cGMP-dependent 3',5'-cyclic phosphodiesterase

Function

cGMP-activated cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP. Plays a role in cell growth and migration.

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 · 42

• 1Z1L X-ray 1.70A
• 3IBJ X-ray 3.02A
• 3ITM X-ray 2.49A
• 3ITU X-ray 1.58A
• 4C1I X-ray 2.40A
• 4D08 X-ray 1.90A
• 4D09 X-ray 2.50A
• 4HTX X-ray 1.90A
• 4HTZ X-ray 2.00A
• 4JIB X-ray 1.72A
• 5TZ3 X-ray 1.72A
• 5TZA X-ray 1.70A
• … and 30 more

A predicted model is available from AlphaFold.

Gene Ontology · 47

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005783 endoplasmic reticulum
• GO:0005794 Golgi apparatus
• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix
• GO:0005741 mitochondrial outer membrane
• GO:0005634 nucleus
• GO:0048471 perinuclear region of cytoplasm
• GO:0005886 plasma membrane
• GO:0042734 presynaptic membrane
• GO:0097060 synaptic membrane
• GO:0004118 3',5'-cGMP-stimulated cyclic-nucleotide phosphodiesterase activity
• GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
• GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
• GO:0030552 cAMP binding
• GO:0030553 cGMP binding
• GO:0042802 identical protein binding
• GO:0000287 magnesium ion binding
• GO:0042301 phosphate ion binding
• GO:0042803 protein homodimerization activity
• GO:0030911 TPR domain binding
• GO:0008270 zinc ion binding
• GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• GO:0035904 aorta development
• GO:1904613 cellular response to 2,3,7,8-tetrachlorodibenzodioxine
• GO:0071320 cellular response to cAMP
• GO:0071321 cellular response to cGMP
• GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus
• GO:0036006 cellular response to macrophage colony-stimulating factor stimulus
• GO:0071260 cellular response to mechanical stimulus
• GO:0071560 cellular response to transforming growth factor beta stimulus
• GO:0071466 cellular response to xenobiotic stimulus
• GO:0046069 cGMP catabolic process
• GO:0061028 establishment of endothelial barrier
• GO:0003170 heart valve development
• GO:0030224 monocyte differentiation
• GO:0106072 negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0141162 negative regulation of cAMP/PKA signal transduction
• GO:0010754 negative regulation of receptor guanylyl cyclase signaling pathway
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0043116 negative regulation of vascular permeability
• GO:0010628 positive regulation of gene expression
• GO:0050729 positive regulation of inflammatory response
• GO:0043117 positive regulation of vascular permeability
• GO:0010821 regulation of mitochondrion organization
• GO:0003281 ventricular septum development

Disease associations

• intellectual developmental disorder with paroxysmal dyskinesia or seizures MONDO:0030900

Drugs targeting this protein · 2

• PENTOXIFYLLINE inhibitor
• DIPYRIDAMOLE inhibitor

Related proteins · sequence + function similarity

• cGMP-dependent 3',5'-cyclic phosphodiesterase 0.99
• cGMP-dependent 3',5'-cyclic phosphodiesterase 0.99
• cGMP-dependent 3',5'-cyclic phosphodiesterase 0.98
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.82
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.81
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.81
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.81
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.80
• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 0.76
• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 0.74
• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 0.73
• Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta 0.72

Co-cited proteins · studied together in the literature

• cGMP-dependent 3',5'-cyclic phosphodiesterase 1 shared papers
• cGMP-dependent 3',5'-cyclic phosphodiesterase 1 shared papers
• Dynamin-1-like protein 1 shared papers
• Ankyrin repeat and IBR domain-containing protein 1 1 shared papers
• Endonuclease/exonuclease/phosphatase family domain-containing protein 1 1 shared papers
• BTB/POZ domain-containing protein 7 1 shared papers
• PHD finger protein 24 1 shared papers
• Protein FAM131B 1 shared papers
• NHS-like protein 3 1 shared papers
• E3 ubiquitin ligase RNF157 1 shared papers
• Paladin 1 shared papers
• Serine incorporator 1 1 shared papers

Literature · 14 cited papers

• Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia. Eur. J. Hum. Genet. · 2020
• A homozygous splicing mutation in PDE2A in a family with atypical Rett syndrome. Mov. Disord. · 2020
• A homozygous loss-of-function mutation in PDE2A associated to early-onset hereditary chorea. Mov. Disord. · 2018
• PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling. Elife · 2017
• Role of phosphodiesterase 2 in growth and invasion of human malignant melanoma cells. Cell. Signal. · 2014
• X-ray crystal structure of phosphodiesterase 2 in complex with a highly selective, nanomolar inhibitor reveals a binding-induced pocket important for selectivity. J. Am. Chem. Soc. · 2013
• Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system. Proteomics · 2010
• Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes. J. Biol. Chem. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system. Biochemistry · 2005
• … and 2 more in the literature graph