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FUNCTION 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 (PubMed:7685021). 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) (PubMed:19847289, PubMed:20037584, PubMed:23395392). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (PubMed:30605677). Mechanistically, palmitoylated CD36 captures fatty acids on the cell surface, the binding of fatty acids activates downstream kinase LYN, which phosphorylates the palmitoyltransferase ZDHHC5 and inactivates it, resulting in the subsequent depalmitoylation of CD36, a step needed to initiate the endocytic process and delivery of fatty acids into the cell (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:17507371, PubMed:18753675, PubMed:21610069). Involved in oral fat perception and preferences (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 intracellular calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (PubMed:18162488). 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 thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (PubMed:15748999). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting together with THBS1 (PubMed:25835637). 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 (PubMed:20037584, PubMed:23812099). 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:15690042, PubMed:19847289).FUNCTION (Microbial infection) Acts as an accessory receptor for M.tuberculosis lipoprotein LprA, in conjunction with coreceptors TLR2 and TLR1; the lipoprotein acts as an agonist to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling (PubMed:19864601, PubMed:23395392). Mediates uptake of E.coli and S.aureus but has no effect on uptake of M.fortuitum (PubMed:16020694).CATALYTIC ACTIVITY a fatty acid(in) = a fatty acid(out)CATALYTIC ACTIVITY a long-chain fatty acid(out) = a long-chain fatty acid(in)CATALYTIC ACTIVITY butanoate(out) = butanoate(in)CATALYTIC ACTIVITY tetradecanoate(out) = tetradecanoate(in)CATALYTIC ACTIVITY hexadecanoate(out) = hexadecanoate(in)CATALYTIC ACTIVITY octadecanoate(in) = octadecanoate(out)CATALYTIC ACTIVITY tetracosanoate(out) = tetracosanoate(in)CATALYTIC ACTIVITY (9Z)-octadecenoate(out) = (9Z)-octadecenoate(in)CATALYTIC ACTIVITY (9Z,12Z)-octadecadienoate(out) = (9Z,12Z)-octadecadienoate(in)CATALYTIC ACTIVITY (5Z,8Z,11Z,14Z)-eicosatetraenoate(out) = (5Z,8Z,11Z,14Z)-eicosatetraenoate(in)SUBUNIT Interacts with THBS1 and THBS2; the interactions mediate the THBS antiangiogenic activity (By similarity) (PubMed:15748999). 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 (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 (PubMed:23395392). Interacts (when palmitoylated) with ARF6; this interaction mediates CD36 transport to the plasma membrane (By similarity).INTERACTION Upon ligand-binding, internalized through dynamin-dependent endocytosis.TISSUE SPECIFICITY Expressed in the apical side of lingual taste bud cells of the circumvallate papillae (PubMed:16276419, PubMed:21901153). Highly expressed in the intestine on the luminal surface of enterocytes. In small intestines expression levels follow a steep decreasing gradient from proximal to distal segments (PubMed:17507371). Expressed in macrophages (PubMed:23395392, PubMed:23812099). Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and lung macrophages (at protein level) (PubMed:19362712).INDUCTION Expressed in a circadian manner in the circumvallate papillae, levels being lower during the dark period. Protein levels decrease in presence of lipids.PTM Palmitoylated by ZDHHC5. Palmitoylation is required for proper localization at the plasma membrane.PTM 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).DISRUPTION PHENOTYPE The preference to lipids such linoleic acid is fully abolished in mutant mice as well as the induction of both flux and protein content of pancreatobiliary secretions (PubMed:16276419, PubMed:21901153). Animals with a double knockout of APOE and CD36, fed a Western diet for 12 weeks, exhibit much lower levels of CXCL1, CXCL2 and CCL5 cytokine mRNA expression in the descending aorta and a corresponding decrease in atherosclerotic lesion formation, compared to APOE single knockout mice. Enterocytes from proximal small intestine exhibit reduced uptake of fatty acid and cholesterol. They also show reduced fatty acid incorporation into triglycerides and triglyceride secretion (PubMed:17507371). After oral fat loading, animals have lipoproteins smaller than chylomicron in size in plasma and intestinal lymph (PubMed:18753675). Fewer apoptotic cells and reduced levels of active caspase 3 in glomeruli.SIMILARITY Belongs to the CD36 family.
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