CD36_BOVIN
ID CD36_BOVIN Reviewed; 472 AA.
AC P26201; P79111; Q28154; Q3ZBT7;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Platelet glycoprotein 4;
DE AltName: Full=Glycoprotein IIIb;
DE Short=GPIIIB;
DE AltName: Full=PAS IV;
DE AltName: Full=PAS-4;
DE AltName: Full=Platelet glycoprotein IV;
DE Short=GPIV;
DE AltName: CD_antigen=CD36;
GN Name=CD36; Synonyms=PAS4;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=Mammary gland;
RA Hwangbo S., Ametani M., Kanno C.;
RT "cDNA cloning of PAS-4 from bovine fat globule membrane.";
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND GLYCOSYLATION AT ASN-79; ASN-102; ASN-172;
RP ASN-205; ASN-235; ASN-247; ASN-321 AND ASN-417.
RC TISSUE=Mammary gland;
RX PubMed=8950178; DOI=10.1016/s0167-4781(96)00143-1;
RA Berglund L., Petersen T.E., Ramussen J.T.;
RT "Structural characterization of bovine CD36 from the milk fat globule
RT membrane.";
RL Biochim. Biophys. Acta 1309:63-68(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 2-22, AND FUNCTION.
RC TISSUE=Heart;
RX PubMed=1697855; DOI=10.1016/s0021-9258(17)46221-1;
RA Greenwalt D.E., Watt K.W.K., Hasler T., Howard R.J., Patel S.;
RT "Structural, functional, and antigenic differences between bovine heart
RT endothelial CD36 and human platelet CD36.";
RL J. Biol. Chem. 265:16296-16299(1990).
RN [5]
RP PROTEIN SEQUENCE OF 4-22 AND 214-223.
RC TISSUE=Mammary epithelium;
RX PubMed=1699598; DOI=10.1021/bi00482a015;
RA Greenwalt D.E., Watt K.W., So O.Y., Jiwani N.;
RT "PAS IV, an integral membrane protein of mammary epithelial cells, is
RT related to platelet and endothelial cell CD36 (GP IV).";
RL Biochemistry 29:7054-7059(1990).
RN [6]
RP DISULFIDE BONDS.
RC TISSUE=Milk;
RX PubMed=9826197; DOI=10.1046/j.1432-1327.1998.2570488.x;
RA Rasmussen J.T., Berglund L., Rasmussen M.S., Petersen T.E.;
RT "Assignment of disulfide bridges in bovine CD36.";
RL Eur. J. Biochem. 257:488-494(1998).
CC -!- FUNCTION: Multifunctional glycoprotein that acts as receptor for a
CC broad range of ligands. Ligands can be of proteinaceous nature like
CC thrombospondin, fibronectin, collagen or amyloid-beta as well as of
CC lipidic nature such as oxidized low-density lipoprotein (oxLDL),
CC anionic phospholipids, long-chain fatty acids and bacterial diacylated
CC lipopeptides. They are generally multivalent and can therefore engage
CC multiple receptors simultaneously, the resulting formation of CD36
CC clusters initiates signal transduction and internalization of receptor-
CC ligand complexes. The dependency on coreceptor signaling is strongly
CC ligand specific. Cellular responses to these ligands are involved in
CC angiogenesis, inflammatory response, fatty acid metabolism, taste and
CC dietary fat processing in the intestine (By similarity). Binds long-
CC chain fatty acids and facilitates their transport into cells, thus
CC participating in muscle lipid utilization, adipose energy storage, and
CC gut fat absorption (By similarity). Mechanistically, binding of fatty
CC acids activates downstream kinase LYN, which phosphorylates the
CC palmitoyltransferase ZDHHC5 and inactivates it resulting in the
CC subsequent depalmitoylation of CD36 and caveolar endocytosis (By
CC similarity). In the small intestine, plays a role in proximal
CC absorption of dietary fatty acid and cholesterol for optimal
CC chylomicron formation, possibly through the activation of MAPK1/3
CC (ERK1/2) signaling pathway (By similarity). Involved in oral fat
CC perception and preferences (By similarity). Detection into the tongue
CC of long-chain fatty acids leads to a rapid and sustained rise in flux
CC and protein content of pancreatobiliary secretions (By similarity). In
CC taste receptor cells, mediates the induction of an increase in
CC intracellular calcium levels by long-chain fatty acids, leading to the
CC activation of the gustatory neurons in the nucleus of the solitary
CC tract (By similarity). Important factor in both ventromedial
CC hypothalamus neuronal sensing of long-chain fatty acid and the
CC regulation of energy and glucose homeostasis (By similarity). Receptor
CC for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic
CC effects (By similarity). As a coreceptor for TLR4:TLR6 heterodimer,
CC promotes inflammation in monocytes/macrophages. Upon ligand binding,
CC such as oxLDL or amyloid-beta 42, interacts with the heterodimer
CC TLR4:TLR6, the complex is internalized and triggers inflammatory
CC response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2
CC and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via
CC TICAM1 signaling pathway, as well as IL1B secretion, through the
CC priming and activation of the NLRP3 inflammasome. Selective and
CC nonredundant sensor of microbial diacylated lipopeptide that signal via
CC TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell
CC surface, leading to the NF-kappa-B-dependent production of TNF, via
CC MYD88 signaling pathway and subsequently is targeted to the Golgi in a
CC lipid-raft dependent pathway (By similarity).
