ID   A4_HUMAN                Reviewed;         695 AA.
AC   P05067-4;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 3.
DT   27-MAR-2024, entry version 310.
DE   RecName: Full=Isoform APP695 of Amyloid-beta precursor protein {ECO:0000312|HGNC:HGNC:620};
DE            Short=APP {ECO:0000312|HGNC:HGNC:620};
DE   AltName: Full=ABPP;
DE   AltName: Full=APPI;
DE   AltName: Full=Alzheimer disease amyloid A4 protein homolog;
DE   AltName: Full=Alzheimer disease amyloid protein;
DE   AltName: Full=Amyloid precursor protein {ECO:0000305};
DE   AltName: Full=Amyloid-beta (A4) precursor protein {ECO:0000250|UniProtKB:P12023};
DE   AltName: Full=Amyloid-beta A4 protein;
DE   AltName: Full=Cerebral vascular amyloid peptide;
DE            Short=CVAP;
DE   AltName: Full=PreA4;
DE   AltName: Full=Protease nexin-II;
DE            Short=PN-II;
DE   Contains:
DE     RecName: Full=N-APP;
DE   Contains:
DE     RecName: Full=Soluble APP-alpha {ECO:0000303|PubMed:10656250};
DE              Short=S-APP-alpha {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=Soluble APP-beta {ECO:0000303|PubMed:10656250};
DE              Short=S-APP-beta {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=C99;
DE     AltName: Full=Beta-secretase C-terminal fragment {ECO:0000303|PubMed:10656250};
DE              Short=Beta-CTF {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=Amyloid-beta protein 42 {ECO:0000303|PubMed:8886002};
DE              Short=Abeta42;
DE     AltName: Full=Beta-APP42;
DE   Contains:
DE     RecName: Full=Amyloid-beta protein 40 {ECO:0000303|PubMed:8886002};
DE              Short=Abeta40;
DE     AltName: Full=Beta-APP40;
DE   Contains:
DE     RecName: Full=C83;
DE     AltName: Full=Alpha-secretase C-terminal fragment {ECO:0000303|PubMed:10656250};
DE              Short=Alpha-CTF {ECO:0000303|PubMed:10656250};
DE   Contains:
DE     RecName: Full=P3(42);
DE   Contains:
DE     RecName: Full=P3(40);
DE   Contains:
DE     RecName: Full=C80;
DE   Contains:
DE     RecName: Full=Gamma-secretase C-terminal fragment 59;
DE     AltName: Full=Amyloid intracellular domain 59;
DE              Short=AICD-59;
DE              Short=AID(59);
DE     AltName: Full=Gamma-CTF(59);
DE   Contains:
DE     RecName: Full=Gamma-secretase C-terminal fragment 57;
DE     AltName: Full=Amyloid intracellular domain 57;
DE              Short=AICD-57;
DE              Short=AID(57);
DE     AltName: Full=Gamma-CTF(57);
DE   Contains:
DE     RecName: Full=Gamma-secretase C-terminal fragment 50;
DE     AltName: Full=Amyloid intracellular domain 50;
DE              Short=AICD-50;
DE              Short=AID(50);
DE     AltName: Full=Gamma-CTF(50);
DE   Contains:
DE     RecName: Full=C31;
DE   Flags: Precursor;
GN   Name=APP {ECO:0000312|HGNC:HGNC:620};
GN   Synonyms=A4 {ECO:0000303|PubMed:2881207}, AD1
GN   {ECO:0000312|HGNC:HGNC:620};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
RC   TISSUE=Brain;
RX   PubMed=2881207; DOI=10.1038/325733a0;
RA   Kang J., Lemaire H.-G., Unterbeck A., Salbaum J.M., Masters C.L.,
RA   Grzeschik K.-H., Multhaup G., Beyreuther K., Mueller-Hill B.;
RT   "The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-
RT   surface receptor.";
RL   Nature 325:733-736(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
RC   TISSUE=Brain;
RX   PubMed=2893289; DOI=10.1038/331525a0;
RA   Ponte P., Gonzalez-Dewhitt P., Schilling J., Miller J., Hsu D.,
RA   Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F., Cordell B.;
RT   "A new A4 amyloid mRNA contains a domain homologous to serine proteinase
RT   inhibitors.";
RL   Nature 331:525-527(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP695).
RX   PubMed=2783775; DOI=10.1093/nar/17.2.517;
RA   Lemaire H.-G., Salbaum J.M., Multhaup G., Kang J., Bayney R.M.,
RA   Unterbeck A., Beyreuther K., Mueller-Hill B.;
RT   "The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is
RT   encoded by 16 exons.";
RL   Nucleic Acids Res. 17:517-522(1989).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
RX   PubMed=2110105; DOI=10.1016/0378-1119(90)90310-n;
RA   Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.;
RT   "Genomic organization of the human amyloid beta-protein precursor gene.";
RL   Gene 87:257-263(1990).
RN   [5]
RP   ERRATUM OF PUBMED:2110105.
RX   PubMed=1908403; DOI=10.1016/0378-1119(91)90093-q;
RA   Yoshikai S., Sasaki H., Doh-ura K., Furuya H., Sakaki Y.;
RL   Gene 102:291-292(1991).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM L-APP733).
RC   TISSUE=Leukocyte;
RX   PubMed=1587857; DOI=10.1016/s0021-9258(19)50090-4;
RA   Koenig G., Moenning U., Czech C., Prior R., Banati R., Schreiter-Gasser U.,
RA   Bauer J., Masters C.L., Beyreuther K.;
RT   "Identification and differential expression of a novel alternative splice
RT   isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes
RT   and brain microglial cells.";
RL   J. Biol. Chem. 267:10804-10809(1992).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM APP770).
RX   PubMed=9108164; DOI=10.1093/nar/25.9.1802;
RA   Hattori M., Tsukahara F., Furuhata Y., Tanahashi H., Hirose M., Saito M.,
RA   Tsukuni S., Sakaki Y.;
RT   "A novel method for making nested deletions and its application for
RT   sequencing of a 300 kb region of human APP locus.";
RL   Nucleic Acids Res. 25:1802-1808(1997).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP639), AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=12859342; DOI=10.1046/j.1460-9568.2003.02731.x;
RA   Tang K., Wang C., Shen C., Sheng S., Ravid R., Jing N.;
RT   "Identification of a novel alternative splicing isoform of human amyloid
RT   precursor protein gene, APP639.";
RL   Eur. J. Neurosci. 18:102-108(2003).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP770 AND 11).
RC   TISSUE=Cerebellum, and Hippocampus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-501.
RG   NIEHS SNPs program;
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10830953; DOI=10.1038/35012518;
RA   Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA   Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA   Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA   Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA   Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA   Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA   Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA   Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA   Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA   Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA   Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT   "The DNA sequence of human chromosome 21.";
RL   Nature 405:311-319(2000).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [13]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS APP305 AND APP751).
RC   TISSUE=Eye, and Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [14]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-10.
RC   TISSUE=Liver;
RX   PubMed=3140222; DOI=10.1093/nar/16.19.9351;
RA   Schon E.A., Mita S., Sadlock J., Herbert J.;
RT   "A cDNA specifying the human amyloid beta precursor protein (ABPP) encodes
RT   a 95-kDa polypeptide.";
RL   Nucleic Acids Res. 16:9351-9351(1988).
RN   [15]
RP   ERRATUM OF PUBMED:3140222, AND SEQUENCE REVISION.
RA   Schon E.A., Mita S., Sadlock J., Herbert J.;
RL   Nucleic Acids Res. 16:11402-11402(1988).
RN   [16]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75.
RX   PubMed=2538123; DOI=10.1016/0006-291x(89)92437-6;
RA   La Fauci G., Lahiri D.K., Salton S.R., Robakis N.K.;
RT   "Characterization of the 5'-end region and the first two exons of the beta-
RT   protein precursor gene.";
RL   Biochem. Biophys. Res. Commun. 159:297-304(1989).
RN   [17]
RP   PROTEIN SEQUENCE OF 18-50.
RC   TISSUE=Fibroblast;
RX   PubMed=3597385; DOI=10.1016/s0021-9258(18)47443-1;
RA   van Nostrand W.E., Cunningham D.D.;
RT   "Purification of protease nexin II from human fibroblasts.";
RL   J. Biol. Chem. 262:8508-8514(1987).
RN   [18]
RP   PROTEIN SEQUENCE OF 18-40.
RC   TISSUE=Platelet;
RX   PubMed=12665801; DOI=10.1038/nbt810;
RA   Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA   Vandekerckhove J.;
RT   "Exploring proteomes and analyzing protein processing by mass spectrometric
RT   identification of sorted N-terminal peptides.";
RL   Nat. Biotechnol. 21:566-569(2003).
RN   [19]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 286-366.
RX   PubMed=2893290; DOI=10.1038/331528a0;
RA   Tanzi R.E., McClatchey A.I., Lamperti E.D., Villa-Komaroff L.,
RA   Gusella J.F., Neve R.L.;
RT   "Protease inhibitor domain encoded by an amyloid protein precursor mRNA
RT   associated with Alzheimer's disease.";
RL   Nature 331:528-530(1988).
RN   [20]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 287-367.
RX   PubMed=2893291; DOI=10.1038/331530a0;
RA   Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H.;
RT   "Novel precursor of Alzheimer's disease amyloid protein shows protease
RT   inhibitory activity.";
RL   Nature 331:530-532(1988).
RN   [21]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 507-770.
RC   TISSUE=Brain cortex;
RX   PubMed=2893379; DOI=10.1073/pnas.85.3.929;
RA   Zain S.B., Salim M., Chou W.G., Sajdel-Sulkowska E.M., Majocha R.E.,
RA   Marotta C.A.;
RT   "Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer
RT   disease brain: coding and noncoding regions of the fetal precursor mRNA are
RT   expressed in the cortex.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:929-933(1988).
RN   [22]
RP   PROTEIN SEQUENCE OF 523-555, AND DOMAIN COLLAGEN-BINDING.
RX   PubMed=8576160; DOI=10.1074/jbc.271.3.1613;
RA   Beher D., Hesse L., Masters C.L., Multhaup G.;
RT   "Regulation of amyloid protein precursor (APP) binding to collagen and
RT   mapping of the binding sites on APP and collagen type I.";
RL   J. Biol. Chem. 271:1613-1620(1996).
RN   [23]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 655-737, AND VARIANTS AD1 GLY-717; ILE-717
RP   AND PHE-717.
RX   PubMed=8476439; DOI=10.1006/bbrc.1993.1386;
RA   Denman R.B., Rosenzcwaig R., Miller D.L.;
RT   "A system for studying the effect(s) of familial Alzheimer disease
RT   mutations on the processing of the beta-amyloid peptide precursor.";
RL   Biochem. Biophys. Res. Commun. 192:96-103(1993).
RN   [24]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 656-737.
RX   PubMed=2675837; DOI=10.1016/0006-291x(89)91112-1;
RA   Johnstone E.M., Chaney M.O., Moore R.E., Ward K.E., Norris F.H.,
RA   Little S.P.;
RT   "Alzheimer's disease amyloid peptide is encoded by two exons and shows
RT   similarity to soybean trypsin inhibitor.";
RL   Biochem. Biophys. Res. Commun. 163:1248-1255(1989).
RN   [25]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 672-723, AND VARIANT AD1 ASN-678.
