAND          163..174
FT                   /evidence="ECO:0007829|PDB:2FMA"
FT   TURN            175..177
FT                   /evidence="ECO:0007829|PDB:2FMA"
FT   STRAND          178..188
FT                   /evidence="ECO:0007829|PDB:2FMA"
FT   HELIX           288..292
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   STRAND          299..301
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   STRAND          304..310
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   TURN            311..314
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   STRAND          315..321
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   STRAND          323..325
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   STRAND          331..333
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   HELIX           334..341
FT                   /evidence="ECO:0007829|PDB:1AAP"
FT   HELIX           374..380
FT                   /evidence="ECO:0007829|PDB:3NYL"
FT   HELIX           389..418
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   STRAND          421..423
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   HELIX           425..480
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   STRAND          482..484
FT                   /evidence="ECO:0007829|PDB:3NYJ"
FT   HELIX           487..518
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   HELIX           520..546
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   HELIX           547..550
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   HELIX           552..566
FT                   /evidence="ECO:0007829|PDB:3UMH"
FT   HELIX           615..618
FT                   /evidence="ECO:0007829|PDB:5BUO"
FT   STRAND          620..622
FT                   /evidence="ECO:0007829|PDB:5BUO"
FT   HELIX           673..675
FT                   /evidence="ECO:0007829|PDB:4OJF"
FT   TURN            677..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
//
ID   APOE_HUMAN              Reviewed;         317 AA.
AC   P02649; B2RC15; C0JYY5; Q9P2S4;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   28-JAN-2026, entry version 278.
DE   RecName: Full=Apolipoprotein E {ECO:0000305};
DE            Short=Apo-E;
DE   Flags: Precursor;
GN   Name=APOE {ECO:0000312|HGNC:HGNC:613};
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] (ALLELE APOE*3).
RX   PubMed=6325438; DOI=10.1016/s0021-9258(18)91039-2;
RA   Zannis V.I., McPherson J., Goldberger G., Karathanasis S.K., Breslow J.L.;
RT   "Synthesis, intracellular processing, and signal peptide of human
RT   apolipoprotein E.";
RL   J. Biol. Chem. 259:5495-5499(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS THR-117 AND PRO-170.
RX   PubMed=6327682; DOI=10.1016/s0021-9258(20)82169-3;
RA   McLean J.W., Elshourbagy N.A., Chang D.J., Mahley R.W., Taylor J.M.;
RT   "Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing of a
RT   new variant.";
RL   J. Biol. Chem. 259:6498-6504(1984).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*4), AND VARIANT AD2 ARG-130.
RX   PubMed=2987927; DOI=10.1073/pnas.82.10.3445;
RA   Paik Y.-K., Chang D.J., Reardon C.A., Davies G.E., Mahley R.W.,
RA   Taylor J.M.;
RT   "Nucleotide sequence and structure of the human apolipoprotein E gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:3445-3449(1985).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*2), AND VARIANT CYS-176.
RX   PubMed=3243553; DOI=10.1016/0888-7543(88)90130-9;
RA   Emi M., Wu L.L., Robertson M.A., Myers R.L., Hegele R.A., Williams R.R.,
RA   White R., Lalouel J.-M.;
RT   "Genotyping and sequence analysis of apolipoprotein E isoforms.";
RL   Genomics 3:373-379(1988).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3).
RX   PubMed=10520737; DOI=10.3109/10425179809086433;
RA   Freitas E.M., Zhang W.J., Lalonde J.P., Tay G.K., Gaudieri S.,
RA   Ashworth L.K., Van Bockxmeer F.M., Dawkins R.L.;
RT   "Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene:
RT   PEREC1.";
RL   DNA Seq. 9:89-100(1998).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3), AND VARIANTS PRO-46;
RP   ARG-130; CYS-163 AND CYS-176.
RX   PubMed=11042151; DOI=10.1101/gr.146900;
RA   Nickerson D.A., Taylor S.L., Fullerton S.M., Weiss K.M., Clark A.G.,
RA   Stengard J.H., Salomaa V., Boerwinkle E., Sing C.F.;
RT   "Sequence diversity and large-scale typing of SNPs in the human
RT   apolipoprotein E gene.";
RL   Genome Res. 10:1532-1545(2000).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE APOE*3).
RC   TISSUE=Cerebellum;
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   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3).
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE APOE*3).
RC   TISSUE=Eye;
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   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-78, AND VARIANT HIS-64.
RC   TISSUE=Blood;
RA   Imura T., Kimura H., Kawasaki M.;
RT   "A new apolipoprotein E variant (Gln46-->His).";
RL   Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 99-317 (ALLELE APOE*3).
RX   PubMed=6897404; DOI=10.1016/s0021-9258(18)33328-3;
RA   Breslow J.L., McPherson J., Nussbaum A.L., Williams H.W., Lofquist-Kahl F.,
RA   Karathanasis S.K., Zannis V.I.;
RT   "Identification and DNA sequence of a human apolipoprotein E cDNA clone.";
RL   J. Biol. Chem. 257:14639-14641(1982).
RN   [12]
RP   ERRATUM OF PUBMED:6897404.
RA   Breslow J.L., McPherson J., Nussbaum A.L., Williams H.W., Lofquist-Kahl F.,
RA   Karathanasis S.K., Zannis V.I.;
RL   J. Biol. Chem. 258:11422-11422(1983).
RN   [13]
RP   PROTEIN SEQUENCE OF 19-317 (ALLELE APOE*2).
RX   PubMed=7068630; DOI=10.1016/s0021-9258(18)34702-1;
RA   Rall S.C. Jr., Weisgraber K.H., Mahley R.W.;
RT   "Human apolipoprotein E. The complete amino acid sequence.";
RL   J. Biol. Chem. 257:4171-4178(1982).
RN   [14]
RP   FUNCTION IN LIPOPROTEINS CONVERSION.
RX   PubMed=6860692; DOI=10.1016/0005-2760(83)90047-4;
RA   Marcel Y.L., Vezina C., Milne R.W.;
RT   "Cholesteryl ester and apolipoprotein E transfer between human high density
RT   lipoproteins and chylomicrons.";
RL   Biochim. Biophys. Acta 750:411-417(1983).
RN   [15]
RP   HEPARIN-BINDING SITES.
RX   PubMed=3947350; DOI=10.1016/s0006-291x(86)80489-2;
RA   Cardin A.D., Hirose N., Blankenship D.T., Jackson R.L., Harmony J.A.K.,
RA   Sparrow D.A., Sparrow J.T.;
RT   "Binding of a high reactive heparin to human apolipoprotein E:
RT   identification of two heparin-binding domains.";
RL   Biochem. Biophys. Res. Commun. 134:783-789(1986).
RN   [16]
RP   TISSUE SPECIFICITY.
RX   PubMed=3115992; DOI=10.1016/s0021-9258(18)47945-8;
RA   Pitas R.E., Boyles J.K., Lee S.H., Hui D., Weisgraber K.H.;
RT   "Lipoproteins and their receptors in the central nervous system.
RT   Characterization of the lipoproteins in cerebrospinal fluid and
RT   identification of apolipoprotein B,E(LDL) receptors in the brain.";
RL   J. Biol. Chem. 262:14352-14360(1987).
RN   [17]
RP   INTERACTION WITH SORL1.
RX   PubMed=30448281; DOI=10.1016/j.cca.2018.11.024;
RA   Yano K., Hirayama S., Misawa N., Furuta A., Ueno T., Motoi Y., Seino U.,
RA   Ebinuma H., Ikeuchi T., Schneider W.J., Bujo H., Miida T.;
RT   "Soluble LR11 competes with amyloid beta in binding to cerebrospinal fluid-
RT   high-density lipoprotein.";
RL   Clin. Chim. Acta 489:29-34(2019).
RN   [18]
RP   CHARACTERIZATION OF VARIANTS SER-154 AND PRO-170, AND MUTAGENESIS OF
RP   SER-157; HIS-158; LYS-161; LEU-162; LEU-167 AND ARG-168.
RX   PubMed=2831187; DOI=10.1016/s0021-9258(18)68957-4;
RA   Lalazar A., Weisgraber K.H., Rall S.C. Jr., Giladi H., Innerarity T.L.,
RA   Levanon A.Z., Boyles J.K., Amit B., Gorecki M., Mahley R.W.;
RT   "Site-specific mutagenesis of human apolipoprotein E. Receptor binding
RT   activity of variants with single amino acid substitutions.";
RL   J. Biol. Chem. 263:3542-3545(1988).
RN   [19]
RP   SUBCELLULAR LOCATION, GLYCOSYLATION AT THR-212, AND MUTAGENESIS OF THR-212.
RX   PubMed=2498325; DOI=10.1016/s0021-9258(18)81907-x;
RA   Wernette-Hammond M.E., Lauer S.J., Corsini A., Walker D., Taylor J.M.,
RA   Rall S.C. Jr.;
RT   "Glycosylation of human apolipoprotein E. The carbohydrate attachment site
RT   is threonine 194.";
RL   J. Biol. Chem. 264:9094-9101(1989).
RN   [20]
RP   FUNCTION IN VLDL CLEARANCE.
RX   PubMed=2762297; DOI=10.1073/pnas.86.15.5810;
RA   Kowal R.C., Herz J., Goldstein J.L., Esser V., Brown M.S.;
RT   "Low density lipoprotein receptor-related protein mediates uptake of
RT   cholesteryl esters derived from apoprotein E-enriched lipoproteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:5810-5814(1989).
RN   [21]
RP   REGION, AND CHARACTERIZATION OF VARIANT ARG-130 AND ARG-176.
RX   PubMed=2280190;
RA   Weisgraber K.H.;
RT   "Apolipoprotein E distribution among human plasma lipoproteins: role of the
RT   cysteine-arginine interchange at residue 112.";
RL   J. Lipid Res. 31:1503-1511(1990).
RN   [22]
RP   FUNCTION IN CHYLOMICRONS CLEARANCE, AND SUBCELLULAR LOCATION.
RX   PubMed=1911868; DOI=10.1016/0005-2760(91)90138-8;
RA   Arnon R., Sehayek E., Vogel T., Eisenberg S.;
RT   "Effects of exogenous apo E-3 and of cholesterol-enriched meals on the
RT   cellular metabolism of human chylomicrons and their remnants.";
RL   Biochim. Biophys. Acta 1085:336-342(1991).
RN   [23]
RP   FUNCTION IN VLDL AND IDL CLEARANCE.
RX   PubMed=1917954; DOI=10.1016/s0021-9258(18)55263-7;
RA   Sehayek E., Eisenberg S.;
RT   "Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent
RT   cellular metabolism of human triglyceride-rich lipoproteins through the low
RT   density lipoprotein receptor pathway.";
RL   J. Biol. Chem. 266:18259-18267(1991).
RN   [24]
RP   SUBUNIT, SUBCELLULAR LOCATION, AND REGION.
RX   PubMed=8340399; DOI=10.1016/s0021-9258(18)82318-3;
RA   Westerlund J.A., Weisgraber K.H.;
RT   "Discrete carboxyl-terminal segments of apolipoprotein E mediate
RT   lipoprotein association and protein oligomerization.";
RL   J. Biol. Chem. 268:15745-15750(1993).
RN   [25]
RP   INTERACTION WITH APP/A4 AMYLOID-BETA PEPTIDE, AND CHARACTERIZATION OF
RP   VARIANT AD2 ARG-130.
RX   PubMed=8367470; DOI=10.1073/pnas.90.17.8098;
RA   Strittmatter W.J., Weisgraber K.H., Huang D.Y., Dong L.M., Salvesen G.S.,
RA   Pericak-Vance M., Schmechel D., Saunders A.M., Goldgaber D., Roses A.D.;
RT   "Binding of human apolipoprotein E to synthetic amyloid beta peptide:
RT   isoform-specific effects and implications for late-onset Alzheimer
RT   disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:8098-8102(1993).
RN   [26]
RP   INTERACTION WITH MAP2, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX   PubMed=7891887; DOI=10.1016/0304-3940(94)90204-6;
RA   Huang D.Y., Goedert M., Jakes R., Weisgraber K.H., Garner C.C.,
RA   Saunders A.M., Pericak-Vance M.A., Schmechel D.E., Roses A.D.,
RA   Strittmatter W.J.;
RT   "Isoform-specific interactions of apolipoprotein E with the microtubule-
RT   associated protein MAP2c: implications for Alzheimer's disease.";
RL   Neurosci. Lett. 182:55-58(1994).
RN   [27]
RP   INTERACTION WITH MAPT, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX   PubMed=7972031; DOI=10.1073/pnas.91.23.11183;
RA   Strittmatter W.J., Saunders A.M., Goedert M., Weisgraber K.H., Dong L.M.,
RA   Jakes R., Huang D.Y., Pericak-Vance M., Schmechel D., Roses A.D.;
RT   "Isoform-specific interactions of apolipoprotein E with microtubule-
RT   associated protein tau: implications for Alzheimer disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:11183-11186(1994).
RN   [28]
RP   FUNCTION, AND LRP2-BINDING.
RX   PubMed=7768901; DOI=10.1074/jbc.270.22.13070;
RA   Kounnas M.Z., Loukinova E.B., Stefansson S., Harmony J.A.K., Brewer B.H.,
RA   Strickland D.K., Argraves W.S.;
RT   "Identification of glycoprotein 330 as an endocytic receptor for
RT   apolipoprotein J/clusterin.";
RL   J. Biol. Chem. 270:13070-13075(1995).
RN   [29]
RP   FUNCTION IN NEURITE OUTGROWTH, LRP-BINDING, AND CHARACTERIZATION OF VARIANT
RP   AD2 ARG-130.
RX   PubMed=8939961; DOI=10.1074/jbc.271.47.30121;
RA   Fagan A.M., Bu G., Sun Y., Daugherty A., Holtzman D.M.;
RT   "Apolipoprotein E-containing high density lipoprotein promotes neurite
RT   outgrowth and is a ligand for the low density lipoprotein receptor-related
RT   protein.";
RL   J. Biol. Chem. 271:30121-30125(1996).
RN   [30]
RP   FUNCTION IN HDL CLEARANCE, AND HEPARAN SULFATE-BINDING.
RX   PubMed=9395455; DOI=10.1074/jbc.272.50.31285;
RA   Ji Z.S., Dichek H.L., Miranda R.D., Mahley R.W.;
RT   "Heparan sulfate proteoglycans participate in hepatic lipase and
RT   apolipoprotein E-mediated binding and uptake of plasma lipoproteins,
RT   including high density lipoproteins.";
RL   J. Biol. Chem. 272:31285-31292(1997).
RN   [31]
RP   FUNCTION, HEPARAN-SULFATE-BINDING, AND SUBCELLULAR LOCATION.
RX   PubMed=9488694; DOI=10.1074/jbc.273.10.5645;
RA   Burgess J.W., Gould D.R., Marcel Y.L.;
RT   "The HepG2 extracellular matrix contains separate heparinase- and lipid-
RT   releasable pools of ApoE. Implications for hepatic lipoprotein
RT   metabolism.";
RL   J. Biol. Chem. 273:5645-5654(1998).
RN   [32]
RP   TISSUE SPECIFICITY.
RX   PubMed=10027417; DOI=10.1016/s0002-9440(10)65305-9;
RA   Xu P.T., Gilbert J.R., Qiu H.L., Ervin J., Rothrock-Christian T.R.,
RA   Hulette C., Schmechel D.E.;
RT   "Specific regional transcription of apolipoprotein E in human brain
RT   neurons.";
RL   Am. J. Pathol. 154:601-611(1999).
