GENOMIC ORGANIZATION OF THE HUMAN ALPHA-ADDUCIN GENE AND ITS ALTERNATELY SPLICED ISOFORMS

The cDNA for the human alpha-adducin gene has been cloned, and differe nt alternately spliced forms have been identified. We report the compl ete genomic organization of the human alpha-adducin gene and these alt ernately spliced forms. The human alpha-adducin gene, spanning approxi mately 85 kb, consists of 16 exons ranging in size from 34 to 1892 bp. One of the spliced forms of the human alpha-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 f orm of alpha-adducin is predicted to result in an altered carboxyl ter minus that would eliminate a protein kinase and calmodulin binding sit e. Seven nucleotide substitutions and 4 insertion/deletions were also identified. The 5' region of the human alpha-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 anot her cDNA within the first intron of the human alpha-adducin gene, sugg esting overlapping genes in this 4p16.3 genomic region. (C) 1995 Acade mic Press, Inc.