RX   PubMed=15201367; DOI=10.1136/jnnp.2003.010611;
RA   Wakutani Y., Watanabe K., Adachi Y., Wada-Isoe K., Urakami K., Ninomiya H.,
RA   Saido T.C., Hashimoto T., Iwatsubo T., Nakashima K.;
RT   "Novel amyloid precursor protein gene missense mutation (D678N) in probable
RT   familial Alzheimer's disease.";
RL   J. Neurol. Neurosurg. Psych. 75:1039-1042(2004).
RN   [26]
RP   PROTEIN SEQUENCE OF 672-681.
RC   TISSUE=Brain cortex;
RX   PubMed=3312495; DOI=10.1111/j.1471-4159.1987.tb01005.x;
RA   Pardridge W.M., Vinters H.V., Yang J., Eisenberg J., Choi T.B.,
RA   Tourtellotte W.W., Huebner V., Shively J.E.;
RT   "Amyloid angiopathy of Alzheimer's disease: amino acid composition and
RT   partial sequence of a 4,200-dalton peptide isolated from cortical
RT   microvessels.";
RL   J. Neurochem. 49:1394-1401(1987).
RN   [27]
RP   PROTEIN SEQUENCE OF 672-704, AND TISSUE SPECIFICITY.
RX   PubMed=1406936; DOI=10.1038/359325a0;
RA   Seubert P., Vigo-Pelfrey C., Esch F., Lee M., Dovey H., Davis D., Sinha S.,
RA   Schlossmacher M., Whaley J., Swindlehurst C.;
RT   "Isolation and quantification of soluble Alzheimer's beta-peptide from
RT   biological fluids.";
RL   Nature 359:325-327(1992).
RN   [28]
RP   PROTEIN SEQUENCE OF 672-701.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=8229004; DOI=10.1111/j.1471-4159.1993.tb09841.x;
RA   Vigo-Pelfrey C., Lee D., Keim P., Lieberburg I., Schenk D.B.;
RT   "Characterization of beta-amyloid peptide from human cerebrospinal fluid.";
RL   J. Neurochem. 61:1965-1968(1993).
RN   [29]
RP   PROTEIN SEQUENCE OF 672-713.
RC   TISSUE=Blood vessel;
RX   PubMed=8248178; DOI=10.1073/pnas.90.22.10836;
RA   Roher A.E., Lowenson J.D., Clarke S., Woods A.S., Cotter R.J., Gowing E.,
RA   Ball M.J.;
RT   "Beta-amyloid-(1-42) is a major component of cerebrovascular amyloid
RT   deposits: implications for the pathology of Alzheimer disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:10836-10840(1993).
RN   [30]
RP   PROTEIN SEQUENCE OF 672-701 AND 707-713.
RX   PubMed=8109908; DOI=10.1002/ana.410350223;
RA   Wisniewski T., Lalowski M., Levy E., Marques M.R.F., Frangione B.;
RT   "The amino acid sequence of neuritic plaque amyloid from a familial
RT   Alzheimer's disease patient.";
RL   Ann. Neurol. 35:245-246(1994).
RN   [31]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 674-770.
RC   TISSUE=Brain;
RX   PubMed=3810169; DOI=10.1126/science.3810169;
RA   Goldgaber D., Lerman M.I., McBride O.W., Saffiotti U., Gajdusek D.C.;
RT   "Characterization and chromosomal localization of a cDNA encoding brain
RT   amyloid of Alzheimer's disease.";
RL   Science 235:877-880(1987).
RN   [32]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 674-703.
RC   TISSUE=Fetal brain;
RX   PubMed=2949367; DOI=10.1126/science.2949367;
RA   Tanzi R.E., Gusella J.F., Watkins P.C., Bruns G.A., St George-Hyslop P.H.,
RA   Van Keuren M.L., Patterson D., Pagan S., Kurnit D.M., Neve R.L.;
RT   "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage
RT   near the Alzheimer locus.";
RL   Science 235:880-884(1987).
RN   [33]
RP   PROTEIN SEQUENCE OF 609-713, AND GLYCOSYLATION AT THR-633; THR-651;
RP   THR-652; THR-659; THR-663; SER-667 AND TYR-681.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=22576872; DOI=10.1002/jms.2987;
RA   Brinkmalm G., Portelius E., Ohrfelt A., Mattsson N., Persson R.,
RA   Gustavsson M.K., Vite C.H., Gobom J., Mansson J.E., Nilsson J., Halim A.,
RA   Larson G., Ruetschi U., Zetterberg H., Blennow K., Brinkmalm A.;
RT   "An online nano-LC-ESI-FTICR-MS method for comprehensive characterization
RT   of endogenous fragments from amyloid beta and amyloid precursor protein in
RT   human and cat cerebrospinal fluid.";
RL   J. Mass Spectrom. 47:591-603(2012).
RN   [34]
RP   PROTEIN SEQUENCE OF 691-698, AND PROTEOLYTIC CLEAVAGE AT PHE-690 BY
RP   THETA-SECRETASE.
RX   PubMed=16816112; DOI=10.1096/fj.05-5632com;
RA   Sun X., He G., Song W.;
RT   "BACE2, as a novel APP theta-secretase, is not responsible for the
RT   pathogenesis of Alzheimer's disease in Down syndrome.";
RL   FASEB J. 20:1369-1376(2006).
RN   [35]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751).
RC   TISSUE=Brain;
RX   PubMed=2569763; DOI=10.1126/science.2569763;
RA   de Sauvage F., Octave J.-N.;
RT   "A novel mRNA of the A4 amyloid precursor gene coding for a possibly
RT   secreted protein.";
RL   Science 245:651-653(1989).
RN   [36]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695).
RC   TISSUE=Brain;
RX   PubMed=3035574; DOI=10.1073/pnas.84.12.4190;
RA   Robakis N.K., Ramakrishna N., Wolfe G., Wisniewski H.M.;
RT   "Molecular cloning and characterization of a cDNA encoding the
RT   cerebrovascular and the neuritic plaque amyloid peptides.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:4190-4194(1987).
RN   [37]
RP   SUBCELLULAR LOCATION, SIGNAL SEQUENCE CLEAVAGE SITE, AND TOPOLOGY.
RX   PubMed=2900137; DOI=10.1002/j.1460-2075.1988.tb02900.x;
RA   Dyrks T., Weidemann A., Multhaup G., Salbaum J.M., Lemaire H.-G., Kang J.,
RA   Mueller-Hill B., Masters C.L., Beyreuther K.;
RT   "Identification, transmembrane orientation and biogenesis of the amyloid A4
RT   precursor of Alzheimer's disease.";
RL   EMBO J. 7:949-957(1988).
RN   [38]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, SULFATION, AND
RP   OX-2 MOTIF.
RX   PubMed=2649245; DOI=10.1016/0092-8674(89)90177-3;
RA   Weidemann A., Koenig G., Bunke D., Fischer P., Salbaum J.M., Masters C.L.,
RA   Beyreuther K.;
RT   "Identification, biogenesis, and localization of precursors of Alzheimer's
RT   disease A4 amyloid protein.";
RL   Cell 57:115-126(1989).
RN   [39]
RP   IDENTITY OF APP WITH NEXIN-II.
RX   PubMed=2506449; DOI=10.1038/341144a0;
RA   Oltersdorf T., Fritz L.C., Schenk D.B., Lieberburg I., Johnson-Wood K.L.,
RA   Beattie E.C., Ward P.J., Blacher R.W., Dovey H.F., Sinha S.;
RT   "The secreted form of the Alzheimer's amyloid precursor protein with the
RT   Kunitz domain is protease nexin-II.";
RL   Nature 341:144-147(1989).
RN   [40]
RP   PROTEASE-SPECIFICITY OF INHIBITOR DOMAIN.
RX   PubMed=1969731; DOI=10.1016/0006-291x(90)92084-d;
RA   Kido H., Fukutomi A., Schilling J., Wang Y., Cordell B., Katunuma N.;
RT   "Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease
RT   amyloid protein precursor.";
RL   Biochem. Biophys. Res. Commun. 167:716-721(1990).
RN   [41]
RP   EXTRACELLULAR ZINC-BINDING DOMAIN.
RX   PubMed=8344894; DOI=10.1016/s0021-9258(19)85394-2;
RA   Bush A.I., Multhaup G., Moir R.D., Williamson T.G., Small D.H., Rumble B.,
RA   Pollwein P., Beyreuther K., Masters C.L.;
RT   "A novel zinc(II) binding site modulates the function of the beta A4
RT   amyloid protein precursor of Alzheimer's disease.";
RL   J. Biol. Chem. 268:16109-16112(1993).
RN   [42]
RP   INTERACTION WITH G(O).
RX   PubMed=8446172; DOI=10.1038/362075a0;
RA   Nishimoto I., Okamoto T., Matsuura Y., Takahashi S., Okamoto T.,
RA   Murayama Y., Ogata E.;
RT   "Alzheimer amyloid protein precursor complexes with brain GTP-binding
RT   protein G(o).";
RL   Nature 362:75-79(1993).
RN   [43]
RP   PHOSPHORYLATION AT THR-743.
RX   PubMed=8131745; DOI=10.1002/j.1460-2075.1994.tb06360.x;
RA   Suzuki T., Oishi M., Marshak D.R., Czernik A.J., Nairn A.C., Greengard P.;
RT   "Cell cycle-dependent regulation of the phosphorylation and metabolism of
RT   the Alzheimer amyloid precursor protein.";
RL   EMBO J. 13:1114-1122(1994).
RN   [44]
RP   EXTRACELLULAR COPPER-BINDING DOMAIN, AND MUTAGENESIS OF HIS-137; MET-141;
RP   CYS-144; HIS-147 AND HIS-151.
RX   PubMed=7913895; DOI=10.1016/0014-5793(94)00658-x;
RA   Hesse L., Beher D., Masters C.L., Multhaup G.;
RT   "The beta A4 amyloid precursor protein binding to copper.";
RL   FEBS Lett. 349:109-116(1994).
RN   [45]
RP   N-TERMINAL HEPARIN-BINDING DOMAIN, AND MUTAGENESIS OF 99-LYS--ARG-102.
RX   PubMed=8158260; DOI=10.1523/jneurosci.14-04-02117.1994;
RA   Small D.H., Nurcombe V., Reed G., Clarris H., Moir R., Beyreuther K.,
RA   Masters C.L.;
RT   "A heparin-binding domain in the amyloid protein precursor of Alzheimer's
RT   disease is involved in the regulation of neurite outgrowth.";
RL   J. Neurosci. 14:2117-2127(1994).
RN   [46]
RP   CHARACTERIZATION OF L-APP733, AND MUTAGENESIS OF SER-656.
RX   PubMed=7737970; DOI=10.1074/jbc.270.18.10388;
RA   Pangalos M.N., Efthimiopoulos S., Shioi J., Robakis N.K.;
RT   "The chondroitin sulfate attachment site of appican is formed by splicing
RT   out exon 15 of the amyloid precursor gene.";
RL   J. Biol. Chem. 270:10388-10391(1995).
RN   [47]
RP   INTERACTION WITH APP-BP1.
RX   PubMed=8626687; DOI=10.1074/jbc.271.19.11339;
RA   Chow N., Korenberg J.R., Chen X.-N., Neve R.L.;
RT   "APP-BP1, a novel protein that binds to the carboxyl-terminal region of the
RT   amyloid precursor protein.";
RL   J. Biol. Chem. 271:11339-11346(1996).
RN   [48]
RP   INTERACTION WITH APBA1 AND APBB1, AND MUTAGENESIS OF TYR-728; TYR-757;
RP   ASN-759 AND TYR-762.
