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Protein

Platelet glycoprotein 4

Gene

CD36

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (By similarity). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (By similarity). In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway (By similarity). Involved in oral fat perception and preferences (By similarity). Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions (By similarity). In taste receptor cells, mediates the induction of an increase in intracellulare calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (By similarity). Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis (By similarity). Receptor for thombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (By similarity). As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome. Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei463 – 4631Critical for TLR4-TLR6 dimerization and signalingBy similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Cell adhesion, Transport

Enzyme and pathway databases

ReactomeiR-BTA-114608. Platelet degranulation.
R-BTA-1236973. Cross-presentation of particulate exogenous antigens (phagosomes).
R-BTA-3000471. Scavenging by Class B Receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Platelet glycoprotein 4
Alternative name(s):
Glycoprotein IIIb
Short name:
GPIIIB
PAS IV
PAS-4
Platelet glycoprotein IV
Short name:
GPIV
CD_antigen: CD36
Gene namesi
Name:CD36
Synonyms:PAS4
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 4

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Membrane raft By similarity
  • Golgi apparatus By similarity
  • Apical cell membrane By similarity

  • Note: Upon ligand-binding, internalized through dynamin-dependent endocytosis.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 76CytoplasmicSequence analysis
Transmembranei8 – 2922HelicalSequence analysisAdd
BLAST
Topological domaini30 – 439410ExtracellularSequence analysisAdd
BLAST
Transmembranei440 – 46122HelicalSequence analysisAdd
BLAST
Topological domaini462 – 47211CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 472471Platelet glycoprotein 4PRO_0000144150Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi3 – 31S-palmitoyl cysteineBy similarity
Lipidationi7 – 71S-palmitoyl cysteineBy similarity
Glycosylationi79 – 791N-linked (GlcNAc...)1 Publication
Glycosylationi102 – 1021N-linked (GlcNAc...)1 Publication
Glycosylationi172 – 1721N-linked (GlcNAc...)1 Publication
Glycosylationi205 – 2051N-linked (GlcNAc...)1 Publication
Glycosylationi235 – 2351N-linked (GlcNAc...)1 Publication
Disulfide bondi243 ↔ 3111 Publication
Glycosylationi247 – 2471N-linked (GlcNAc...)1 Publication
Disulfide bondi272 ↔ 3331 Publication
Disulfide bondi313 ↔ 3221 Publication
Glycosylationi321 – 3211N-linked (GlcNAc...)1 Publication
Glycosylationi417 – 4171N-linked (GlcNAc...)1 Publication
Lipidationi464 – 4641S-palmitoyl cysteineBy similarity
Lipidationi466 – 4661S-palmitoyl cysteineBy similarity
Cross-linki469 – 469Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubituitin)By similarity

Post-translational modificationi

Ubiquitinated at Lys-469. Ubiquitination is induced by fatty acids such as oleic acid and leads to degradation by the proteasome. Ubiquitination and degradation are inhibited by insulin which blocks the effect of fatty acids.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PaxDbiP26201.

PTM databases

UniCarbKBiP26201.

Interactioni

Subunit structurei

Interacts with THBS1 and THBS2; the interactions mediate the THBS antiangiogenic activity. Upon interaction with a ligand, such as oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42, rapidly forms a complex with TLR4 and TLR6; the complex is internalized and triggers an inflammatory signal. Through its C-terminus, interacts with PTK2, PXN and LYN, but not with SRC. LYN kinase activity is required for facilitating TLR4:TLR6 heterodimerization and signal initiation. Upon interaction with ligands such as diacylated lipopeptides, interacts with the TLR2:TLR6 heterodimer (By similarity). Interacts with CD9, CD81, FCER1G, ITGB2 and/or ITGB2; forming a membrane heteromeric complex required for the internalization of CD36 and its ligands (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000023750.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni93 – 12028Required for interaction with thrombospondins, THBS1 and THBS2Add
BLAST
Regioni460 – 47213Interaction with PTK2, PXN and LYNBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the CD36 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3776. Eukaryota.
ENOG410XS17. LUCA.
GeneTreeiENSGT00530000062927.
HOGENOMiHOG000252951.
HOVERGENiHBG002754.
InParanoidiP26201.
KOiK06259.
OMAiNTVSFLQ.
OrthoDBiEOG79SDWX.
TreeFamiTF317925.

