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FLASH GENE
Symbol CD36 contributors: mct/pgu - updated : 02-04-2016
HGNC name CD36 molecule (thrombospondin receptor)
HGNC id 1663
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • cytoplasmic and transmembrane regions at both terminal ends
  • cytoplasmic C terminus playing a role in localization of the molecule to the plasma membrane, and required for localization of the receptor to the cell surface and its ability to enhance cellular oleate uptake
  • conjugated GlycoP , LipoP
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Cd36 (84.1pc)
    homolog to rattus Cd36 (86.4pc)
    Homologene
    FAMILY
  • CD36 family
  • CATEGORY adhesion , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text
  • localized to both lipid raft and nonraft domains of the plasma membrane
  • found on mitochondrial membranes (in skeletal muscle, resides on the outer mitochondrial membrane)
  • basic FUNCTION
  • major receptor that internalizes oxidized LDL
  • playing a role in platelet-collagen adhesion and in the transport and/or the regulation of fatty acid transport
  • acting as a facilitator or co-receptor for di-acylglyceride recognition through the TLR2/6 complex
  • playing an important role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, whereas CD36-independent mechanisms predominate in distal segments
  • CD36-mediated fatty acid oxidation is an important determinant for aerobic exercise capacity
  • major contributor to the macrophage uptake of lipoproteins modified by various oxidative pathways and subsequently to foam cell formation
  • may mediate albumin-induced cellular fibrosis since CD36 siRNA appeared to have anti-fibrosis effects
  • may have important functions as a cell adhesion molecule
  • directly mediates cyto-adherence of plasmodium falciparum parasitized erythrocytes
  • may function in the transport and/or as a regulator of fatty acids transport
  • selective and non redundant sensor of microbial diacylglycerides that signal through the TLR2/6 heterodimer
  • may be responsible for the internalization of FSTL1
  • novel serum amyloid A (SAA) receptor mediating SAA proinflammatory activity
  • involved in the vascular oxidative stress and neurovascular dysfunction induced by APP
  • participation of CD36 in membrane calcium influx in response to ER stress or purinergic receptor stimulation resulting in arachidonic acid liberation for PGE2 (prostaglandin E2) formation
  • participates in the phosphorylation and translocation of PLA2G4A to membranes to release arachidonic acid from phospholipids
  • located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation
  • diffusion of CD36 in the membrane of macrophages is regulated by interactions between CD36 and the cytoskeleton
  • CD36 and MSR1 involved in the development and/or progression of Acute Coronary Syndromes (ACS)
  • involved in the cytokine-induced fusion of macrophage
  • plays an important role in cell fusion during myogenic differentiation
  • promotes potentially vascular amyloid deposition and the resulting cerebrovascular damage, leading to neurovascular dysfunction and cognitive deficits
  • implicated in the mechanisms of vascular amyloid deposition
  • is involved in key upstream events leading to cerebral amyloid angiopathy (CAA) and to the associated vascular damage and neurovascular dysfunction
  • involvement of CD36 in monocyte activation by antiphospholipid antibodies
  • is likely central to fatty acid (FA) uptake via its effects on intracellular metabolism
  • plays a central role in lipid metabolism by promoting macrophage cholesterol efflux with the potential to reduce atherosclerotic lesions
  • is a novel regulator of HMG-CoA reductase function and INSIG-1/2 expression, 2 critical steps regulating cholesterol synthesis in hepatocytes
  • essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • surface receptor for thrombospondin-1 (THBS1), that has been reported to interact with latent transforming growth factor-beta1 (TGF-beta1) and activate its fibrogenic bioactivity
  • interacting with fibrillary forms of APP and triggering NADPH oxidase-dependent ROS production in monocytic cells
  • binding collagen
  • new role for THBS1 and CD36 in the activation of the KDR signaling pathway that requires SYK
  • OLR1 stimulates PPARG and subsequently enhances CD36 and inhibits MSR1 in macrophages
  • VAMP3, is able to protect insulin-stimulated SLC2A4 translocation during early stages of diet-induced insulin resistance and preserves normal CD36 distribution
  • CD36 is a novel transcriptional target of KLF2
  • phagocytosis of apoptotic cells engages CD36 and PTAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype
  • THBS1-CD36 tandem is another platelet ligand-receptor axis contributing to the maintenance of a stable thrombus
  • WNT1 regulates the expression of CD36 through TCF4 and PPARG
  • CD36 is involved in autophagy and there is a significant contribution of the CD5L-CD36 axis to the induction of macrophage autophagy
  • CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with CUL7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex
  • RRAS2 is essential for CD36-FCER1G-mediated platelet activation and for thrombus stability via control of RAP1B and integrins
  • cell & other
  • CEOOH (cholesteryl ester hydroperoxides) present in oxidized LDL increase CD36 gene expression in a pathway involving PPARalpha
  • binding anionic phospholipids and oxidized LDL
  • REGULATION
    Other enhanced by AGER in monocytes in diabete
    regulated by NFE2L2 (regulates oxidized LDL-mediated CD36 expression in macrophages)
    ASSOCIATED DISORDERS
    corresponding disease(s) CD36D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    in insulin resistance
    constitutional     --low  
    in PWS point to an abnormal control of lipid and glucose homeostasis which may explain the insatiable hunger in these patients
    constitutional     --low  
    reduced the capability of monocytes to phagocyte apoptotic neutrophils
    Susceptibility
  • to severe malaria, cerebral form
  • to atherosclerosis
  • to insulin resistance
  • to hypertension
  • Variant & Polymorphism SNP
  • 14T/C and 53G/T increase the risk of cerebral malaria
  • AGGIG haplotype modulating lipid metabolism and cardiovascular risk
  • mutations within the kidney can increase blood pressure
  • SNPs of CD36 are associated with metabolic syndrome in Puerto Ricans
  • Candidate gene
  • high soluble CD36 is associated with increased type 2 diabetes risk
  • involved in sterile inflammation through assembly of TLR4/TLR6 heterodimer in atherosclerosis and Alzeihmer's disease
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    target for treatment and/or prevention of cardiovascular disease
    diabetetype 2 
    novel therapeutic strategies aimed at reducing CD36-mediated fatty acids uptake show promise for the prevention or treatment of cardiac dysfunction related to obesity and diabetes
    diabetetype 2 
    novel and potential therapeutic target for diabetic renal tubule fibrosis
    neurologyneurodegenerativealzheimer
    potential therapeutical target to counteract the cerebrovascular dysfunction associated with APP.
    neurologyneurodegenerative 
    is a putative therapeutic target for cerebral amyloid angiopathy (CAA)
    ANIMAL & CELL MODELS
  • CD36 is necessary for the development of lipotoxic cardiomyopathy in MHC-PPARalpha mice
  • Cd36 deletion ameliorates cerebrovascular function in Tg2576 mice at an age marked by extensive amyloid deposition in brain and cerebral blood vessels