Genomic organization of the human α-adducin gene and its alternately spliced isoforms

Abstract The cDNA for the human α-adducin gene has been cloned, and different alternately spliced forms have been identified. We report the complete genomic organization of the human α-adducin gene and these alternately spliced forms. The human α-adducin gene, spanning approximately 85 kb, consists of 16 exons ranging in size from 34 to 1892 bp. One of the spliced forms of the human α-adducin gene results from alternate use of the 5′ splice donor site for exon 10, while another results in a truncated protein following insertion of 34 bp comprising exon 15, followed by a premature stop codon. This alternate spliced form of α-adducin is predicted to result in an altered carboxyl terminus that would eliminate a protein kinase and calmodulin binding site. Seven nucleotide substitutions and 4 insertion/deletions were also identified. The 5′ region of the human α-adducin gene contains one Sp1 site, two AP2 sites, and two CAAT boxes. No TATA box was apparent, consistent with features of a housekeeping gene. We have mapped another cDNA within the first intron of the human α-adducin gene, suggesting overlapping genes in this 4p16.3 genomic region.