Human Ca2+/calmodulin-dependent phosphodiesterase PDE1A: novel splice variants, their specific expression, genomic organization, and chromosomal localization.
We report here the identification of novel human PDE1A splice variants, their tissue distribution patterns, genomic structure, and chromosomal localization of the gene. We identified one N-terminus (N3) and one C-terminus (C3) by cDNA library screening and dbEST database search. These N- and C-termini, including the reported N-termini (N1 and N2) and C-termini (C1 and C2), combined to generate nine different PDE1A cDNAs. N1 and N2 are similar to the 5' ends of the bovine PDE1A proteins of 61 kDa and 59 kDa, respectively, and C1 and C2 are the 3' ends of the reported human PDE1A variants. The results of PCR and Southern blot analysis show that nine PDE1A splice variants exhibit distinctive tissue distribution patterns by the difference of the N-terminus. PDE1As with N2 were widely expressed in various tissues, mainly in the kidney, liver, and pancreas. On the other hand, PDE1As with N1 and N3 were particularly expressed at a high level in the brain and testis, respectively. These findings suggest that the distinct expression patterns among PDE1A variants depend on the several promoters situated upstream of exons encoding 5' ends of the variants. The PDE1A gene spans over 120 kb of genomic DNA, and consists of at least 17 exons and 16 introns. The PDE1A gene was located on human chromosome 2q32 by fluorescent in situ hybridization analysis.
Michibata
H
H
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 2-50 Kawagishi-2-chome, Toda, Saitama 335-8505, Japan.
Yanaka
N
N
Kanoh
Y
Y
Okumura
K
K
Omori
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D018076:DNA, Complementary / Q000096:biosynthesis / Q000737:chemistry; D005091:Exons; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D013737:Testis / Q000378:metabolism
D018076:DNA, Complementary; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517265:PDE1A protein, human