RN   [33]
RP   GLYCATION AT LYS-93, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=10452964; DOI=10.1016/s0925-4439(99)00047-2;
RA   Shuvaev V.V., Fujii J., Kawasaki Y., Itoh H., Hamaoka R., Barbier A.,
RA   Ziegler O., Siest G., Taniguchi N.;
RT   "Glycation of apolipoprotein E impairs its binding to heparin:
RT   identification of the major glycation site.";
RL   Biochim. Biophys. Acta 1454:296-308(1999).
RN   [34]
RP   PTM, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX   PubMed=11447277; DOI=10.1073/pnas.151254698;
RA   Huang Y., Liu X.Q., Wyss-Coray T., Brecht W.J., Sanan D.A., Mahley R.W.;
RT   "Apolipoprotein E fragments present in Alzheimer's disease brains induce
RT   neurofibrillary tangle-like intracellular inclusions in neurons.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:8838-8843(2001).
RN   [35]
RP   FUNCTION, LRP8-BINDING, AND CHARACTERIZATION OF VARIANT CYS-176.
RX   PubMed=12950167; DOI=10.1021/bi027093c;
RA   Li X., Kypreos K., Zanni E.E., Zannis V.;
RT   "Domains of apoE required for binding to apoE receptor 2 and to
RT   phospholipids: implications for the functions of apoE in the brain.";
RL   Biochemistry 42:10406-10417(2003).
RN   [36]
RP   FUNCTION IN REVERSE CHOLESTEROL TRANSPORT, AND INTERACTION WITH ABCA1.
RX   PubMed=14754908; DOI=10.1194/jlr.m300418-jlr200;
RA   Krimbou L., Denis M., Haidar B., Carrier M., Marcil M., Genest J. Jr.;
RT   "Molecular interactions between apoE and ABCA1: impact on apoE
RT   lipidation.";
RL   J. Lipid Res. 45:839-848(2004).
RN   [37]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-212; THR-307 AND SER-308, AND
RP   STRUCTURE OF CARBOHYDRATES.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=19838169; DOI=10.1038/nmeth.1392;
RA   Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA   Larson G.;
RT   "Enrichment of glycopeptides for glycan structure and attachment site
RT   identification.";
RL   Nat. Methods 6:809-811(2009).
RN   [38]
RP   FUNCTION, LRP1-BINDING, AND REGION.
RX   PubMed=20030366; DOI=10.1021/bi9017208;
RA   Guttman M., Prieto J.H., Croy J.E., Komives E.A.;
RT   "Decoding of lipoprotein-receptor interactions: properties of ligand
RT   binding modules governing interactions with apolipoprotein E.";
RL   Biochemistry 49:1207-1216(2010).
RN   [39]
RP   GLYCOSYLATION AT SER-308.
RX   PubMed=20511397; DOI=10.1074/mcp.m900430-mcp200;
RA   Lee Y., Kockx M., Raftery M.J., Jessup W., Griffith R., Kritharides L.;
RT   "Glycosylation and sialylation of macrophage-derived human apolipoprotein E
RT   analyzed by SDS-PAGE and mass spectrometry: evidence for a novel site of
RT   glycosylation on Ser290.";
RL   Mol. Cell. Proteomics 9:1968-1981(2010).
RN   [40]
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   [41]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22905912; DOI=10.1021/pr300539b;
RA   Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA   Mariman E.C., Renes J.;
RT   "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL   J. Proteome Res. 11:4733-4743(2012).
RN   [42]
RP   FUNCTION IN LIPOPROTEIN CLEARANCE, AND HEPARAN-SULFATE PROTEOGLYCANS
RP   BINDING.
RX   PubMed=23676495; DOI=10.1172/jci67398;
RA   Gonzales J.C., Gordts P.L., Foley E.M., Esko J.D.;
RT   "Apolipoproteins E and AV mediate lipoprotein clearance by hepatic
RT   proteoglycans.";
RL   J. Clin. Invest. 123:2742-2751(2013).
RN   [43]
RP   GLYCOSYLATION AT THR-26; THR-36 AND SER-314, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=23234360; DOI=10.1021/pr300963h;
RA   Halim A., Ruetschi U., Larson G., Nilsson J.;
RT   "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT   of human cerebrospinal fluid glycoproteins.";
RL   J. Proteome Res. 12:573-584(2013).
RN   [44]
RP   FUNCTION IN CHOLESTEROL EFFLUX, AND INTERACTION WITH APP/A4 AMYLOID-BETA
RP   PEPTIDE.
RX   PubMed=23620513; DOI=10.1073/pnas.1220484110;
RA   Verghese P.B., Castellano J.M., Garai K., Wang Y., Jiang H., Shah A.,
RA   Bu G., Frieden C., Holtzman D.M.;
RT   "ApoE influences amyloid-beta (Abeta) clearance despite minimal apoE/Abeta
RT   association in physiological conditions.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:E1807-E1816(2013).
RN   [45]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147, 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   [46]
RP   INTERACTION WITH HCV ENVELOPE GLYCOPROTEIN E2 (MICROBIAL INFECTION), AND
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=25122793; DOI=10.1128/jvi.01660-14;
RA   Lee J.Y., Acosta E.G., Stoeck I.K., Long G., Hiet M.S., Mueller B.,
RA   Fackler O.T., Kallis S., Bartenschlager R.;
RT   "Apolipoprotein E likely contributes to a maturation step of infectious
RT   hepatitis C virus particles and interacts with viral envelope
RT   glycoproteins.";
RL   J. Virol. 88:12422-12437(2014).
RN   [47]
RP   PHOSPHORYLATION AT SER-147.
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   [48]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH PMEL.
RX   PubMed=26387950; DOI=10.1016/j.celrep.2015.08.057;
RA   van Niel G., Bergam P., Di Cicco A., Hurbain I., Lo Cicero A., Dingli F.,
RA   Palmulli R., Fort C., Potier M.C., Schurgers L.J., Loew D., Levy D.,
RA   Raposo G.;
RT   "Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment
RT   Cells.";
RL   Cell Rep. 13:43-51(2015).
RN   [49]
RP   FUNCTION IN APP TRANSCRIPTION, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX   PubMed=28111074; DOI=10.1016/j.cell.2016.12.044;
RA   Huang Y.A., Zhou B., Wernig M., Suedhof T.C.;
RT   "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and
RT   Abeta Secretion.";
RL   Cell 168:427-441(2017).
RN   [50]
RP   INTERACTION WITH HCV ENVELOPE GLYCOPROTEIN E2 (MICROBIAL INFECTION), AND
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=29695434; DOI=10.1128/jvi.00211-18;
RA   Kim J.Y., Ou J.J.;
RT   "Regulation of Apolipoprotein E Trafficking by Hepatitis C Virus-Induced
RT   Autophagy.";
RL   J. Virol. 92:e00211-e00218(2018).
RN   [51]
RP   FUNCTION, SUBCELLULAR LOCATION, AND ROLE IN TUMOR CELL INFILTRATION.
RX   PubMed=30333625; DOI=10.1038/s41586-018-0615-z;
RA   Deng M., Gui X., Kim J., Xie L., Chen W., Li Z., He L., Chen Y., Chen H.,
RA   Luo W., Lu Z., Xie J., Churchill H., Xu Y., Zhou Z., Wu G., Yu C., John S.,
RA   Hirayasu K., Nguyen N., Liu X., Huang F., Li L., Deng H., Tang H.,
RA   Sadek A.H., Zhang L., Huang T., Zou Y., Chen B., Zhu H., Arase H., Xia N.,
RA   Jiang Y., Collins R., You M.J., Homsi J., Unni N., Lewis C., Chen G.Q.,
RA   Fu Y.X., Liao X.C., An Z., Zheng J., Zhang N., Zhang C.C.;
RT   "LILRB4 signalling in leukaemia cells mediates T cell suppression and
RT   tumour infiltration.";
RL   Nature 562:605-609(2018).
RN   [52] {ECO:0007744|PDB:1LPE}
RP   X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 41-184, FUNCTION, AND REGION.
RX   PubMed=2063194; DOI=10.1126/science.2063194;
RA   Wilson C., Wardell M.R., Weisgraber K.H., Mahley R.W., Agard D.A.;
RT   "Three-dimensional structure of the LDL receptor-binding domain of human
RT   apolipoprotein E.";
RL   Science 252:1817-1822(1991).
RN   [53] {ECO:0007744|PDB:1LE4}
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 41-184 OF VARIANT AD2 ARG-130,
RP   CHARACTERIZATION OF VARIANT AD2 ARG-130, MUTAGENESIS OF ARG-79 AND GLU-127,
RP   AND REGION.
RX   PubMed=8071364; DOI=10.1016/s0021-9258(17)31797-0;
RA   Dong L.M., Wilson C., Wardell M.R., Simmons T., Mahley R.W.,
RA   Weisgraber K.H., Agard D.A.;
RT   "Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein
RT   preferences of the E3 and E4 isoforms.";
RL   J. Biol. Chem. 269:22358-22365(1994).
RN   [54] {ECO:0007744|PDB:1LE2}
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 41-184 OF VARIANT CYS-176, AND
RP   CHARACTERIZATION OF VARIANT CYS-176.
RX   PubMed=7994571; DOI=10.1016/s0969-2126(00)00072-1;
RA   Wilson C., Mau T., Weisgraber K.H., Wardell M.R., Mahley R.W., Agard D.A.;
RT   "Salt bridge relay triggers defective LDL receptor binding by a mutant
RT   apolipoprotein.";
RL   Structure 2:713-718(1994).
RN   [55] {ECO:0007744|PDB:1NFN, ECO:0007744|PDB:1NFO}
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 19-209 OF VARIANT CYS-176,
RP   MUTAGENESIS OF ASP-172, CHARACTERIZATION OF VARIANT CYS-176, FUNCTION, AND
RP   LDLR-BINDING.
RX   PubMed=8756331; DOI=10.1038/nsb0896-718;
RA   Dong L.-M., Parkin S., Trakhanov S.D., Rupp B., Simmons T., Arnold K.S.,
RA   Newhouse Y.M., Innerarity T.L., Weisgraber K.H.;
RT   "Novel mechanism for defective receptor binding of apolipoprotein E2 in
RT   type III hyperlipoproteinemia.";
RL   Nat. Struct. Biol. 3:718-722(1996).
RN   [56] {ECO:0007744|PDB:1BZ4, ECO:0007744|PDB:1OR2, ECO:0007744|PDB:1OR3}
RP   X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 19-183.
RX   PubMed=10850798; DOI=10.1110/ps.9.5.886;
RA   Segelke B.W., Forstner M., Knapp M., Trakhanov S.D., Parkin S.,
RA   Newhouse Y.M., Bellamy H.D., Weisgraber K.H., Rupp B.;
RT   "Conformational flexibility in the apolipoprotein E amino-terminal domain
RT   structure determined from three new crystal forms: implications for lipid
RT   binding.";
RL   Protein Sci. 9:886-897(2000).
RN   [57] {ECO:0007744|PDB:1B68}
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 19-209 OF VARIANT AD2 ARG-130.
RX   PubMed=11258893; DOI=10.1021/bi002417n;
RA   Dong J., Peters-Libeu C.A., Weisgraber K.H., Segelke B.W., Rupp B.,
RA   Capila I., Hernaiz M.J., LeBrun L.A., Linhardt R.J.;
RT   "Interaction of the N-terminal domain of apolipoprotein E4 with heparin.";
RL   Biochemistry 40:2826-2834(2001).
RN   [58] {ECO:0007744|PDB:2KNY}
RP   STRUCTURE BY NMR OF 147-167 IN COMPLEX WITH LRP1, FUNCTION, AND
RP   LRP1-BINDING.
RX   PubMed=20303980; DOI=10.1016/j.jmb.2010.03.022;
RA   Guttman M., Prieto J.H., Handel T.M., Domaille P.J., Komives E.A.;
RT   "Structure of the minimal interface between ApoE and LRP.";
RL   J. Mol. Biol. 398:306-319(2010).
RN   [59]
RP   VARIANT HLPP3 262-GLU-GLU-263 DELINS LYS-LYS.
RX   PubMed=2738044; DOI=10.1093/oxfordjournals.jbchem.a122618;
RA   Maeda H., Nakamura H., Kobori S., Okada M., Mori H., Niki H., Ogura T.,
RA   Hiraga S.;
RT   "Identification of human apolipoprotein E variant gene: apolipoprotein E7
RT   (Glu244,245----Lys244,245).";
RL   J. Biochem. 105:51-54(1989).
RN   [60]
RP   VARIANT LYS-21.
RX   PubMed=2760009; DOI=10.1093/oxfordjournals.jbchem.a122692;
RA   Maeda H., Nakamura H., Kobori S., Okada M., Niki H., Ogura T., Hiraga S.;
RT   "Molecular cloning of a human apolipoprotein E variant: E5 (Glu-3-->Lys).";
RL   J. Biochem. 105:491-493(1989).
RN   [61]
RP   VARIANTS HLPP3 ARG-130 AND GLU-VAL-GLN-ALA-MET-LEU-GLY-145 INS.
RX   PubMed=2556398; DOI=10.1016/s0021-9258(19)30067-5;
RA   Wardell M.R., Weisgraber K.H., Havekes L.M., Rall S.C. Jr.;
RT   "Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a
RT   tandem repeat of residues 121-127.";
RL   J. Biol. Chem. 264:21205-21210(1989).
RN   [62]
RP   VARIANT HLPP3 HIS-163.
RX   PubMed=2101409; DOI=10.2169/internalmedicine1962.29.587;
RA   Suehiro T., Yoshida K., Yamano T., Ohno F.;
RT   "Identification and characterization of a new variant of apolipoprotein E
RT   (apo E-Kochi).";
RL   Jpn. J. Med. 29:587-594(1990).
RN   [63]
RP   VARIANT CYS-246.
RX   PubMed=2341812;
RA   Wardell M.R., Rall S.C. Jr., Brennan S.O., Nye E.R., George P.M.,
RA   Janus E.D., Weisgraber K.H.;
RT   "Apolipoprotein E2-Dunedin (228 Arg replaced by Cys): an apolipoprotein E2
RT   variant with normal receptor-binding activity.";
RL   J. Lipid Res. 31:535-543(1990).
RN   [64]
RP   VARIANT HLPP3 GLN-164.
RX   PubMed=2313204;
RA   Smit M., de Knijff P., van der Kooij-Meijs E., Groenendijk C.,
RA   van den Maagdenberg A.M., Gevers Leuven J.A., Stalenhoef A.F., Stuyt P.M.,
RA   Frants R.R., Havekes L.M.;
RT   "Genetic heterogeneity in familial dysbetalipoproteinemia. The
RT   E2(lys146----gln) variant results in a dominant mode of inheritance.";
RL   J. Lipid Res. 31:45-53(1990).
RN   [65]
RP   VARIANTS HLPP3 LYS-31 AND CYS-163.
RX   PubMed=1674745; DOI=10.1016/s0021-9258(18)99249-5;
RA   Lohse P., Mann W.A., Stein E.A., Brewer H.B. Jr.;
RT   "Apolipoprotein E-4 Philadelphia (Glu-13-->Lys,Arg-145-->Cys). Homozygosity
RT   for two rare point mutations in the apolipoprotein E gene combined with
RT   severe type III hyperlipoproteinemia.";
RL   J. Biol. Chem. 266:10479-10484(1991).
