cGMP-specific 3',5'-cyclic phosphodiesterase

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. Specifically regulates nitric-oxide-generated cGMP.

Classification

Family (Pfam)

PF01590 GAF, PF00233 PDEase_I

InterPro

GAF, GAF-like_dom_sf, HD/PDEase_dom, PDEase, PDEase_catalytic_dom, PDEase_catalytic_dom_sf, PDEase_CS

Functional cluster

Serine/Threonine Protein Kinases

Experimental structures · PDB · 49

• 1RKP X-ray 2.05A
• 1T9R X-ray 2.10A
• 1T9S X-ray 2.00A
• 1TBF X-ray 1.30A
• 1UDT X-ray 2.30A
• 1UDU X-ray 2.83A
• 1UHO X-ray 2.50A
• 1XOZ X-ray 1.37A
• 1XP0 X-ray 1.79A
• 2CHM X-ray 1.60A
• 2H40 X-ray 1.85A
• 2H42 X-ray 2.30A
• … and 37 more

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0005829 cytosol
• GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
• GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
• GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
• GO:0030553 cGMP binding
• GO:0046872 metal ion binding
• GO:0046069 cGMP catabolic process
• GO:0141162 negative regulation of cAMP/PKA signal transduction
• GO:0007165 signal transduction

Drugs targeting this protein · 11

• VARDENAFIL HYDROCHLORIDE inhibitor
• SILDENAFIL CITRATE inhibitor
• GISADENAFIL inhibitor
• IBUDILAST inhibitor
• AVANAFIL inhibitor
• UDENAFIL inhibitor
• PF-00489791 inhibitor
• PF-03049423 inhibitor
• PENTOXIFYLLINE inhibitor
• TADALAFIL inhibitor
• DIPYRIDAMOLE inhibitor

Related proteins · sequence + function similarity

• cGMP-specific 3',5'-cyclic phosphodiesterase 0.99
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.99
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.99
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.99
• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 0.90
• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 0.86
• Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta 0.86
• Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta 0.85
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.84
• Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' 0.84
• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 0.83
• cGMP-dependent 3',5'-cyclic phosphodiesterase 0.83

Co-cited proteins · studied together in the literature

• cGMP-dependent protein kinase 1 1 shared papers
• High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A 1 shared papers
• High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A 1 shared papers
• Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B 1 shared papers
• 3',5'-cyclic-AMP phosphodiesterase 4B 1 shared papers
• 3',5'-cyclic-AMP phosphodiesterase 4D 1 shared papers

Literature · 11 cited papers

• Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature · 2015
• Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol. Cell · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature · 2003
• Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J. Biol. Chem. · 2002
• Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci. · 1999
• Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. Eur. J. Biochem. · 1998
• Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase. Gene · 1998
• Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase. Biochem. Biophys. Res. Commun. · 1998