RX   PubMed=8887653; DOI=10.1128/mcb.16.11.6229;
RA   Borg J.-P., Ooi J., Levy E., Margolis B.;
RT   "The phosphotyrosine interaction domains of X11 and FE65 bind to distinct
RT   sites on the YENPTY motif of amyloid precursor protein.";
RL   Mol. Cell. Biol. 16:6229-6241(1996).
RN   [49]
RP   INTERACTION WITH APBB2.
RX   PubMed=8855266; DOI=10.1073/pnas.93.20.10832;
RA   Guenette S.Y., Chen J., Jondro P.D., Tanzi R.E.;
RT   "Association of a novel human FE65-like protein with the cytoplasmic domain
RT   of the amyloid-beta precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:10832-10837(1996).
RN   [50]
RP   FUNCTION OF AMYLOID-BETA PEPTIDE AS LIPID PEROXIDATION INHIBITOR, AND
RP   MUTAGENESIS OF MET-706.
RX   PubMed=9168929; DOI=10.1006/bbrc.1997.6547;
RA   Walter M.F., Mason P.E., Mason R.P.;
RT   "Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation
RT   as a result of its membrane interactions.";
RL   Biochem. Biophys. Res. Commun. 233:760-764(1997).
RN   [51]
RP   HEPARIN-BINDING DOMAINS.
RX   PubMed=9357988; DOI=10.1016/s0014-5793(97)01146-0;
RA   Mok S.S., Sberna G., Heffernan D., Cappai R., Galatis D., Clarris H.J.,
RA   Sawyer W.H., Beyreuther K., Masters C.L., Small D.H.;
RT   "Expression and analysis of heparin-binding regions of the amyloid
RT   precursor protein of Alzheimer's disease.";
RL   FEBS Lett. 415:303-307(1997).
RN   [52]
RP   INTERACTION OF AMYLOID-BETA PEPTIDE WITH HADH2.
RC   TISSUE=Brain;
RX   PubMed=9338779; DOI=10.1038/39522;
RA   Yan S.D., Fu J., Soto C., Chen X., Zhu H., Al-Mohanna F., Collinson K.,
RA   Zhu A., Stern E., Saido T., Tohyama M., Ogawa S., Roher A., Stern D.;
RT   "An intracellular protein that binds amyloid-beta peptide and mediates
RT   neurotoxicity in Alzheimer's disease.";
RL   Nature 389:689-695(1997).
RN   [53]
RP   COPPER-BINDING, AND DISULFIDE BOND FORMATION.
RX   PubMed=9585534; DOI=10.1021/bi980022m;
RA   Multhaup G., Ruppert T., Schlicksupp A., Hesse L., Bill E., Pipkorn R.,
RA   Masters C.L., Beyreuther K.;
RT   "Copper-binding amyloid precursor protein undergoes a site-specific
RT   fragmentation in the reduction of hydrogen peroxide.";
RL   Biochemistry 37:7224-7230(1998).
RN   [54]
RP   INTERACTION WITH APPBP2, MUTAGENESIS OF TYR-728, AND DOMAIN.
RX   PubMed=9843960; DOI=10.1073/pnas.95.25.14745;
RA   Zheng P., Eastman J., Vande Pol S., Pimplikar S.W.;
RT   "PAT1, a microtubule-interacting protein, recognizes the basolateral
RT   sorting signal of amyloid precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:14745-14750(1998).
RN   [55]
RP   AMYLOID-BETA ZINC-BINDING, AND MUTAGENESIS OF ARG-676; TYR-681 AND HIS-684.
RX   PubMed=10413512; DOI=10.1021/bi990205o;
RA   Liu S.T., Howlett G., Barrow C.J.;
RT   "Histidine-13 is a crucial residue in the zinc ion-induced aggregation of
RT   the A beta peptide of Alzheimer's disease.";
RL   Biochemistry 38:9373-9378(1999).
RN   [56]
RP   PROTEOLYTIC CLEAVAGE AT ASP-197; ASP-219 AND ASP-739 BY CASPASES, AND
RP   MUTAGENESIS OF ASP-739.
RX   PubMed=10319819; DOI=10.1016/s0092-8674(00)80748-5;
RA   Gervais F.G., Xu D., Robertson G.S., Vaillancourt J.P., Zhu Y., Huang J.,
RA   LeBlanc A., Smith D., Rigby M., Shearman M.S., Clarke E.E., Zheng H.,
RA   van der Ploeg L.H.T., Ruffolo S.C., Thornberry N.A., Xanthoudakis S.,
RA   Zamboni R.J., Roy S., Nicholson D.W.;
RT   "Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-
RT   beta precursor protein and amyloidogenic A beta peptide formation.";
RL   Cell 97:395-406(1999).
RN   [57]
RP   IMPORTANCE OF MET-706 IN FREE RADICAL OXIDATIVE STRESS, AND MUTAGENESIS OF
RP   MET-706.
RX   PubMed=10535332; DOI=10.1016/s0361-9230(99)00093-3;
RA   Varadarajan S., Yatin S., Kanski J., Jahanshahi F., Butterfield D.A.;
RT   "Methionine residue 35 is important in amyloid beta-peptide-associated free
RT   radical oxidative stress.";
RL   Brain Res. Bull. 50:133-141(1999).
RN   [58]
RP   SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF THR-743.
RX   PubMed=10341243; DOI=10.1523/jneurosci.19-11-04421.1999;
RA   Ando K., Oishi M., Takeda S., Iijima K., Isohara T., Nairn A.C., Kirino Y.,
RA   Greengard P., Suzuki T.;
RT   "Role of phosphorylation of Alzheimer's amyloid precursor protein during
RT   neuronal differentiation.";
RL   J. Neurosci. 19:4421-4427(1999).
RN   [59]
RP   INTERACTION WITH APBA2.
RX   PubMed=9890987; DOI=10.1074/jbc.274.4.2243;
RA   Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S.,
RA   Kirino Y., Suzuki T.;
RT   "Interaction of a neuron-specific protein containing PDZ domains with
RT   Alzheimer's amyloid precursor protein.";
RL   J. Biol. Chem. 274:2243-2254(1999).
RN   [60]
RP   SUBCELLULAR LOCATION, ENDOCYTOSIS SIGNAL, AND MUTAGENESIS OF TYR-728;
RP   GLY-756; TYR-757; ASN-759; PRO-760 AND TYR-762.
RX   PubMed=10383380; DOI=10.1074/jbc.274.27.18851;
RA   Perez R.G., Soriano S., Hayes J.D., Ostaszewski B., Xia W., Selkoe D.J.,
RA   Chen X., Stokin G.B., Koo E.H.;
RT   "Mutagenesis identifies new signals for beta-amyloid precursor protein
RT   endocytosis, turnover, and the generation of secreted fragments, including
RT   Abeta42.";
RL   J. Biol. Chem. 274:18851-18856(1999).
RN   [61]
RP   IMPORTANCE OF CYS-144 IN COPPER REDUCTION, AND MUTAGENESIS OF CYS-144 AND
RP   147-HIS--HIS-149.
RX   PubMed=10461923; DOI=10.1046/j.1471-4159.1999.0731288.x;
RA   Ruiz F.H., Gonzalez M., Bodini M., Opazo C., Inestrosa N.C.;
RT   "Cysteine 144 is a key residue in the copper reduction by the beta-amyloid
RT   precursor protein.";
RL   J. Neurochem. 73:1288-1292(1999).
RN   [62]
RP   CLEAVAGE BY BACE1, SUBCELLULAR LOCATION (SOLUBLE APP-BETA), AND
RP   CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX   PubMed=10656250; DOI=10.1006/mcne.1999.0811;
RA   Hussain I., Powell D.J., Howlett D.R., Tew D.G., Meek T.D., Chapman C.,
RA   Gloger I.S., Murphy K.E., Southan C.D., Ryan D.M., Smith T.S.,
RA   Simmons D.L., Walsh F.S., Dingwall C., Christie G.;
RT   "Identification of a novel aspartic proteinase (Asp 2) as beta-secretase.";
RL   Mol. Cell. Neurosci. 14:419-427(1999).
RN   [63]
RP   INTERACTION WITH APBB3.
RX   PubMed=10081969; DOI=10.1016/s0304-3940(98)00995-1;
RA   Tanahashi H.;
RT   "Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's
RT   beta-amyloid precursor protein.";
RL   Neurosci. Lett. 261:143-146(1999).
RN   [64]
RP   INTERACTION OF AMYLOID-BETA WITH APOE.
RX   PubMed=10816430; DOI=10.1042/bj3480359;
RA   Tokuda T., Calero M., Matsubara E., Vidal R., Kumar A., Permanne B.,
RA   Zlokovic B., Smith J.D., Ladu M.J., Rostagno A., Frangione B., Ghiso J.;
RT   "Lipidation of apolipoprotein E influences its isoform-specific interaction
RT   with Alzheimer's amyloid beta peptides.";
RL   Biochem. J. 348:359-365(2000).
RN   [65]
RP   INTERACTION OF APP42-BETA WITH CHRNA7.
RX   PubMed=10681545; DOI=10.1074/jbc.275.8.5626;
RA   Wang H.-Y., Lee D.H.S., D'Andrea M.R., Peterson P.A., Shank R.P.,
RA   Reitz A.B.;
RT   "Beta-amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with
RT   high affinity. Implications for Alzheimer's disease pathology.";
RL   J. Biol. Chem. 275:5626-5632(2000).
RN   [66]
RP   IDENTIFICATION OF GAMMA-CTFS BY MASS SPECTROMETRY, MUTAGENESIS OF ASP-739,
RP   AND PROTEOLYTIC CLEAVAGE.
RX   PubMed=12214090; DOI=10.3233/jad-2000-23-408;
RA   Passer B., Pellegrini L., Russo C., Siegel R.M., Lenardo M.J.,
RA   Schettini G., Bachmann M., Tabaton M., D'Adamio L.;
RT   "Generation of an apoptotic intracellular peptide by gamma-secretase
RT   cleavage of Alzheimer's amyloid beta protein precursor.";
RL   J. Alzheimers Dis. 2:289-301(2000).
RN   [67]
RP   REVIEW ON FUNCTION OF AMYLOID-BETA AS ANTIOXIDANT.
RX   PubMed=11775062; DOI=10.1023/a:1012629603390;
RA   Kontush A.;
RT   "Alzheimer's amyloid-beta as a preventive antioxidant for brain
RT   lipoproteins.";
RL   Cell. Mol. Neurobiol. 21:299-315(2001).
RN   [68]
RP   INTERACTION WITH FPR2 (AMYLOID-BETA PROTEIN 42), AND SUBCELLULAR LOCATION
RP   (AMYLOID-BETA PROTEIN 42).
RX   PubMed=11689470; DOI=10.1096/fj.01-0251com;
RA   Yazawa H., Yu Z.-X., Takeda K., Le Y., Gong W., Ferrans V.J.,
RA   Oppenheim J.J., Li C.C.H., Wang J.M.;
RT   "Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled
RT   receptor FPRL1 and forms fibrillar aggregates in macrophages.";
RL   FASEB J. 15:2454-2462(2001).
RN   [69]
RP   INTERACTION WITH BBP.
RX   PubMed=11278849; DOI=10.1074/jbc.m011161200;
RA   Kajkowski E.M., Lo C.F., Ning X., Walker S., Sofia H.J., Wang W., Edris W.,
RA   Chanda P., Wagner E., Vile S., Ryan K., McHendry-Rinde B., Smith S.C.,
RA   Wood A., Rhodes K.J., Kennedy J.D., Bard J., Jacobsen J.S.,
RA   Ozenberger B.A.;
RT   "Beta-amyloid peptide-induced apoptosis regulated by a novel protein
RT   containing a G protein activation module.";
RL   J. Biol. Chem. 276:18748-18756(2001).
