PDE9A

Phosphodiesterase 9A
PDB rendering based on 2hd1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2HD1​, 2YY2​, 3DY8​, 3DYL​, 3DYN​, 3DYQ​, 3DYS​, 3JSI​, 3JSW​, 3K3E​, 3K3H​, 3N3Z​, 3QI3​, 3QI4​, 4E90​, 4G2J​, 4G2L​, 4GH6​
Identifiers
Symbols	PDE9A ; HSPDE9A2
External IDs	OMIM: 602973 MGI: 1277179 HomoloGene: 113565 IUPHAR: 1309 ChEMBL: 3535 GeneCards: PDE9A Gene
EC number	3.1.4.35
Gene ontology Molecular function • 3',5'-cyclic-nucleotide phosphodiesterase activity • protein binding • metal ion binding • 3',5'-cyclic-GMP phosphodiesterase activity Cellular component • endoplasmic reticulum • Golgi apparatus • cytosol • ruffle membrane • sarcolemma • perinuclear region of cytoplasm Biological process • signal transduction • blood coagulation • positive regulation of cardiac muscle hypertrophy • cGMP metabolic process • cGMP catabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5152	18585
Ensembl	ENSG00000160191	ENSMUSG00000041119
UniProt	O76083	O70628
RefSeq (mRNA)	NM_001001567	NM_001163748
RefSeq (protein)	NP_001001567	NP_001157220
Location (UCSC)	Chr 21: 42.65 – 42.78 Mb	Chr 17: 31.39 – 31.48 Mb
PubMed search

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.^[2]

Inhibitors

• BAY 73-6691
• PF-04447943 ^[3][4]

References

1. Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB (Jul 1998). "Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase". J Biol Chem 273 (25): 15559–64. doi:10.1074/jbc.273.25.15559. PMID 9624146.
2. "Entrez Gene: PDE9A phosphodiesterase 9A".
3. Verhoest PR, Fonseca KR, Hou X, et al. (2012). "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. doi:10.1021/jm3007799. PMID 22780914.
4. Hutson PH, Finger EN, Magliaro BC, et al. (2011). "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. doi:10.1016/j.neuropharm.2011.05.009. PMID 21619887.

Further reading

• Guipponi M, Scott HS, Kudoh J, et al. (1998). "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. doi:10.1007/s004390050838. PMID 9856478.
• Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
• 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.
• Rentero C, Monfort A, Puigdomènech P (2003). "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. doi:10.1016/S0006-291X(03)00021-4. PMID 12565835.
• Wang P, Wu P, Egan RW, Billah MM (2003). "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. doi:10.1016/S0378-1119(03)00733-9. PMID 14527714.
• 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.
• Huai Q, Wang H, Zhang W, et al. (2004). "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. doi:10.1073/pnas.0401120101. PMC 470725. PMID 15210993.
• 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.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Hu YH, Warnatz HJ, Vanhecke D, et al. (2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics 7: 155. doi:10.1186/1471-2164-7-155. PMC 1526728. PMID 16780588.
• Rentero C, Puigdomènech P (2007). "Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene". BMC Mol. Biol. 7: 39. doi:10.1186/1471-2199-7-39. PMC 1647287. PMID 17090334.