STRUCTURE AND ORGANIZATION OF THE HUMAN THROMBOSPONDIN-3 GENE (THBS3)

The promoter/5' flank sequence, cDNA sequence, and exon/intron structu res of the human thrombospondin 3 (THBS3) gene have been determined. T HBS3 cDNA clones were obtained by PCR amplification of human fetal lun g cDNA using THBS3-specific primers. Analysis of cDNA and genomic sequ ences showed the THBS3 gene to be composed of 23 exons, 1 more than th e 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 h ighly acidic, with a clustering of acidic side chains in the third qua rter of the polypeptide. This region corresponds to seven type III (Ca 2+-binding) repeats, a feature shared with other thrombospondins. In a ddition to these type III repeats, four type II (EGF-like) repeats and NH2- and COOH-terminal domains are present in thrombospondin 3. The T HBS3 and mouse TSP3 genes differ in intron sizes, but exon sequences a nd 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 share s a common promoter sequence, and to the gene encoding glucocerebrosid ase, a deficiency in which causes Gaucher disease. (C) 1995 Academic P ress, Inc.