Structure and organization of the human thrombospondin 3 gene (thbs3)

The promoter/5′ flank sequence, cDNA sequence, and exon/intron structures of the human thrombospondin 3 (THBS3) gene have been determined. THBS3 cDNA clones were obtained by PCR amplification of human fetal lung cDNA using THBS3-specific primers. Analysis of cDNA and genomic sequences showed the THBS3 gene to be composed of 23 exons, 1 more than the number of exons in the previously characterized mouse TSP3 gene. The additional exon results from the division of mouse exon F into exons F1 and F2. The cDNA encodes a polypeptide of 956 amino acids that is highly acidic, with a clustering of acidic side chains in the third quarter of the polypeptide. This region corresponds to seven type III (Ca²⁺-binding) repeats, a feature shared with other thrombospondins. In addition to these type III repeats, four type II (EGF-like) repeats and NH₂ - and COOH-terminal domains are present in thrombospondin 3. The THBS3 and mouse TSP3 genes differ in intron sizes, but exon sequences and sizes and positions of insertion of introns are conserved to a high degree. The structural organization of the THBS3 gene is of interest because of its close proximity to that of metaxin, with which it shares a common promoter sequence, and to the gene encoding glucocerebrosidase, a deficiency in which causes Gaucher disease.