CC {ECO:0000250|UniProtKB:P16671, ECO:0000250|UniProtKB:Q07969,
CC ECO:0000250|UniProtKB:Q08857}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoate(out) = butanoate(in); Xref=Rhea:RHEA:45248,
CC ChEBI:CHEBI:17968; Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45249;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate(out) = (9Z)-octadecenoate(in);
CC Xref=Rhea:RHEA:33655, ChEBI:CHEBI:30823;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33656;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate(out) = (9Z,12Z)-
CC octadecadienoate(in); Xref=Rhea:RHEA:45264, ChEBI:CHEBI:30245;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45265;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetradecanoate(out) = tetradecanoate(in);
CC Xref=Rhea:RHEA:45252, ChEBI:CHEBI:30807;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45253;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate(out) = hexadecanoate(in); Xref=Rhea:RHEA:45256,
CC ChEBI:CHEBI:7896; Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45257;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetracosanoate(out) = tetracosanoate(in);
CC Xref=Rhea:RHEA:45260, ChEBI:CHEBI:31014;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45261;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- SUBUNIT: Interacts with THBS1 and THBS2; the interactions mediate the
CC THBS antiangiogenic activity. Upon interaction with a ligand, such as
CC oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42, rapidly
CC forms a complex with TLR4 and TLR6; the complex is internalized and
CC triggers an inflammatory signal. Through its C-terminus, interacts with
CC PTK2, PXN and LYN, but not with SRC. LYN kinase activity is required
CC for facilitating TLR4:TLR6 heterodimerization and signal initiation.
CC Upon interaction with ligands such as diacylated lipopeptides,
CC interacts with the TLR2:TLR6 heterodimer (By similarity). Interacts
CC with CD9, CD81, FCER1G, ITGB2 and/or ITGB2; forming a membrane
CC heteromeric complex required for the internalization of CD36 and its
CC ligands (By similarity). {ECO:0000250|UniProtKB:P16671,
CC ECO:0000250|UniProtKB:Q08857}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P16671};
CC Multi-pass membrane protein {ECO:0000255}. Membrane raft
CC {ECO:0000250|UniProtKB:P16671}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P16671}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q08857}. Note=Upon ligand-binding, internalized
CC through dynamin-dependent endocytosis. {ECO:0000250|UniProtKB:P16671}.
CC -!- PTM: Palmitoylated by ZDHHC5. Palmitoylation is required for proper
CC localization at the plasma membrane. {ECO:0000250|UniProtKB:P16671}.
CC -!- PTM: Ubiquitinated at Lys-469. Ubiquitination is induced by fatty acids
CC such as oleic acid and leads to degradation by the proteasome.
CC Ubiquitination and degradation are inhibited by insulin which blocks
CC the effect of fatty acids. {ECO:0000250|UniProtKB:P16671,
CC ECO:0000250|UniProtKB:Q08857}.
CC -!- SIMILARITY: Belongs to the CD36 family. {ECO:0000305}.
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DR EMBL; D45364; BAA08224.1; -; mRNA.
DR EMBL; X91503; CAA62803.1; -; mRNA.
DR EMBL; BC103112; AAI03113.1; -; mRNA.
DR RefSeq; NP_001265550.1; NM_001278621.1.
DR RefSeq; NP_776435.2; NM_174010.3.
DR RefSeq; XP_005205381.1; XM_005205324.3.
DR RefSeq; XP_005205382.1; XM_005205325.3.
DR RefSeq; XP_005205383.1; XM_005205326.3.
DR RefSeq; XP_010802458.1; XM_010804156.2.
DR RefSeq; XP_010802459.1; XM_010804157.2.
DR RefSeq; XP_015324298.1; XM_015468812.1.
DR RefSeq; XP_015324300.1; XM_015468814.1.
DR RefSeq; XP_015324301.1; XM_015468815.1.
DR RefSeq; XP_015324304.1; XM_015468818.1.
DR AlphaFoldDB; P26201; -.
DR SMR; P26201; -.
DR STRING; 9913.ENSBTAP00000023750; -.
DR CarbonylDB; P26201; -.
DR GlyConnect; 506; 37 N-Linked glycans.
DR iPTMnet; P26201; -.
DR PaxDb; P26201; -.
DR PeptideAtlas; P26201; -.
DR PRIDE; P26201; -.
DR Ensembl; ENSBTAT00000023750; ENSBTAP00000023750; ENSBTAG00000017866.
DR Ensembl; ENSBTAT00000073723; ENSBTAP00000066341; ENSBTAG00000017866.