RN   [70]
RP   AMYLOID-BETA COPPER AND ZINC-BINDING SITES.
RX   PubMed=11274207; DOI=10.1074/jbc.m100175200;
RA   Curtain C.C., Ali F., Volitakis I., Cherny R.A., Norton R.S.,
RA   Beyreuther K., Barrow C.J., Masters C.L., Bush A.I., Barnham K.J.;
RT   "Alzheimer's disease amyloid-beta binds copper and zinc to generate an
RT   allosterically ordered structure containing superoxide dismutase-like
RT   subunits.";
RL   J. Biol. Chem. 276:20466-20473(2001).
RN   [71]
RP   SUBUNIT.
RX   PubMed=11438549; DOI=10.1074/jbc.m105410200;
RA   Scheuermann S., Hambsch B., Hesse L., Stumm J., Schmidt C., Beher D.,
RA   Bayer T.A., Beyreuther K., Multhaup G.;
RT   "Homodimerization of amyloid precursor protein and its implication in the
RT   amyloidogenic pathway of Alzheimer's disease.";
RL   J. Biol. Chem. 276:33923-33929(2001).
RN   [72]
RP   INTERACTION WITH APBB1, FUNCTION, AND SUBCELLULAR LOCATION (GAMMA-SECRETASE
RP   C-TERMINAL FRAGMENT 59).
RX   PubMed=11544248; DOI=10.1074/jbc.c100447200;
RA   Kimberly W.T., Zheng J.B., Guenette S.Y., Selkoe D.J.;
RT   "The intracellular domain of the beta-amyloid precursor protein is
RT   stabilized by Fe65 and translocates to the nucleus in a notch-like
RT   manner.";
RL   J. Biol. Chem. 276:40288-40292(2001).
RN   [73]
RP   INTERACTION WITH FBLN1.
RX   PubMed=11238726; DOI=10.1046/j.1471-4159.2001.00144.x;
RA   Ohsawa I., Takamura C., Kohsaka S.;
RT   "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein
RT   and modulates its physiological function.";
RL   J. Neurochem. 76:1411-1420(2001).
RN   [74]
RP   INTERACTION WITH MAPT, AND FUNCTION.
RX   PubMed=11943163; DOI=10.1016/s0014-5793(02)02376-1;
RA   Rank K.B., Pauley A.M., Bhattacharya K., Wang Z., Evans D.B., Fleck T.J.,
RA   Johnston J.A., Sharma S.K.;
RT   "Direct interaction of soluble human recombinant tau protein with Abeta 1-
RT   42 results in tau aggregation and hyperphosphorylation by tau protein
RT   kinase II.";
RL   FEBS Lett. 514:263-268(2002).
RN   [75]
RP   INTERACTION WITH MAPK8IP1, AND MUTAGENESIS OF TYR-757.
RX   PubMed=11724784; DOI=10.1074/jbc.m108357200;
RA   Scheinfeld M.H., Roncarati R., Vito P., Lopez P.A., Abdallah M.,
RA   D'Adamio L.;
RT   "Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the
RT   cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein
RT   (APP).";
RL   J. Biol. Chem. 277:3767-3775(2002).
RN   [76]
RP   COPPER-MEDIATED LIPID PEROXIDATION, AND MUTAGENESIS OF HIS-147 AND HIS-151.
RX   PubMed=11784781; DOI=10.1523/jneurosci.22-02-00365.2002;
RA   White A.R., Multhaup G., Galatis D., McKinstry W.J., Parker M.W.,
RA   Pipkorn R., Beyreuther K., Masters C.L., Cappai R.;
RT   "Contrasting species-dependent modulation of copper-mediated neurotoxicity
RT   by the Alzheimer's disease amyloid precursor protein.";
RL   J. Neurosci. 22:365-376(2002).
RN   [77]
RP   REVIEW ON ZINC-BINDING.
RX   PubMed=12032279; DOI=10.1073/pnas.122249699;
RA   Bush A.I., Tanzi R.E.;
RT   "The galvanization of beta-amyloid in Alzheimer's disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:7317-7319(2002).
RN   [78]
RP   PHOSPHORYLATION AT SER-198 AND SER-206 BY CASEIN KINASES, AND MUTAGENESIS
RP   OF SER-198 AND SER-206.
RX   PubMed=8999878; DOI=10.1074/jbc.272.3.1896;
RA   Walter J., Capell A., Hung A.Y., Langen H., Schnoelzer M., Thinakaran G.,
RA   Sisodia S.S., Selkoe D.J., Haass C.;
RT   "Ectodomain phosphorylation of beta-amyloid precursor protein at two
RT   distinct cellular locations.";
RL   J. Biol. Chem. 272:1896-1903(1997).
RN   [79]
RP   CHARACTERIZATION OF CASEIN KINASE PHOSPHORYLATION, AND MUTAGENESIS OF
RP   SER-198 AND SER-206.
RX   PubMed=10806211; DOI=10.1074/jbc.m002850200;
RA   Walter J., Schindzielorz A., Hartung B., Haass C.;
RT   "Phosphorylation of the beta-amyloid precursor protein at the cell surface
RT   by ectocasein kinases 1 and 2.";
RL   J. Biol. Chem. 275:23523-23529(2000).
RN   [80]
RP   PROTEOLYTIC CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-739.
RX   PubMed=10742146; DOI=10.1038/74656;
RA   Lu D.C., Rabizadeh S., Chandra S., Shayya R.F., Ellerby L.M., Ye X.,
RA   Salvesen G.S., Koo E.H., Bredesen D.E.;
RT   "A second cytotoxic proteolytic peptide derived from amyloid beta-protein
RT   precursor.";
RL   Nat. Med. 6:397-404(2000).
RN   [81]
RP   PHOSPHORYLATION, INTERACTION WITH APBB1, AND MUTAGENESIS OF THR-743.
RX   PubMed=11517218; DOI=10.1074/jbc.m104059200;
RA   Ando K., Iijima K., Elliott J.I., Kirino Y., Suzuki T.;
RT   "Phosphorylation-dependent regulation of the interaction of amyloid
RT   precursor protein with Fe65 affects the production of beta-amyloid.";
RL   J. Biol. Chem. 276:40353-40361(2001).
RN   [82]
RP   PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42).
RX   PubMed=11604391; DOI=10.1074/jbc.m104068200;
RA   Hu J., Igarashi A., Kamata M., Nakagawa H.;
RT   "Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A
RT   beta); retards A beta aggregation, deposition, fibril formation; and
RT   inhibits cytotoxicity.";
RL   J. Biol. Chem. 276:47863-47868(2001).
RN   [83]
RP   PHOSPHORYLATION BY MAPK10, AND MUTAGENESIS OF THR-743.
RX   PubMed=11146006; DOI=10.1046/j.1471-4159.2001.00102.x;
RA   Standen C.L., Brownlees J., Grierson A.J., Kesavapany S., Lau K.-F.,
RA   McLoughlin D.M., Miller C.C.J.;
RT   "Phosphorylation of thr(668) in the cytoplasmic domain of the Alzheimer's
RT   disease amyloid precursor protein by stress-activated protein kinase 1b
RT   (Jun N-terminal kinase-3).";
RL   J. Neurochem. 76:316-320(2001).
RN   [84]
RP   PROTEOLYTIC CLEAVAGE AT MET-671; LYS-687; VAL-711; ALA-713 AND LEU-720.
RX   PubMed=11851430; DOI=10.1021/bi015794o;
RA   Weidemann A., Eggert S., Reinhard F.B.M., Vogel M., Paliga K., Baier G.,
RA   Masters C.L., Beyreuther K., Evin G.;
RT   "A novel epsilon-cleavage within the transmembrane domain of the Alzheimer
RT   amyloid precursor protein demonstrates homology with Notch processing.";
RL   Biochemistry 41:2825-2835(2002).
RN   [85]
RP   PHOSPHORYLATION AT TYR-757, INTERACTION WITH SHC1, AND MUTAGENESIS OF
RP   THR-743 AND TYR-757.
RX   PubMed=11877420; DOI=10.1074/jbc.m110286200;
RA   Tarr P.E., Roncarati R., Pelicci G., Pelicci P.G., D'Adamio L.;
RT   "Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic
RT   tail promotes interaction with Shc.";
RL   J. Biol. Chem. 277:16798-16804(2002).
RN   [86]
RP   REVIEW.
RX   PubMed=12142279; DOI=10.1146/annurev.cellbio.18.020402.142302;
RA   Annaert W., De Strooper B.;
RT   "A cell biological perspective on Alzheimer's disease.";
RL   Annu. Rev. Cell Dev. Biol. 18:25-51(2002).
RN   [87]
RP   INTERACTION WITH APBB2.
RX   PubMed=14527950; DOI=10.1074/jbc.m309561200;
RA   Chang Y., Tesco G., Jeong W.J., Lindsley L., Eckman E.A., Eckman C.B.,
RA   Tanzi R.E., Guenette S.Y.;
RT   "Generation of the beta-amyloid peptide and the amyloid precursor protein
RT   C-terminal fragment gamma are potentiated by FE65L1.";
RL   J. Biol. Chem. 278:51100-51107(2003).
RN   [88]
RP   SUBCELLULAR LOCATION, AND ASSOCIATION OF AMYLOID FIBRILS WITH GCP1.
RX   PubMed=15084524; DOI=10.1096/fj.03-1040fje;
RA   Watanabe N., Araki W., Chui D.H., Makifuchi T., Ihara Y., Tabira T.;
RT   "Glypican-1 as an Abeta binding HSPG in the human brain: its localization
RT   in DIG domains and possible roles in the pathogenesis of Alzheimer's
RT   disease.";
RL   FASEB J. 18:1013-1015(2004).
RN   [89]
RP   INTERACTION WITH ANKS1B.
RX   PubMed=15347684; DOI=10.1074/jbc.m405329200;
RA   Ghersi E., Noviello C., D'Adamio L.;
RT   "Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated
RT   protein-1 proteins bind to AbetaPP and modulate its processing in an
RT   isoform-specific manner.";
RL   J. Biol. Chem. 279:49105-49112(2004).
RN   [90]
RP   PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42),
RP   AND SUBCELLULAR LOCATION (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN
RP   42).
RX   PubMed=16154999; DOI=10.1074/jbc.m508460200;
RA   Hemming M.L., Selkoe D.J.;
RT   "Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme
RT   (ACE) and elevated by an ACE inhibitor.";
RL   J. Biol. Chem. 280:37644-37650(2005).
RN   [91]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-542.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [92]
RP   INTERACTION WITH SORL1, AND SUBCELLULAR LOCATION.
RX   PubMed=16174740; DOI=10.1073/pnas.0503689102;
RA   Andersen O.M., Reiche J., Schmidt V., Gotthardt M., Spoelgen R., Behlke J.,
RA   von Arnim C.A., Breiderhoff T., Jansen P., Wu X., Bales K.R., Cappai R.,
RA   Masters C.L., Gliemann J., Mufson E.J., Hyman B.T., Paul S.M., Nykjaer A.,
RA   Willnow T.E.;
RT   "Neuronal sorting protein-related receptor sorLA/LR11 regulates processing
RT   of the amyloid precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005).
RN   [93]
RP   INTERACTION WITH SORL1, AND MUTAGENESIS OF 757-TYR--TYR-762.
