CHARACTERIZATION OF THE HUMAN ADENYLYL CYCLASE GENE FAMILY: cDNA, GENE STRUCTURE, AND TISSUE DISTRIBUTION OF THE NINE ISOFORMS

The membrane-bound adenylyl cyclases (ACs) represent one of the major families of effector enzymes for G protein-coupled receptors. Eight human AC isoforms, encoded by separate genes, have been identified up to now. However, in several cases only partial cDNA sequences are available (ADCY1,2,5). A ninth expected isoform, the human ortholog of rat ADCY4, has not been described yet. Using the high inter-species homology of mammalian AC isoforms, we searched the human genome and we succeeded to identify full-length coding sequences for all enzymes. Where required, missing sequence information was provided experimentally. Analysis of genomic sequences from the Celera database also allowed us to determine the exon–intron boundaries for ADCY1–9 and to establish the gene structures. We found that human AC genes comprise 11 to 26 exons, which are distributed over 16 to 430 kb. We further report expression profiles for the nine ACs in a panel of 16 human tissues and in human embryonic kidney (HEK) cells.