Molecule Information

General Information of the Molecule (ID: Mol03008)

• Name: CD36 molecule (CD36) ,Homo sapiens
• Synonyms: CD36; GP3B; GP4
• Molecule Type: Protein
• Gene Name: CD36
• Gene ID: 948
• Location: chr7:80,369,575-80,679,277[+]
• Sequence:
  MGCDRNCGLIAGAVIGAVLAVFGGILMPVGDLLIQKTIKKQVVLEEGTIAFKNWVKTGTE
  VYRQFWIFDVQNPQEVMMNSSNIQVKQRGPYTYRVRFLAKENVTQDAEDNTVSFLQPNGA
  IFEPSLSVGTEADNFTVLNLAVAAASHIYQNQFVQMILNSLINKSKSSMFQVRTLRELLW
  GYRDPFLSLVPYPVTTTVGLFYPYNNTADGVYKVFNGKDNISKVAIIDTYKGKRNLSYWE
  SHCDMINGTDAASFPPFVEKSQVLQFFSSDICRSIYAVFESDVNLKGIPVYRFVLPSKAF
  ASPVENPDNYCFCTEKIISKNCTSYGVLDISKCKEGRPVYISLPHFLYASPDVSEPIDGL
  NPNEEEHRTYLDIEPITGFTLQFAKRLQVNLLVKPSEKIQVLKNLKRNYIVPILWLNETG
  TIGDEKANMFRSQVTGKINLLGLIEMILLSVGVVMFVAFMISYCACRSKTIK
• Function: 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 (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. 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. 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. Involved in oral fat perception and preferences. Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions. 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. Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis. Receptor for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects. 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.
• Uniprot ID: CD36_HUMAN
• Ensembl ID: ENSG00000135218
• HGNC ID: HGNC:1663

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Insulin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Type 2 diabetes mellitus [1]

• Sensitive Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Sensitive Drug: Insulin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Several studies have shown that lipid accumulation in liver and skeletal muscle caused by short-term HFD feeding or lipid/heparin infusions induce insulin resistance in rats. In addition, overexpression of lipoprotein lipase (LPL) in liver or muscle induced peripheral insulin resistance and the accumulation of lipid in respective tissues, and skeletal muscle-specific LPL deletion enhanced insulin signaling in HFD challenged muscle. Furthermore, deleting fat transport proteins such as CD36 or FATP-1 increased insulin-mediated glucose uptake in skeletal muscle, and liver-specific knockdown of FATP2 or FATP5 significantly reduced HFD-induced hepatosteatosis and increased glucose tolerance.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 05

Type 2 diabetes mellitus [ICD-11: 5A11]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Omental adipose tissue
• The Specified Disease: Obesity related type 2 diabetes
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.73E-01; Fold-change: 2.08E-01; Z-score: 3.24E-01
• The Studied Tissue: Liver
• The Specified Disease: Type 2 diabetes mellitus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.08E-01; Fold-change: 2.48E-01; Z-score: 6.99E-01

References

• Ref 1: Insulin Resistance: From Mechanisms to Therapeutic Strategies .Diabetes Metab J. 2022 Jan;46(1):15-37. doi: 10.4093/dmj.2021.0280. Epub 2021 Dec 30. 10.4093/dmj.2021.0280