ID A0A2R8ZBQ3_PANPA Unreviewed; 760 AA. AC A0A2R8ZBQ3; DT 20-JUN-2018, integrated into UniProtKB/TrEMBL. DT 20-JUN-2018, sequence version 1. DT 24-JAN-2024, entry version 28. DE RecName: Full=Amyloid-beta precursor protein {ECO:0000256|ARBA:ARBA00021782}; DE AltName: Full=ABPP {ECO:0000256|ARBA:ARBA00032275}; DE AltName: Full=Alzheimer disease amyloid A4 protein homolog {ECO:0000256|ARBA:ARBA00031698}; DE AltName: Full=Alzheimer disease amyloid protein {ECO:0000256|ARBA:ARBA00032685}; DE AltName: Full=Amyloid precursor protein {ECO:0000256|ARBA:ARBA00030489}; DE AltName: Full=Amyloid-beta (A4) precursor protein {ECO:0000256|ARBA:ARBA00030741}; DE AltName: Full=Amyloid-beta A4 protein {ECO:0000256|ARBA:ARBA00030344}; GN Name=APP {ECO:0000313|Ensembl:ENSPPAP00000002501.1}; OS Pan paniscus (Pygmy chimpanzee) (Bonobo). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pan. OX NCBI_TaxID=9597 {ECO:0000313|Ensembl:ENSPPAP00000002501.1, ECO:0000313|Proteomes:UP000240080}; RN [1] {ECO:0000313|Ensembl:ENSPPAP00000002501.1, ECO:0000313|Proteomes:UP000240080} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=22722832; DOI=10.1038/nature11128; RA Prufer K., Munch K., Hellmann I., Akagi K., Miller J.R., Walenz B., RA Koren S., Sutton G., Kodira C., Winer R., Knight J.R., Mullikin J.C., RA Meader S.J., Ponting C.P., Lunter G., Higashino S., Hobolth A., Dutheil J., RA Karakoc E., Alkan C., Sajjadian S., Catacchio C.R., Ventura M., RA Marques-Bonet T., Eichler E.E., Andre C., Atencia R., Mugisha L., RA Junhold J., Patterson N., Siebauer M., Good J.M., Fischer A., Ptak S.E., RA Lachmann M., Symer D.E., Mailund T., Schierup M.H., Andres A.M., Kelso J., RA Paabo S.; RT "The bonobo genome compared with the chimpanzee and human genomes."; RL Nature 486:527-531(2012). RN [2] {ECO:0000313|Ensembl:ENSPPAP00000002501.1} RP IDENTIFICATION. RG Ensembl; RL Submitted (SEP-2023) to UniProtKB. 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 Single-pass type I membrane protein {ECO:0000256|ARBA:ARBA00004251}. CC Cell projection, growth cone {ECO:0000256|ARBA:ARBA00004624}. Cell CC surface {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}. 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 EMBL; AJFE02056590; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056591; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056592; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056593; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056594; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056595; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056596; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02056597; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02065450; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJFE02065451; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR AlphaFoldDB; A0A2R8ZBQ3; -. DR Ensembl; ENSPPAT00000012046.1; ENSPPAP00000002501.1; ENSPPAG00000002732.1. DR GeneTree; ENSGT00530000063252; -. DR Proteomes; UP000240080; Chromosome 21. DR Bgee; ENSPPAG00000002732; Expressed in prefrontal cortex and 6 other cell types or 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: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: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:SF16; AMYLOID-BETA A4 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 Apoptosis {ECO:0000256|ARBA:ARBA00022703}; KW Cell membrane {ECO:0000256|ARBA:ARBA00022475}; 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 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 Glycoprotein {ECO:0000256|ARBA:ARBA00023180}; KW Golgi apparatus {ECO:0000256|ARBA:ARBA00023034}; KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius}; 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 Proteoglycan {ECO:0000256|ARBA:ARBA00022974}; KW Reference proteome {ECO:0000313|Proteomes:UP000240080}; KW Secreted {ECO:0000256|ARBA:ARBA00022525}; KW Signal {ECO:0000256|ARBA:ARBA00022729}; KW Sulfation {ECO:0000256|ARBA:ARBA00022641}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|SAM:Phobius}; Ubl conjugation {ECO:0000256|ARBA:ARBA00022843}; KW Zinc {ECO:0000256|ARBA:ARBA00022833}. FT TRANSMEM 691..713 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 18..179 FT /note="E1" FT /evidence="ECO:0000259|PROSITE:PS51869" FT DOMAIN 281..331 FT /note="BPTI/Kunitz inhibitor" FT /evidence="ECO:0000259|PROSITE:PS50279" FT DOMAIN 364..555 FT /note="E2" FT /evidence="ECO:0000259|PROSITE:PS51870" FT REGION 18..113 FT /note="GFLD subdomain" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT REGION 121..179 FT /note="CuBD subdomain" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT REGION 184..274 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 389..449 FT /evidence="ECO:0000256|SAM:Coils" FT COMPBIAS 185..200 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 215..253 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 257..274 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT DISULFID 63..107 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 88..95 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 123..177 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 134..164 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" FT DISULFID 148..176 FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217" SQ SEQUENCE 760 AA; 86077 MW; BAAF0A30E0C1593C CRC64; MLPSLFFFQV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSVMSQSLL KTTQEPLARD PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN //