ID A0A2K6MR25_RHIBE Unreviewed; 767 AA.
AC A0A2K6MR25;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 30.
DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156};
GN Name=APP {ECO:0000313|Ensembl:ENSRBIP00000038254.1};
OS Rhinopithecus bieti (Black snub-nosed monkey) (Pygathrix bieti).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Colobinae; Rhinopithecus.
OX NCBI_TaxID=61621 {ECO:0000313|Ensembl:ENSRBIP00000038254.1, ECO:0000313|Proteomes:UP000233180};
RN [1] {ECO:0000313|Ensembl:ENSRBIP00000038254.1, ECO:0000313|Proteomes:UP000233180}
RP NUCLEOTIDE SEQUENCE.
RA Wu, C.-I. and Zhang, Y.;
RT "Genome of Rhinopithecus bieti.";
RL Submitted (JUN-2016) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSRBIP00000038254.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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}. 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}.
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DR AlphaFoldDB; A0A2K6MR25; -.
DR Ensembl; ENSRBIT00000062271.1; ENSRBIP00000038254.1; ENSRBIG00000040908.1.
DR GeneTree; ENSGT00530000063252; -.
DR Proteomes; UP000233180; Unplaced.
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: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 Proteoglycan {ECO:0000256|ARBA:ARBA00022974};
KW Reference proteome {ECO:0000313|Proteomes:UP000233180};
KW Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Serine protease inhibitor {ECO:0000256|ARBA:ARBA00022900};
KW Signal {ECO:0000256|ARBA:ARBA00022729};
KW Sulfation {ECO:0000256|ARBA:ARBA00022641};
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 TRANSMEM 698..720
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU367156"
FT DOMAIN 25..186
FT /note="E1"
FT /evidence="ECO:0000259|PROSITE:PS51869"
FT DOMAIN 288..338
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000259|PROSITE:PS50279"
FT DOMAIN 371..562
FT /note="E2"
FT /evidence="ECO:0000259|PROSITE:PS51870"
FT REGION 25..120
FT /note="GFLD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 128..186
FT /note="CuBD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 191..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 396..456
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 192..207
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..260
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 70..114
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 95..102
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 130..184
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 141..171
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 155..183
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
SQ SEQUENCE 767 AA; 86713 MW; 784E0910BBC5FA2A CRC64;
LLPAMVIGLL TYYPAGVPTD GNAGLLAEPQ IAMFCGRLNM HMNVQNGKWD SDPSGTKTCI
DTKEGILQYC QEVYPELQIT NVVEANQPVT IQNWCKRGRK QCKTHPHFVI PYRCLVGEFV
SDALLVPDKC KFLHQERMDV CETHLHWHTV AKETCSEKST NLHDYGMLLP CGIDKFRGVE
FVCCPLAEES DNVDSADAEE DDSDVWWGGA DTDYADGSED KVVEVAEEEE VAEVEEEEAD
DDEDDEDGDE VEEEAEEPYE EATERTTSIA TTTTTTTESV EEVVREVCSE QAETGPCRAM
ISRWYFDVTE GKCAPFFYGG CGGNRNNFDT EEYCMAVCGS VMSQSLRKTT REPLTQDPVK
LPTTAASTPD AVDKYLETPG DENEHAHFQK AKERLEAKHR ERMSQVMREW EEAERQAKNL
PKADKKAVIQ HFQEKVESLE QEAANERQQL VETHMARVEA MLNDRRRLAL ENYITALQAV
PPRPRHVFNM LKKYVRAEQK DRQHTLKHFE HVRMVDPKKA AQIRSQVMTH LRVIYERMNQ
SLSLLYNVPA VAEEIQDEVD ELLQKEQNYS DDVLANMISE PRISYGNDAL MPSLTETKTT
VELLPVNGEF SLDDLQPWHS FGADSVPANT ENEVEPVDAR PAADRGLTTR PGSGLTNIKT
EEISEVKMDA EFRHDSGYEV HHQKLVFFAE DVGSNKGAII GLMVGGVVIA TVIVITLVML
KKKQYTSIHH GVVEVDAAVT PEERHLSKMQ QNGYENPTYK FFEQMQN
//
