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Protein

Platelet glycoprotein 4

Gene

Cd36

Organism
Rattus norvegicus (Rat)
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) (PubMed:8320718). 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) (PubMed:8320718). 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) (PubMed:16276419, PubMed:21610069). Involved in oral fat perception and preferences (By similarity) (PubMed:16276419). 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) (PubMed:16276419). 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) (PubMed:23557700). 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 similarity4 Publications

Sites

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

GO - Molecular functioni

  • oleic acid binding Source: RGD
  • thrombospondin receptor activity Source: BHF-UCL
  • transforming growth factor beta binding Source: BHF-UCL

GO - Biological processi

  • amyloid fibril formation Source: UniProtKB
  • cell adhesion Source: UniProtKB-KW
  • cell surface receptor signaling pathway Source: InterPro
  • cellular response to diacyl bacterial lipopeptide Source: UniProtKB
  • cellular response to insulin stimulus Source: RGD
  • cellular response to low-density lipoprotein particle stimulus Source: UniProtKB
  • cholesterol import Source: UniProtKB
  • digestive tract development Source: RGD
  • fatty acid metabolic process Source: RGD
  • fatty acid oxidation Source: RGD
  • fatty acid transport Source: RGD
  • immune response Source: InterPro
  • interleukin-1 beta secretion Source: UniProtKB
  • intestinal absorption Source: UniProtKB
  • intestinal cholesterol absorption Source: UniProtKB
  • long-chain fatty acid import Source: UniProtKB
  • long-chain fatty acid metabolic process Source: RGD
  • long-chain fatty acid transport Source: RGD
  • negative regulation of angiogenesis Source: RGD
  • negative regulation of systemic arterial blood pressure Source: RGD
  • positive regulation of cytokine secretion Source: RGD
  • positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  • positive regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
  • receptor internalization Source: UniProtKB
  • regulation of energy homeostasis Source: UniProtKB
  • response to activity Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to fatty acid Source: UniProtKB
  • response to growth hormone Source: RGD
  • response to linoleic acid Source: UniProtKB
  • response to lipid Source: UniProtKB
  • response to mechanical stimulus Source: RGD
  • response to nutrient Source: RGD
  • sensory perception of taste Source: UniProtKB
  • triglyceride metabolic process Source: RGD
  • triglyceride transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Cell adhesion, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Platelet glycoprotein 4
Alternative name(s):
Adipocyte membrane protein
Fatty acid translocase
Fatty acid transport protein
Glycoprotein IIIb
Short name:
GPIIIB
PAS IV
PAS-4
Platelet glycoprotein IV
Short name:
GPIV
CD_antigen: CD36
Gene namesi
Name:Cd36
Synonyms:Fat
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2301. Cd36.

Subcellular locationi

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

  • apical part of cell Source: RGD
  • apical plasma membrane Source: UniProtKB-SubCell
  • brush border membrane Source: UniProtKB
  • caveola Source: RGD
  • cell surface Source: BHF-UCL
  • endoplasmic reticulum Source: RGD
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • intracellular Source: RGD
  • intracellular membrane-bounded organelle Source: RGD
  • mitochondrion Source: RGD
  • plasma membrane Source: RGD
  • protein complex Source: RGD
  • sarcolemma Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2163174.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved2 Publications
Chaini2 – 472471Platelet glycoprotein 4PRO_0000144154Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi3 – 31S-palmitoyl cysteine1 Publication
Lipidationi7 – 71S-palmitoyl cysteine1 Publication
Glycosylationi79 – 791N-linked (GlcNAc...)Sequence analysis
Glycosylationi102 – 1021N-linked (GlcNAc...)Sequence analysis
Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence analysis
Glycosylationi205 – 2051N-linked (GlcNAc...)Sequence analysis
Glycosylationi220 – 2201N-linked (GlcNAc...)Sequence analysis
Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence analysis
Disulfide bondi243 ↔ 311By similarity
Glycosylationi247 – 2471N-linked (GlcNAc...)Sequence analysis
Disulfide bondi272 ↔ 333By similarity
Disulfide bondi313 ↔ 322By similarity
Glycosylationi321 – 3211N-linked (GlcNAc...)Sequence analysis
Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence analysis
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
Cross-linki472 – 472Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubituitin)By similarity

Post-translational modificationi

Ubiquitinated at Lys-469 and Lys-472. Ubiquitination is induced by fatty acids such as oleic acid and leads to degradation by the proteasome (PubMed:21610069). Ubiquitination and degradation are inhibited by insulin which blocks the effect of fatty acids (By similarity).By similarity1 Publication

Keywords - PTMi

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

Proteomic databases

PaxDbiQ07969.
PRIDEiQ07969.

PTM databases

iPTMnetiQ07969.

Expressioni

Tissue specificityi

Expressed at high levels in heart, intestine, spleen, adipose tissue, skeletal muscle and, at lower levels, in testes.1 Publication

Developmental stagei

Induced during preadipocyte differentiation.1 Publication

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

GO - Molecular functioni

  • transforming growth factor beta binding Source: BHF-UCL

Protein-protein interaction databases

MINTiMINT-4997133.
STRINGi10116.ENSRNOP00000058398.

Chemistry

BindingDBiQ07969.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni93 – 12028Required for interaction with thrombospondins, THBS1 and THBS2By similarityAdd
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.
HOGENOMiHOG000252951.
HOVERGENiHBG002754.
InParanoidiQ07969.
PhylomeDBiQ07969.

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.