RN   [66]
RP   VARIANT APOE5 FRENCH-CANADIAN LYS-31.
RX   PubMed=1713245;
RA   Mailly F., Xu C.F., Xhignesse M., Lussier-Cacan S., Talmud P.J.,
RA   Davignon J., Humphries S.E., Nestruck A.C.;
RT   "Characterization of a new apolipoprotein E5 variant detected in two
RT   French-Canadian subjects.";
RL   J. Lipid Res. 32:613-620(1991).
RN   [67]
RP   CHARACTERIZATION OF VARIANT LYS-21, FUNCTION, AND LDLR-BINDING.
RX   PubMed=1530612; DOI=10.1016/0006-291x(92)91321-g;
RA   Dong L.M., Yamamura T., Tajima S., Yamamoto A.;
RT   "Site-directed mutagenesis of an apolipoprotein E mutant, apo E5(Glu3----
RT   Lys) and its binding to low density lipoprotein receptors.";
RL   Biochem. Biophys. Res. Commun. 187:1180-1186(1992).
RN   [68]
RP   VARIANT HLPP3 228-TRP--HIS-317 DEL.
RX   PubMed=1361196;
RA   Lohse P., Brewer H.B. III, Meng M.S., Skarlatos S.I., LaRosa J.C.,
RA   Brewer H.B. Jr.;
RT   "Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due
RT   to a premature stop codon in the apolipoprotein E gene.";
RL   J. Lipid Res. 33:1583-1590(1992).
RN   [69]
RP   VARIANTS GLU-254; GLY-269; GLU-270; HIS-292 AND ARG-314.
RX   PubMed=8488843;
RA   van den Maagdenberg A.M.J.M., Weng W., de Bruijn I.H., de Knijff P.,
RA   Funke H., Smelt A.H.M., Leuven J.A.G., van 't Hooft F.M., Assmann G.,
RA   Hofker M.H., Havekes L.M., Frants R.R.;
RT   "Characterization of five new mutants in the carboxyl-terminal domain of
RT   human apolipoprotein E: no cosegregation with severe hyperlipidemia.";
RL   Am. J. Hum. Genet. 52:937-946(1993).
RN   [70]
RP   VARIANTS LYS-99 AND ARG-130.
RX   PubMed=8125051; DOI=10.1002/elps.11501401164;
RA   Ruzicka V., Maerz W., Russ A., Fisher E., Mondorf W., Gross W.;
RT   "Characterization of the gene for apolipoprotein E5-Frankfurt (Gln81->Lys,
RT   Cys112->Arg) by polymerase chain reaction, restriction isotyping, and
RT   temperature gradient gel electrophoresis.";
RL   Electrophoresis 14:1032-1037(1993).
RN   [71]
RP   CHARACTERIZATION OF VARIANT GLU-VAL-GLN-ALA-MET-LEU-GLY-145 INS.
RX   PubMed=8468528;
RA   Fazio S., Horie Y., Weisgraber K.H., Havekes L.M., Rall S.C. Jr.;
RT   "Preferential association of apolipoprotein E Leiden with very low density
RT   lipoproteins of human plasma.";
RL   J. Lipid Res. 34:447-453(1993).
RN   [72]
RP   INVOLVEMENT IN AD2, AND VARIANT AD2 ARG-130.
RX   PubMed=8346443; DOI=10.1126/science.8346443;
RA   Corder E.H., Saunders A.M., Strittmatter W.J., Schmechel D.E.,
RA   Gaskell P.C., Small G.W., Roses A.D., Haines J.L., Pericak-Vance M.A.;
RT   "Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's
RT   disease in late onset families.";
RL   Science 261:921-923(1993).
RN   [73]
RP   VARIANTS HLPP3 ARG-130; SER-154; CYS-160 AND CYS-176, AND VARIANT ASP-145.
RX   PubMed=8287539;
RA   Richard P., Thomas G., de Zulueta M.P., de Gennes J.-L., Thomas M.,
RA   Cassaigne A., Bereziat G., Iron A.;
RT   "Common and rare genotypes of human apolipoprotein E determined by specific
RT   restriction profiles of polymerase chain reaction-amplified DNA.";
RL   Clin. Chem. 40:24-29(1994).
RN   [74]
RP   VARIANTS HLPP3 LYS-31; ARG-130 AND CYS-154, AND VARIANTS ARG-102 AND
RP   GLN-152.
RX   PubMed=7833947; DOI=10.1002/humu.1380040303;
RA   de Knijff P., van den Maagdenberg A.M.J.M., Frants R.R., Havekes L.M.;
RT   "Genetic heterogeneity of apolipoprotein E and its influence on plasma
RT   lipid and lipoprotein levels.";
RL   Hum. Mutat. 4:178-194(1994).
RN   [75]
RP   VARIANT HLPP3 GLU-164, CHARACTERIZATION OF VARIANT HLPP3 GLU-164 AND
RP   CYS-176, FUNCTION, LDLR-BINDING, AND HEPARIN-BINDING.
RX   PubMed=7635945; DOI=10.1172/jci118096;
RA   Mann W.A., Lohse P., Gregg R.E., Ronan R., Hoeg J.M., Zech L.A.,
RA   Brewer H.B. Jr.;
RT   "Dominant expression of type III hyperlipoproteinemia. Pathophysiological
RT   insights derived from the structural and kinetic characteristics of ApoE-1
RT   (Lys146-->Glu).";
RL   J. Clin. Invest. 96:1100-1107(1995).
RN   [76]
RP   VARIANT GLN-242.
RX   PubMed=8664327; DOI=10.1016/0005-2760(96)00014-8;
RA   Moriyama K., Sasaki J., Takada Y., Arakawa F., Matsunaga A., Ito Y.,
RA   Arakawa K.;
RT   "Characterization of a novel variant of apolipoprotein E, E2 Fukuoka (Arg-
RT   224 --> Gln) in a hyperlipidemic patient with xanthomatosis.";
RL   Biochim. Biophys. Acta 1301:185-190(1996).
RN   [77]
RP   VARIANT LPG PRO-163.
RX   PubMed=9176854; DOI=10.1681/asn.v85820;
RA   Oikawa S., Matsunaga A., Saito T., Sato H., Seki T., Hoshi K., Hayasaka K.,
RA   Kotake H., Midorikawa H., Sekikawa A., Hara S., Abe K., Toyota T.,
RA   Jingami H., Nakamura H., Sasaki J.;
RT   "Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated
RT   with lipoprotein glomerulopathy.";
RL   J. Am. Soc. Nephrol. 8:820-823(1997).
RN   [78]
RP   VARIANTS ARG-130 AND GLY-269.
RX   PubMed=9360638; DOI=10.1016/s1383-5726(97)00009-5;
RA   Kang A.K., Jenkins D.J.A., Wolever T.M.S., Huff M.W., Maguire G.F.,
RA   Connelly P.W., Hegele R.A.;
RT   "Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients
RT   with hyperlipidemia and coronary heart disease.";
RL   Mutat. Res. 382:57-65(1997).
RN   [79]
RP   VARIANT LPG CYS-43.
RX   PubMed=10432380; DOI=10.1046/j.1523-1755.1999.00572.x;
RA   Matsunaga A., Sasaki J., Komatsu T., Kanatsu K., Tsuji E., Moriyama K.,
RA   Koga T., Arakawa K., Oikawa S., Saito T., Kita T., Doi T.;
RT   "A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein
RT   glomerulopathy.";
RL   Kidney Int. 56:421-427(1999).
RN   [80]
RP   CHARACTERIZATION OF VARIANT LPG PRO-163, AND CHARACTERIZATION OF VARIANT
RP   AD2 ARG-130.
RX   PubMed=10903326; DOI=10.1074/jbc.m005906200;
RA   Ishigaki Y., Oikawa S., Suzuki T., Usui S., Magoori K., Kim D.H.,
RA   Suzuki H., Sasaki J., Sasano H., Okazaki M., Toyota T., Saito T.,
RA   Yamamoto T.T.;
RT   "Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops
RT   lipoprotein glomerulopathy in ApoE-deficient mice.";
RL   J. Biol. Chem. 275:31269-31273(2000).
RN   [81]
RP   VARIANT SBHD LEU-167 DEL.
RX   PubMed=11095479; DOI=10.1210/jcem.85.11.6981;
RA   Nguyen T.T., Kruckeberg K.E., O'Brien J.F., Ji Z.-S., Karnes P.S.,
RA   Crotty T.B., Hay I.D., Mahley R.W., O'Brien T.;
RT   "Familial splenomegaly: macrophage hypercatabolism of lipoproteins
RT   associated with apolipoprotein E mutation [apolipoprotein E (delta149
RT   Leu)].";
RL   J. Clin. Endocrinol. Metab. 85:4354-4358(2000).
RN   [82]
RP   VARIANT VAL-124.
RX   PubMed=12864777; DOI=10.1046/j.1365-2362.2003.01180.x;
RA   Miserez A.R., Scharnagl H., Muller P.Y., Mirsaidi R., Stahelin H.B.,
RA   Monsch A., Marz W., Hoffmann M.M.;
RT   "Apolipoprotein E3Basel: new insights into a highly conserved protein
RT   region.";
RL   Eur. J. Clin. Invest. 33:677-685(2003).
RN   [83]
RP   VARIANTS ARG-130 AND CYS-176.
RX   PubMed=12966036; DOI=10.1093/hmg/ddg314;
RA   Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S.,
RA   Alvin G.B., Das K., Gilliam T.C.;
RT   "Association of extreme blood lipid profile phenotypic variation with 11
RT   reverse cholesterol transport genes and 10 non-genetic cardiovascular
RT   disease risk factors.";
RL   Hum. Mol. Genet. 12:2733-2743(2003).
RN   [84]
RP   VARIANT SBHD LEU-167 DEL.
RX   PubMed=16094309; DOI=10.1038/sj.ejhg.5201480;
RA   Faivre L., Saugier-Veber P., Pais de Barros J.-P., Verges B., Couret B.,
RA   Lorcerie B., Thauvin C., Charbonnier F., Huet F., Gambert P., Frebourg T.,
RA   Duvillard L.;
RT   "Variable expressivity of the clinical and biochemical phenotype associated
RT   with the apolipoprotein E p.Leu149del mutation.";
RL   Eur. J. Hum. Genet. 13:1186-1191(2005).
RN   [85]
RP   VARIANT LPG CYS-43.
RX   PubMed=18077821; DOI=10.1056/nejmc072088;
RA   Rovin B.H., Roncone D., McKinley A., Nadasdy T., Korbet S.M.,
RA   Schwartz M.M.;
RT   "APOE Kyoto mutation in European Americans with lipoprotein
RT   glomerulopathy.";
RL   N. Engl. J. Med. 357:2522-2524(2007).
RN   [86]
RP   VARIANT HIS-64, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=22028381; DOI=10.1093/jmcb/mjr024;
RA   Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X.,
RA   Zeng R., Wu J.R.;
RT   "Quantitative detection of single amino acid polymorphisms by targeted
RT   proteomics.";
RL   J. Mol. Cell Biol. 3:309-315(2011).
RN   [87]
RP   VARIANT HLPP3 SER-154, AND VARIANT SBHD LEU-167 DEL.
RX   PubMed=22481068; DOI=10.1016/j.atherosclerosis.2012.03.011;
RA   Solanas-Barca M., de Castro-Oros I., Mateo-Gallego R., Cofan M., Plana N.,
RA   Puzo J., Burillo E., Martin-Fuentes P., Ros E., Masana L., Pocovi M.,
RA   Civeira F., Cenarro A.;
RT   "Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and
RT   a clinical diagnosis of familial combined hyperlipidemia.";
RL   Atherosclerosis 222:449-455(2012).
RN   [88]
RP   VARIANT SBHD LEU-167 DEL.
RX   PubMed=24267230; DOI=10.1016/j.atherosclerosis.2013.09.007;
RA   Awan Z., Choi H.Y., Stitziel N., Ruel I., Bamimore M.A., Husa R.,
RA   Gagnon M.H., Wang R.H., Peloso G.M., Hegele R.A., Seidah N.G.,
RA   Kathiresan S., Genest J.;
RT   "APOE p.Leu167del mutation in familial hypercholesterolemia.";
RL   Atherosclerosis 231:218-222(2013).
RN   [89]
RP   VARIANT SBHD LEU-167 DEL.
RX   PubMed=22949395; DOI=10.1002/humu.22215;
RA   Marduel M., Ouguerram K., Serre V., Bonnefont-Rousselot D.,
RA   Marques-Pinheiro A., Erik Berge K., Devillers M., Luc G., Lecerf J.M.,
RA   Tosolini L., Erlich D., Peloso G.M., Stitziel N., Nitchke P., Jais J.P.,
RA   Abifadel M., Kathiresan S., Leren T.P., Rabes J.P., Boileau C., Varret M.;
RT   "Description of a large family with autosomal dominant hypercholesterolemia
RT   associated with the APOE p.Leu167del mutation.";
RL   Hum. Mutat. 34:83-87(2013).
RN   [90]
RP   VARIANTS PRO-46 AND ASP-145, VARIANT HLPP3 CYS-163, AND VARIANT SBHD
RP   LEU-167 DEL.
RX   PubMed=26802169; DOI=10.1194/jlr.p055699;
RA   Wintjens R., Bozon D., Belabbas K., Mbou F., Girardet J.P., Tounian P.,
RA   Jolly M., Boccara F., Cohen A., Karsenty A., Dubern B., Carel J.C.,
RA   Azar-Kolakez A., Feillet F., Labarthe F., Gorsky A.M., Horovitz A.,
RA   Tamarindi C., Kieffer P., Lienhardt A., Lascols O., Di Filippo M.,
RA   Dufernez F.;
RT   "Global molecular analysis and APOE mutations in a cohort of autosomal
RT   dominant hypercholesterolemia patients in France.";
RL   J. Lipid Res. 57:482-491(2016).
RN   [91]
RP   REVIEW, POLYMORPHISM, AND TISSUE SPECIFICITY.
RX   PubMed=25173806; DOI=10.1016/j.nbd.2014.08.025;
RA   Huang Y., Mahley R.W.;
RT   "Apolipoprotein E: structure and function in lipid metabolism,
RT   neurobiology, and Alzheimer's diseases.";
RL   Neurobiol. Dis. 72:3-12(2014).
RN   [92]
RP   REVIEW, FUNCTION, AND PTM.
RX   PubMed=29516132; DOI=10.1007/s00109-018-1632-y;
RA   Kockx M., Traini M., Kritharides L.;
RT   "Cell-specific production, secretion, and function of apolipoprotein E.";
RL   J. Mol. Med. 96:361-371(2018).
RN   [93]
RP   POLYMORPHISM, AND VARIANT ARG-130.
RX   PubMed=33450186; DOI=10.1016/j.stem.2020.12.018;
RA   Wang C., Zhang M., Garcia G. Jr., Tian E., Cui Q., Chen X., Sun G.,
RA   Wang J., Arumugaswami V., Shi Y.;
RT   "ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response.";
RL   Cell Stem Cell 0:0-0(2021).