RX   PubMed=16407538; DOI=10.1523/jneurosci.3882-05.2006;
RA   Spoelgen R., von Arnim C.A., Thomas A.V., Peltan I.D., Koker M., Deng A.,
RA   Irizarry M.C., Andersen O.M., Willnow T.E., Hyman B.T.;
RT   "Interaction of the cytosolic domains of sorLA/LR11 with the amyloid
RT   precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme.";
RL   J. Neurosci. 26:418-428(2006).
RN   [94]
RP   FUNCTION.
RX   PubMed=17062754; DOI=10.1073/pnas.0607527103;
RA   Satpute-Krishnan P., DeGiorgis J.A., Conley M.P., Jang M., Bearer E.L.;
RT   "A peptide zipcode sufficient for anterograde transport within amyloid
RT   precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:16532-16537(2006).
RN   [95]
RP   INTERACTION WITH SORL1.
RX   PubMed=17855360; DOI=10.1074/jbc.m705073200;
RA   Schmidt V., Sporbert A., Rohe M., Reimer T., Rehm A., Andersen O.M.,
RA   Willnow T.E.;
RT   "SorLA/LR11 regulates processing of amyloid precursor protein via
RT   interaction with adaptors GGA and PACS-1.";
RL   J. Biol. Chem. 282:32956-32964(2007).
RN   [96]
RP   INTERACTION WITH APBB1.
RX   PubMed=18468999; DOI=10.1074/jbc.m801827200;
RA   Nakaya T., Kawai T., Suzuki T.;
RT   "Regulation of FE65 nuclear translocation and function by amyloid beta-
RT   protein precursor in osmotically stressed cells.";
RL   J. Biol. Chem. 283:19119-19131(2008).
RN   [97]
RP   INTERACTION WITH ITM2C.
RX   PubMed=19366692; DOI=10.1074/jbc.m109.006403;
RA   Matsuda S., Matsuda Y., D'Adamio L.;
RT   "BRI3 inhibits amyloid precursor protein processing in a mechanistically
RT   distinct manner from its homologue dementia gene BRI2.";
RL   J. Biol. Chem. 284:15815-15825(2009).
RN   [98]
RP   FUNCTION, PROTEOLYTIC CLEAVAGE, AND INTERACTION WITH TNFRSF21.
RX   PubMed=19225519; DOI=10.1038/nature07767;
RA   Nikolaev A., McLaughlin T., O'Leary D.D.M., Tessier-Lavigne M.;
RT   "APP binds DR6 to trigger axon pruning and neuron death via distinct
RT   caspases.";
RL   Nature 457:981-989(2009).
RN   [99]
RP   FUNCTION, AND INTERACTION WITH AGER.
RX   PubMed=19901339; DOI=10.1073/pnas.0905686106;
RA   Takuma K., Fang F., Zhang W., Yan S., Fukuzaki E., Du H., Sosunov A.,
RA   McKhann G., Funatsu Y., Nakamichi N., Nagai T., Mizoguchi H., Ibi D.,
RA   Hori O., Ogawa S., Stern D.M., Yamada K., Yan S.S.;
RT   "RAGE-mediated signaling contributes to intraneuronal transport of
RT   amyloid-{beta} and neuronal dysfunction.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:20021-20026(2009).
RN   [100]
RP   SUBCELLULAR LOCATION.
RX   PubMed=20580937; DOI=10.1016/j.bbalip.2010.05.010;
RA   Cossec J.C., Simon A., Marquer C., Moldrich R.X., Leterrier C., Rossier J.,
RA   Duyckaerts C., Lenkei Z., Potier M.C.;
RT   "Clathrin-dependent APP endocytosis and Abeta secretion are highly
RT   sensitive to the level of plasma membrane cholesterol.";
RL   Biochim. Biophys. Acta 1801:846-852(2010).
RN   [101]
RP   INTERACTION WITH GSAP.
RX   PubMed=20811458; DOI=10.1038/nature09325;
RA   He G., Luo W., Li P., Remmers C., Netzer W.J., Hendrick J., Bettayeb K.,
RA   Flajolet M., Gorelick F., Wennogle L.P., Greengard P.;
RT   "Gamma-secretase activating protein is a therapeutic target for Alzheimer's
RT   disease.";
RL   Nature 467:95-98(2010).
RN   [102]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [103]
RP   GLYCOSYLATION AT THR-633; THR-651; THR-652; SER-656; THR-663 AND SER-667
RP   PROTEOLYTIC PROCESSING, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=21712440; DOI=10.1073/pnas.1102664108;
RA   Halim A., Brinkmalm G., Ruetschi U., Westman-Brinkmalm A., Portelius E.,
RA   Zetterberg H., Blennow K., Larson G., Nilsson J.;
RT   "Site-specific characterization of threonine, serine, and tyrosine
RT   glycosylations of amyloid precursor protein/amyloid beta-peptides in human
RT   cerebrospinal fluid.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:11848-11853(2011).
RN   [104]
RP   FUNCTION, AND INTERACTION WITH KIF5B.
RX   PubMed=23011729; DOI=10.1088/1478-3975/9/5/055005;
RA   Seamster P.E., Loewenberg M., Pascal J., Chauviere A., Gonzales A.,
RA   Cristini V., Bearer E.L.;
RT   "Quantitative measurements and modeling of cargo-motor interactions during
RT   fast transport in the living axon.";
RL   Phys. Biol. 9:055005-055005(2012).
RN   [105]
RP   INTERACTION WITH S100A9.
RX   PubMed=22457725; DOI=10.1371/journal.pone.0032953;
RA   Zhang C., Liu Y., Gilthorpe J., van der Maarel J.R.;
RT   "MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and
RT   induces its fibrillization.";
RL   PLoS ONE 7:E32953-E32953(2012).
RN   [106]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-743, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [107]
RP   INTERACTION WITH PLD3.
RX   PubMed=24336208; DOI=10.1038/nature12825;
RG   UK Brain Expression Consortium;
RA   Cruchaga C., Karch C.M., Jin S.C., Benitez B.A., Cai Y., Guerreiro R.,
RA   Harari O., Norton J., Budde J., Bertelsen S., Jeng A.T., Cooper B.,
RA   Skorupa T., Carrell D., Levitch D., Hsu S., Choi J., Ryten M., Hardy J.,
RA   Ryten M., Trabzuni D., Weale M.E., Ramasamy A., Smith C., Sassi C.,
RA   Bras J., Gibbs J.R., Hernandez D.G., Lupton M.K., Powell J., Forabosco P.,
RA   Ridge P.G., Corcoran C.D., Tschanz J.T., Norton M.C., Munger R.G.,
RA   Schmutz C., Leary M., Demirci F.Y., Bamne M.N., Wang X., Lopez O.L.,
RA   Ganguli M., Medway C., Turton J., Lord J., Braae A., Barber I., Brown K.,
RA   Passmore P., Craig D., Johnston J., McGuinness B., Todd S., Heun R.,
RA   Kolsch H., Kehoe P.G., Hooper N.M., Vardy E.R., Mann D.M.,
RA   Pickering-Brown S., Brown K., Kalsheker N., Lowe J., Morgan K.,
RA   David Smith A., Wilcock G., Warden D., Holmes C., Pastor P.,
RA   Lorenzo-Betancor O., Brkanac Z., Scott E., Topol E., Morgan K., Rogaeva E.,
RA   Singleton A.B., Hardy J., Kamboh M.I., St George-Hyslop P., Cairns N.,
RA   Morris J.C., Kauwe J.S., Goate A.M.;
RT   "Rare coding variants in the phospholipase D3 gene confer risk for
RT   Alzheimer's disease.";
RL   Nature 505:550-554(2014).
RN   [108]
RP   INTERACTION WITH VDAC1.
RX   PubMed=25168729; DOI=10.1016/j.neuroscience.2014.07.079;
RA   Fernandez-Echevarria C., Diaz M., Ferrer I., Canerina-Amaro A., Marin R.;
RT   "Abeta promotes VDAC1 channel dephosphorylation in neuronal lipid rafts.
RT   Relevance to the mechanisms of neurotoxicity in Alzheimer's disease.";
RL   Neuroscience 278:354-366(2014).
RN   [109]
RP   INTERACTION WITH SORL1.
RX   PubMed=24523320; DOI=10.1126/scitranslmed.3007747;
RA   Caglayan S., Takagi-Niidome S., Liao F., Carlo A.S., Schmidt V.,
RA   Burgert T., Kitago Y., Fuechtbauer E.M., Fuechtbauer A., Holtzman D.M.,
RA   Takagi J., Willnow T.E.;
RT   "Lysosomal sorting of amyloid-beta by the SORLA receptor is impaired by a
RT   familial Alzheimer's disease mutation.";
RL   Sci. Transl. Med. 6:223RA20-223RA20(2014).
RN   [110]
RP   PHOSPHORYLATION AT SER-441 AND TYR-497.
RX   PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA   Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA   Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA   Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT   "A single kinase generates the majority of the secreted phosphoproteome.";
RL   Cell 161:1619-1632(2015).
RN   [111]
RP   INTERACTION WITH LRRK2, PHOSPHORYLATION AT THR-743, AND MUTAGENESIS OF
RP   THR-743.
RX   PubMed=28720718; DOI=10.1126/scisignal.aam6790;
RA   Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z.,
RA   Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L.,
RA   Tan E.K.;
RT   "Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD
RT   activity and neurotoxicity in Parkinson's disease.";
RL   Sci. Signal. 10:0-0(2017).
RN   [112]
RP   X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 287-344.
RX   PubMed=2125487; DOI=10.1021/bi00495a002;
RA   Hynes T.R., Randal M., Kennedy L.A., Eigenbrot C., Kossiakof A.A.;
RT   "X-ray crystal structure of the protease inhibitor domain of Alzheimer's
RT   amyloid beta-protein precursor.";
RL   Biochemistry 29:10018-10022(1990).
RN   [113]
RP   STRUCTURE BY NMR OF 289-344.
RX   PubMed=1718421; DOI=10.1021/bi00107a015;
RA   Heald S.L., Tilton R.F. Jr., Hammond L.S., Lee A., Bayney R.M.,
RA   Kamarck M.E., Ramabhadran T.V., Dreyer R.N., Davis G., Unterbeck A.,
RA   Tamburini P.P.;
RT   "Sequential NMR resonance assignment and structure determination of the
RT   Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor
RT   protein.";
RL   Biochemistry 30:10467-10478(1991).
RN   [114]
RP   STRUCTURE BY NMR OF 672-699.
RX   PubMed=7516706; DOI=10.1021/bi00191a006;
RA   Talafous J., Marcinowski K.J., Klopman G., Zagorski M.G.;
RT   "Solution structure of residues 1-28 of the amyloid beta-peptide.";
RL   Biochemistry 33:7788-7796(1994).
RN   [115]
RP   STRUCTURE BY NMR OF 672-711.
RX   PubMed=7588758; DOI=10.1111/j.1432-1033.1995.293_1.x;
RA   Sticht H., Bayer P., Willbold D., Dames S., Hilbich C., Beyreuther K.,
RA   Frank R.W., Rosch P.;
RT   "Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease.";
RL   Eur. J. Biochem. 233:293-298(1995).
RN   [116]
RP   STRUCTURE BY NMR OF 696-706.
RX   PubMed=8973180; DOI=10.1021/bi961598j;
RA   Kohno T., Kobayashi K., Maeda T., Sato K., Takashima A.;
RT   "Three-dimensional structures of the amyloid beta peptide (25-35) in
RT   membrane-mimicking environment.";
RL   Biochemistry 35:16094-16104(1996).
