Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic nucleotide-specific phosphodiesterases (PDEs) play an essential role in signal transduction by regulating the intracellular concentration of second messengers (cAMP and cGMP). We have identified and made an initial characterization of a full-length cDNA encoding a novel human cyclic nucleotide phosphodiesterase, PDE9A. At least four different mRNA transcripts (PDE9A1, A2, A3, A4) are produced as a result of alternative splicing of 5' exons, potentially changing the N-terminal amino acid sequences of the encoded proteins. All these predicted proteins would contain a 3',5'-cyclic nucleotide phosphodiesterase signature motif (Prosite no. PDOC00116). Northern blot analysis revealed several mRNA species of approximately 2.4 kb with varying expression patterns and intensities in most tissues examined, except blood. We have also isolated the mouse homolog of the human PDE9A2 mRNA transcript, pde9A2. The human and mouse isoforms have 93 and 83% sequence identity at the amino acid and nucleotide levels, respectively. PDE9A was mapped to 21q22.3, between TFF1 and D21S360. Comparison of the PDE9A1 cDNA with the genomic sequence from the region revealed that the gene is split into 20 exons that extend over 122 kb. Comparison of the physical map of the region and the genomic sequence further refines the mapping, with D21S113 being derived from intron 15. Several genetic disorders map to 21q22.3, including one form of bipolar affective disorder. Since functional disturbances in intraneuronal signal transmission via second messengers play an important role in the pathophysiology of affective disorders, PDE9A is a strong candidate for such a role by position and function.
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PMID:Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: alternative splicing of mRNA transcripts, genomic structure and sequence. 985 78

An autosomal recessive nonsyndromic deafness locus, DFNB10, was previously localized to a 12-cM region near the telomere of chromosome 21 (21q22.3). This locus was discovered in a large, consanguineous Palestinian family. We have identified and ordered a total of 50 polymorphic microsatellite markers in 21q22.3, comprising 16 published and 34 new markers, precisely mapped and ordered on BAC/cosmid contigs. Using these microsatellite markers, the locus for DFNB10 has been refined to an area of less than 1 Mb between markers 1016E7.CA60 and 1151C12.GT45. Six previously published cDNAs were mapped to this critical region, and their genomic structures were determined to facilitate mutation analysis in DFNB10. All six genes in this region (in order from centromere to telomere: White/ABCG1, TFF3, TFF2, TFF1, PDE9A, and NDUVF3) have been screened and eliminated as candidates for DFNB10. The new microsatellite markers and single nucleotide polymorphisms identified in this study should enable the refined mapping of other genetic diseases that map to 21q22.3. In addition, the critical region for DFNB10 has been reduced to a size amenable to an intensive positional cloning effort.
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PMID:Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region. 1095 Sep 23