CD36

94812491ENSG00000135218ENSMUSG00000002944P16671Q08857NM_001289908NM_001289909NM_001289911NM_001159555NM_001159556NM_001159557NM_001159558NM_007643NP_001276837NP_001276838NP_001276840NP_001153027NP_001153028NP_001153029NP_001153030NP_031669CD36 (cluster of differentiation 36), also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is encoded by the CD36 gene. The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids. CD36 (cluster of differentiation 36), also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is encoded by the CD36 gene. The CD36 antigen is an integral membrane protein found on the surface of many cell types in vertebrate animals. It imports fatty acids inside cells and is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids. Work in genetically modified rodents suggest a role for CD36 in fatty acid metabolism, heart disease, taste, and dietary fat processing in the intestine. It may be involved in glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy and Alzheimer's disease. In humans, rats and mice, CD36 consists of 472 amino acids with a predicted molecular weight of approximately 53,000 Da. However, CD36 is extensively glycosylated and has an apparent molecular weight of 88,000 Da as determined by SDS polyacrylamide gel electrophoresis. Using Kyte-Doolittle analysis, the amino acid sequence of CD36 predicts a hydrophobic region near each end of the protein large enough to span cellular membranes. Based on this notion and the observation that CD36 is found on the surface of cells, CD36 is thought to have a 'hairpin-like' structure with α-helices at the C- and N- termini projecting through the membrane and a larger extracellular loop (Fig. 1). This topology is supported by transfection experiments in cultured cells using deletion mutants of CD36. Based on the crystal structure of the homologous SCARB2, a model of the extracellullar domain of CD36 has been produced. Like SCARB2, CD36 is proposed to contain an antiparallel β-barrel core with many short α-helices adorning it. The structure is predicted to contain a hydrophobic transport tunnel. Disulfide linkages between 4 of the 6 cysteine residues in the extracellular loop are required for efficient intracellular processing and transport of CD36 to the plasma membrane. It is not clear what role these linkages play on the function of the mature CD36 protein on the cell surface. Besides glycosylation, additional posttranslational modifications have been reported for CD36. CD36 is modified with 4 palmitoyl chains, 2 on each of the two intracellular domains. The function of these lipid modifications is currently unknown but they likely promote the association of CD36 with the membrane and possibly lipid rafts which appear to be important for some CD36 functions. CD36 could be also phosphorylated at Y62, T92, T323, ubiquitinated at K56, K469, K472 and acetylated at K52, K56, K166, K231, K394, K398, K403. In the absence of ligand, membrane bound CD36 exists primarily in a monomeric state. However exposure to the thrombospondin ligand causes CD36 to dimerize. This dimerization has been proposed to play an important role in CD36 signal transduction. In humans, the gene is located on the long arm of chromosome 7 at band 11.2 (7q11.2) and is encoded by 15 exons that extend over more than 32 kilobases. Both the 5' and the 3' untranslated regions contain introns: the 5' with two and the 3' one. Exons 1, 2 and first 89 nucleotides of exon 3 and as well as exon 15 are non-coding. Exon 3 contains encodes the N-terminal cytoplasmic and transmembrane domains. The C-terminal cytoplasmic and transmembrane regions is encoded by exon 14. The extracellular domain is encoded by the central 11 exons. Alternative splicing of the untranslated regions gives rise to at least two mRNA species. The transcription initiation site of the CD36 gene has been mapped to 289 nucleotides upstream from the translational start codon and a TATA box and several putative cis regulatory regions lie further 5'. A binding site for PEBP2/CBF factors has been identified between -158 and -90 and disruption of this site reduces expression. The gene is the transcriptional control of the nuclear receptor PPAR/RXR heterodimer (Peroxisome proliferator-activated receptor – Retinoid X receptor) and gene expression can be up regulated using synthetic and natural ligands for PPAR and RXR, including the thiazolidinedione class of anti-diabetic drugs and the vitamin A metabolite 9-cis-retinoic acid respectively.