ID A0A2K6FBI5_PROCO Unreviewed; 772 AA.
AC A0A2K6FBI5;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 38.
DE RecName: Full=Amyloid-beta A4 protein {ECO:0000256|RuleBase:RU367156};
GN Name=APP {ECO:0000313|Ensembl:ENSPCOP00000011346.1};
OS Propithecus coquereli (Coquerel's sifaka) (Propithecus verreauxi
OS coquereli).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lemuriformes;
OC Indriidae; Propithecus.
OX NCBI_TaxID=379532 {ECO:0000313|Ensembl:ENSPCOP00000011346.1, ECO:0000313|Proteomes:UP000233160};
RN [1] {ECO:0000313|Ensembl:ENSPCOP00000011346.1}
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; A0A2K6FBI5; -.
DR STRING; 379532.ENSPCOP00000011346; -.
DR Ensembl; ENSPCOT00000021934.1; ENSPCOP00000011346.1; ENSPCOG00000017074.1.
DR GeneTree; ENSGT00530000063252; -.
DR OMA; RERMSQX; -.
DR Proteomes; UP000233160; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IEA:Ensembl.
DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
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:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0005641; C:nuclear envelope lumen; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0048786; C:presynaptic active zone; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; IEA:Ensembl.
DR GO; GO:0055037; C:recycling endosome; IEA:Ensembl.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:GOC.
DR GO; GO:0051233; C:spindle midzone; IEA:Ensembl.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0051425; F:PTB domain binding; IEA:Ensembl.
DR GO; GO:0048018; F:receptor ligand activity; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
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:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:1990000; P:amyloid fibril formation; IEA:Ensembl.
DR GO; GO:0002265; P:astrocyte activation involved in immune response; IEA:Ensembl.
DR GO; GO:0008088; P:axo-dendritic transport; IEA:Ensembl.
DR GO; GO:0016199; P:axon midline choice point recognition; IEA:Ensembl.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0048669; P:collateral sprouting in absence of injury; IEA:Ensembl.
DR GO; GO:0180011; P:cytoplasmic polyadenylation; IEA:Ensembl.
DR GO; GO:0016358; P:dendrite development; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0006878; P:intracellular copper ion homeostasis; IEA:Ensembl.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007617; P:mating behavior; IEA:Ensembl.
DR GO; GO:0014005; P:microglia development; IEA:Ensembl.
DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl.
DR GO; GO:0098815; P:modulation of excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:1990535; P:neuron projection maintenance; IEA:Ensembl.
DR GO; GO:0016322; P:neuron remodeling; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; IEA:Ensembl.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:2000406; P:positive regulation of T cell migration; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:1905606; P:regulation of presynapse assembly; IEA:Ensembl.
DR GO; GO:0150003; P:regulation of spontaneous synaptic transmission; IEA:Ensembl.
DR GO; GO:0006417; P:regulation of translation; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl.
DR GO; GO:0051124; P:synaptic assembly at neuromuscular junction; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
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:UP000233160};
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 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 SIGNAL 1..22
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 23..772
FT /note="Amyloid-beta A4 protein"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5014343921"
FT TRANSMEM 703..725
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU367156"
FT DOMAIN 31..192
FT /note="E1"
FT /evidence="ECO:0000259|PROSITE:PS51869"
FT DOMAIN 293..343
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000259|PROSITE:PS50279"
FT DOMAIN 376..567
FT /note="E2"
FT /evidence="ECO:0000259|PROSITE:PS51870"
FT REGION 31..126
FT /note="GFLD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 134..192
FT /note="CuBD subdomain"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT REGION 198..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 401..461
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 198..213
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 228..265
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 76..120
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 101..108
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 136..190
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 147..177
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
FT DISULFID 161..189
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01217"
SQ SEQUENCE 772 AA; 87400 MW; 16CED4422A079010 CRC64;
MCLLTPWFPI TLLLLWVYFS SLVPTDGNAG LLAEPQIAMF CGKLNMHMNV QNGKWESDPS
GTKTCIGTKE GILQYCQEVY PELQITNVVE ANQPVTIQNW CKRGRKQCKT HAHIVIPYRC
LVGEFVSDAL LVPDKCKFLH QERMDVCETH LHWHTVAKET CSEKSTNLHD YGMLLPCGID
KFRGVEFVCC PMAEESDNID SADAEEDDSD VWWGGADTDY ADGSEDKVVE VAEEEEVADV
EEEIEDDEDD EDGDEVEEEA EEPYEEATER TTSIAATTTT TTESVEEVVR EVCSEQAETG
PCRAMISRWY FDVTEGKCAP FFYGGCGGNR NNFDTEEYCM AVCGSVMSQS LLKTTQEPLP
QDPVKLPTTA ASTPDAVDKY LETPGDENEH AHFQKAKERL EAKHRERMSQ VMREWEEAER
QAKNLPKADK KAVIQHFQEK VESLEQEAAN ERQQLVETHM ARVEAMLNDR RRLALENYIT
ALQAVPPRPR HVFNMLKKYV RAEQKDRQHT LKHFEHVRMV DPKKAAQIRS QVMTHLRVIY
ERMNQSLSLL YNVPAVAEEI QDEVDELLQK EQNYSDDVLA NMISEPRISY GNDALMPSLT
ETKTTVELLP VNGEFSLDEL QPWHSFGADS VPANTENEVE PVDARPAADR GLTTRPGSGL
TNIKTEEISE VKMDAEFRHD SGYEVHHQKL VFFAEDVGSN KGAIIGLMVG GVVIATVIVI
TLVMLKKKQY TSIHHGVVEV DAAVTPEERH LSKMQQNGYE NPTYKFFEQM QN
//