CC   -!- FUNCTION: APOE is an apolipoprotein, a protein associating with lipid
CC       particles, that mainly functions in lipoprotein-mediated lipid
CC       transport between organs via the plasma and interstitial fluids
CC       (PubMed:14754908, PubMed:1911868, PubMed:6860692). APOE is a core
CC       component of plasma lipoproteins and is involved in their production,
CC       conversion and clearance (PubMed:14754908, PubMed:1911868,
CC       PubMed:1917954, PubMed:23620513, PubMed:2762297, PubMed:6860692,
CC       PubMed:9395455). Apolipoproteins are amphipathic molecules that
CC       interact both with lipids of the lipoprotein particle core and the
CC       aqueous environment of the plasma (PubMed:2762297, PubMed:6860692,
CC       PubMed:9395455). As such, APOE associates with chylomicrons,
CC       chylomicron remnants, very low density lipoproteins (VLDL) and
CC       intermediate density lipoproteins (IDL) but shows a preferential
CC       binding to high-density lipoproteins (HDL) (PubMed:1911868,
CC       PubMed:6860692). It also binds a wide range of cellular receptors
CC       including the LDL receptor/LDLR, the LDL receptor-related proteins
CC       LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR
CC       that mediate the cellular uptake of the APOE-containing lipoprotein
CC       particles (PubMed:12950167, PubMed:1530612, PubMed:1917954,
CC       PubMed:20030366, PubMed:20303980, PubMed:2063194, PubMed:2762297,
CC       PubMed:7635945, PubMed:7768901, PubMed:8756331, PubMed:8939961).
CC       Finally, APOE also has a heparin-binding activity and binds heparan-
CC       sulfate proteoglycans on the surface of cells, a property that supports
CC       the capture and the receptor-mediated uptake of APOE-containing
CC       lipoproteins by cells (PubMed:23676495, PubMed:7635945, PubMed:9395455,
CC       PubMed:9488694). A main function of APOE is to mediate lipoprotein
CC       clearance through the uptake of chylomicrons, VLDLs, and HDLs by
CC       hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:23676495,
CC       PubMed:29516132, PubMed:9395455). APOE is also involved in the
CC       biosynthesis by the liver of VLDLs as well as their uptake by
CC       peripheral tissues ensuring the delivery of triglycerides and energy
CC       storage in muscle, heart and adipose tissues (PubMed:2762297,
CC       PubMed:29516132). By participating in the lipoprotein-mediated
CC       distribution of lipids among tissues, APOE plays a critical role in
CC       plasma and tissues lipid homeostasis (PubMed:1917954, PubMed:2762297,
CC       PubMed:29516132). APOE is also involved in two steps of reverse
CC       cholesterol transport, the HDLs-mediated transport of cholesterol from
CC       peripheral tissues to the liver, and thereby plays an important role in
CC       cholesterol homeostasis (PubMed:14754908, PubMed:23620513,
CC       PubMed:9395455). First, it is functionally associated with ABCA1 in the
CC       biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513).
CC       Second, it is enriched in circulating HDLs and mediates their uptake by
CC       hepatocytes (PubMed:9395455). APOE also plays an important role in
CC       lipid transport in the central nervous system, regulating neuron
CC       survival and sprouting (PubMed:25173806, PubMed:8939961). APOE is also
CC       involved in innate and adaptive immune responses, controlling for
CC       instance the survival of myeloid-derived suppressor cells (By
CC       similarity). Binds to the immune cell receptor LILRB4
CC       (PubMed:30333625). APOE may also play a role in transcription
CC       regulation through a receptor-dependent and cholesterol-independent
CC       mechanism, that activates MAP3K12 and a non-canonical MAPK signal
CC       transduction pathway that results in enhanced AP-1-mediated
CC       transcription of APP (PubMed:28111074). {ECO:0000250|UniProtKB:P08226,
CC       ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:14754908,
CC       ECO:0000269|PubMed:1530612, ECO:0000269|PubMed:1911868,
CC       ECO:0000269|PubMed:1917954, ECO:0000269|PubMed:20030366,
CC       ECO:0000269|PubMed:20303980, ECO:0000269|PubMed:2063194,
CC       ECO:0000269|PubMed:23620513, ECO:0000269|PubMed:23676495,
CC       ECO:0000269|PubMed:2762297, ECO:0000269|PubMed:28111074,
CC       ECO:0000269|PubMed:30333625, ECO:0000269|PubMed:6860692,
CC       ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7768901,
CC       ECO:0000269|PubMed:8756331, ECO:0000269|PubMed:8939961,
CC       ECO:0000269|PubMed:9395455, ECO:0000269|PubMed:9488694,
CC       ECO:0000303|PubMed:25173806, ECO:0000303|PubMed:29516132}.
CC   -!- FUNCTION: (Microbial infection) Through its interaction with HCV
CC       envelope glycoprotein E2, participates in the attachment of HCV to
CC       HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface
CC       and to the assembly, maturation and infectivity of HCV viral particles
CC       (PubMed:25122793, PubMed:29695434). This interaction is probably
CC       promoted via the up-regulation of cellular autophagy by the virus
CC       (PubMed:29695434). {ECO:0000269|PubMed:25122793,
CC       ECO:0000269|PubMed:29695434}.
CC   -!- SUBUNIT: Homotetramer (PubMed:8340399). May interact with ABCA1;
CC       functionally associated with ABCA1 in the biogenesis of HDLs
CC       (PubMed:14754908). May interact with APP/A4 amyloid-beta peptide; the
CC       interaction is extremely stable in vitro but its physiological
CC       significance is unclear (PubMed:23620513, PubMed:8367470). May interact
CC       with MAPT (PubMed:7972031). May interact with MAP2 (PubMed:7891887). In
CC       the cerebrospinal fluid, interacts with secreted SORL1
CC       (PubMed:30448281). Interacts with PMEL; this allows the loading of PMEL
CC       luminal fragment on ILVs to induce fibril nucleation.
CC       {ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:23620513,
CC       ECO:0000269|PubMed:26387950, ECO:0000269|PubMed:30448281,
CC       ECO:0000269|PubMed:7891887, ECO:0000269|PubMed:7972031,
CC       ECO:0000269|PubMed:8340399, ECO:0000269|PubMed:8367470}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus (HCV)
CC       envelope glycoprotein E2; this interaction is required for HCV
CC       infectivity and production. {ECO:0000269|PubMed:25122793,
CC       ECO:0000269|PubMed:29695434}.
CC   -!- INTERACTION:
CC       P02649; Q9UIJ7: AK3; NbExp=3; IntAct=EBI-1222467, EBI-3916527;
CC       P02649; Q06481-5: APLP2; NbExp=3; IntAct=EBI-1222467, EBI-25646567;
CC       P02649; PRO_0000000093 [P05067]: APP; NbExp=4; IntAct=EBI-1222467, EBI-2431589;
CC       P02649; Q9HBG4: ATP6V0A4; NbExp=3; IntAct=EBI-1222467, EBI-25832286;
CC       P02649; Q9NUB4: C20orf141; NbExp=3; IntAct=EBI-1222467, EBI-9088162;
CC       P02649; P02748: C9; NbExp=2; IntAct=EBI-1222467, EBI-6677628;
CC       P02649; Q16543: CDC37; NbExp=3; IntAct=EBI-1222467, EBI-295634;
CC       P02649; P08603: CFH; NbExp=8; IntAct=EBI-1222467, EBI-1223708;
CC       P02649; Q9UBD9: CLCF1; NbExp=3; IntAct=EBI-1222467, EBI-2880701;
CC       P02649; Q8IUW6: CLSTN3; NbExp=3; IntAct=EBI-1222467, EBI-25832219;
CC       P02649; P26441: CNTF; NbExp=3; IntAct=EBI-1222467, EBI-1050897;
CC       P02649; Q9H6J7-2: CSTPP1; NbExp=3; IntAct=EBI-1222467, EBI-13328871;
CC       P02649; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-1222467, EBI-3508943;
CC       P02649; Q9BQ95: ECSIT; NbExp=4; IntAct=EBI-1222467, EBI-712452;
CC       P02649; Q9Y6C2-2: EMILIN1; NbExp=3; IntAct=EBI-1222467, EBI-11748557;
CC       P02649; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-1222467, EBI-6425864;
CC       P02649; Q8IY40: GRIK2; NbExp=3; IntAct=EBI-1222467, EBI-25832107;
CC       P02649; O75409: H2AP; NbExp=3; IntAct=EBI-1222467, EBI-6447217;
CC       P02649; P00738: HP; NbExp=7; IntAct=EBI-1222467, EBI-1220767;
CC       P02649; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-1222467, EBI-1108377;
CC       P02649; P01130: LDLR; NbExp=4; IntAct=EBI-1222467, EBI-988319;
CC       P02649; P09382: LGALS1; NbExp=3; IntAct=EBI-1222467, EBI-1048875;
CC       P02649; Q07954: LRP1; NbExp=23; IntAct=EBI-1222467, EBI-1046087;
CC       P02649; Q14114: LRP8; NbExp=2; IntAct=EBI-1222467, EBI-2681187;
CC       P02649; Q14114-3: LRP8; NbExp=3; IntAct=EBI-1222467, EBI-25832196;
CC       P02649; P11137-4: MAP2; NbExp=3; IntAct=EBI-1222467, EBI-25832133;
CC       P02649; P10636-6: MAPT; NbExp=3; IntAct=EBI-1222467, EBI-7796455;
CC       P02649; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-1222467, EBI-9092052;
CC       P02649; P02795: MT2A; NbExp=3; IntAct=EBI-1222467, EBI-996616;
CC       P02649; Q53EL6: PDCD4; NbExp=3; IntAct=EBI-1222467, EBI-935824;
CC       P02649; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-1222467, EBI-438710;
CC       P02649; P52756: RBM5; NbExp=3; IntAct=EBI-1222467, EBI-714003;
CC       P02649; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-1222467, EBI-21535400;
CC       P02649; Q8WTV0-2: SCARB1; NbExp=3; IntAct=EBI-1222467, EBI-21529758;
CC       P02649; P37840: SNCA; NbExp=11; IntAct=EBI-1222467, EBI-985879;
CC       P02649; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-1222467, EBI-2510414;
CC       P02649; P50502: ST13; NbExp=3; IntAct=EBI-1222467, EBI-357285;
CC       P02649; O75069: TMCC2; NbExp=5; IntAct=EBI-1222467, EBI-726731;
CC       P02649; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-1222467, EBI-2505861;
CC       P02649; Q9NZC2: TREM2; NbExp=4; IntAct=EBI-1222467, EBI-14036387;
CC       P02649; Q6PID6: TTC33; NbExp=3; IntAct=EBI-1222467, EBI-2555404;
CC       P02649; Q8TBC4: UBA3; NbExp=3; IntAct=EBI-1222467, EBI-717567;
CC       P02649; Q9NYH9: UTP6; NbExp=3; IntAct=EBI-1222467, EBI-749211;
CC       P02649; P21796: VDAC1; NbExp=2; IntAct=EBI-1222467, EBI-354158;
CC       P02649; P17028: ZNF24; NbExp=3; IntAct=EBI-1222467, EBI-707773;
CC       P02649; PRO_0000037570 [P27958]; Xeno; NbExp=4; IntAct=EBI-1222467, EBI-6904269;
CC       PRO_0000001987; P10636: MAPT; NbExp=3; IntAct=EBI-9209835, EBI-366182;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2498325,
CC       ECO:0000269|PubMed:30333625}. Secreted, extracellular space
CC       {ECO:0000269|PubMed:8340399}. Secreted, extracellular space,
CC       extracellular matrix {ECO:0000269|PubMed:9488694}. Extracellular
CC       vesicle {ECO:0000269|PubMed:26387950}. Endosome, multivesicular body
CC       {ECO:0000269|PubMed:26387950}. Note=In the plasma, APOE is associated
CC       with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL
CC       lipoproteins (PubMed:1911868, PubMed:8340399). Lipid poor oligomeric
CC       APOE is associated with the extracellular matrix in a calcium- and
CC       heparan-sulfate proteoglycans-dependent manner (PubMed:9488694).
CC       Lipidation induces the release from the extracellular matrix
CC       (PubMed:9488694). Colocalizes with CD63 and PMEL at exosomes and in
CC       intraluminal vesicles within multivesicular endosomes.
CC       {ECO:0000269|PubMed:1911868, ECO:0000269|PubMed:26387950,
CC       ECO:0000269|PubMed:8340399, ECO:0000269|PubMed:9488694}.
CC   -!- TISSUE SPECIFICITY: Produced by several tissues and cell types and
CC       mainly found associated with lipid particles in the plasma, the
CC       interstitial fluid and lymph (PubMed:25173806). Mainly synthesized by
CC       liver hepatocytes (PubMed:25173806). Significant quantities are also
CC       produced in brain, mainly by astrocytes and glial cells in the cerebral
CC       cortex, but also by neurons in frontal cortex and hippocampus
CC       (PubMed:10027417, PubMed:3115992). It is also expressed by cells of the
CC       peripheral nervous system (PubMed:10027417, PubMed:25173806). Also
CC       expressed by adrenal gland, testis, ovary, skin, kidney, spleen and
CC       adipose tissue and macrophages in various tissues (PubMed:25173806).
CC       {ECO:0000269|PubMed:10027417, ECO:0000269|PubMed:3115992,
CC       ECO:0000303|PubMed:25173806}.
CC   -!- PTM: APOE exists as multiple glycosylated and sialylated glycoforms
CC       within cells and in plasma (PubMed:29516132). The extent of
CC       glycosylation and sialylation are tissue and context specific
CC       (PubMed:29516132). Plasma APOE undergoes desialylation and is less
CC       glycosylated and sialylated than the cellular form (PubMed:19838169,
CC       PubMed:20511397, PubMed:23234360, PubMed:2498325). Glycosylation is not
CC       required for proper expression and secretion (PubMed:2498325). O-
CC       glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-
CC       314 are minor glycosylation sites compared to Ser-308 (PubMed:19838169,
CC       PubMed:23234360). {ECO:0000269|PubMed:19838169,
CC       ECO:0000269|PubMed:20511397, ECO:0000269|PubMed:23234360,
CC       ECO:0000269|PubMed:2498325, ECO:0000303|PubMed:29516132}.
CC   -!- PTM: Glycated in plasma VLDL of normal subjects, and of hyperglycemic
CC       diabetic patients at a higher level (2-3 fold).
CC       {ECO:0000269|PubMed:10452964}.
CC   -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC       {ECO:0000269|PubMed:26091039}.
CC   -!- PTM: Undergoes C-terminal proteolytic processing in neurons. C-
CC       terminally truncated APOE has a tendency to form neurotoxic
CC       intracellular neurofibrillary tangle-like inclusions in neurons.
CC       {ECO:0000269|PubMed:11447277}.
CC   -!- POLYMORPHISM: There are three common APOE alleles identified:
CC       APOE*2/APOE-epsilon2/E2, APOE*3/APOE-epsilon3/E3, and APOE*4/APOE-
CC       epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms
CC       differentially present Cys and Arg residues at positions 130 and 176.
CC       The most common allele in the human population is APOE*3 which sequence
CC       is the one displayed in that entry with a Cys at position 130 and an
CC       Arg at position 176. Common APOE variants influence lipoprotein
CC       metabolism in healthy individuals. Additional variants have been
CC       described and are described relative to the three common alleles.
CC       Allele APOE*4 is strongly associated with risk for severe COVID-19,
CC       increases susceptibility to SARS-CoV-2 infection in neurons and
CC       astrocytes (PubMed:33450186). {ECO:0000269|PubMed:2987927,
CC       ECO:0000269|PubMed:3243553, ECO:0000269|PubMed:33450186,
CC       ECO:0000269|PubMed:6325438, ECO:0000303|PubMed:25173806}.
