• CD36 [HUGO gene name]
• GPIIIb
• GPIV
• OKM5-antigen
• PASIV

MAJOR LINKS FOR CD36  

• NCBI LocusLink Record: 948
• Mendelian Inheritance in Man (OMIM): 173510
• SwissProt annotated protein record: P16671

• Recognizes oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin (TSP) and Plasmodium falciparum infected erythrocytes
• Recognition of apoptotic neutrophils in co-operation with TSP and avb3
• Other ligands may still be unknown

CELLULAR FUNCTION OF CD36  

• Scavenger receptor for oxidized LDL and shed photoreceptor outer segments
• Recognition and phagocytosis of apoptotic cells
• Cell adhesion molecule in platelet adhesion and aggregation, platelet-monocyte and platelet-tumor cell interaction
• Cytoadherence of Plasmodium falciparum-infected erythrocytes

DISEASE RELEVANCE OF CD36 AND FUNCTION OF CD36 IN INTACT ANIMAL Link to additional info in FORUM  

• Atherogenesis: Attachment to the vessel wall, infiltration and macrophage foam cell formation
• Malaria: Cytoadherence of infected cells to microvascular endothelial cells is an important factor in the virulence of cerebral malaria
• Inflammation: Resolution of inflammation by phagocytosis of aged PMN
• Vision: CD36-mediated phagocytosis of rod outer segment cells is thought to be critical for normal visual function
• CD36 deficiency: Naka-negative individuals do not express CD36 on their platelets (type II variant) or on their platelets and monocytes (type I variant) (Yamamoto et al. 1994). This may be predominantly due to a Pro90 to Ser substitution mutation, but as yet no physiological problems have been associated with this deficiency

• Families in which CD36 is a member
  • CD36-->SR-B class-->host defense scavenger receptors-->scavenger receptor superfamily

MOLECULAR STRUCTURE OF CD36  

• 471 amino acid residues
• Transmembrane region (residues 439-465),
• 438 amino acid amino-terminal region may be entirely extracellular or may have a second potential transmembrane region near the amino terminal end (controversial)
• aa short cytoplasmic tail (residues 466-471)
• Within the extracellular region resides a hydrophobic region which probably associates with the outer cell membrane (residues 184-204)

MOLECULAR MASS OF CD36  

POST-TRANSCRIPTIONAL MODIFICATION OF CD36  

• Two alternate CD36 mRNA forms have been identified
• The first is expressed in HEL cells and omits amino acid residues 41-143
• The second has not yet been translated but in which the last 89 residues have been omitted

POST-TRANSLATIONAL MODIFICATION OF CD36  

• CD36 is purported to be heavily glycosylated, with 10 N-linked glycosylation sites in the extracellular portion. Glycosylation has been suggested to confer its resistance to proteolytic cleavage
• Threonine 92 has been shown to be phosphorylated
• CD36 is also palmitoylated on both N- and C-terminal cytoplasmic tails

SUBSTRATES FOR CD36  

• Unknown. It may be possible that CD36 regulates autophosphorylation of residue Thr92

ENZYMES WHICH MODIFY CD36  

• Unknown. May be possible that Thr92 is phosphorylated by extracellular threonine kinase(s)

LIGANDS FOR CD36 AND MOLECULES ASSOCIATED WITH CD36  

• Intracellular signaling is probably associated with phosphorylation of Fyn, Lyn and Yes, but the manner by which the cytoplasmic tail interacts with these PTKs is unknown

• CD36 is expressed on platelets, mature monocytes and macrophages, microvascular endothelial cells, mammary endothelial cells, during stages of erythroid cell development and on some macrophage derived dendritic cells

• The physiological events regulated by CD36 ligation are still very much unknown
• Up to 50% of oxidized LDL are ingested through CD36, thus CD36 appears to be a major scavenger receptor. However, given the apparent absence of disease states in CD36 deficient subjects, other mechanisms appear to be capable of compensating for its absence

SELECTION OF OTHER CD36-SPECIFIC REFERENCE MAB  

REVIEWS

1. Daviet, L. et al. 1996. Platelets 7:117-124.

2. Greenwalt DE,Lipsky RH,Ockenhouse CF,Ikeda H,Tandon NN,Jamieson GA Membrane glycoprotein CD36: a review of its roles in adherence, signal transduction, and transfusion medicine. Blood 1992 80:1105 PubMed

3. Krieger M,Herz J Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem 1994 63:601 PubMed

4. Savill J,Fadok V,Henson P,Haslett C Phagocyte recognition of cells undergoing apoptosis. Immunol Today 1993 14:131 PubMed

PRIMARY CITATIONS

5. Armesilla AL,Vega MA Structural organization of the gene for human CD36 glycoprotein. J Biol Chem 1994 269:18985 PubMed

6. Asch AS,Liu I,Briccetti FM,Barnwell JW,Kwakye-Berko F,Dokun A,Goldberger J,Pernambuco M Analysis of CD36 binding domains: ligand specificity controlled by dephosphorylation of an ectodomain. Science 1993 262:1436 PubMed

7. Endemann G,Stanton LW,Madden KS,Bryant CM,White RT,Protter AA CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 1993 268:11811 PubMed

8. Huang MM,Bolen JB,Barnwell JW,Shattil SJ,Brugge JS Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. Proc Natl Acad Sci U S A 1991 88:7844 PubMed

9. Konig H,Pfisterer P,Corcoran LM,Wirth T Identification of CD36 as the first gene dependent on the B-cell differentiation factor Oct-2. Genes Dev 1995 9:1598 PubMed

10. Tang Y,Taylor KT,Sobieski DA,Medved ES,Lipsky RH Identification of a human CD36 isoform produced by exon skipping. Conservation of exon organization and pre-mRNA splicing patterns with a CD36 gene family member, CLA-1. J Biol Chem 1994 269:6011 PubMed

11. Yamamoto N,Akamatsu N,Sakuraba H,Yamazaki H,Tanoue K Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes. Blood 1994 83:392 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov