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Details on Person UniProt:O76074 PDE5A
| Class:Id | ReferenceGeneProduct:52392 |
|---|---|
| _chainChangeLog | chain:1-875 added on Fri February 6 2015 |
| _displayName | UniProt:O76074 PDE5A |
| _timestamp | 2024-11-03 20:06:55 |
| chain | chain:1-875 |
| checksum | 9E30C6C182F13388 |
| comment | 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 (PubMed:15489334, PubMed:9714779). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).CATALYTIC ACTIVITY 3',5'-cyclic GMP + H2O = GMP + H(+)COFACTOR Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc.COFACTOR Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.ACTIVITY 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.INTERACTION 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.CAUTION Was initially thought to act as a major regulator of cardiac hypertrophy in myocytes and muscle and investigations have been made on selective PDE5A inhibitors that could protect against cardiovascular disease. However, while PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signaling is often depressed by heart disease, limiting its effect. Moreover, clinical trial using PDE5A inhibitors were disappointing. |
| description | recommendedName: fullName evidence="19"cGMP-specific 3',5'-cyclic phosphodiesterase ecNumber evidence="9 13"3.1.4.35 alternativeName: cGMP-binding cGMP-specific phosphodiesterase shortName: CGB-PDE |
| geneName | PDE5A PDE5 |
| identifier | O76074 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Allosteric enzyme Alternative splicing cGMP cGMP-binding Hydrolase Metal-binding Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Repeat Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | PDE5A |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8997903] ENSEMBL:ENSG00000138735 PDE5A [Homo sapiens] |
| secondaryIdentifier | PDE5A_HUMAN A0AV69 A8K2C4 O75026 O75887 Q86UI0 Q86V66 Q9Y6Z6 |
| sequenceLength | 875 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:145694] UniProt:O76074-2 PDE5A [Homo sapiens] [ReferenceIsoform:401923] UniProt:O76074-1 PDE5A [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:418508] PDE5A [cytosol] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:O76074 PDE5A (52392)