CC   -!- DISEASE: Hyperlipoproteinemia 3 (HLPP3) [MIM:617347]: A disorder
CC       characterized by the accumulation of intermediate-density lipoprotein
CC       particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical
CC       features include xanthomas, yellowish lipid deposits in the palmar
CC       crease, or less specific on tendons and on elbows. The disorder rarely
CC       manifests before the third decade in men. In women, it is usually
CC       expressed only after the menopause. {ECO:0000269|PubMed:1361196,
CC       ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:2101409,
CC       ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2313204,
CC       ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:26802169,
CC       ECO:0000269|PubMed:2738044, ECO:0000269|PubMed:7635945,
CC       ECO:0000269|PubMed:7833947, ECO:0000269|PubMed:8287539}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry. The vast majority of the patients are homozygous for APOE*2
CC       alleles. More severe cases of HLPP3 have also been observed in
CC       individuals heterozygous for rare APOE variants. The influence of APOE
CC       on lipid levels is often suggested to have major implications for the
CC       risk of coronary artery disease (CAD). Individuals carrying the common
CC       APOE*4 variant are at higher risk of CAD.
CC   -!- DISEASE: Alzheimer disease 2 (AD2) [MIM:104310]: A late-onset form of
CC       Alzheimer disease. Alzheimer disease is a neurodegenerative disorder
CC       characterized by progressive dementia, loss of cognitive abilities, and
CC       deposition of fibrillar amyloid proteins as intraneuronal
CC       neurofibrillary tangles, extracellular amyloid plaques and vascular
CC       amyloid deposits. The major constituents of these plaques are
CC       neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that
CC       are produced by the proteolysis of the transmembrane APP protein. The
CC       cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products,
CC       such as C31, are also implicated in neuronal death.
CC       {ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:11258893,
CC       ECO:0000269|PubMed:11447277, ECO:0000269|PubMed:28111074,
CC       ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887,
CC       ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364,
CC       ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470,
CC       ECO:0000269|PubMed:8939961}. Note=Disease susceptibility is associated
CC       with variants affecting the gene represented in this entry. The APOE*4
CC       allele (APOE form E4) is genetically associated with the common late
CC       onset familial and sporadic forms of Alzheimer disease. Risk for AD
CC       increased from 20% to 90% and mean age at onset decreased from 84 to 68
CC       years with increasing number of APOE*4 alleles in 42 families with late
CC       onset AD. Thus APOE*4 gene dose is a major risk factor for late onset
CC       AD and, in these families, homozygosity for APOE*4 was virtually
CC       sufficient to cause AD by age 80. The mechanism by which APOE*4
CC       participates in pathogenesis is not known.
CC       {ECO:0000269|PubMed:8346443}.
CC   -!- DISEASE: Sea-blue histiocyte disease (SBHD) [MIM:269600]: Characterized
CC       by splenomegaly, mild thrombocytopenia and, in the bone marrow,
CC       numerous histiocytes containing cytoplasmic granules which stain bright
CC       blue with the usual hematologic stains. The syndrome is the consequence
CC       of an inherited metabolic defect analogous to Gaucher disease and other
CC       sphingolipidoses. {ECO:0000269|PubMed:11095479,
CC       ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068,
CC       ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230,
CC       ECO:0000269|PubMed:26802169}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney
CC       disease characterized by proteinuria, progressive kidney failure, and
CC       distinctive lipoprotein thrombi in glomerular capillaries.
CC       {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:10903326,
CC       ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- MISCELLANEOUS: Binds to and activates LILRB4 on acute myeloid leukemia
CC       (AML) cells which leads to suppression of T cell proliferation and
CC       promotion of AML cell migration and infiltration.
CC       {ECO:0000269|PubMed:30333625}.
CC   -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Apolipoprotein E entry;
CC       URL="https://en.wikipedia.org/wiki/Apolipoprotein_E";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Tangled - Issue 83 of June
CC       2007;
CC       URL="https://www.proteinspotlight.org/back_issues/083";
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; M12529; AAB59518.1; -; mRNA.
DR   EMBL; K00396; AAB59546.1; -; mRNA.
DR   EMBL; M10065; AAB59397.1; -; Genomic_DNA.
DR   EMBL; AF050154; AAD02505.1; -; Genomic_DNA.
DR   EMBL; AF261279; AAG27089.1; -; Genomic_DNA.
DR   EMBL; AK314898; BAG37412.1; -; mRNA.
DR   EMBL; FJ525876; ACN81314.1; -; Genomic_DNA.
DR   EMBL; BC003557; AAH03557.1; -; mRNA.
DR   EMBL; AB035149; BAA96080.1; -; Genomic_DNA.
DR   CCDS; CCDS12647.1; -.
DR   PIR; A92478; LPHUE.
DR   RefSeq; NP_000032.1; NM_000041.4.
DR   RefSeq; NP_001289617.1; NM_001302688.1.
DR   RefSeq; NP_001289618.1; NM_001302689.2.
DR   RefSeq; NP_001289619.1; NM_001302690.2.
DR   RefSeq; NP_001289620.1; NM_001302691.2.
DR   PDB; 1B68; X-ray; 2.00 A; A=19-209.
DR   PDB; 1BZ4; X-ray; 1.85 A; A=40-183.
DR   PDB; 1EA8; X-ray; 1.95 A; A=19-209.
DR   PDB; 1GS9; X-ray; 1.70 A; A=19-183.
DR   PDB; 1H7I; X-ray; 1.90 A; A=19-209.
DR   PDB; 1LE2; X-ray; 3.00 A; A=41-184.
DR   PDB; 1LE4; X-ray; 2.50 A; A=41-184.
DR   PDB; 1LPE; X-ray; 2.25 A; A=41-184.
DR   PDB; 1NFN; X-ray; 1.80 A; A=19-209.
DR   PDB; 1NFO; X-ray; 2.00 A; A=19-209.
DR   PDB; 1OEF; NMR; -; A=281-304.
DR   PDB; 1OEG; NMR; -; A=285-307.
DR   PDB; 1OR2; X-ray; 2.50 A; A=19-183.
DR   PDB; 1OR3; X-ray; 1.73 A; A=19-183.
DR   PDB; 2KC3; NMR; -; A=19-201.
DR   PDB; 2KNY; NMR; -; A=147-167.
DR   PDB; 2L7B; NMR; -; A=19-317.
DR   PDB; 6IWB; X-ray; 2.50 A; A/C=41-186.
DR   PDB; 6NCN; X-ray; 1.82 A; A=19-180.
DR   PDB; 6NCO; X-ray; 1.71 A; A=19-180.
DR   PDB; 6V7M; X-ray; 2.00 A; A=1-100, B=101-183.
DR   PDB; 7FCR; X-ray; 1.40 A; A=19-209.
DR   PDB; 7FCS; X-ray; 1.60 A; A=19-209.
DR   PDB; 7UVJ; X-ray; 1.99 A; A/B=40-183.
DR   PDB; 8AX8; X-ray; 1.55 A; A=19-317.
DR   PDB; 8AX9; X-ray; 1.55 A; A=19-317.
DR   PDB; 8CDY; X-ray; 1.90 A; A=19-317.
DR   PDB; 8CE0; X-ray; 1.75 A; A=19-317.
DR   PDB; 8GRX; EM; 3.00 A; A/C=41-180.
DR   PDBsum; 1B68; -.
DR   PDBsum; 1BZ4; -.
DR   PDBsum; 1EA8; -.
DR   PDBsum; 1GS9; -.
DR   PDBsum; 1H7I; -.
DR   PDBsum; 1LE2; -.
DR   PDBsum; 1LE4; -.
DR   PDBsum; 1LPE; -.
DR   PDBsum; 1NFN; -.
DR   PDBsum; 1NFO; -.
DR   PDBsum; 1OEF; -.
DR   PDBsum; 1OEG; -.
DR   PDBsum; 1OR2; -.
DR   PDBsum; 1OR3; -.
DR   PDBsum; 2KC3; -.
DR   PDBsum; 2KNY; -.
DR   PDBsum; 2L7B; -.
DR   PDBsum; 6IWB; -.
DR   PDBsum; 6NCN; -.
DR   PDBsum; 6NCO; -.
DR   PDBsum; 6V7M; -.
DR   PDBsum; 7FCR; -.
DR   PDBsum; 7FCS; -.
DR   PDBsum; 7UVJ; -.
DR   PDBsum; 8AX8; -.
DR   PDBsum; 8AX9; -.
DR   PDBsum; 8CDY; -.
DR   PDBsum; 8CE0; -.
DR   PDBsum; 8GRX; -.
DR   AlphaFoldDB; P02649; -.
DR   BMRB; P02649; -.
DR   EMDB; EMD-34216; -.
DR   EMDB; EMD-53251; -.
DR   EMDB; EMD-53269; -.
DR   EMDB; EMD-53271; -.
DR   EMDB; EMD-53272; -.
DR   EMDB; EMD-53273; -.
DR   EMDB; EMD-53280; -.
DR   EMDB; EMD-53289; -.
DR   EMDB; EMD-53292; -.
DR   EMDB; EMD-53293; -.
DR   SASBDB; P02649; -.
DR   SMR; P02649; -.
DR   BioGRID; 106845; 168.
DR   CORUM; P02649; -.
DR   DIP; DIP-1120N; -.
DR   FunCoup; P02649; 41.
DR   IntAct; P02649; 102.
DR   MINT; P02649; -.
DR   STRING; 9606.ENSP00000252486; -.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB11886; Infigratinib.
DR   DrugBank; DB00877; Sirolimus.
DR   DrugBank; DB00460; Verteporfin.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   MoonDB; P02649; Predicted.
DR   TCDB; 9.B.445.2.1; the apolipoprotein a2 (alp-a2) family.
DR   CarbonylDB; P02649; -.
DR   GlyConnect; 648; 2 O-Linked glycans (5 sites).
DR   GlyCosmos; P02649; 8 sites, 5 glycans.
DR   GlyGen; P02649; 9 sites, 7 O-linked glycans (8 sites).
DR   iPTMnet; P02649; -.
DR   MetOSite; P02649; -.
DR   PhosphoSitePlus; P02649; -.
DR   SwissPalm; P02649; -.
DR   BioMuta; APOE; -.
DR   DMDM; 114039; -.
DR   CPTAC; non-CPTAC-1087; -.
DR   jPOST; P02649; -.
DR   MassIVE; P02649; -.
DR   PaxDb; 9606-ENSP00000252486; -.
DR   PeptideAtlas; P02649; -.
DR   ProteomicsDB; 51537; -.
DR   Pumba; P02649; -.
DR   ABCD; P02649; 7 sequenced antibodies.
DR   Antibodypedia; 3639; 1465 antibodies from 51 providers.
DR   DNASU; 348; -.
DR   YCharOS; P02649; Tested 14 antibodies from 8 manufacturers.
DR   Ensembl; ENST00000252486.9; ENSP00000252486.3; ENSG00000130203.11.
DR   GeneID; 348; -.
DR   KEGG; hsa:348; -.
DR   MANE-Select; ENST00000252486.9; ENSP00000252486.3; NM_000041.4; NP_000032.1.
DR   UCSC; uc002pab.4; human.
DR   AGR; HGNC:613; -.
DR   ClinPGx; PA55; -.
DR   CTD; 348; -.
DR   DisGeNET; 348; -.
DR   GeneCards; APOE; -.
DR   HGNC; HGNC:613; APOE.
DR   HPA; ENSG00000130203; Group enriched (adrenal gland, brain, liver).
DR   MalaCards; APOE; -.
DR   MIM; 104310; phenotype.
DR   MIM; 107741; gene.
DR   MIM; 269600; phenotype.
DR   MIM; 611771; phenotype.
DR   MIM; 617347; phenotype.
DR   OpenTargets; ENSG00000130203; -.
DR   Orphanet; 412; Dysbetalipoproteinemia.
DR   Orphanet; 329481; Lipoprotein glomerulopathy.
DR   VEuPathDB; HostDB:ENSG00000130203; -.
DR   eggNOG; ENOG502QVD6; Eukaryota.
DR   GeneTree; ENSGT00950000182929; -.
DR   HOGENOM; CLU_066029_0_0_1; -.
DR   InParanoid; P02649; -.
DR   OMA; GHMTDAR; -.
DR   OrthoDB; 9048614at2759; -.
DR   PAN-GO; P02649; 9 GO annotations based on evolutionary models.
DR   PhylomeDB; P02649; -.
DR   PathwayCommons; P02649; -.
DR   Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR   Reactome; R-HSA-3000480; Scavenging by Class A Receptors.
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-8864260; Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors.
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   Reactome; R-HSA-8963888; Chylomicron assembly.
DR   Reactome; R-HSA-8963901; Chylomicron remodeling.
DR   Reactome; R-HSA-8964026; Chylomicron clearance.
DR   Reactome; R-HSA-8964058; HDL remodeling.
DR   Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR   Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR   Reactome; R-HSA-977225; Amyloid fiber formation.
DR   SignaLink; P02649; -.
DR   SIGNOR; P02649; -.
DR   Agora; ENSG00000130203; Agora Nominated Target for Alzheimer's Disease.
DR   BioGRID-ORCS; 348; 20 hits in 1163 CRISPR screens.
DR   CD-CODE; DEE660B4; Stress granule.
DR   CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities.
DR   ChiTaRS; APOE; human.
DR   EvolutionaryTrace; P02649; -.
DR   GeneWiki; Apolipoprotein_E; -.
DR   GenomeRNAi; 348; -.
DR   Pharos; P02649; Tbio.
DR   PRO; PR:P02649; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; P02649; protein.
DR   Bgee; ENSG00000130203; Expressed in right adrenal gland cortex and 179 other cell types or tissues.
DR   ExpressionAtlas; P02649; baseline and differential.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0042627; C:chylomicron; IDA:BHF-UCL.
DR   GO; GO:0034360; C:chylomicron remnant; IDA:ARUK-UCL.
DR   GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; NAS:BHF-UCL.
DR   GO; GO:0034365; C:discoidal high-density lipoprotein particle; TAS:ARUK-UCL.
DR   GO; GO:0005769; C:early endosome; TAS:Reactome.
DR   GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:AgBase.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:ARUK-UCL.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:AgBase.
DR   GO; GO:0034364; C:high-density lipoprotein particle; IDA:UniProtKB.
DR   GO; GO:0034363; C:intermediate-density lipoprotein particle; IDA:UniProtKB.
DR   GO; GO:1990777; C:lipoprotein particle; IDA:ARUK-UCL.
DR   GO; GO:0034362; C:low-density lipoprotein particle; IDA:UniProtKB.
DR   GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0097487; C:multivesicular body, internal vesicle; IDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; NAS:BHF-UCL.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0043083; C:synaptic cleft; IDA:SynGO.
DR   GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:UniProtKB.
DR   GO; GO:0001540; F:amyloid-beta binding; IDA:UniProtKB.
DR   GO; GO:0016209; F:antioxidant activity; IDA:BHF-UCL.
DR   GO; GO:0120020; F:cholesterol transfer activity; IBA:GO_Central.
DR   GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR   GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR   GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR   GO; GO:0005319; F:lipid transporter activity; IDA:BHF-UCL.
DR   GO; GO:0071813; F:lipoprotein particle binding; IEA:Ensembl.
DR   GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:UniProtKB.
DR   GO; GO:0046911; F:metal chelating activity; IDA:BHF-UCL.
DR   GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IDA:BHF-UCL.