RN   [117]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF KUNITZ DOMAIN IN COMPLEX WITH
RP   CHYMOTRYPSIN; TRYPSIN AND BASIC PANCREATIC TRYPSIN INHIBITOR.
RX   PubMed=9300481; DOI=10.1002/pro.5560060902;
RA   Scheidig A.J., Hynes T.R., Pelletier L.A., Wells J.A., Kossiakoff A.A.;
RT   "Crystal structures of bovine chymotrypsin and trypsin complexed to the
RT   inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and
RT   basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with
RT   altered specificities.";
RL   Protein Sci. 6:1806-1824(1997).
RN   [118]
RP   STRUCTURE BY NMR OF 672-711.
RX   PubMed=9693002; DOI=10.1021/bi972979f;
RA   Coles M., Bicknell W., Watson A.A., Fairlie D.P., Craik D.J.;
RT   "Solution structure of amyloid beta-peptide(1-40) in a water-micelle
RT   environment. Is the membrane-spanning domain where we think it is?";
RL   Biochemistry 37:11064-11077(1998).
RN   [119]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 28-123.
RX   PubMed=10201399; DOI=10.1038/7562;
RA   Rossjohn J., Cappai R., Feil S.C., Henry A., McKinstry W.J., Galatis D.,
RA   Hesse L., Multhaup G., Beyreuther K., Masters C.L., Parker M.W.;
RT   "Crystal structure of the N-terminal, growth factor-like domain of
RT   Alzheimer amyloid precursor protein.";
RL   Nat. Struct. Biol. 6:327-331(1999).
RN   [120]
RP   STRUCTURE OF CAA-APP VARIANTS.
RX   PubMed=10821838; DOI=10.1074/jbc.m003154200;
RA   Miravalle L., Tokuda T., Chiarle R., Giaccone G., Bugiani O.,
RA   Tagliavini F., Frangione B., Ghiso J.;
RT   "Substitutions at codon 22 of Alzheimer's Abeta peptide induce diverse
RT   conformational changes and apoptotic effects in human cerebral endothelial
RT   cells.";
RL   J. Biol. Chem. 275:27110-27116(2000).
RN   [121]
RP   STRUCTURE BY NMR OF 681-706.
RX   PubMed=10940221; DOI=10.1006/jsbi.2000.4288;
RA   Zhang S., Iwata K., Lachenmann M.J., Peng J.W., Li S., Stimson E.R., Lu Y.,
RA   Felix A.M., Maggio J.E., Lee J.P.;
RT   "The Alzheimer's peptide a beta adopts a collapsed coil structure in
RT   water.";
RL   J. Struct. Biol. 130:130-141(2000).
RN   [122]
RP   STRUCTURE BY NMR OF 672-699.
RX   PubMed=10940222; DOI=10.1006/jsbi.2000.4267;
RA   Poulsen S.-A., Watson A.A., Craik D.J.;
RT   "Solution structures in aqueous SDS micelles of two amyloid beta peptides
RT   of Abeta(1-28) mutated at the alpha-secretase cleavage site.";
RL   J. Struct. Biol. 130:142-152(2000).
RN   [123] {ECO:0007744|PDB:1OWT}
RP   STRUCTURE BY NMR OF 124-189, DISULFIDE BONDS, AND COPPER-BINDING SITES.
RX   PubMed=12611883; DOI=10.1074/jbc.m300629200;
RA   Barnham K.J., McKinstry W.J., Multhaup G., Galatis D., Morton C.J.,
RA   Curtain C.C., Williamson N.A., White A.R., Hinds M.G., Norton R.S.,
RA   Beyreuther K., Masters C.L., Parker M.W., Cappai R.;
RT   "Structure of the Alzheimer's disease amyloid precursor protein copper
RT   binding domain. A regulator of neuronal copper homeostasis.";
RL   J. Biol. Chem. 278:17401-17407(2003).
RN   [124]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 346-551, PARTIAL PROTEIN SEQUENCE,
RP   MUTAGENESIS OF ARG-499 AND LYS-503, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=15304215; DOI=10.1016/j.molcel.2004.06.037;
RA   Wang Y., Ha Y.;
RT   "The X-ray structure of an antiparallel dimer of the human amyloid
RT   precursor protein E2 domain.";
RL   Mol. Cell 15:343-353(2004).
RN   [125]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 672-711 IN COMPLEX WITH IDE.
RX   PubMed=17051221; DOI=10.1038/nature05143;
RA   Shen Y., Joachimiak A., Rosner M.R., Tang W.-J.;
RT   "Structures of human insulin-degrading enzyme reveal a new substrate
RT   recognition mechanism.";
RL   Nature 443:870-874(2006).
RN   [126]
RP   X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 133-189, AND DISULFIDE BONDS.
RX   PubMed=17909280; DOI=10.1107/s1744309107041139;
RA   Kong G.K., Adams J.J., Cappai R., Parker M.W.;
RT   "Structure of Alzheimer's disease amyloid precursor protein copper-binding
RT   domain at atomic resolution.";
RL   Acta Crystallogr. F 63:819-824(2007).
RN   [127] {ECO:0007744|PDB:2FJZ, ECO:0007744|PDB:2FK1, ECO:0007744|PDB:2FK2, ECO:0007744|PDB:2FK3, ECO:0007744|PDB:2FKL}
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 133-189 IN COMPLEXES WITH COPPER
RP   IONS, AND DISULFIDE BONDS.
RX   PubMed=17239395; DOI=10.1016/j.jmb.2006.12.041;
RA   Kong G.K., Adams J.J., Harris H.H., Boas J.F., Curtain C.C., Galatis D.,
RA   Masters C.L., Barnham K.J., McKinstry W.J., Cappai R., Parker M.W.;
RT   "Structural studies of the Alzheimer's amyloid precursor protein copper-
RT   binding domain reveal how it binds copper ions.";
RL   J. Mol. Biol. 367:148-161(2007).
RN   [128]
RP   X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 672-679 IN COMPLEX WITH IGG.
RX   PubMed=17895381; DOI=10.1073/pnas.0705888104;
RA   Gardberg A.S., Dice L.T., Ou S., Rich R.L., Helmbrecht E., Ko J.,
RA   Wetzel R., Myszka D.G., Patterson P.H., Dealwis C.;
RT   "Molecular basis for passive immunotherapy of Alzheimer's disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:15659-15664(2007).
RN   [129]
RP   X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 672-678 IN COMPLEXES WITH
RP   ANTIBODY FAB FRAGMENTS.
RX   PubMed=19923222; DOI=10.1074/jbc.m109.045187;
RA   Basi G.S., Feinberg H., Oshidari F., Anderson J., Barbour R., Baker J.,
RA   Comery T.A., Diep L., Gill D., Johnson-Wood K., Goel A., Grantcharova K.,
RA   Lee M., Li J., Partridge A., Griswold-Prenner I., Piot N., Walker D.,
RA   Widom A., Pangalos M.N., Seubert P., Jacobsen J.S., Schenk D., Weis W.I.;
RT   "Structural correlates of antibodies associated with acute reversal of
RT   amyloid beta-related behavioral deficits in a mouse model of Alzheimer
RT   disease.";
RL   J. Biol. Chem. 285:3417-3427(2010).
RN   [130]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 18-190, PARTIAL PROTEIN SEQUENCE,
RP   SUBUNIT, DISULFIDE BONDS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=20212142; DOI=10.1073/pnas.0911326107;
RA   Dahms S.O., Hoefgen S., Roeser D., Schlott B., Guhrs K.H., Than M.E.;
RT   "Structure and biochemical analysis of the heparin-induced E1 dimer of the
RT   amyloid precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:5381-5386(2010).
RN   [131] {ECO:0007744|PDB:2LOH}
RP   STRUCTURE BY NMR OF 686-726, AND SUBCELLULAR LOCATION.
RX   PubMed=22584060; DOI=10.1016/j.febslet.2012.04.062;
RA   Nadezhdin K.D., Bocharova O.V., Bocharov E.V., Arseniev A.S.;
RT   "Dimeric structure of transmembrane domain of amyloid precursor protein in
RT   micellar environment.";
RL   FEBS Lett. 586:1687-1692(2012).
RN   [132] {ECO:0007744|PDB:2LP1}
RP   STRUCTURE BY NMR OF 671-770, AND SUBCELLULAR LOCATION.
RX   PubMed=22654059; DOI=10.1126/science.1219988;
RA   Barrett P.J., Song Y., Van Horn W.D., Hustedt E.J., Schafer J.M.,
RA   Hadziselimovic A., Beel A.J., Sanders C.R.;
RT   "The amyloid precursor protein has a flexible transmembrane domain and
RT   binds cholesterol.";
RL   Science 336:1168-1171(2012).
RN   [133] {ECO:0007744|PDB:4JFN}
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 23-185 IN COMPLEX WITH COPPER,
RP   FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, DISULFIDE BONDS, AND
RP   MUTAGENESIS OF HIS-108; HIS-110; HIS-147 AND HIS-151.
RX   PubMed=25122912; DOI=10.1523/jneurosci.0180-14.2014;
RA   Baumkotter F., Schmidt N., Vargas C., Schilling S., Weber R., Wagner K.,
RA   Fiedler S., Klug W., Radzimanowski J., Nickolaus S., Keller S., Eggert S.,
RA   Wild K., Kins S.;
RT   "Amyloid precursor protein dimerization and synaptogenic function depend on
RT   copper binding to the growth factor-like domain.";
RL   J. Neurosci. 34:11159-11172(2014).
RN   [134] {ECO:0007744|PDB:2MGT}
RP   STRUCTURE BY NMR OF 672-687, ZINC-BINDING SITES, AND DOMAIN.
RX   PubMed=26898943; DOI=10.1038/srep21734;
RA   Istrate A.N., Kozin S.A., Zhokhov S.S., Mantsyzov A.B., Kechko O.I.,
RA   Pastore A., Makarov A.A., Polshakov V.I.;
RT   "Interplay of histidine residues of the Alzheimer's disease Abeta peptide
RT   governs its Zn-induced oligomerization.";
RL   Sci. Rep. 6:21734-21734(2016).
RN   [135] {ECO:0007744|PDB:5LFY}
RP   STRUCTURE BY NMR OF 672-681, AND DOMAIN.
RX   PubMed=28570778; DOI=10.1002/anie.201704615;
RA   Polshakov V.I., Mantsyzov A.B., Kozin S.A., Adzhubei A.A., Zhokhov S.S.,
RA   van Beek W., Kulikova A.A., Indeykina M.I., Mitkevich V.A., Makarov A.A.;
RT   "A Binuclear Zinc Interaction Fold Discovered in the Homodimer of
RT   Alzheimer's Amyloid-beta Fragment with Taiwanese Mutation D7H.";
RL   Angew. Chem. Int. Ed. Engl. 56:11734-11739(2017).
RN   [136] {ECO:0007744|PDB:5OQV}
RP   STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS) OF 672-713.
RX   PubMed=28882996; DOI=10.1126/science.aao2825;
RA   Gremer L., Scholzel D., Schenk C., Reinartz E., Labahn J., Ravelli R.B.G.,
RA   Tusche M., Lopez-Iglesias C., Hoyer W., Heise H., Willbold D.,
RA   Schroder G.F.;
RT   "Fibril structure of amyloid-beta(1-42) by cryo-electron microscopy.";
RL   Science 358:116-119(2017).
RN   [137] {ECO:0007744|PDB:5VOS}
RP   STRUCTURE BY ELECTRON MICROSCOPY (1.42 ANGSTROMS) OF 695-705.