Family and domain databases

InterProiIPR005428. CD36/SCARB1/SNMP1.
IPR033076. CD36_chordates.
IPR002159. CD36_fam.
[Graphical view]
PANTHERiPTHR11923. PTHR11923. 1 hit.
PTHR11923:SF12. PTHR11923:SF12. 1 hit.
PfamiPF01130. CD36. 1 hit.
[Graphical view]
PRINTSiPR01610. CD36ANTIGEN.
PR01609. CD36FAMILY.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P26201-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCNRNCGLI AGAVIGAVLA VFGGILMPVG DMLIEKTIKK EVVLEEGTIA
60 70 80 90 100
FKNWVKTGTD VYRQFWIFDV QNPDEVTVNS SKIKVKQRGP YTYRVRYLAK
110 120 130 140 150
ENITQDPETH TVSFLQPNGA IFEPSLSVGT EDDTFTILNL AVAAAPQLYP
160 170 180 190 200
NTFMQGILNS FIKKSKSSMF QNRTLKELLW GYTDPFLNLV PYPITTTIGV
210 220 230 240 250
FYPYNNTADG IYKVFNGKDD ISKVAIIDTY KGRKNLSYWS SYCDLINGTD
260 270 280 290 300
AASFPPFVEK TRVLQFFSSD ICRSIYAVFG AEINLKGIPV YRFILPSFAF
310 320 330 340 350
ASPFQNPDNH CFCTEKIISK NCTLYGVLDI GKCKEGKPVY ISLPHFLHGS
360 370 380 390 400
PELAEPIESL SPNEEEHSTY LDVEPITGFT LRFAKRLQVN MLVKPAKKIE
410 420 430 440 450
ALKNLKHNYI VPILWLNETG TIGDEKAEMF RNQVTGKINL LGLVEIVLLS
460 470
VGVVMFIAFM ISYCACRSKR VN
Length:472
Mass (Da):52,940
Last modified:January 23, 2007 - v5
Checksum:iD864D6D3D6E8622F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 391K → N in CAA62803 (PubMed:8950178).Curated
Sequence conflicti110 – 1101H → N in BAA08224 (Ref. 1) Curated
Sequence conflicti125 – 1251S → L in BAA08224 (Ref. 1) Curated
Sequence conflicti134 – 1341T → K in BAA08224 (Ref. 1) Curated
Sequence conflicti257 – 2571F → L in BAA08224 (Ref. 1) Curated
Sequence conflicti294 – 2941I → V in BAA08224 (Ref. 1) Curated
Sequence conflicti305 – 3051Q → E in BAA08224 (Ref. 1) Curated
Sequence conflicti359 – 3591S → G in BAA08224 (Ref. 1) Curated
Sequence conflicti391 – 3966MLVKPA → TGQARQ in BAA08224 (Ref. 1) Curated
Sequence conflicti466 – 4661C → Y in BAA08224 (Ref. 1) Curated
Sequence conflicti470 – 4723RVN → TIK in BAA08224 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D45364 mRNA. Translation: BAA08224.1.
X91503 mRNA. Translation: CAA62803.1.
BC103112 mRNA. Translation: AAI03113.1.
RefSeqiNP_001265550.1. NM_001278621.1.
NP_776435.2. NM_174010.3.
XP_005205381.1. XM_005205324.3.
XP_005205382.1. XM_005205325.3.
XP_005205383.1. XM_005205326.3.
XP_010802458.1. XM_010804156.2.
XP_010802459.1. XM_010804157.2.
XP_015324298.1. XM_015468812.1.
XP_015324300.1. XM_015468814.1.
XP_015324301.1. XM_015468815.1.
XP_015324304.1. XM_015468818.1.
UniGeneiBt.43948.

