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Details on Person UniProt:P16671-2 CD36
| Class:Id | ReferenceIsoform:8970909 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 17 2017;chain:2-472 added on Fri February 17 2017;initiator methionine:1 for 8970909 removed on Fri Nov 03 2023;initiator methionine: for 8970909 added on Fri Nov 03 2023;initiator methionine: for 8970909 removed on Fri Aug 15 2025;initiator methionine:1 for 8970909 added on Fri Aug 15 2025 |
| _displayName | UniProt:P16671-2 CD36 |
| _timestamp | 2026-02-20 23:03:51 |
| chain | initiator methionine:1 chain:2-472 |
| checksum | 543E748259A094FA |
| comment | 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. 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:21395585, PubMed:21610069). 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: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).FUNCTION (Microbial infection) Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling.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 tetradecanoate(out) = tetradecanoate(in)CATALYTIC ACTIVITY hexadecanoate(out) = hexadecanoate(in)CATALYTIC ACTIVITY octadecanoate(in) = octadecanoate(out)CATALYTIC ACTIVITY butanoate(out) = butanoate(in)CATALYTIC ACTIVITY (9Z)-octadecenoate(out) = (9Z)-octadecenoate(in)CATALYTIC ACTIVITY (9Z,12Z)-octadecadienoate(out) = (9Z,12Z)-octadecadienoate(in)CATALYTIC ACTIVITY tetracosanoate(out) = tetracosanoate(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 (PubMed:10613822, PubMed:1371676). 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 (PubMed:1371676, PubMed:20037584). Upon interaction with ligands such as diacylated lipopeptides, interacts with the TLR2:TLR6 heterodimer (PubMed:16880211). 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). Interacts (when palmitoylated) with ARF6; this interaction mediates CD36 transport to the plasma membrane (PubMed:37461827).SUBUNIT (Microbial infection) Binds to Plasmodium falciparum EMP1.INTERACTION Upon ligand-binding, internalized through dynamin-dependent endocytosis.ALTERNATIVE PRODUCTS N-glycosylated and O-glycosylated with a ratio of 2:1.PTM Palmitoylated by ZDHHC5 (PubMed:32958780). Palmitoylation is required for proper localization at the plasma membrane (PubMed:32958780, PubMed:37461827).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).POLYMORPHISM Genetic variations in CD36 are involved in susceptibility to malaria and influence the severity and outcome of malaria infection [MIM:611162].DISEASE 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.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.SIMILARITY Belongs to the CD36 family.SEQUENCE CAUTION CD36 entry |
| created | [InstanceEdit:8964659] Weiser, JD |
| description | recommendedName: Platelet glycoprotein 4 alternativeName: Fatty acid translocase shortName: FAT alternativeName: Glycoprotein IIIb shortName: GPIIIB alternativeName: Leukocyte differentiation antigen CD36 alternativeName: PAS IV alternativeName: PAS-4 alternativeName: Platelet collagen receptor alternativeName: Platelet glycoprotein IV shortName: GPIV alternativeName: Thrombospondin receptor cdAntigenNameCD36/cdAntigenName |
| geneName | CD36 GP3B GP4 |
| identifier | P16671 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell adhesion Cell membrane Direct protein sequencing Disease variant Disulfide bond Glycoprotein Golgi apparatus Isopeptide bond Lipid transport Lipoprotein Membrane Palmitate Proteomics identification Receptor Reference proteome Transmembrane Transmembrane helix Transport Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | CD36 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:5640171] ENSEMBL:ENSG00000135218 CD36 [Homo sapiens] |
| secondaryIdentifier | CD36_HUMAN D9IX66 D9IX67 D9IX68 D9IX69 Q13966 Q16093 Q8TCV7 Q9BPZ8 Q9BQC2 Q9BZM8 Q9BZN3 Q9BZN4 Q9BZN5 |
| sequenceLength | 472 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | P16671-2 |
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No pathways have been reviewed or authored by UniProt:P16671-2 CD36 (8970909)
