The human phosphodiesterase PDE10A gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains.
PDE10A is a cyclic nucleotide phosphodiesterase (PDE) exhibiting properties of a cAMP PDE and a cAMP-inhibited cGMP PDE. The transcripts are specifically expressed in the striatum. The human gene encoding PDE10A was cloned and investigated. The PDE10A gene spanned > 200 kb and contained 24 exons. The exon-intron organization of PDE10A was different from those of PDE5A and PDE6B, although these three PDEs include two GAF domains and have similar amino-acid sequences. The promoter sequence of PDE10A was highly GC-rich and did not contain a TATA motif and a CAAT box, suggesting it is a housekeeping gene. In Caenorhabditis elegans, the C32E12.2 gene encoding a probable PDE that is 48% identical to the human PDE10A protein showed similar exon organization to PDE10A but not PDE5A and PDE6B. This, together with the phylogenic tree analysis, suggested that the ancestral gene for PDE10A existed in a lower organism such as C. elegans.
Fujishige
K
K
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd, Saitama, Japan.
Kotera
J
J
Yuasa
K
K
Omori
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D003001:Cloning, Molecular; D003342:Corpus Striatum / Q000201:enzymology*; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005796:Genes; D015801:Helminth Proteins / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013737:Testis / Q000201:enzymology; D014158:Transcription, Genetic
D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases