ID A0A3Q2HIF9_HORSE Unreviewed; 752 AA. AC A0A3Q2HIF9; DT 10-APR-2019, integrated into UniProtKB/TrEMBL. DT 13-SEP-2023, sequence version 2. DT 13-SEP-2023, entry version 23. DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156}; GN Name=APP {ECO:0000313|Ensembl:ENSECAP00000032992.2, 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:ENSECAP00000032992.2, ECO:0000313|Proteomes:UP000002281}; RN [1] {ECO:0000313|Ensembl:ENSECAP00000032992.2, ECO:0000313|Proteomes:UP000002281} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000032992.2, 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:ENSECAP00000032992.2} RP IDENTIFICATION. RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000032992.2}; RG Ensembl; RL Submitted (MAY-2023) 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}. 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; ENSECAT00000031786.3; ENSECAP00000032992.2; ENSECAG00000021011.4. 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: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:InterPro. 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:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW. DR CDD; cd22607; Kunitz_ABPP-like; 1. DR Gene3D; 1.20.120.770; Amyloid precursor protein, E2 domain; 2. 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 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; 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|ARBA:ARBA00023087, ECO:0000256|RuleBase:RU367156}; KW Apoptosis {ECO:0000256|ARBA:ARBA00022703}; KW Cell membrane {ECO:0000256|ARBA:ARBA00022475, KW ECO:0000256|RuleBase:RU367156}; Coated pit {ECO:0000256|ARBA:ARBA00023176}; 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 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 Reference proteome {ECO:0000313|Proteomes:UP000002281}; KW Secreted {ECO:0000256|ARBA:ARBA00022525}; KW Signal {ECO:0000256|ARBA:ARBA00022729}; 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}. SQ SEQUENCE 752 AA; 84940 MW; 9F12D513C759FC3F 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 KHRERMSQVM REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET KTTVELLPVN GEFSLDDLQP WHPFGVDSVP ANTENEGSGL TNIKTEEISE VKMDAEFRHD SGYEVHHQKL VFFAEDVGSN KGAIIGLMVG GVVIATVIVI TLVMLKKKQY TSIHHGVVEV DAAVTPEERH LSKMQQNGYE NPTYKFFEQM QN //