ID G3VGV5_SARHA Unreviewed; 688 AA.
AC G3VGV5;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 07-APR-2021, sequence version 2.
DT 27-MAR-2024, entry version 60.
DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156};
GN Name=APP {ECO:0000313|Ensembl:ENSSHAP00000002409.2};
OS Sarcophilus harrisii (Tasmanian devil) (Sarcophilus laniarius).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Dasyuromorphia; Dasyuridae; Sarcophilus.
OX NCBI_TaxID=9305 {ECO:0000313|Ensembl:ENSSHAP00000002409.2, ECO:0000313|Proteomes:UP000007648};
RN [1] {ECO:0000313|Ensembl:ENSSHAP00000002409.2, ECO:0000313|Proteomes:UP000007648}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21709235; DOI=10.1073/pnas.1102838108;
RA Miller W., Hayes V.M., Ratan A., Petersen D.C., Wittekindt N.E., Miller J.,
RA Walenz B., Knight J., Qi J., Zhao F., Wang Q., Bedoya-Reina O.C.,
RA Katiyar N., Tomsho L.P., Kasson L.M., Hardie R.A., Woodbridge P.,
RA Tindall E.A., Bertelsen M.F., Dixon D., Pyecroft S., Helgen K.M.,
RA Lesk A.M., Pringle T.H., Patterson N., Zhang Y., Kreiss A., Woods G.M.,
RA Jones M.E., Schuster S.C.;
RT "Genetic diversity and population structure of the endangered marsupial
RT Sarcophilus harrisii (Tasmanian devil).";
RL Proc. Natl. Acad. Sci. U.S.A. 108:12348-12353(2011).
RN [2] {ECO:0000313|Ensembl:ENSSHAP00000002409.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-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; G3VGV5; -.
DR Ensembl; ENSSHAT00000002435.2; ENSSHAP00000002409.2; ENSSHAG00000002134.2.
DR GeneTree; ENSGT00530000063252; -.
DR Proteomes; UP000007648; Unassembled WGS sequence.
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 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|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:UP000007648};
KW Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Serine protease inhibitor {ECO:0000256|ARBA:ARBA00022900};
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}.
FT TRANSMEM 619..641
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU367156"
FT DOMAIN 1..127
FT /note="E1"
FT /evidence="ECO:0000259|PROSITE:PS51869"
FT DOMAIN 228..278
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000259|PROSITE:PS50279"
FT DOMAIN 292..483
FT /note="E2"
FT /evidence="ECO:0000259|PROSITE:PS51870"
FT REGION 1..61
FT /note="GFLD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 69..127
FT /note="CuBD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 170..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 343..377
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 170..198
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 36..43
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 71..125
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 82..112
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 96..124
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
SQ SEQUENCE 688 AA; 78212 MW; F4168B9CFDB68ACD CRC64;
MFHPTSYLCP QAKVYPELQI TNVVEANQPV TIQNWCKRGR KQCKSSPHIV IPYRCLVGEF
VSDALLVPDK CKFLHQERMD ICETHLHWHT VAKETCSEKS MNLHNYGMLL PCGIDKFRGV
EFVCCPLADE NDNVDSADAE DDDSEVWWGG ADADYADGSD DKVIEVAEEE EVVDVEDEDN
NDDDGDGDEV EETEEQYEEA TERTTSVAST TTTTTTTESV EEVVREVCSE QAETGPCQAM
ISRWYFDVTE RKCAPFFYGG CGGNRNNFGT EEYCMAVCGN IIPTTAASTP DAVDKYLETP
GDENEHAHFQ KAKERLEAKH RERMSQVMRE WEEAEHQAKN LPKADKKAVI QHFQEKVESL
EQEAANERQQ LVETHMARVE AMLNDRRRMA LENYITALQA VPPRPRHVFN MLKKYVRAEQ
KDRQHTLKHF EHVRMVDPKK AAQIRSQVMT HLRVIYERMN QSLSLLYNVP AVAEEIQDEV
DELLQKEQNY SDDVLANMIS EPRISYGNDA LMPSLSETKT TVELLPVDGE FSLDDLQPWH
PFGVDSVPAN TENEVEPVDA RPAADRGLTT RPGSGLTNIK TEEISEVKMD AEFRHDSGYE
VHHQKLVFFA EDMSSNKGAI IGLMVGGIVI ATVIVFTLVM LRKKQYTSIH HGVVEIDAAV
TPEERHLSKM QQNGYENPTY KFFEQMQN
//
