Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): Organization, nucleotide sequence and alternative splicing

We have recently demonstrated that cyclic ADP-ribose (cADPR) serves as a second messenger for glucose-induced insulin secretion [Takasawa et al. (1993a) Science 259, 370-373] and that CD38 has both ADP-ribosyl cyclase (ADRC) and cADPR hydrolase activities [Takasawa et al. (1993b) J. Biol. Chem, 268, 26052-26054]. In this study, we determined the structure of the human CD38 gene, and showed that two mRNA forms originated by alternative splicing from the CD38 gene. The human CD38 gene consists of 8 exons that extend more than 77 kb on the human genome. Exon 1 encoded the 5'-untranslated region of the mRNA, the N-terminal end of CD38 and the putative transmembrane domain, and exon 2-8 encoded the remainder of CD38: the exon-intron organization of the human CD38 gene is similar to that of the Aplysia ADRC gene [Nata et al. (1995) Gene 158, 213-218]. This structural conservation between human and Aplysia genes suggests that both genes may have evolved from a common ancestral gene.