ID A0A3Q2HIF9_HORSE Unreviewed; 752 AA. AC A0A3Q2HIF9; DT 10-APR-2019, integrated into UniProtKB/TrEMBL. DT 13-SEP-2023, sequence version 2. DT 24-JUL-2024, entry version 28. 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 (APR-2024) 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 RefSeq; XP_003364222.1; XM_003364174.3. DR AlphaFoldDB; A0A3Q2HIF9; -. DR Ensembl; ENSECAT00000031786.3; ENSECAP00000032992.2; ENSECAG00000021011.4. DR GeneID; 100066294; -. DR CTD; 351; -. DR VGNC; VGNC:15428; APP. DR GeneTree; ENSGT00530000063252; -. DR Proteomes; UP000002281; Chromosome 26. DR Bgee; ENSECAG00000021011; Expressed in prefrontal cortex and 23 other cell types or tissues. DR ExpressionAtlas; A0A3Q2HIF9; baseline. 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:0005886; C:plasma membrane; 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: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; 1. DR Gene3D; 4.10.230.10; Amyloidogenic glycoprotein, amyloid-beta peptide; 1. DR Gene3D; 3.30.1490.140; Amyloidogenic glycoprotein, copper-binding domain; 1. DR Gene3D; 3.90.570.10; Amyloidogenic glycoprotein, heparin-binding domain; 1. DR Gene3D; 4.10.410.10; Pancreatic trypsin inhibitor Kunitz domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR036669; Amyloid_Cu-bd_sf. DR InterPro; IPR008155; Amyloid_glyco. DR InterPro; IPR013803; Amyloid_glyco_Abeta. DR InterPro; IPR037071; Amyloid_glyco_Abeta_sf. DR InterPro; IPR011178; Amyloid_glyco_Cu-bd. DR InterPro; IPR024329; Amyloid_glyco_E2_domain. DR InterPro; IPR008154; Amyloid_glyco_extra. DR InterPro; IPR015849; Amyloid_glyco_heparin-bd. DR InterPro; IPR036454; Amyloid_glyco_heparin-bd_sf. DR InterPro; IPR019745; Amyloid_glyco_intracell_CS. DR InterPro; IPR019543; APP_amyloid_C. DR InterPro; IPR019744; APP_CUBD_CS. DR InterPro; IPR036176; E2_sf. DR InterPro; IPR002223; Kunitz_BPTI. DR InterPro; IPR036880; Kunitz_BPTI_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR020901; Prtase_inh_Kunz-CS. DR PANTHER; PTHR23103; ALZHEIMER'S DISEASE BETA-AMYLOID RELATED; 1. DR PANTHER; PTHR23103:SF7; AMYLOID-BETA PRECURSOR PROTEIN; 1. DR Pfam; PF10515; APP_amyloid; 1. DR Pfam; PF12924; APP_Cu_bd; 1. DR Pfam; PF12925; APP_E2; 1. DR Pfam; PF02177; APP_N; 1. DR Pfam; PF03494; Beta-APP; 1. DR Pfam; PF00014; Kunitz_BPTI; 1. DR PRINTS; PR00203; AMYLOIDA4. DR PRINTS; PR00759; BASICPTASE. DR PRINTS; PR00204; BETAAMYLOID. DR SMART; SM00006; A4_EXTRA; 1. DR SMART; SM00131; KU; 1. DR SUPFAM; SSF56491; A heparin-binding domain; 1. DR SUPFAM; SSF89811; Amyloid beta a4 protein copper binding domain (domain 2); 1. DR SUPFAM; SSF57362; BPTI-like; 1. DR SUPFAM; SSF109843; CAPPD, an extracellular domain of amyloid beta A4 protein; 1. DR PROSITE; PS00319; APP_CUBD; 1. DR PROSITE; PS51869; APP_E1; 1. DR PROSITE; PS51870; APP_E2; 1. DR PROSITE; PS00320; APP_INTRA; 1. DR PROSITE; PS00280; BPTI_KUNITZ_1; 1. DR PROSITE; PS50279; BPTI_KUNITZ_2; 1. PE 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}; 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 Secreted {ECO:0000256|ARBA:ARBA00022525}; 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}. FT SIGNAL 1..17 FT /evidence="ECO:0000256|SAM:SignalP" FT CHAIN 18..752 FT /note="Amyloid-beta A4 protein" FT /evidence="ECO:0000256|SAM:SignalP" FT /id="PRO_5040292819" FT TRANSMEM 683..705 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..565 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 399..459 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 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 //