DR   GO; GO:0005543; F:phospholipid binding; IDA:BHF-UCL.
DR   GO; GO:0046983; F:protein dimerization activity; IPI:ARUK-UCL.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:ARUK-UCL.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:ARUK-UCL.
DR   GO; GO:0048018; F:receptor ligand activity; IDA:UniProt.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR   GO; GO:0005198; F:structural molecule activity; TAS:ARUK-UCL.
DR   GO; GO:0048156; F:tau protein binding; IPI:BHF-UCL.
DR   GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; IDA:BHF-UCL.
DR   GO; GO:0055090; P:acylglycerol homeostasis; IBA:GO_Central.
DR   GO; GO:0097113; P:AMPA glutamate receptor clustering; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0042982; P:amyloid precursor protein metabolic process; IDA:UniProtKB.
DR   GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR   GO; GO:0071402; P:cellular response to lipoprotein particle stimulus; IDA:UniProt.
DR   GO; GO:0006707; P:cholesterol catabolic process; IEA:Ensembl.
DR   GO; GO:0033344; P:cholesterol efflux; IDA:UniProtKB.
DR   GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR   GO; GO:0008203; P:cholesterol metabolic process; IDA:BHF-UCL.
DR   GO; GO:0034382; P:chylomicron remnant clearance; IDA:UniProtKB.
DR   GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR   GO; GO:0055089; P:fatty acid homeostasis; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR   GO; GO:0034380; P:high-density lipoprotein particle assembly; IDA:UniProtKB.
DR   GO; GO:0034384; P:high-density lipoprotein particle clearance; IDA:BHF-UCL.
DR   GO; GO:0034375; P:high-density lipoprotein particle remodeling; IGI:BHF-UCL.
DR   GO; GO:0044794; P:host-mediated activation of viral process; IMP:AgBase.
DR   GO; GO:0071831; P:intermediate-density lipoprotein particle clearance; IDA:UniProtKB.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl.
DR   GO; GO:0046907; P:intracellular transport; TAS:UniProtKB.
DR   GO; GO:0010877; P:lipid transport involved in lipid storage; ISS:BHF-UCL.
DR   GO; GO:0042158; P:lipoprotein biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
DR   GO; GO:0035641; P:locomotory exploration behavior; IMP:ARUK-UCL.
DR   GO; GO:0015909; P:long-chain fatty acid transport; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0007616; P:long-term memory; IGI:ARUK-UCL.
DR   GO; GO:0034374; P:low-density lipoprotein particle remodeling; IEA:Ensembl.
DR   GO; GO:0051651; P:maintenance of location in cell; IEA:Ensembl.
DR   GO; GO:0032438; P:melanosome organization; IMP:UniProtKB.
DR   GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISS:UniProtKB.
DR   GO; GO:1902430; P:negative regulation of amyloid-beta formation; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0030195; P:negative regulation of blood coagulation; IDA:BHF-UCL.
DR   GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:ARUK-UCL.
DR   GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0010596; P:negative regulation of endothelial cell migration; IMP:ARUK-UCL.
DR   GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:BHF-UCL.
DR   GO; GO:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; IDA:BHF-UCL.
DR   GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IDA:ARUK-UCL.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; IDA:BHF-UCL.
DR   GO; GO:0010977; P:negative regulation of neuron projection development; IDA:ARUK-UCL.
DR   GO; GO:0010544; P:negative regulation of platelet activation; IDA:BHF-UCL.
DR   GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0051248; P:negative regulation of protein metabolic process; IGI:ARUK-UCL.
DR   GO; GO:0050709; P:negative regulation of protein secretion; IMP:UniProtKB.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISS:BHF-UCL.
DR   GO; GO:0090209; P:negative regulation of triglyceride metabolic process; IEA:Ensembl.
DR   GO; GO:0031175; P:neuron projection development; IDA:UniProtKB.
DR   GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling; IDA:BHF-UCL.
DR   GO; GO:0097114; P:NMDA glutamate receptor clustering; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0033700; P:phospholipid efflux; IDA:BHF-UCL.
DR   GO; GO:1905908; P:positive regulation of amyloid fibril formation; TAS:ARUK-UCL.
DR   GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:UniProtKB.
DR   GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IDA:BHF-UCL.
DR   GO; GO:0060999; P:positive regulation of dendritic spine development; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:1902952; P:positive regulation of dendritic spine maintenance; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB.
DR   GO; GO:0045807; P:positive regulation of endocytosis; IDA:ARUK-UCL.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR   GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:1903002; P:positive regulation of lipid transport across blood-brain barrier; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0140077; P:positive regulation of lipoprotein transport; IDA:ARUK-UCL.
DR   GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; IDA:BHF-UCL.
DR   GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; IDA:ARUK-UCL.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:1902995; P:positive regulation of phospholipid efflux; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0017038; P:protein import; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IDA:BHF-UCL.
DR   GO; GO:1905906; P:regulation of amyloid fibril formation; IDA:ARUK-UCL.
DR   GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; IDA:UniProtKB.
DR   GO; GO:1900221; P:regulation of amyloid-beta clearance; IDA:Alzheimers_University_of_Toronto.
DR   GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0030516; P:regulation of axon extension; TAS:UniProtKB.
DR   GO; GO:2000822; P:regulation of behavioral fear response; IMP:ARUK-UCL.
DR   GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IDA:BHF-UCL.
DR   GO; GO:1905890; P:regulation of cellular response to very-low-density lipoprotein particle stimulus; IDA:ARUK-UCL.
DR   GO; GO:0090181; P:regulation of cholesterol metabolic process; IGI:ARUK-UCL.
DR   GO; GO:0045088; P:regulation of innate immune response; IEA:Ensembl.
DR   GO; GO:0048168; P:regulation of neuronal synaptic plasticity; TAS:UniProtKB.
DR   GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0051246; P:regulation of protein metabolic process; IGI:ARUK-UCL.
DR   GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:ARUK-UCL.
DR   GO; GO:0061771; P:response to caloric restriction; IGI:ARUK-UCL.
DR   GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR   GO; GO:0000302; P:response to reactive oxygen species; NAS:UniProtKB.
DR   GO; GO:0043691; P:reverse cholesterol transport; IDA:BHF-UCL.
DR   GO; GO:0007271; P:synaptic transmission, cholinergic; TAS:UniProtKB.
DR   GO; GO:0070328; P:triglyceride homeostasis; ISS:BHF-UCL.
DR   GO; GO:0006641; P:triglyceride metabolic process; IDA:BHF-UCL.
DR   GO; GO:0071830; P:triglyceride-rich lipoprotein particle clearance; IMP:UniProtKB.
DR   GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR   GO; GO:0034447; P:very-low-density lipoprotein particle clearance; IDA:UniProtKB.
DR   GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR   GO; GO:0019068; P:virion assembly; IMP:AgBase.
DR   DisProt; DP04133; -.
DR   FunFam; 1.20.120.20:FF:000002; Apolipoprotein E; 1.
DR   FunFam; 1.20.120.20:FF:000003; Apolipoprotein E; 1.
DR   Gene3D; 1.20.120.20; Apolipoprotein; 2.
DR   InterPro; IPR000074; ApoA_E.
DR   InterPro; IPR050163; Apolipoprotein_A1/A4/E.
DR   PANTHER; PTHR18976; APOLIPOPROTEIN; 1.
DR   PANTHER; PTHR18976:SF2; APOLIPOPROTEIN E; 1.
DR   Pfam; PF01442; Apolipoprotein; 1.
DR   SUPFAM; SSF58113; Apolipoprotein A-I; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alzheimer disease; Amyloidosis; Cholesterol metabolism;
KW   Chylomicron; Direct protein sequencing; Disease variant; Endosome;
KW   Extracellular matrix; Glycation; Glycoprotein; HDL; Heparin-binding;
KW   Host-virus interaction; Hyperlipidemia; Lipid metabolism; Lipid transport;
KW   Lipid-binding; Neurodegeneration; Oxidation; Phosphoprotein;
KW   Proteomics identification; Reference proteome; Repeat; Secreted; Signal;
KW   Steroid metabolism; Sterol metabolism; Transport; VLDL.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:7068630"
FT   CHAIN           19..317
FT                   /note="Apolipoprotein E"
FT                   /id="PRO_0000001987"
FT   REPEAT          80..101
FT                   /note="1"
FT   REPEAT          102..123
FT                   /note="2"
FT   REPEAT          124..145
FT                   /note="3"
FT   REPEAT          146..167
FT                   /note="4"
FT   REPEAT          168..189
FT                   /note="5"
FT   REPEAT          190..211
FT                   /note="6"
FT   REPEAT          212..233
FT                   /note="7"
FT   REPEAT          234..255
FT                   /note="8"
FT   REGION          80..255
FT                   /note="8 X 22 AA approximate tandem repeats"
FT   REGION          158..168
FT                   /note="LDL and other lipoprotein receptors binding"
FT                   /evidence="ECO:0000269|PubMed:20030366,
FT                   ECO:0000269|PubMed:2063194"
FT   REGION          210..290
FT                   /note="Lipid-binding and lipoprotein association"
FT                   /evidence="ECO:0000269|PubMed:2280190,
FT                   ECO:0000269|PubMed:8071364"
FT   REGION          266..317
FT                   /note="Homooligomerization"
FT                   /evidence="ECO:0000269|PubMed:8340399"
FT   REGION          278..290
FT                   /note="Specificity for association with VLDL"
FT                   /evidence="ECO:0000269|PubMed:8071364"
FT   BINDING         162..165
FT                   /ligand="heparin"
FT                   /ligand_id="ChEBI:CHEBI:28304"
FT                   /evidence="ECO:0000269|PubMed:3947350"
FT   BINDING         229..236
FT                   /ligand="heparin"
FT                   /ligand_id="ChEBI:CHEBI:28304"
FT                   /evidence="ECO:0000269|PubMed:3947350"
FT   MOD_RES         143
FT                   /note="Methionine sulfoxide"
FT                   /evidence="ECO:0000250|UniProtKB:P08226"
FT   MOD_RES         147
FT                   /note="Phosphoserine; by FAM20C"
FT                   /evidence="ECO:0000269|PubMed:26091039,
FT                   ECO:0007744|PubMed:24275569"
FT   CARBOHYD        26
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:23234360"
FT   CARBOHYD        36
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:23234360"
FT   CARBOHYD        93
FT                   /note="N-linked (Glc) (glycation) lysine"
FT                   /evidence="ECO:0000269|PubMed:10452964"
FT   CARBOHYD        212
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19838169,
FT                   ECO:0000269|PubMed:2498325"
FT   CARBOHYD        307
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19838169"
FT   CARBOHYD        308
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:19838169,
FT                   ECO:0000269|PubMed:20511397"
FT   CARBOHYD        314
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:23234360"
FT   VARIANT         21
FT                   /note="E -> K (in ApoE5; associated with
FT                   hyperlipoproteinemia and atherosclerosis; increased binding
FT                   to LDL receptor; dbSNP:rs121918392)"
FT                   /evidence="ECO:0000269|PubMed:1530612,
FT                   ECO:0000269|PubMed:2760009"
FT                   /id="VAR_000645"
FT   VARIANT         31
FT                   /note="E -> K (in HLPP3; ApoE4 Philadelphia, ApoE5 French-
FT                   Canadian and ApoE5-type; only ApoE4 Philadelphia is
FT                   associated with HLPP3; dbSNP:rs201672011)"
FT                   /evidence="ECO:0000269|PubMed:1674745,
FT                   ECO:0000269|PubMed:1713245, ECO:0000303|PubMed:7833947"
FT                   /id="VAR_000646"
FT   VARIANT         43
FT                   /note="R -> C (in LPG; ApoE2 Kyoto; dbSNP:rs121918399)"
FT                   /evidence="ECO:0000269|PubMed:10432380,
FT                   ECO:0000269|PubMed:18077821"
FT                   /id="VAR_042734"
FT   VARIANT         46
FT                   /note="L -> P (found in a patient with
FT                   hypercholesterolemia; uncertain significance; ApoE4
FT                   Freiburg; dbSNP:rs769452)"
FT                   /evidence="ECO:0000269|PubMed:11042151,
FT                   ECO:0000269|PubMed:26802169"
FT                   /id="VAR_000647"
FT   VARIANT         60
FT                   /note="T -> A (in ApoE3 Freiburg; dbSNP:rs28931576)"
FT                   /id="VAR_000648"
FT   VARIANT         64
FT                   /note="Q -> H (confirmed at protein level;
FT                   dbSNP:rs370594287)"
FT                   /evidence="ECO:0000269|PubMed:22028381, ECO:0000269|Ref.10"
FT                   /id="VAR_014114"
FT   VARIANT         99
FT                   /note="Q -> K (in ApoE5 Frankfurt; dbSNP:rs1180612218)"
FT                   /evidence="ECO:0000269|PubMed:8125051"
FT                   /id="VAR_000649"
FT   VARIANT         102
FT                   /note="P -> R (apoE5-type; no hyperlipidemia;
FT                   dbSNP:rs11083750)"
FT                   /evidence="ECO:0000269|PubMed:7833947"
FT                   /id="VAR_000650"
FT   VARIANT         117
FT                   /note="A -> T (in ApoE3*; dbSNP:rs28931577)"
FT                   /evidence="ECO:0000269|PubMed:6327682"
FT                   /id="VAR_000651"
FT   VARIANT         124
FT                   /note="A -> V (in ApoE3 Basel; dbSNP:rs937063425)"
FT                   /evidence="ECO:0000269|PubMed:12864777"
FT                   /id="VAR_016789"
FT   VARIANT         130
FT                   /note="C -> R (in HLPP3 and AD2; ApoE4, ApoE3 Leiden,
FT                   ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and
FT                   ApoE3** are associated with HLPP3; ApoE4 is associated with
FT                   AD2; changed protein structure; no effect on binding to LDL
FT                   receptor; decreased association with HDL and enrichment in
FT                   VLDL and IDL; may prevent the interaction with MAP2 and
FT                   MAPT; changed interaction with APP/A4 amyloid-beta peptide;
FT                   increased ability to induce APP transcription; increased C-
FT                   terminal proteolytic processing in neurons; decreased
FT                   function in neurite outgrowth; ApoE4 is associated with
FT                   higher susceptibility to SARS-CoV-2 infection in neurons
FT                   and astrocytes; dbSNP:rs429358)"
FT                   /evidence="ECO:0000269|PubMed:10903326,
FT                   ECO:0000269|PubMed:11042151, ECO:0000269|PubMed:11447277,
FT                   ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:2280190,
FT                   ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:28111074,
FT                   ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887,