Q07969-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCDRNCGLI TGAVIGAVLA VFGGILMPVG DLLIEKTIKR EVVLEEGTIA
60 70 80 90 100
FKNWVKTGTT VYRQFWIFDV QNPEEVAKNS SKIKVKQRGP YTYRVRYLAK
110 120 130 140 150
ENITQDPKDS TVSFVQPNGA IFEPSLSVGT ENDNFTVLNL AVAAAPHIYT
160 170 180 190 200
NSFVQGVLNS LIKKSKSSMF QTRSLKELLW GYKDPFLSLV PYPISTTVGV
210 220 230 240 250
FYPYNNTVDG VYKVFNGKDN ISKVAIIDTY KGKRNLSYWE SYCDMINGTD
260 270 280 290 300
AASFPPFVEK SQTLRFFSSD ICRSIYAVFE SEVNLKGIPV YRFVLPANAF
310 320 330 340 350
ASPLQNPDNH CFCTEKVISN NCTSYGVLDI GKCKEGKPVY ISLPHFLHAS
360 370 380 390 400
PDVSEPIEGL NPNEDEHRTY LDVEPITGFT LQFAKRLQVN ILVKPARKIE
410 420 430 440 450
ALKNLKRPYI VPILWLNETG TIGDEKAEMF RNQVTGKIKL LGLVEMVLLG
460 470
VGVVMFVAFM ISYCACRSKN GK
Length:472
Mass (Da):52,731
Last modified:May 1, 2007 - v3
Checksum:i69F9513B1B85CBF0
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti67 – 671I → V in AAA02878 (PubMed:7688729).Curated
Sequence conflicti86 – 861K → I in AAA02878 (PubMed:7688729).Curated
Sequence conflicti215 – 2151F → S in AAA02878 (PubMed:7688729).Curated
Sequence conflicti257 – 2582FV → LG in AAA02878 (PubMed:7688729).Curated
Sequence conflicti262 – 2621Q → R in AAA02878 (PubMed:7688729).Curated
Sequence conflicti341 – 3411I → N in AAA02878 (PubMed:7688729).Curated
Sequence conflicti363 – 3631N → T in AAA02878 (PubMed:7688729).Curated
Sequence conflicti384 – 3841A → S in AAA02878 (PubMed:7688729).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19658 mRNA. Translation: AAA02878.1.
AF072411 mRNA. Translation: AAC24876.1.
AF113914 mRNA. Translation: AAF25552.1.
PIRiA47402.
UniGeneiRn.102418.
Rn.203220.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19658 mRNA. Translation: AAA02878.1.
AF072411 mRNA. Translation: AAC24876.1.
AF113914 mRNA. Translation: AAF25552.1.
PIRiA47402.
UniGeneiRn.102418.
Rn.203220.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4997133.
STRINGi10116.ENSRNOP00000058398.

Chemistry

BindingDBiQ07969.
ChEMBLiCHEMBL2163174.

PTM databases

iPTMnetiQ07969.

Proteomic databases

PaxDbiQ07969.
PRIDEiQ07969.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi2301. Cd36.

Phylogenomic databases

eggNOGiKOG3776. Eukaryota.
ENOG410XS17. LUCA.
HOGENOMiHOG000252951.
HOVERGENiHBG002754.
InParanoidiQ07969.
PhylomeDBiQ07969.

Miscellaneous databases

PROiQ07969.

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

  1. "Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36."
    Abumrad N.A., El-Maghrabi M.R., Amri E.-Z., Lopez E., Grimaldi P.A.
    J. Biol. Chem. 268:17665-17668(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Adipocyte.
  2. "Fatty acid translocase/CD36 mediates the uptake of palmitate by type II pneumocytes."
    Guthmann F., Haupt R., Looman A.C., Spener F., Ruestow B.
    Am. J. Physiol. 277:L191-L196(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
  3. "Potential allele of rat CD36 antigen."
    Zhang X., Mayrhofer G., Ey P.L.
    Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Dark agouti.
  4. "Purification of the major substrate for palmitoylation in rat adipocytes: N-terminal homology with CD36 and evidence for cell surface acylation."
    Jochen A., Hays J.
    J. Lipid Res. 34:1783-1792(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-31, PALMITOYLATION AT CYS-3 AND CYS-7.
    Tissue: Adipocyte.
  5. "Binding of sulfosuccinimidyl fatty acids to adipocyte membrane proteins: isolation and amino-terminal sequence of an 88-kD protein implicated in transport of long-chain fatty acids."
    Harmon C.M., Abumrad N.A.
    J. Membr. Biol. 133:43-49(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-16, FUNCTION.
    Strain: Sprague-Dawley.
    Tissue: Adipocyte.
  6. "CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions."
    Laugerette F., Passilly-Degrace P., Patris B., Niot I., Febbraio M., Montmayeur J.P., Besnard P.
    J. Clin. Invest. 115:3177-3184(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Luminal lipid regulates CD36 levels and downstream signaling to stimulate chylomicron synthesis."
    Tran T.T., Poirier H., Clement L., Nassir F., Pelsers M.M., Petit V., Degrace P., Monnot M.C., Glatz J.F., Abumrad N.A., Besnard P., Niot I.
    J. Biol. Chem. 286:25201-25210(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, UBIQUITINATION.
  8. "FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice."
    Le Foll C., Dunn-Meynell A., Musatov S., Magnan C., Levin B.E.
    Diabetes 62:2709-2716(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiCD36_RAT
AccessioniPrimary (citable) accession number: Q07969
Secondary accession number(s): Q925W0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: May 1, 2007
Last modified: May 11, 2016
This is version 118 of the entry and version 3 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.