Description: Homo sapiens phosphodiesterase 5A, cGMP-specific (PDE5A), transcript variant 1, mRNA. RefSeq Summary (NM_001083): This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr4:120,415,550-120,549,981 Size: 134,432 Total Exon Count: 21 Strand: - Coding Region Position: hg19 chr4:120,419,756-120,549,826 Size: 130,071 Coding Exon Count: 21
ID:PDE5A_HUMAN DESCRIPTION: RecName: Full=cGMP-specific 3',5'-cyclic phosphodiesterase; EC=3.1.4.35; AltName: Full=cGMP-binding cGMP-specific phosphodiesterase; Short=CGB-PDE; FUNCTION: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'- GMP. CATALYTIC ACTIVITY: Guanosine 3',5'-cyclic phosphate + H(2)O = guanosine 5'-phosphate. COFACTOR: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. ENZYME REGULATION: Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast. PATHWAY: Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1. TISSUE SPECIFICITY: Expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. DOMAIN: Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B. PTM: Phosphorylation is regulated by binding of cGMP to the two allosteric sites (By similarity). Phosphorylation by PRKG1 leads to its activation. SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. SIMILARITY: Contains 2 GAF domains.
Anemia, Sickle Cell Pallav Bhatnagar et al. Journal of human genetics 2011, Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients., Journal of human genetics.
[PubMed 21326311]
Blood Flow Velocity Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903301]
In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
Blood Flow Velocity Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903301]
In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O76074
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0007165 signal transduction GO:0008152 metabolic process GO:0010613 positive regulation of cardiac muscle hypertrophy GO:0030823 regulation of cGMP metabolic process GO:0042130 negative regulation of T cell proliferation GO:0043406 positive regulation of MAP kinase activity GO:0046068 cGMP metabolic process GO:0046069 cGMP catabolic process GO:0055118 negative regulation of cardiac muscle contraction GO:0055119 relaxation of cardiac muscle GO:0060282 positive regulation of oocyte development
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