FT                   ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364,
FT                   ECO:0000269|PubMed:8125051, ECO:0000269|PubMed:8287539,
FT                   ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470,
FT                   ECO:0000269|PubMed:8939961, ECO:0000269|PubMed:9360638,
FT                   ECO:0000303|PubMed:7833947"
FT                   /id="VAR_000652"
FT   VARIANT         145
FT                   /note="G -> D (found in a patient with
FT                   hypercholesterolemia; uncertain significance; ApoE1
FT                   Weisgraber; dbSNP:rs267606664)"
FT                   /evidence="ECO:0000269|PubMed:26802169,
FT                   ECO:0000269|PubMed:8287539"
FT                   /id="VAR_000653"
FT   VARIANT         145
FT                   /note="G -> GEVQAMLG (in HLPP3; ApoE3 Leiden; no effect on
FT                   glycosylation)"
FT                   /evidence="ECO:0000269|PubMed:2556398,
FT                   ECO:0000269|PubMed:8468528"
FT                   /id="VAR_000654"
FT   VARIANT         152
FT                   /note="R -> Q (apoE2-type; no hyperlipidemia;
FT                   dbSNP:rs28931578)"
FT                   /evidence="ECO:0000269|PubMed:7833947"
FT                   /id="VAR_000655"
FT   VARIANT         154
FT                   /note="R -> C (in HLPP3; ApoE2-type; dbSNP:rs121918393)"
FT                   /evidence="ECO:0000303|PubMed:7833947"
FT                   /id="VAR_000657"
FT   VARIANT         154
FT                   /note="R -> S (in HLPP3; ApoE2 Christchurch; decreased
FT                   binding to LDL receptor; dbSNP:rs121918393)"
FT                   /evidence="ECO:0000269|PubMed:22481068,
FT                   ECO:0000269|PubMed:2831187, ECO:0000269|PubMed:8287539"
FT                   /id="VAR_000656"
FT   VARIANT         160
FT                   /note="R -> C (in HLPP3; ApoE3**; dbSNP:rs387906567)"
FT                   /evidence="ECO:0000269|PubMed:8287539"
FT                   /id="VAR_000658"
FT   VARIANT         163
FT                   /note="R -> C (in HLPP3; also found in a patient with
FT                   hypercholesterolemia; ApoE4 Philadelphia and ApoE2-type;
FT                   dbSNP:rs769455)"
FT                   /evidence="ECO:0000269|PubMed:11042151,
FT                   ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:26802169"
FT                   /id="VAR_000659"
FT   VARIANT         163
FT                   /note="R -> H (in HLPP3; uncertain significance; ApoE
FT                   Kochi; dbSNP:rs121918397)"
FT                   /evidence="ECO:0000269|PubMed:2101409"
FT                   /id="VAR_000660"
FT   VARIANT         163
FT                   /note="R -> P (in LPG; ApoE2 Sendai; decreased binding to
FT                   LDL receptor; induces intraglomerular deposition of ApoE-
FT                   containing lipoproteins; dbSNP:rs121918397)"
FT                   /evidence="ECO:0000269|PubMed:10903326,
FT                   ECO:0000269|PubMed:9176854"
FT                   /id="VAR_042735"
FT   VARIANT         164
FT                   /note="K -> E (in HLPP3; ApoE1 Harrisburg; decreased
FT                   binding to LDL receptor; probable dominant negative effect;
FT                   decreased in vitro binding to heparin; dbSNP:rs121918394)"
FT                   /evidence="ECO:0000269|PubMed:7635945"
FT                   /id="VAR_000662"
FT   VARIANT         164
FT                   /note="K -> Q (in HLPP3; ApoE2**; dbSNP:rs121918394)"
FT                   /evidence="ECO:0000269|PubMed:2313204"
FT                   /id="VAR_000661"
FT   VARIANT         167
FT                   /note="Missing (in SBHD; also found in patients with a
FT                   diagnosis of familial combined hyperlipidemia)"
FT                   /evidence="ECO:0000269|PubMed:11095479,
FT                   ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068,
FT                   ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230,
FT                   ECO:0000269|PubMed:26802169"
FT                   /id="VAR_035015"
FT   VARIANT         170
FT                   /note="A -> P (in ApoE3*; decreased binding to LDL
FT                   receptor; dbSNP:rs267606662)"
FT                   /evidence="ECO:0000269|PubMed:2831187,
FT                   ECO:0000269|PubMed:6327682"
FT                   /id="VAR_000663"
FT   VARIANT         176
FT                   /note="R -> C (in HLPP3; ApoE2, ApoE2 Fukuoka, ApoE1
FT                   Weisgraber and ApoE3**; ApoE3** is associated with HLPP3;
FT                   changed protein structure; decreased binding to LDLR and
FT                   other lipoprotein receptors; decreased in vitro binding to
FT                   heparin; no effect on distribution among plasma
FT                   lipoproteins; dbSNP:rs7412)"
FT                   /evidence="ECO:0000269|PubMed:11042151,
FT                   ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:12966036,
FT                   ECO:0000269|PubMed:2280190, ECO:0000269|PubMed:3243553,
FT                   ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7994571,
FT                   ECO:0000269|PubMed:8287539, ECO:0000269|PubMed:8756331"
FT                   /id="VAR_000664"
FT   VARIANT         228..317
FT                   /note="Missing (in HLPP3; ApoE3 Washington)"
FT                   /evidence="ECO:0000269|PubMed:1361196"
FT                   /id="VAR_081136"
FT   VARIANT         242
FT                   /note="R -> Q (in ApoE2 Fukuoka; dbSNP:rs267606663)"
FT                   /evidence="ECO:0000269|PubMed:8664327"
FT                   /id="VAR_000665"
FT   VARIANT         246
FT                   /note="R -> C (in ApoE2 Dunedin; dbSNP:rs121918395)"
FT                   /evidence="ECO:0000269|PubMed:2341812"
FT                   /id="VAR_000666"
FT   VARIANT         254
FT                   /note="V -> E (in ApoE2 WG; dbSNP:rs199768005)"
FT                   /evidence="ECO:0000269|PubMed:8488843"
FT                   /id="VAR_000667"
FT   VARIANT         262..263
FT                   /note="EE -> KK (in HLPP3; ApoE7 Suita)"
FT                   /evidence="ECO:0000269|PubMed:2738044"
FT                   /id="VAR_000668"
FT   VARIANT         269
FT                   /note="R -> G (in ApoE3 HB; dbSNP:rs267606661)"
FT                   /evidence="ECO:0000269|PubMed:8488843,
FT                   ECO:0000269|PubMed:9360638"
FT                   /id="VAR_000669"
FT   VARIANT         270
FT                   /note="L -> E (in ApoE1 HE; requires 2 nucleotide
FT                   substitutions)"
FT                   /evidence="ECO:0000269|PubMed:8488843"
FT                   /id="VAR_000670"
FT   VARIANT         292
FT                   /note="R -> H (in ApoE4 PD; dbSNP:rs121918398)"
FT                   /evidence="ECO:0000269|PubMed:8488843"
FT                   /id="VAR_000671"
FT   VARIANT         314
FT                   /note="S -> R (in ApoE4 HG; dbSNP:rs28931579)"
FT                   /evidence="ECO:0000269|PubMed:8488843"
FT                   /id="VAR_000672"
FT   MUTAGEN         79
FT                   /note="R->T: Changes the plasma lipoprotein distribution of
FT                   ApoE4 to the HDL."
FT                   /evidence="ECO:0000269|PubMed:8071364"
FT   MUTAGEN         127
FT                   /note="E->A: No effect on plasma lipoprotein distribution."
FT                   /evidence="ECO:0000269|PubMed:8071364"
FT   MUTAGEN         157
FT                   /note="S->R: Increased binding to LDL receptor; when
FT                   associated with A-167."
FT                   /evidence="ECO:0000269|PubMed:2831187"
FT   MUTAGEN         158
FT                   /note="H->A: Decreased binding to LDL receptor."
FT                   /evidence="ECO:0000269|PubMed:2831187"
FT   MUTAGEN         161
FT                   /note="K->A: Decreased binding to LDL receptor."
FT                   /evidence="ECO:0000269|PubMed:2831187"
FT   MUTAGEN         162
FT                   /note="L->P: Decreased binding to LDL receptor."
FT                   /evidence="ECO:0000269|PubMed:2831187"
FT   MUTAGEN         167
FT                   /note="L->A: Increased binding to LDL receptor; when
FT                   associated with R-157."
FT                   /evidence="ECO:0000269|PubMed:2831187"
FT   MUTAGEN         168
FT                   /note="R->A: Decreased binding to LDL receptor."
FT                   /evidence="ECO:0000269|PubMed:2831187"
FT   MUTAGEN         172
FT                   /note="D->A: Restores the LDL receptor binding activity of
FT                   ApoE2."
FT                   /evidence="ECO:0000269|PubMed:8756331"
FT   MUTAGEN         212
FT                   /note="T->A: Loss of O-glycosylation."
FT                   /evidence="ECO:0000269|PubMed:2498325"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:2KC3"
FT   HELIX           31..39
FT                   /evidence="ECO:0007829|PDB:2KC3"
FT   TURN            40..42
FT                   /evidence="ECO:0007829|PDB:2KC3"
FT   HELIX           43..60
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   HELIX           63..70
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   HELIX           73..96
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   HELIX           97..99
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   STRAND          103..105
FT                   /evidence="ECO:0007829|PDB:7UVJ"
FT   HELIX           107..142
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   TURN            143..145
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   HELIX           149..180
FT                   /evidence="ECO:0007829|PDB:7FCR"
FT   TURN            187..190
FT                   /evidence="ECO:0007829|PDB:2KC3"
FT   HELIX           193..198
FT                   /evidence="ECO:0007829|PDB:2KC3"
FT   STRAND          200..202
FT                   /evidence="ECO:0007829|PDB:2L7B"
FT   HELIX           209..217
FT                   /evidence="ECO:0007829|PDB:2L7B"
FT   HELIX           228..241
FT                   /evidence="ECO:0007829|PDB:2L7B"
FT   HELIX           257..283
FT                   /evidence="ECO:0007829|PDB:2L7B"
FT   HELIX           286..303
FT                   /evidence="ECO:0007829|PDB:1OEF"
FT   STRAND          307..309
FT                   /evidence="ECO:0007829|PDB:2L7B"
SQ   SEQUENCE   317 AA;  36154 MW;  91AFC04210A30689 CRC64;
     MKVLWAALLV TFLAGCQAKV EQAVETEPEP ELRQQTEWQS GQRWELALGR FWDYLRWVQT
     LSEQVQEELL SSQVTQELRA LMDETMKELK AYKSELEEQL TPVAEETRAR LSKELQAAQA
     RLGADMEDVC GRLVQYRGEV QAMLGQSTEE LRVRLASHLR KLRKRLLRDA DDLQKRLAVY
     QAGAREGAER GLSAIRERLG PLVEQGRVRA ATVGSLAGQP LQERAQAWGE RLRARMEEMG
     SRTRDRLDEV KEQVAEVRAK LEEQAQQIRL QAEAFQARLK SWFEPLVEDM QRQWAGLVEK
     VQAAVGTSAA PVPSDNH
//
ID   GPC1_HUMAN              Reviewed;         558 AA.
AC   P35052; B3KTD1; Q53QM4;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 2.
DT   28-JAN-2026, entry version 201.
DE   RecName: Full=Glypican-1;
DE   Contains:
DE     RecName: Full=Secreted glypican-1;
DE   Flags: Precursor;
GN   Name=GPC1;
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 1), PROTEIN SEQUENCE OF 24-53; 100-118
RP   AND 298-317, GPI-ANCHOR AT SER-530, GLYCOSYLATION AT ASN-116, AND VARIANT
RP   GLY-500.
RC   TISSUE=Lung fibroblast;
RX   PubMed=2148568; DOI=10.1083/jcb.111.6.3165;
RA   David G., Lories V., Decock B., Marynen P., Cassiman J.-J.,
RA   van den Berghe H.;
RT   "Molecular cloning of a phosphatidylinositol-anchored membrane heparan
RT   sulfate proteoglycan from human lung fibroblasts.";
RL   J. Cell Biol. 111:3165-3176(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain, and Tongue;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-500.
RC   TISSUE=Salivary gland;
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   [6]
RP   COPPER-BINDING, S-NITROSYLATION, AND GLYCOSYLATION.
RX   PubMed=12732622; DOI=10.1074/jbc.m300394200;
RA   Mani K., Cheng F., Havsmark B., Jonsson M., Belting M., Fransson L.A.;
RT   "Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-
RT   nitroso-dependent autocleavage of glypican-1 heparan sulfate.";
RL   J. Biol. Chem. 278:38956-38965(2003).
RN   [7]
RP   SUBCELLULAR LOCATION, AND POSSIBLE ASSOCIATION WITH ALZHEIMER DISEASE.
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   [8]
RP   S-NITROSYLATION, AND ASSOCIATION WITH NIEMANN-PICK TYPE C1 DISEASE.
RX   PubMed=16645004; DOI=10.1093/glycob/cwj121;
RA   Mani K., Cheng F., Fransson L.A.;
RT   "Defective nitric oxide-dependent, deaminative cleavage of glypican-1
RT   heparan sulfate in Niemann-Pick C1 fibroblasts.";
RL   Glycobiology 16:711-718(2006).
RN   [9]
RP   SUBCELLULAR LOCATION, S-NITROSYLATION, AND GLYCOSYLATION.
RX   PubMed=16971378; DOI=10.1093/glycob/cwl045;
RA   Mani K., Cheng F., Fransson L.A.;
RT   "Constitutive and vitamin C-induced, NO-catalyzed release of heparan
RT   sulfate from recycling glypican-1 in late endosomes.";
RL   Glycobiology 16:1251-1261(2006).
RN   [10]
RP   GLYCOSYLATION, AND LACK OF GLYCOSYLATION AT SER-55.
RX   PubMed=19775117; DOI=10.1021/bi901402x;
RA   Svensson G., Linse S., Mani K.;
RT   "Chemical and thermal unfolding of glypican-1: protective effect of heparan
RT   sulfate against heat-induced irreversible aggregation.";
RL   Biochemistry 48:9994-10004(2009).
RN   [11]
RP   S-NITROSYLATION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX   PubMed=19479373; DOI=10.1007/s10719-009-9243-z;
RA   Svensson G., Mani K.;
RT   "S-Nitrosylation of secreted recombinant human glypican-1.";
RL   Glycoconj. J. 26:1247-1257(2009).
RN   [12]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=19936054; DOI=10.1371/journal.ppat.1000666;
RA   Taylor D.R., Whitehouse I.J., Hooper N.M.;
RT   "Glypican-1 mediates both prion protein lipid raft association and disease
RT   isoform formation.";
RL   PLoS Pathog. 5:E1000666-E1000666(2009).
RN   [13]
RP   GLYCOSYLATION AT ASN-79 AND ASN-116, AND MUTAGENESIS OF ASN-79 AND ASN-116.
RX   PubMed=21932778; DOI=10.1021/bi200218s;
RA   Svensson G., Hyrenius Wittsten A., Linse S., Mani K.;
RT   "The structural role of N-linked glycans on human glypican-1.";
RL   Biochemistry 50:9377-9387(2011).
RN   [14]
RP   S-NITROSYLATION, GLYCOSYLATION, AND FUNCTION.
RX   PubMed=21642435; DOI=10.1074/jbc.m111.243345;
RA   Cheng F., Cappai R., Ciccotosto G.D., Svensson G., Multhaup G.,
RA   Fransson L.A., Mani K.;
RT   "Suppression of amyloid beta A11 antibody immunoreactivity by vitamin C:
RT   possible role of heparan sulfate oligosaccharides derived from glypican-1
RT   by ascorbate-induced, nitric oxide (NO)-catalyzed degradation.";
RL   J. Biol. Chem. 286:27559-27572(2011).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), DISULFIDE BONDS, LACK OF
RP   GLYCOSYLATION AT SER-55, AND GLYCOSYLATION AT ASN-79 AND ASN-116.
RX   PubMed=22351761; DOI=10.1074/jbc.m111.322487;
RA   Svensson G., Awad W., Hakansson M., Mani K., Logan D.T.;
RT   "Crystal structure of N-glycosylated human glypican-1 core protein:
RT   Structure of two loops evolutionarily conserved in vertebrate glypican-1.";
RL   J. Biol. Chem. 287:14040-14051(2012).
