CD36

Multifunctional glycoprotein that acts as a 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 (Probable). 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:18353783, PubMed:21610069). Mechanistically, binding of fatty acids activates downstream kinase LYN, which phosphorylates the palmitoyltransferase ZDHHC5 and inactivates it, resulting in the subsequent depalmitoylation of CD36 and caveolar endocytosis (PubMed:32958780). 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:18753675). Involved in oral fat perception and preferences (PubMed:22240721, PubMed:25822988). 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 intracellular 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 thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (By similarity). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting together with THBS1 (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 (By similarity) (PubMed:20037584). 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) (PubMed:16880211).

(Microbial infection) Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling.

Platelet glycoprotein IV deficiency

PG4D

A disorder characterized by macrothrombocytopenia without notable hemostatic problems and bleeding tendency. Platelet glycoprotein IV deficiency can be divided into 2 subgroups. The type I phenotype is characterized by platelets and monocytes/macrophages exhibiting complete CD36 deficiency. The type II phenotype lacks the surface expression of CD36 in platelets, but expression in monocytes/macrophages is near normal.

None

The disease is caused by variants affecting the gene represented in this entry. Patients also have postprandial hypertriglyceridemia, insulin resistance and hypertension increasing atherosclerotic risk.

Coronary heart disease 7

CHDS7

A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

N-glycosylated and O-glycosylated with a ratio of 2:1.

Palmitoylated by ZDHHC5 (PubMed:32958780). Palmitoylation is required for proper localization at the plasma membrane (PubMed:32958780, PubMed:37461827).

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:18353783, PubMed:21610069). Ubiquitination and degradation are inhibited by insulin which blocks the effect of fatty acids (PubMed:18353783).

Belongs to the CD36 family.

• Cell membrane
• Multi-pass membrane protein
• Membrane raft
• Golgi apparatus
• Apical cell membrane
• Upon ligand-binding, internalized through dynamin-dependent endocytosis.

CD36, GP3B, GP4, Platelet glycoprotein 4, Fatty acid translocase, Glycoprotein IIIb, Leukocyte differentiation antigen CD36, PAS IV, PAS-4, Platelet collagen receptor, Platelet glycoprotein IV, Thrombospondin receptor, FAT, GPIIIB, GPIV

• entrezGene:948
• omim:173510
• swissprot:P16671

Proteins

Immunology & Infectious Disease

53053Da