Genome annotation databases

EnsembliENSBTAT00000023750; ENSBTAP00000023750; ENSBTAG00000017866.
GeneIDi281052.
KEGGibta:281052.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D45364 mRNA. Translation: BAA08224.1.
X91503 mRNA. Translation: CAA62803.1.
BC103112 mRNA. Translation: AAI03113.1.
RefSeqiNP_001265550.1. NM_001278621.1.
NP_776435.2. NM_174010.3.
XP_005205381.1. XM_005205324.3.
XP_005205382.1. XM_005205325.3.
XP_005205383.1. XM_005205326.3.
XP_010802458.1. XM_010804156.2.
XP_010802459.1. XM_010804157.2.
XP_015324298.1. XM_015468812.1.
XP_015324300.1. XM_015468814.1.
XP_015324301.1. XM_015468815.1.
XP_015324304.1. XM_015468818.1.
UniGeneiBt.43948.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000023750.

PTM databases

UniCarbKBiP26201.

Proteomic databases

PaxDbiP26201.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000023750; ENSBTAP00000023750; ENSBTAG00000017866.
GeneIDi281052.
KEGGibta:281052.

Organism-specific databases

CTDi948.

Phylogenomic databases

eggNOGiKOG3776. Eukaryota.
ENOG410XS17. LUCA.
GeneTreeiENSGT00530000062927.
HOGENOMiHOG000252951.
HOVERGENiHBG002754.
InParanoidiP26201.
KOiK06259.
OMAiNTVSFLQ.
OrthoDBiEOG79SDWX.
TreeFamiTF317925.

Enzyme and pathway databases

ReactomeiR-BTA-114608. Platelet degranulation.
R-BTA-1236973. Cross-presentation of particulate exogenous antigens (phagosomes).
R-BTA-3000471. Scavenging by Class B Receptors.

Family and domain databases

InterProiIPR005428. CD36/SCARB1/SNMP1.
IPR033076. CD36_chordates.
IPR002159. CD36_fam.
[Graphical view]
PANTHERiPTHR11923. PTHR11923. 1 hit.
PTHR11923:SF12. PTHR11923:SF12. 1 hit.
PfamiPF01130. CD36. 1 hit.
[Graphical view]
PRINTSiPR01610. CD36ANTIGEN.
PR01609. CD36FAMILY.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA cloning of PAS-4 from bovine fat globule membrane."
    Hwangbo S., Ametani M., Kanno C.
    Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Holstein.
    Tissue: Mammary gland.
  2. "Structural characterization of bovine CD36 from the milk fat globule membrane."
    Berglund L., Petersen T.E., Ramussen J.T.
    Biochim. Biophys. Acta 1309:63-68(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION AT ASN-79; ASN-102; ASN-172; ASN-205; ASN-235; ASN-247; ASN-321 AND ASN-417.
    Tissue: Mammary gland.
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Heart ventricle.
  4. "Structural, functional, and antigenic differences between bovine heart endothelial CD36 and human platelet CD36."
    Greenwalt D.E., Watt K.W.K., Hasler T., Howard R.J., Patel S.
    J. Biol. Chem. 265:16296-16299(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-22, FUNCTION.
    Tissue: Heart.
  5. "PAS IV, an integral membrane protein of mammary epithelial cells, is related to platelet and endothelial cell CD36 (GP IV)."
    Greenwalt D.E., Watt K.W., So O.Y., Jiwani N.
    Biochemistry 29:7054-7059(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 4-22 AND 214-223.
    Tissue: Mammary epithelium.
  6. Cited for: DISULFIDE BONDS.
    Tissue: Milk.

Entry informationi

Entry nameiCD36_BOVIN
AccessioniPrimary (citable) accession number: P26201
Secondary accession number(s): P79111, Q28154, Q3ZBT7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: January 23, 2007
Last modified: June 8, 2016
This is version 120 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.