cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Function

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition.

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

Radical-SAM & Cofactor Biosynthesis Enzymes

Experimental structures · PDB · 358

• 2OUN X-ray 1.56A
• 2OUP X-ray 1.56A
• 2OUQ X-ray 1.90A
• 2OUR X-ray 1.45A
• 2OUS X-ray 1.45A
• 2OUU X-ray 1.52A
• 2OUV X-ray 1.56A
• 2OUY X-ray 1.90A
• 2WEY X-ray 2.80A
• 2Y0J X-ray 2.43A
• 2ZMF X-ray 2.10A
• 3SN7 X-ray 1.82A
• … and 346 more

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0005829 cytosol
• GO:0098978 glutamatergic synapse
• 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:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
• GO:0030552 cAMP binding
• GO:0030553 cGMP binding
• GO:0046872 metal ion binding
• GO:0006198 cAMP catabolic process
• GO:0046069 cGMP catabolic process
• GO:0141162 negative regulation of cAMP/PKA signal transduction
• GO:0010754 negative regulation of receptor guanylyl cyclase signaling pathway
• GO:0007165 signal transduction

Disease associations

• infantile-onset generalized dyskinesia with orofacial involvement MONDO:0044637
• striatal degeneration, autosomal dominant 2 MONDO:0014835

Drugs targeting this protein · 6

• IBUDILAST inhibitor
• PBF-999 inhibitor
• BALIPODECT inhibitor
• MARDEPODECT inhibitor
• PENTOXIFYLLINE inhibitor
• DIPYRIDAMOLE inhibitor

Related proteins · sequence + function similarity

• Serine/threonine-protein kinase 35 0.68
• Serine/threonine-protein kinase 35 0.68
• cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A 0.67
• cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A 0.66
• Ankyrin repeat domain-containing protein 60 0.56
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.55
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.54
• Uncharacterized gene 1 protein 0.53
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.53
• cGMP-specific 3',5'-cyclic phosphodiesterase 0.53
• Putative uncharacterized protein UNQ6190/PRO20217 0.52
• Putative uncharacterized protein encoded by MAPKAPK5-AS1 0.52

Co-cited proteins · studied together in the literature

• Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A 1 shared papers
• cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A 1 shared papers

Literature · 13 cited papers

• De novo mutations in PDE10A cause childhood-onset chorea with bilateral striatal lesions. Am. J. Hum. Genet. · 2016
• Biallelic mutations in PDE10A Lead to loss of striatal PDE10A and a hyperkinetic movement disorder with onset in infancy. Am. J. Hum. Genet. · 2016
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP. J. Biol. Chem. · 2008
• Structural insight into substrate specificity of phosphodiesterase 10. Proc. Natl. Acad. Sci. U.S.A. · 2007
• cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11. J. Biol. Chem. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The DNA sequence and analysis of human chromosome 6. Nature · 2003
• The human phosphodiesterase PDE10A gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains. Eur. J. Biochem. · 2000
• Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP. Biochem. Biophys. Res. Commun. · 1999
• Isolation and characterization of PDE10A, a novel human 3',5'-cyclic nucleotide phosphodiesterase. Gene · 1999
• … and 1 more in the literature graph