ID A0A3Q2HIF9_HORSE Unreviewed; 793 AA. AC A0A3Q2HIF9; DT 10-APR-2019, integrated into UniProtKB/TrEMBL. DT 10-APR-2019, sequence version 1. DT 14-DEC-2022, entry version 19. DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156}; GN Name=APP {ECO:0000313|Ensembl:ENSECAP00000032992.1, GN ECO:0000313|VGNC:VGNC:15428}; OS Equus caballus (Horse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus. OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000032992.1, ECO:0000313|Proteomes:UP000002281}; RN [1] {ECO:0000313|Ensembl:ENSECAP00000032992.1, ECO:0000313|Proteomes:UP000002281} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000032992.1, RC ECO:0000313|Proteomes:UP000002281}; RX PubMed=19892987; DOI=10.1126/science.1178158; RG Broad Institute Genome Sequencing Platform; RG Broad Institute Whole Genome Assembly Team; RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F., RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O., RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T., RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T., RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S., RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G., RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R., RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A., RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J., RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.; RT "Genome sequence, comparative analysis, and population genetics of the RT domestic horse."; RL Science 326:865-867(2009). RN [2] {ECO:0000313|Ensembl:ENSECAP00000032992.1} RP IDENTIFICATION. RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000032992.1}; RG Ensembl; RL Submitted (AUG-2022) to UniProtKB. 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. CC {ECO:0000256|RuleBase:RU367156}. CC -!- FUNCTION: N-APP binds TNFRSF21 triggering caspase activation and CC degeneration of both neuronal cell bodies (via caspase-3) and axons CC (via caspase-6). {ECO:0000256|ARBA:ARBA00003551}. CC -!- FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved CC peptides, including C31, are potent enhancers of neuronal apoptosis. CC {ECO:0000256|ARBA:ARBA00002651}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004251, CC ECO:0000256|RuleBase:RU367156}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004251, ECO:0000256|RuleBase:RU367156}. Cell CC projection, growth cone {ECO:0000256|ARBA:ARBA00004624}. Cell surface CC {ECO:0000256|ARBA:ARBA00004241}. Cytoplasmic vesicle CC {ECO:0000256|ARBA:ARBA00004541}. Early endosome CC {ECO:0000256|ARBA:ARBA00004412}. Endoplasmic reticulum CC {ECO:0000256|ARBA:ARBA00004240}. Endosome CC {ECO:0000256|ARBA:ARBA00004177}. Golgi apparatus CC {ECO:0000256|ARBA:ARBA00004555}. Membrane, clathrin-coated pit CC {ECO:0000256|ARBA:ARBA00004600}. Membrane CC {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane protein CC {ECO:0000256|ARBA:ARBA00004479}. Nucleus CC {ECO:0000256|ARBA:ARBA00004123}. Perikaryon CC {ECO:0000256|ARBA:ARBA00004484}. Secreted CC {ECO:0000256|ARBA:ARBA00004613}. Vesicle CC {ECO:0000256|ARBA:ARBA00004373}. CC -!- SIMILARITY: Belongs to the APP family. {ECO:0000256|ARBA:ARBA00009449, CC ECO:0000256|PROSITE-ProRule:PRU01217, ECO:0000256|RuleBase:RU367156}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU01217}. 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 AlphaFoldDB; A0A3Q2HIF9; -. DR Ensembl; ENSECAT00000031786.2; ENSECAP00000032992.1; ENSECAG00000021011.3. DR VGNC; VGNC:15428; APP. DR GeneTree; ENSGT00530000063252; -. DR Proteomes; UP000002281; Chromosome 26. DR Bgee; ENSECAG00000021011; Expressed in prefrontal cortex and 23 other tissues. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005798; C:Golgi-associated vesicle; IEA:UniProtKB-UniRule. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-UniRule. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0046914; F:transition metal ion binding; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0007399; P:nervous system development; IEA:InterPro. DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW. DR CDD; cd00109; KU; 1. DR Gene3D; 1.20.120.770; -; 2. DR Gene3D; 2.30.29.30; -; 1. DR Gene3D; 3.30.1490.140; -; 1. DR Gene3D; 3.90.570.10; -; 1. DR Gene3D; 4.10.230.10; -; 1. DR Gene3D; 4.10.410.10; -; 1. DR InterPro; IPR036669; Amyloid_Cu-bd_sf. DR InterPro; IPR008155; Amyloid_glyco. DR InterPro; IPR013803; Amyloid_glyco_Abeta. DR InterPro; IPR037071; Amyloid_glyco_Abeta_sf. DR InterPro; IPR011178; Amyloid_glyco_Cu-bd. DR InterPro; IPR024329; Amyloid_glyco_E2_domain. DR InterPro; IPR008154; Amyloid_glyco_extra. DR InterPro; IPR015849; Amyloid_glyco_heparin-bd. DR InterPro; IPR036454; Amyloid_glyco_heparin-bd_sf. DR InterPro; IPR019745; Amyloid_glyco_intracell_CS. DR InterPro; IPR028866; APP. DR InterPro; IPR019543; APP_amyloid_C. DR InterPro; IPR019744; APP_CUBD_CS. DR InterPro; IPR036176; E2_sf. DR InterPro; IPR002223; Kunitz_BPTI. DR InterPro; IPR036880; Kunitz_BPTI_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR020901; Prtase_inh_Kunz-CS. DR PANTHER; PTHR23103; 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; 2. 