PDE9A

High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene.[5][6]

PDE9A
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, 4Y86, 4Y87, 4Y8C
Identifiers
Aliases	PDE9A, HSPDE9A2, phosphodiesterase 9A
External IDs	OMIM: 602973 MGI: 1277179 HomoloGene: 113565 GeneCards: PDE9A
EC number	3.1.4.35
Gene location (Human) Chr. Chromosome 21 (human)[1] Band 21q22.3 Start 42,653,621 bp[1] End 42,775,509 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B1 Start 31,386,210 bp[2] End 31,476,310 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • 3',5'-cyclic-nucleotide phosphodiesterase activity • metal ion binding • GO:0001948 protein binding • phosphoric diester hydrolase activity • hydrolase activity • 3',5'-cyclic-GMP phosphodiesterase activity Cellular component • cytoplasm • cytosol • perikaryon • Golgi apparatus • cell projection • membrane • cell membrane • ruffle membrane • endoplasmic reticulum • perinuclear region of cytoplasm • sarcolemma Biological process • cGMP metabolic process • cGMP-mediated signaling • positive regulation of cardiac muscle hypertrophy • cGMP catabolic process • signal transduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5152	18585
Ensembl	ENSG00000160191	ENSMUSG00000041119
UniProt	O76083	O70628
RefSeq (mRNA)	NM_001001567 NM_001001568 NM_001001569 NM_001001570 NM_001001571 NM_001001572 NM_001001573 NM_001001574 NM_001001575 NM_001001576 NM_001001577 NM_001001578 NM_001001579 NM_001001580 NM_001001581 NM_001001582 NM_001001583 NM_001001584 NM_001001585 NM_002606 NM_001315533	NM_001163748 NM_008804
RefSeq (protein)	NP_001001567 NP_001001568 NP_001001569 NP_001001570 NP_001001571 NP_001001572 NP_001001573 NP_001001574 NP_001001575 NP_001001576 NP_001001577 NP_001001578 NP_001001579 NP_001001580 NP_001001581 NP_001001582 NP_001001583 NP_001001584 NP_001001585 NP_001302462 NP_002597	NP_001157220 NP_032830
Location (UCSC)	Chr 21: 42.65 – 42.78 Mb	Chr 17: 31.39 – 31.48 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

Inhibitors

• BAY 73-6691
• PF-04447943 [7][8]

References

1. GRCh38: Ensembl release 89: ENSG00000160191 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041119 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: PDE9A phosphodiesterase 9A".
7. 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.
8. 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. S2CID 143527784.

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. S2CID 24883234.
• Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. 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. Bibcode:2004PNAS..101.9624H. 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• 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.