RN   [16]
RP   VARIANT [LARGE SCALE ANALYSIS] ASP-337.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Binds,
CC       via the heparan sulfate side chains, alpha-4 (V) collagen and
CC       participates in Schwann cell myelination (By similarity). May act as a
CC       catalyst in increasing the rate of conversion of prion protein PRPN(C)
CC       to PRNP(Sc) via associating (via the heparan sulfate side chains) with
CC       both forms of PRPN, targeting them to lipid rafts and facilitating
CC       their interaction. Required for proper skeletal muscle differentiation
CC       by sequestering FGF2 in lipid rafts preventing its binding to receptors
CC       (FGFRs) and inhibiting the FGF-mediated signaling. {ECO:0000250,
CC       ECO:0000269|PubMed:19936054, ECO:0000269|PubMed:21642435}.
CC   -!- INTERACTION:
CC       P35052; Q6PRD1: GPR179; NbExp=2; IntAct=EBI-8307554, EBI-20895185;
CC       P35052; Q8C419: Gpr158; Xeno; NbExp=3; IntAct=EBI-8307554, EBI-776313;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor;
CC       Extracellular side. Endosome. Note=S-nitrosylated form recycled in
CC       endosomes. Localizes to CAV1-containing vesicles close to the cell
CC       surface. Cleavage of heparan sulfate side chains takes place mainly in
CC       late endosomes. Associates with both forms of PRNP in lipid rafts.
CC       Colocalizes with APP in perinuclear compartments and with CP in
CC       intracellular compartments. Associates with fibrillar APP amyloid-beta
CC       peptides in lipid rafts in Alzheimer disease brains.
CC   -!- SUBCELLULAR LOCATION: [Secreted glypican-1]: Secreted, extracellular
CC       space.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P35052-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P35052-2; Sequence=VSP_055225, VSP_055226, VSP_055227;
CC   -!- PTM: S-nitrosylated in a Cu(2+)-dependent manner. Nitric acid (NO) is
CC       released from the nitrosylated cysteines by ascorbate or by some other
CC       reducing agent, in a Cu(2+) or Zn(2+) dependent manner. This free
CC       nitric oxide is then capable of cleaving the heparan sulfate side
CC       chains.
CC   -!- PTM: N- and O-glycosylated. N-glycosylation is mainly of the complex
CC       type containing sialic acid. O-glycosylated with heparan sulfate. The
CC       heparan sulfate chains can be cleaved either by the action of
CC       heparanase or, degraded by a deaminative process that uses nitric oxide
CC       (NO) released from the S-nitrosylated cysteines. This process is
CC       triggered by ascorbate, or by some other reducing agent, in a
CC       Cu(2+)- or Zn(2+) dependent manner. Cu(2+) ions are provided by
CC       ceruloproteins such as APP, PRNP or CP which associate with GCP1 in
CC       intracellular compartments or lipid rafts.
CC       {ECO:0000269|PubMed:12732622, ECO:0000269|PubMed:16971378,
CC       ECO:0000269|PubMed:19479373, ECO:0000269|PubMed:19775117,
CC       ECO:0000269|PubMed:2148568, ECO:0000269|PubMed:21642435,
CC       ECO:0000269|PubMed:21932778, ECO:0000269|PubMed:22351761}.
CC   -!- PTM: This cell-associated glypican is further processed to give rise to
CC       a medium-released species.
CC   -!- DISEASE: Note=Associates (via the heparan sulfate side chains) with
CC       fibrillar APP amyloid-beta peptides in primitive and classic amyloid
CC       plaques and may be involved in the deposition of these senile plaques
CC       in the Alzheimer disease (AD) brain (PubMed:15084524).
CC       {ECO:0000269|PubMed:15084524}.
CC   -!- DISEASE: Note=Misprocessing of GPC1 is found in fibroblasts of patients
CC       with Niemann-Pick Type C1 disease. This is due to the defective
CC       deaminative degradation of heparan sulfate chains (PubMed:16645004).
CC       {ECO:0000269|PubMed:16645004}.
CC   -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
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; X54232; CAA38139.1; -; mRNA.
DR   EMBL; AK095397; BAG53043.1; -; mRNA.
DR   EMBL; AK096638; BAG53345.1; -; mRNA.
DR   EMBL; AC110619; AAY24160.1; -; Genomic_DNA.
DR   EMBL; CH471063; EAW71180.1; -; Genomic_DNA.
DR   EMBL; CH471063; EAW71183.1; -; Genomic_DNA.
DR   EMBL; BC051279; AAH51279.1; -; mRNA.
DR   CCDS; CCDS2534.1; -. [P35052-1]
DR   PIR; A36347; A36347.
DR   RefSeq; NP_002072.2; NM_002081.3. [P35052-1]
DR   PDB; 4ACR; X-ray; 2.55 A; A/B/C/D=24-479.
DR   PDB; 4AD7; X-ray; 2.94 A; A/B/C/D=24-529.
DR   PDB; 4BWE; X-ray; 2.46 A; A/B/C/D=24-479.
DR   PDB; 4YWT; X-ray; 2.38 A; A/B/C/D=24-527.
DR   PDBsum; 4ACR; -.
DR   PDBsum; 4AD7; -.
DR   PDBsum; 4BWE; -.
DR   PDBsum; 4YWT; -.
DR   AlphaFoldDB; P35052; -.
DR   SMR; P35052; -.
DR   BioGRID; 109079; 199.
DR   FunCoup; P35052; 649.
DR   IntAct; P35052; 335.
DR   MINT; P35052; -.
DR   STRING; 9606.ENSP00000264039; -.
DR   GlyConnect; 1279; 2 N-Linked glycans (1 site).
DR   GlyCosmos; P35052; 6 sites, 3 glycans.
DR   GlyGen; P35052; 13 sites, 15 N-linked glycans (2 sites), 3 O-linked glycans (7 sites).
DR   iPTMnet; P35052; -.
DR   PhosphoSitePlus; P35052; -.
DR   SwissPalm; P35052; -.
DR   BioMuta; GPC1; -.
DR   DMDM; 292495012; -.
DR   jPOST; P35052; -.
DR   MassIVE; P35052; -.
DR   PaxDb; 9606-ENSP00000264039; -.
DR   PeptideAtlas; P35052; -.
DR   ProteomicsDB; 54976; -. [P35052-1]
DR   Pumba; P35052; -.
DR   Antibodypedia; 34516; 376 antibodies from 38 providers.
DR   DNASU; 2817; -.
DR   Ensembl; ENST00000264039.7; ENSP00000264039.2; ENSG00000063660.10. [P35052-1]
DR   GeneID; 2817; -.
DR   KEGG; hsa:2817; -.
DR   MANE-Select; ENST00000264039.7; ENSP00000264039.2; NM_002081.3; NP_002072.2.
DR   UCSC; uc002vyw.5; human. [P35052-1]
DR   AGR; HGNC:4449; -.
DR   ClinPGx; PA28830; -.
DR   CTD; 2817; -.
DR   DisGeNET; 2817; -.
DR   GeneCards; GPC1; -.
DR   HGNC; HGNC:4449; GPC1.
DR   HPA; ENSG00000063660; Tissue enhanced (skin).
DR   MIM; 600395; gene.
DR   OpenTargets; ENSG00000063660; -.
DR   VEuPathDB; HostDB:ENSG00000063660; -.
DR   eggNOG; KOG3821; Eukaryota.
DR   GeneTree; ENSGT01050000244897; -.
DR   HOGENOM; CLU_024658_2_0_1; -.
DR   InParanoid; P35052; -.
DR   OMA; CNSYCRN; -.
DR   OrthoDB; 10010764at2759; -.
DR   PAN-GO; P35052; 6 GO annotations based on evolutionary models.
DR   PhylomeDB; P35052; -.
DR   PathwayCommons; P35052; -.
DR   Reactome; R-HSA-1971475; Glycosaminoglycan-protein linkage region biosynthesis.
DR   Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR   Reactome; R-HSA-2024096; HS-GAG degradation.
DR   Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR   Reactome; R-HSA-3560783; Defective B4GALT7 causes EDS, progeroid type.
DR   Reactome; R-HSA-3560801; Defective B3GAT3 causes JDSSDHD.
DR   Reactome; R-HSA-3656237; Defective EXT2 causes exostoses 2.
DR   Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
DR   Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR   Reactome; R-HSA-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1.
DR   Reactome; R-HSA-9694614; Attachment and Entry.
DR   Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR   Reactome; R-HSA-9820960; Respiratory syncytial virus (RSV) attachment and entry.
DR   Reactome; R-HSA-9833110; RSV-host interactions.
DR   SignaLink; P35052; -.
DR   SIGNOR; P35052; -.
DR   Agora; ENSG00000063660; -.
DR   BioGRID-ORCS; 2817; 14 hits in 1149 CRISPR screens.
DR   CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities.
DR   ChiTaRS; GPC1; human.
DR   EvolutionaryTrace; P35052; -.
DR   GeneWiki; Glypican_1; -.
DR   GenomeRNAi; 2817; -.
DR   Pharos; P35052; Tbio.
DR   PRO; PR:P35052; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P35052; protein.
DR   Bgee; ENSG00000063660; Expressed in ventricular zone and 196 other cell types or tissues.
DR   ExpressionAtlas; P35052; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0005507; F:copper ion binding; IDA:UniProtKB.
DR   GO; GO:0017134; F:fibroblast growth factor binding; ISS:UniProtKB.
DR   GO; GO:0043236; F:laminin binding; ISS:UniProtKB.
DR   GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR   GO; GO:0030200; P:heparan sulfate proteoglycan catabolic process; IDA:UniProtKB.
DR   GO; GO:0032288; P:myelin assembly; ISS:UniProtKB.
DR   GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:2001016; P:positive regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
DR   GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR   GO; GO:0014037; P:Schwann cell differentiation; ISS:UniProtKB.
DR   DisProt; DP03324; -.
DR   InterPro; IPR001863; Glypican.
DR   InterPro; IPR019803; Glypican_CS.
DR   PANTHER; PTHR10822; GLYPICAN; 1.
DR   PANTHER; PTHR10822:SF8; GLYPICAN-1; 1.
DR   Pfam; PF01153; Glypican; 1.
DR   PROSITE; PS01207; GLYPICAN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Copper;
KW   Direct protein sequencing; Disulfide bond; Endosome; Glycoprotein;
KW   GPI-anchor; Heparan sulfate; Lipoprotein; Membrane; Proteoglycan;
KW   Proteomics identification; Reference proteome; S-nitrosylation; Secreted;
KW   Signal; Zinc.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:2148568"
FT   CHAIN           24..530
FT                   /note="Glypican-1"
FT                   /id="PRO_0000012295"
FT   CHAIN           24..?
FT                   /note="Secreted glypican-1"
FT                   /id="PRO_0000333837"
FT   PROPEP          531..558
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000012296"
FT   REGION          341..374
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          505..534
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        355..370
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           530
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000305|PubMed:2148568"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:21932778,
FT                   ECO:0000269|PubMed:22351761"
FT   CARBOHYD        116
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:2148568,
FT                   ECO:0000269|PubMed:21932778, ECO:0000269|PubMed:22351761"
FT   CARBOHYD        486
FT                   /note="O-linked (Xyl...) (heparan sulfate) serine"
FT                   /evidence="ECO:0000305"
FT   CARBOHYD        488
FT                   /note="O-linked (Xyl...) (heparan sulfate) serine"
FT                   /evidence="ECO:0000305"
FT   CARBOHYD        490
FT                   /note="O-linked (Xyl...) (heparan sulfate) serine"
FT                   /evidence="ECO:0000305"
FT   DISULFID        32..68
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   DISULFID        62..256
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   DISULFID        69..259
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   DISULFID        191..343
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   DISULFID        246..279
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   DISULFID        268..415
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   DISULFID        272..401
FT                   /evidence="ECO:0000269|PubMed:22351761"
FT   VAR_SEQ         1..72
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055225"
FT   VAR_SEQ         295..359
FT                   /note="DSMVLITDKFWGTSGVESVIGSVHTWLAEAINALQDNRDTLTAKVIQGCGNP
FT                   KVNPQGPGPEEKR -> GEPPPARAAWNCLGECTTGGPGGRVVPSLELGPRDLIRDALT
FT                   RARSGWCCRVEGPGCLLNVLSDV (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055226"
FT   VAR_SEQ         360..558
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055227"
FT   VARIANT         337
FT                   /note="A -> D (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036044"
FT   VARIANT         500
FT                   /note="S -> G (in dbSNP:rs2228331)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:2148568"
FT                   /id="VAR_033977"
FT   MUTAGEN         79
FT                   /note="N->Q: Protein yield reduced by half. Protein yield
FT                   reduced by 90%, abolishes N-glycosylation but no effect on
FT                   secondary structure; when associated with Q-116."
FT                   /evidence="ECO:0000269|PubMed:21932778"
FT   MUTAGEN         116
FT                   /note="N->Q: No effect on protein yield. Protein yield
FT                   reduced by 90%, abolishes N-glycosylation but no effect on
FT                   secondary structure; when associated with Q-79."
FT                   /evidence="ECO:0000269|PubMed:21932778"
FT   HELIX           33..40
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   TURN            41..43
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           46..48
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           56..58
FT                   /evidence="ECO:0007829|PDB:4BWE"
FT   STRAND          60..62
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   STRAND          64..68
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           71..130
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           132..135
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           138..153
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           159..178
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   STRAND          180..182
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           187..192
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   TURN            201..204
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           205..237
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           244..254
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           256..259
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           269..279
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           281..284
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           287..300
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           301..304
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   STRAND          307..310
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           313..315
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           317..329
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           332..335
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           340..343
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           374..388
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           392..403
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   STRAND          418..422
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   STRAND          431..433
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           434..436
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   STRAND          440..442
FT                   /evidence="ECO:0007829|PDB:4YWT"
FT   HELIX           451..472
FT                   /evidence="ECO:0007829|PDB:4YWT"
SQ   SEQUENCE   558 AA;  61680 MW;  16553B56080A83C8 CRC64;
     MELRARGWWL LCAAAALVAC ARGDPASKSR SCGEVRQIYG AKGFSLSDVP QAEISGEHLR
     ICPQGYTCCT SEMEENLANR SHAELETALR DSSRVLQAML ATQLRSFDDH FQHLLNDSER
     TLQATFPGAF GELYTQNARA FRDLYSELRL YYRGANLHLE ETLAEFWARL LERLFKQLHP
     QLLLPDDYLD CLGKQAEALR PFGEAPRELR LRATRAFVAA RSFVQGLGVA SDVVRKVAQV
     PLGPECSRAV MKLVYCAHCL GVPGARPCPD YCRNVLKGCL ANQADLDAEW RNLLDSMVLI
     TDKFWGTSGV ESVIGSVHTW LAEAINALQD NRDTLTAKVI QGCGNPKVNP QGPGPEEKRR
     RGKLAPRERP PSGTLEKLVS EAKAQLRDVQ DFWISLPGTL CSEKMALSTA SDDRCWNGMA
     RGRYLPEVMG DGLANQINNP EVEVDITKPD MTIRQQIMQL KIMTNRLRSA YNGNDVDFQD
     ASDDGSGSGS GDGCLDDLCS RKVSRKSSSS RTPLTHALPG LSEQEGQKTS AASCPQPPTF
     LLPLLLFLAL TVARPRWR
//