PDE10A

Phosphodiesterase 10A

PDB rendering based on 2o8h.

Available structures
PDB	1LRB, 2OUN, 2OUP, 2OUQ, 2OUR, 2OUS, 2OUU, 2OUV, 2OUY, 2WEY, 2ZMF

Identifiers

Symbols

PDE10A; FLJ11894; FLJ25677; HSPDE10A

External IDs

OMIM: 610652 MGI: 1345143 HomoloGene: 4852 GeneCards: PDE10A Gene

EC number

3.1.4.17

Gene Ontology
Molecular function	• nucleotide binding • 3',5'-cyclic-nucleotide phosphodiesterase activity • 3',5'-cyclic-AMP phosphodiesterase activity • phosphoric diester hydrolase activity • hydrolase activity • cAMP binding • cGMP binding • metal ion binding • 3',5'-cyclic-GMP phosphodiesterase activity
Cellular component	• cytoplasm • cytosol • cytosol
Biological process	• signal transduction • blood coagulation • platelet activation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 6:
165.74 – 166.08 Mb

Chr 17:
8.72 – 9.18 Mb

PubMed search

[1]

[2]

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.^[1]^[2]

Various cellular responses are regulated by the second messengers cAMP and cGMP. Phosphodiesterases, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate.^[2]^[3]

Inhibitors

PF-2545920^[4]

References

^ Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K (Jul 1999). "Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A)". J Biol Chem 274 (26): 18438–45. doi:10.1074/jbc.274.26.18438. PMID 10373451.
^ ^a ^b "Entrez Gene: PDE10A phosphodiesterase 10A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10846.
^ Fujishige K, Kotera J, Yuasa K, Omori K (October 2000). "The human phosphodiesterase PDE10A gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains". Eur. J. Biochem. 267 (19): 5943–51. doi:10.1046/j.1432-1327.2000.01661.x. PMID 10998054.
^ Verhoest PR, Chapin DS, Corman M, et al. (August 2009). "Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia". J. Med. Chem. 52 (16): 5188–96. doi:10.1021/jm900521k. PMID 19630403.

Loughney K, Snyder PB, Uher L, et al. (1999). "Isolation and characterization of PDE10A, a novel human 3', 5'-cyclic nucleotide phosphodiesterase.". Gene 234 (1): 109–17. doi:10.1016/S0378-1119(99)00171-7. PMID 10393245.
Kotera J, Fujishige K, Yuasa K, Omori K (1999). "Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP.". Biochem. Biophys. Res. Commun. 261 (3): 551–7. doi:10.1006/bbrc.1999.1013. PMID 10441464.
Zauli G, Milani D, Mirandola P, et al. (2001). "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway.". FASEB J. 15 (2): 483–91. doi:10.1096/fj.00-0354com. PMID 11156964.
Frame M, Wan KF, Tate R, et al. (2001). "The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3.". Cell. Signal. 13 (10): 735–41. doi:10.1016/S0898-6568(01)00193-0. PMID 11602184.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6.". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
Gross-Langenhoff M, Hofbauer K, Weber J, et al. (2006). "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. 281 (5): 2841–6. doi:10.1074/jbc.M511468200. PMID 16330539.

PDB gallery

2o8h: Crystal structure of the catalytic domain of rat phosphodiesterase 10A

2oun: crystal structure of PDE10A2 in complex with AMP

2oup: crystal structure of PDE10A

2ouq: crystal structure of PDE10A2 in complex with GMP

2our: crystal structure of PDE10A2 mutant D674A in complex with cAMP

2ous: crystal structure of PDE10A2 mutant D674A

2ouu: crystal structure of PDE10A2 mutant D674A in complex with cGMP

2ouv: crystal structure of pde10a2 mutant of D564N

2ouy: crystal structure of pde10a2 mutant D564A in complex with cAMP.

2ovv: Crystal structure of the catalytic domain of rat phosphodiesterase 10A

2ovy: Crystal structure of the catalytic domain of rat phosphodiesterase 10A

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDE10A

Inhibitors

References

Further reading