Structural organization of the gene for human CD36 glycoprotein.

Abstract

The cell-surface glycoprotein CD36 interacts with a large variety of ligands, including collagen types I and IV, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, platelet-agglutinating protein p37, oxidized low density lipoprotein, and long-chain fatty acids. Its expression is restricted to platelets, monocytes, adipocytes, and some endothelial and epithelial cells and is regulated during cell activation, differentiation, and development. CD36 belongs to a novel gene family of structurally related glycoproteins that includes CLA-1 and the lysosomal membrane glycoprotein LIMPII. To advance our knowledge on the genomic organization and the regulation of the cellular expression of the genes of this family, we have investigated the structural organization of the human CD36 gene and of its 5'-proximal flanking region. The CD36 gene is encoded by 15 exons that extend more than 32 kilobases on the human genome. Interestingly, the CD36 mRNA 5'-untranslated region is encoded by three exons. The 3'-untranslated region is contained in two exons, whose expression pattern can originate two mRNA forms. The cytoplasmic and transmembrane regions predicted at both terminal ends of the polypeptide chain are encoded by single exons, while the extracellular domain is encoded by 11 exons. The transcription initiation site of the CD36 gene is located 289 nucleotides upstream from the translational start codon. Sequence analysis of the proximal 5'-flanking region of the gene reveals the existence of a TATA box appropriately located with respect to the transcription initiation site and several potential cis-regulatory elements that might contribute to the transcriptional regulation of the CD36 gene. Delineation of the structural organization of the CD36 gene may help in defining the boundaries of relevant structural and/or functional domains in CD36 and, by extension, in the other members of the family.