DR Ensembl; ENSBTAT00000080828; ENSBTAP00000061478; ENSBTAG00000017866.
DR GeneID; 281052; -.
DR KEGG; bta:281052; -.
DR CTD; 948; -.
DR VEuPathDB; HostDB:ENSBTAG00000017866; -.
DR eggNOG; KOG3776; Eukaryota.
DR GeneTree; ENSGT00940000153372; -.
DR HOGENOM; CLU_019853_0_0_1; -.
DR InParanoid; P26201; -.
DR OMA; NCTIAGV; -.
DR OrthoDB; 1106566at2759; -.
DR TreeFam; TF317925; -.
DR Reactome; R-BTA-114608; Platelet degranulation.
DR Reactome; R-BTA-434313; Intracellular metabolism of fatty acids regulates insulin secretion.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 4.
DR Bgee; ENSBTAG00000017866; Expressed in omental fat pad and 103 other tissues.
DR ExpressionAtlas; P26201; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005901; C:caveola; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; IBA:GO_Central.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IBA:GO_Central.
DR GO; GO:0005044; F:scavenger receptor activity; IBA:GO_Central.
DR GO; GO:1990000; P:amyloid fibril formation; ISS:UniProtKB.
DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
DR GO; GO:0070508; P:cholesterol import; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0050892; P:intestinal absorption; ISS:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; ISS:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IBA:GO_Central.
DR GO; GO:0042953; P:lipoprotein transport; IBA:GO_Central.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; ISS:UniProtKB.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:0070543; P:response to linoleic acid; ISS:UniProtKB.
DR GO; GO:0033993; P:response to lipid; ISS:UniProtKB.
DR GO; GO:0050909; P:sensory perception of taste; ISS:UniProtKB.
DR GO; GO:0034197; P:triglyceride transport; ISS:UniProtKB.
DR InterPro; IPR005428; CD36/SCARB1/SNMP1.
DR InterPro; IPR033076; CD36_chordates.
DR InterPro; IPR002159; CD36_fam.
DR PANTHER; PTHR11923; PTHR11923; 1.
DR PANTHER; PTHR11923:SF12; PTHR11923:SF12; 1.
DR Pfam; PF01130; CD36; 1.
DR PRINTS; PR01610; CD36ANTIGEN.
DR PRINTS; PR01609; CD36FAMILY.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Isopeptide bond; Lipid transport;
KW Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1697855"
FT CHAIN 2..472
FT /note="Platelet glycoprotein 4"
FT /id="PRO_0000144150"
FT TOPO_DOM 2..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..439
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 93..120
FT /note="Required for interaction with thrombospondins, THBS1
FT and THBS2"
FT REGION 460..472
FT /note="Interaction with PTK2, PXN and LYN"
FT /evidence="ECO:0000250|UniProtKB:P16671"
FT SITE 463
FT /note="Critical for TLR4-TLR6 dimerization and signaling"
FT /evidence="ECO:0000250|UniProtKB:P16671"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 7
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 464
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 466
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8950178"
FT DISULFID 243..311
FT /evidence="ECO:0000269|PubMed:9826197"
FT DISULFID 272..333
FT /evidence="ECO:0000269|PubMed:9826197"
FT DISULFID 313..322
FT /evidence="ECO:0000269|PubMed:9826197"
FT CROSSLNK 469
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16671"
FT CONFLICT 39
FT /note="K -> N (in Ref. 2; CAA62803)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="H -> N (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="S -> L (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="T -> K (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 257
FT /note="F -> L (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="I -> V (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="Q -> E (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="S -> G (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 391..396
FT /note="MLVKPA -> TGQARQ (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 466
FT /note="C -> Y (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
FT CONFLICT 470..472
FT /note="RVN -> TIK (in Ref. 1; BAA08224)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 472 AA; 52940 MW; D864D6D3D6E8622F CRC64;
MGCNRNCGLI AGAVIGAVLA VFGGILMPVG DMLIEKTIKK EVVLEEGTIA FKNWVKTGTD
VYRQFWIFDV QNPDEVTVNS SKIKVKQRGP YTYRVRYLAK ENITQDPETH TVSFLQPNGA
IFEPSLSVGT EDDTFTILNL AVAAAPQLYP NTFMQGILNS FIKKSKSSMF QNRTLKELLW
GYTDPFLNLV PYPITTTIGV FYPYNNTADG IYKVFNGKDD ISKVAIIDTY KGRKNLSYWS
SYCDLINGTD AASFPPFVEK TRVLQFFSSD ICRSIYAVFG AEINLKGIPV YRFILPSFAF
ASPFQNPDNH CFCTEKIISK NCTLYGVLDI GKCKEGKPVY ISLPHFLHGS PELAEPIESL
SPNEEEHSTY LDVEPITGFT LRFAKRLQVN MLVKPAKKIE ALKNLKHNYI VPILWLNETG
TIGDEKAEMF RNQVTGKINL LGLVEIVLLS VGVVMFIAFM ISYCACRSKR VN