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; 2. 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 3: Inferred from homology; KW Amyloid {ECO:0000256|RuleBase:RU367156}; KW Apoptosis {ECO:0000256|ARBA:ARBA00022703}; KW Cell adhesion {ECO:0000256|ARBA:ARBA00022889}; KW Cell membrane {ECO:0000256|ARBA:ARBA00022475, KW ECO:0000256|RuleBase:RU367156}; KW Cell projection {ECO:0000256|ARBA:ARBA00023273}; KW Coated pit {ECO:0000256|ARBA:ARBA00023176}; KW Coiled coil {ECO:0000256|SAM:Coils}; KW Copper {ECO:0000256|ARBA:ARBA00023008}; KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490}; KW Cytoplasmic vesicle {ECO:0000256|ARBA:ARBA00023329}; KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, ECO:0000256|PROSITE- KW ProRule:PRU01217}; Endocytosis {ECO:0000256|ARBA:ARBA00022583}; KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824}; KW Endosome {ECO:0000256|ARBA:ARBA00022753}; KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180}; KW Golgi apparatus {ECO:0000256|ARBA:ARBA00023034}; KW Heparin-binding {ECO:0000256|ARBA:ARBA00022674}; KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU367156}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723}; KW Notch signaling pathway {ECO:0000256|ARBA:ARBA00022976}; KW Nucleus {ECO:0000256|ARBA:ARBA00023242}; KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553}; KW Protease inhibitor {ECO:0000256|ARBA:ARBA00022690}; KW Reference proteome {ECO:0000313|Proteomes:UP000002281}; KW Serine protease inhibitor {ECO:0000256|ARBA:ARBA00022900}; KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, KW ECO:0000256|RuleBase:RU367156}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|RuleBase:RU367156}; KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843}; KW Zinc {ECO:0000256|ARBA:ARBA00022833}. FT SIGNAL 1..17 FT /evidence="ECO:0000256|SAM:SignalP" FT CHAIN 18..793 FT /note="Amyloid-beta A4 protein" FT /evidence="ECO:0000256|SAM:SignalP" FT /id="PRO_5018645516" FT TRANSMEM 724..746 FT /note="Helical" FT /evidence="ECO:0000256|RuleBase:RU367156" FT DOMAIN 28..189 FT /note="E1" FT /evidence="ECO:0000259|PROSITE:PS51869" FT DOMAIN 291..341 FT /note="BPTI/Kunitz inhibitor" FT /evidence="ECO:0000259|PROSITE:PS50279" FT DOMAIN 374..606 FT /note="E2" FT /evidence="ECO:0000259|PROSITE:PS51870" FT REGION 28..123 FT /note="GFLD subdomain" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT REGION 131..189 FT /note="CuBD subdomain" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT REGION 194..284 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 466..500 FT /evidence="ECO:0000256|SAM:Coils" FT COMPBIAS 195..210 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 225..263 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 267..284 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT DISULFID 73..117 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 98..105 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 133..187 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 144..174 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 158..186 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" SQ SEQUENCE 793 AA; 89742 MW; DB87BD4953F3E252 CRC64; MLPGLALVLL AAWTARALEV PTDGNAGLLA EPQIAMFCGK LNMHMNVQNG KWESDPSGTK TCIGTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHAH IVIPYRCLVG EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEDVADVEEE EAEDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVMSQSLL KTPQEPLPQD PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQAQ LQTFPLAFGS VHELISRKSW VDIKDEKRKL YFPTKQISLV MREWEEAERQ AKNLPKADKK AVIQHFQEKV ESLEQEAANE RQQLVETHMA RVEAMLNDRR RLALENYITA LQAVPPRPRH VFNMLKKYVR AEQKDRQHTL KHFEHVRMVD PKKAAQIRSQ VMTHLRVIYE RMNQSLSLLY NVPAVAEEIQ DEVDELLQKE QNYSDDVLAN MISEPRISYG NDALMPSLTE TKTTVELLPV NGEFSLDDLQ PWHPFGVDSV PANTENEGSG LTNIKTEEIS EVKMDAEFRH DSGYEVHHQK LVFFAEDVGS NKGAIIGLMV GGVVIATVIV ITLVMLKKKQ YTSIHHGVVE VDAAVTPEER HLSKMQQNGY ENPTYKFFEQ MQN //