RX   PubMed=29282295; DOI=10.1074/jbc.m117.806109;
RA   Krotee P., Griner S.L., Sawaya M.R., Cascio D., Rodriguez J.A., Shi D.,
RA   Philipp S., Murray K., Saelices L., Lee J., Seidler P., Glabe C.G.,
RA   Jiang L., Gonen T., Eisenberg D.S.;
RT   "Common fibrillar spines of amyloid-beta and human islet amyloid
RT   polypeptide revealed by microelectron diffraction and structure-based
RT   inhibitors.";
RL   J. Biol. Chem. 293:2888-2902(2018).
RN   [138]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 688-770 IN COMPLEX
RP   WITH GAMMA-SECRETASE, INTERACTION WITH PSEN1, SUBUNIT, PROTEOLYTIC CLEAVAGE
RP   BY PSEN1, TOPOLOGY, AND MUTAGENESIS OF VAL-695.
RX   PubMed=30630874; DOI=10.1126/science.aaw0930;
RA   Zhou R., Yang G., Guo X., Zhou Q., Lei J., Shi Y.;
RT   "Recognition of the amyloid precursor protein by human gamma-secretase.";
RL   Science 0:0-0(2019).
RN   [139]
RP   REVIEW ON VARIANTS.
RX   PubMed=1363811; DOI=10.1038/ng0792-233;
RA   Hardy J.;
RT   "Framing beta-amyloid.";
RL   Nat. Genet. 1:233-234(1992).
RN   [140]
RP   VARIANT CAA-APP GLN-693.
RX   PubMed=2111584; DOI=10.1126/science.2111584;
RA   Levy E., Carman M.D., Fernandez-Madrid I.J., Power M.D., Lieberburg I.,
RA   van Duinen S.G., Bots G.T.A.M., Luyendijk W., Frangione B.;
RT   "Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral
RT   hemorrhage, Dutch type.";
RL   Science 248:1124-1126(1990).
RN   [141]
RP   VARIANT AD1 ILE-717.
RX   PubMed=1671712; DOI=10.1038/349704a0;
RA   Goate A., Chartier-Harlin M.-C., Mullan M., Brown J., Crawford F.,
RA   Fidani L., Giuffra L., Haynes A., Irving N., James L., Mant R., Newton P.,
RA   Rooke K., Roques P., Talbot C., Pericak-Vance M., Roses A.D.,
RA   Williamson R., Rossor M., Owen M., Hardy J.;
RT   "Segregation of a missense mutation in the amyloid precursor protein gene
RT   with familial Alzheimer's disease.";
RL   Nature 349:704-706(1991).
RN   [142]
RP   VARIANT AD1 ILE-717.
RX   PubMed=1908231; DOI=10.1016/0006-291x(91)91011-z;
RA   Yoshioka K., Miki T., Katsuya T., Ogihara T., Sakaki Y.;
RT   "The 717Val-->Ile substitution in amyloid precursor protein is associated
RT   with familial Alzheimer's disease regardless of ethnic groups.";
RL   Biochem. Biophys. Res. Commun. 178:1141-1146(1991).
RN   [143]
RP   VARIANT AD1 ILE-717.
RX   PubMed=1678058; DOI=10.1016/0140-6736(91)91612-x;
RA   Naruse S., Igarashi S., Kobayashi H., Aoki K., Inuzuka T., Kaneko K.,
RA   Shimizu T., Iihara K., Kojima T., Miyatake T., Tsuji S.;
RT   "Mis-sense mutation Val->Ile in exon 17 of amyloid precursor protein gene
RT   in Japanese familial Alzheimer's disease.";
RL   Lancet 337:978-979(1991).
RN   [144]
RP   VARIANT AD1 GLY-717.
RX   PubMed=1944558; DOI=10.1038/353844a0;
RA   Chartier-Harlin M.-C., Crawford F., Houlden H., Warren A., Hughes D.,
RA   Fidani L., Goate A., Rossor M., Roques P., Hardy J., Mullan M.;
RT   "Early-onset Alzheimer's disease caused by mutations at codon 717 of the
RT   beta-amyloid precursor protein gene.";
RL   Nature 353:844-846(1991).
RN   [145]
RP   VARIANT AD1 PHE-717.
RX   PubMed=1925564; DOI=10.1126/science.1925564;
RA   Murrell J.R., Farlow M., Ghetti B., Benson M.D.;
RT   "A mutation in the amyloid precursor protein associated with hereditary
RT   Alzheimer's disease.";
RL   Science 254:97-99(1991).
RN   [146]
RP   VARIANT AD1 GLY-693.
RX   PubMed=1415269;
RA   Kamino K., Orr H.T., Payami H., Wijsman E.M., Alonso M.E., Pulst S.M.,
RA   Anderson L., O'Dahl S., Nemens E., White J.A., Sadovnick A.D., Ball M.J.,
RA   Kaye J., Warren A., McInnis M.G., Antonarakis S.E., Korenberg J.R.,
RA   Sharma V., Kukull W., Larson E., Heston L.L., Martin G.M., Bird T.D.,
RA   Schellenberg G.D.;
RT   "Linkage and mutational analysis of familial Alzheimer disease kindreds for
RT   the APP gene region.";
RL   Am. J. Hum. Genet. 51:998-1014(1992).
RN   [147]
RP   VARIANT AD1 GLY-692.
RX   PubMed=1303239; DOI=10.1038/ng0692-218;
RA   Hendriks L., van Duijn C.M., Cras P., Cruts M., Van Hul W.,
RA   van Harskamp F., Warren A., McInnis M.G., Antonarakis S.E., Martin J.J.,
RA   Hofman A., Van Broeckhoven C.;
RT   "Presenile dementia and cerebral haemorrhage linked to a mutation at codon
RT   692 of the beta-amyloid precursor protein gene.";
RL   Nat. Genet. 1:218-221(1992).
RN   [148]
RP   VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX   PubMed=1302033; DOI=10.1038/ng0892-345;
RA   Mullan M., Crawford F., Axelman K., Houlden H., Lilius L., Winblad B.,
RA   Lannfelt L.;
RT   "A pathogenic mutation for probable Alzheimer's disease in the APP gene at
RT   the N-terminus of beta-amyloid.";
RL   Nat. Genet. 1:345-347(1992).
RN   [149]
RP   CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX   PubMed=1465129; DOI=10.1038/360672a0;
RA   Citron M., Oltersdorf T., Haass C., McConlogue L., Hung A.Y., Seubert P.,
RA   Vigo-Pelfrey C., Lieberburg I., Selkoe D.J.;
RT   "Mutation of the beta-amyloid precursor protein in familial Alzheimer's
RT   disease increases beta-protein production.";
RL   Nature 360:672-674(1992).
RN   [150]
RP   VARIANT VAL-713.
RX   PubMed=1307241; DOI=10.1038/ng0792-306;
RA   Jones C.T., Morris S., Yates C.M., Moffoot A., Sharpe C., Brock D.J.H.,
RA   St Clair D.;
RT   "Mutation in codon 713 of the beta amyloid precursor protein gene
RT   presenting with schizophrenia.";
RL   Nat. Genet. 1:306-309(1992).
RN   [151]
RP   VARIANT AD1 THR-713.
RX   PubMed=1303275; DOI=10.1038/ng1292-255;
RA   Carter D.A., Desmarais E., Bellis M., Campion D., Clerget-Darpoux F.,
RA   Brice A., Agid Y., Jaillard-Serradt A., Mallet J.;
RT   "More missense in amyloid gene.";
RL   Nat. Genet. 2:255-256(1992).
RN   [152]
RP   VARIANTS AD1 ILE-717 AND PHE-717.
RX   PubMed=8267572; DOI=10.1006/bbrc.1993.2491;
RA   Liepnieks J.J., Ghetti B., Farlow M., Roses A.D., Benson M.D.;
RT   "Characterization of amyloid fibril beta-peptide in familial Alzheimer's
RT   disease with APP717 mutations.";
RL   Biochem. Biophys. Res. Commun. 197:386-392(1993).
RN   [153]
RP   VARIANT ASP-665.
RX   PubMed=8154870; DOI=10.1002/ana.410350410;
RA   Peacock M.L., Murman D.L., Sima A.A.F., Warren J.T. Jr., Roses A.D.,
RA   Fink J.K.;
RT   "Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient
RT   with late-onset Alzheimer's disease.";
RL   Ann. Neurol. 35:432-438(1994).
RN   [154]
RP   VARIANT AD1 PHE-717.
RX   PubMed=8290042; DOI=10.1212/wnl.44.1.105;
RA   Farlow M., Murrell J., Ghetti B., Unverzagt F., Zeldenrust S., Benson M.D.;
RT   "Clinical characteristics in a kindred with early-onset Alzheimer's disease
RT   and their linkage to a G-->T change at position 2149 of the amyloid
RT   precursor protein gene.";
RL   Neurology 44:105-111(1994).
RN   [155]
RP   VARIANT AD1 ILE-717.
RX   PubMed=8577393; DOI=10.1016/0304-3940(95)12046-7;
RA   Brooks W.S., Martins R.N., De Voecht J., Nicholson G.A., Schofield P.R.,
RA   Kwok J.B.J., Fisher C., Yeung L.U., Van Broeckhoven C.;
RT   "A mutation in codon 717 of the amyloid precursor protein gene in an
RT   Australian family with Alzheimer's disease.";
RL   Neurosci. Lett. 199:183-186(1995).
RN   [156]
RP   CHARACTERIZATION OF VARIANTS AD1 GLY-717; ILE-717 AND PHE-717, AND
RP   MUTAGENESIS OF VAL-717.
RX   PubMed=8886002; DOI=10.1006/bbrc.1996.1577;
RA   Maruyama K., Tomita T., Shinozaki K., Kume H., Asada H., Saido T.C.,
RA   Ishiura S., Iwatsubo T., Obata K.;
RT   "Familial Alzheimer's disease-linked mutations at Val717 of amyloid
RT   precursor protein are specific for the increased secretion of A beta
RT   42(43).";
RL   Biochem. Biophys. Res. Commun. 227:730-735(1996).
RN   [157]
RP   VARIANT AD1 VAL-716.
RX   PubMed=9328472; DOI=10.1093/hmg/6.12.2087;
RA   Eckman C.B., Mehta N.D., Crook R., Perez-Tur J., Prihar G., Pfeiffer E.,
RA   Graff-Radford N., Hinder P., Yager D., Zenk B., Refolo L.M., Prada C.M.,
RA   Younkin S.G., Hutton M., Hardy J.;
RT   "A new pathogenic mutation in the APP gene (I716V) increases the relative
RT   proportion of A beta 42(43).";
RL   Hum. Mol. Genet. 6:2087-2089(1997).
RN   [158]
RP   VARIANT AD1 GLY-692, AND CHARACTERIZATION OF PHENOTYPE.
RX   PubMed=9754958; DOI=10.1007/s004010050892;
RA   Cras P., van Harskamp F., Hendriks L., Ceuterick C., van Duijn C.M.,
RA   Stefanko S.Z., Hofman A., Kros J.M., Van Broeckhoven C., Martin J.J.;
RT   "Presenile Alzheimer dementia characterized by amyloid angiopathy and large
RT   amyloid core type senile plaques in the APP 692Ala-->Gly mutation.";
RL   Acta Neuropathol. 96:253-260(1998).
RN   [159]
RP   VARIANT AD1 MET-715, AND CHARACTERIZATION OF VARIANT AD1 MET-715.
