PDE9A explained

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene.^{[1] [2]}

The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene.

Inhibitors

• BAY 73-6691
• PF-04447943^{[3] [4]}

See also

• Phosphodiesterase

Further reading

• Guipponi M, Scott HS, Kudoh J, etal . Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: alternative splicing of mRNA transcripts, genomic structure and sequence . Hum. Genet. . 103 . 4 . 386–92 . 1998 . 9856478 . 10.1007/s004390050838 . 24883234 .
• Hattori M, Fujiyama A, Taylor TD, etal . The DNA sequence of human chromosome 21 . Nature . 405 . 6784 . 311–9 . 2000 . 10830953 . 10.1038/35012518 . 2000Natur.405..311H . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Rentero C, Monfort A, Puigdomènech P . Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene . Biochem. Biophys. Res. Commun. . 301 . 3 . 686–92 . 2003 . 12565835 . 10.1016/S0006-291X(03)00021-4 .
• Wang P, Wu P, Egan RW, Billah MM . Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants . Gene . 314 . 15–27 . 2003 . 14527714 . 10.1016/S0378-1119(03)00733-9 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Huai Q, Wang H, Zhang W, etal . Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding . Proc. Natl. Acad. Sci. U.S.A. . 101 . 26 . 9624–9 . 2004 . 15210993 . 10.1073/pnas.0401120101 . 470725 . 2004PNAS..101.9624H . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Hu YH, Warnatz HJ, Vanhecke D, etal . Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins . BMC Genomics . 7. 155 . 2006 . 16780588 . 10.1186/1471-2164-7-155 . 1526728 . free .
• Rentero C, Puigdomènech P . Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene . BMC Mol. Biol. . 7. 39 . 2007 . 17090334 . 10.1186/1471-2199-7-39 . 1647287 . free .

Notes and References

1. Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB . Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase . J Biol Chem . 273 . 25 . 15559–64 . Jul 1998 . 9624146 . 10.1074/jbc.273.25.15559 . free .
2. Web site: Entrez Gene: PDE9A phosphodiesterase 9A.
3. Verhoest PR, Fonseca KR, Hou X, etal . Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders . J. Med. Chem. . 55 . 21 . 9045–54 . 2012 . 22780914 . 10.1021/jm3007799 .
4. Hutson PH, Finger EN, Magliaro BC, etal . The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) enhances synaptic plasticity and cognitive function in rodents . Neuropharmacology . 61 . 4 . 665–76 . 2011 . 21619887 . 10.1016/j.neuropharm.2011.05.009 . 143527784 .