RX   PubMed=10097173; DOI=10.1073/pnas.96.7.4119;
RA   Ancolio K., Dumanchin C., Barelli H., Warter J.-M., Brice A., Campion D.,
RA   Frebourg T., Checler F.;
RT   "Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP)
RT   maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for
RT   probable early-onset Alzheimer's disease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:4119-4124(1999).
RN   [160]
RP   VARIANT AD1 ILE-717.
RX   PubMed=10631141; DOI=10.1086/302702;
RA   Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J.,
RA   Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.;
RT   "High prevalence of pathogenic mutations in patients with early-onset
RT   dementia detected by sequence analyses of four different genes.";
RL   Am. J. Hum. Genet. 66:110-117(2000).
RN   [161]
RP   VARIANT AD1 PRO-723.
RX   PubMed=10665499;
RX   DOI=10.1002/1531-8249(200002)47:2<249::aid-ana18>3.0.co;2-8;
RA   Kwok J.B.J., Li Q.X., Hallupp M., Whyte S., Ames D., Beyreuther K.,
RA   Masters C.L., Schofield P.R.;
RT   "Novel Leu723Pro amyloid precursor protein mutation increases amyloid
RT   beta42(43) peptide levels and induces apoptosis.";
RL   Ann. Neurol. 47:249-253(2000).
RN   [162]
RP   VARIANT AD1 LEU-717.
RX   PubMed=10867787; DOI=10.1001/archneur.57.6.885;
RA   Murrell J.R., Hake A.M., Quaid K.A., Farlow M.R., Ghetti B.;
RT   "Early-onset Alzheimer disease caused by a new mutation (V717L) in the
RT   amyloid precursor protein gene.";
RL   Arch. Neurol. 57:885-887(2000).
RN   [163]
RP   VARIANT AD1 ILE-714, AND CHARACTERIZATION OF VARIANTS AD1 ILE-714 AND
RP   ILE-717.
RX   PubMed=11063718; DOI=10.1093/hmg/9.18.2589;
RA   Kumar-Singh S., De Jonghe C., Cruts M., Kleinert R., Wang R., Mercken M.,
RA   De Strooper B., Vanderstichele H., Loefgren A., Vanderhoeven I.,
RA   Backhovens H., Vanmechelen E., Kroisel P.M., Van Broeckhoven C.;
RT   "Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site
RT   mutation points to an essential role for N-truncated A beta(42) in
RT   Alzheimer's disease.";
RL   Hum. Mol. Genet. 9:2589-2598(2000).
RN   [164]
RP   CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU.
RX   PubMed=10677483; DOI=10.1073/pnas.97.4.1456;
RA   Lin X., Koelsch G., Wu S., Downs D., Dashti A., Tang J.;
RT   "Human aspartic protease memapsin 2 cleaves the beta-secretase site of
RT   beta-amyloid precursor protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:1456-1460(2000).
RN   [165]
RP   VARIANT CAA-APP ASN-694.
RX   PubMed=11409420; DOI=10.1002/ana.1009;
RA   Grabowski T.J., Cho H.S., Vonsattel J.P.G., Rebeck G.W., Greenberg S.M.;
RT   "Novel amyloid precursor protein mutation in an Iowa family with dementia
RT   and severe cerebral amyloid angiopathy.";
RL   Ann. Neurol. 49:697-705(2001).
RN   [166]
RP   CHARACTERIZATION OF VARIANT AD1 GLY-692.
RX   PubMed=11311152; DOI=10.1042/bj3550869;
RA   Walsh D.M., Hartley D.M., Condron M.M., Selkoe D.J., Teplow D.B.;
RT   "In vitro studies of amyloid beta-protein fibril assembly and toxicity
RT   provide clues to the aetiology of Flemish variant (Ala692-->Gly)
RT   Alzheimer's disease.";
RL   Biochem. J. 355:869-877(2001).
RN   [167]
RP   VARIANT AD1 GLY-693.
RX   PubMed=11528419; DOI=10.1038/nn0901-887;
RA   Nilsberth C., Westlind-Danielsson A., Eckman C.B., Condron M.M.,
RA   Axelman K., Forsell C., Stenh C., Luthman J., Teplow D.B., Younkin S.G.,
RA   Naeslund J., Lannfelt L.;
RT   "The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced
RT   Abeta protofibril formation.";
RL   Nat. Neurosci. 4:887-893(2001).
RN   [168]
RP   VARIANT AD1 ALA-714.
RX   PubMed=12034808; DOI=10.1212/wnl.58.10.1574;
RA   Pasalar P., Najmabadi H., Noorian A.R., Moghimi B., Jannati A.,
RA   Soltanzadeh A., Krefft T., Crook R., Hardy J.;
RT   "An Iranian family with Alzheimer's disease caused by a novel APP mutation
RT   (Thr714Ala).";
RL   Neurology 58:1574-1575(2002).
RN   [169]
RP   VARIANT CAA-APP ASN-694.
RX   PubMed=12654973; DOI=10.1212/01.wnl.0000050140.10044.a8;
RA   Greenberg S.M., Shin Y., Grabowski T.J., Cooper G.E., Rebeck G.W.,
RA   Iglesias S., Chapon F., Tournier-Lasserve E., Baron J.-C.;
RT   "Hemorrhagic stroke associated with the Iowa amyloid precursor protein
RT   mutation.";
RL   Neurology 60:1020-1022(2003).
RN   [170]
RP   VARIANT AD1 THR-713.
RX   PubMed=15365148; DOI=10.1212/01.wnl.0000137048.80666.86;
RA   Rossi G., Giaccone G., Maletta R., Morbin M., Capobianco R., Mangieri M.,
RA   Giovagnoli A.R., Bizzi A., Tomaino C., Perri M., Di Natale M.,
RA   Tagliavini F., Bugiani O., Bruni A.C.;
RT   "A family with Alzheimer disease and strokes associated with A713T mutation
RT   of the APP gene.";
RL   Neurology 63:910-912(2004).
RN   [171]
RP   VARIANT CAA-APP VAL-705.
RX   PubMed=16178030; DOI=10.1002/ana.20571;
RA   Obici L., Demarchi A., de Rosa G., Bellotti V., Marciano S., Donadei S.,
RA   Arbustini E., Palladini G., Diegoli M., Genovese E., Ferrari G.,
RA   Coverlizza S., Merlini G.;
RT   "A novel AbetaPP mutation exclusively associated with cerebral amyloid
RT   angiopathy.";
RL   Ann. Neurol. 58:639-644(2005).
RN   [172]
RP   VARIANT AD1 ILE-714.
RX   PubMed=15668448; DOI=10.1212/01.wnl.0000149761.70566.3e;
RA   Edwards-Lee T., Ringman J.M., Chung J., Werner J., Morgan A.,
RA   St George-Hyslop P.H., Thompson P., Dutton R., Mlikotic A., Rogaeva E.,
RA   Hardy J.;
RT   "An African American family with early-onset Alzheimer disease and an APP
RT   (T714I) mutation.";
RL   Neurology 64:377-379(2005).
RN   [173]
RP   VARIANT CAA-APP LYS-693.
RX   PubMed=20697050; DOI=10.1001/archneurol.2010.178;
RA   Bugiani O., Giaccone G., Rossi G., Mangieri M., Capobianco R., Morbin M.,
RA   Mazzoleni G., Cupidi C., Marcon G., Giovagnoli A., Bizzi A., Di Fede G.,
RA   Puoti G., Carella F., Salmaggi A., Romorini A., Patruno G.M., Magoni M.,
RA   Padovani A., Tagliavini F.;
RT   "Hereditary cerebral hemorrhage with amyloidosis associated with the E693K
RT   mutation of APP.";
RL   Arch. Neurol. 67:987-995(2010).
CC   -!- INTERACTION:
CC       P05067-4; O00213: APBB1; NbExp=5; IntAct=EBI-302641, EBI-81694;
CC       P05067-4; P51693: APLP1; NbExp=2; IntAct=EBI-302641, EBI-74648;
CC       P05067-4; Q06481: APLP2; NbExp=2; IntAct=EBI-302641, EBI-79306;
CC       P05067-4; P05067-4: APP; NbExp=8; IntAct=EBI-302641, EBI-302641;
CC       P05067-4; Q13867: BLMH; NbExp=2; IntAct=EBI-302641, EBI-718504;
CC       P05067-4; Q9NZU0: FLRT3; NbExp=3; IntAct=EBI-302641, EBI-1057092;
CC       P05067-4; P46089: GPR3; NbExp=2; IntAct=EBI-302641, EBI-3909653;
CC       P05067-4; O43736: ITM2A; NbExp=3; IntAct=EBI-302641, EBI-2431769;
CC       P05067-4; Q68DU8: KCTD16; NbExp=3; IntAct=EBI-302641, EBI-20768174;
CC       P05067-4; Q96FE5: LINGO1; NbExp=2; IntAct=EBI-302641, EBI-719955;
CC       P05067-4; P04629: NTRK1; NbExp=7; IntAct=EBI-302641, EBI-1028226;
CC       P05067-4; Q13526: PIN1; NbExp=2; IntAct=EBI-302641, EBI-714158;
CC       P05067-4; P60201: PLP1; NbExp=5; IntAct=EBI-302641, EBI-8653150;
CC       P05067-4; P04156: PRNP; NbExp=2; IntAct=EBI-302641, EBI-977302;
CC       P05067-4; P49768: PSEN1; NbExp=4; IntAct=EBI-302641, EBI-297277;
CC       P05067-4; Q92673: SORL1; NbExp=8; IntAct=EBI-302641, EBI-1171329;
CC       P05067-4; PRO_0000033163 [Q99523]: SORT1; NbExp=4; IntAct=EBI-302641, EBI-21467118;
CC       P05067-4; Q9HCB6: SPON1; NbExp=3; IntAct=EBI-302641, EBI-2431846;
CC       P05067-4; O95793: STAU1; NbExp=2; IntAct=EBI-302641, EBI-358174;
CC       P05067-4; Q8VEK0: Tmem30a; Xeno; NbExp=6; IntAct=EBI-302641, EBI-8381028;
CC   -!- 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   -!- MISCELLANEOUS: A major isoform. {ECO:0000305}.
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DR   CCDS; CCDS13577.1; -.
DR   RefSeq; NP_958817.1; NM_201414.2.
DR   ProteomicsDB; 51778; -.
DR   Ensembl; ENST00000348990.9; ENSP00000345463.5; ENSG00000142192.22.
DR   Proteomes; UP000005640; Chromosome 21.
PE   1: Evidence at protein level;
SQ   SEQUENCE   695 AA;  78663 MW;  4F6EA0139F969D56 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 ESVEEVVRVP TTAASTPDAV
     DKYLETPGDE NEHAHFQKAK ERLEAKHRER MSQVMREWEE AERQAKNLPK ADKKAVIQHF
     QEKVESLEQE AANERQQLVE THMARVEAML NDRRRLALEN YITALQAVPP RPRHVFNMLK
     KYVRAEQKDR QHTLKHFEHV RMVDPKKAAQ IRSQVMTHLR VIYERMNQSL SLLYNVPAVA
     EEIQDEVDEL LQKEQNYSDD VLANMISEPR ISYGNDALMP SLTETKTTVE LLPVNGEFSL
     DDLQPWHSFG ADSVPANTEN EVEPVDARPA ADRGLTTRPG SGLTNIKTEE ISEVKMDAEF
     RHDSGYEVHH QKLVFFAEDV GSNKGAIIGL MVGGVVIATV IVITLVMLKK KQYTSIHHGV
     VEVDAAVTPE ERHLSKMQQN GYENPTYKFF EQMQN
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