PDE9A

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; OMA:PDE9A - orthologs
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 Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon muscle layer of sigmoid colon ganglionic eminence ventricular zone oocyte sural nerve prostate rectum optic nerve secondary oocyte Top expressed in colon duodenum left colon jejunum cerebellar vermis ileum lobe of cerebellum crypt of lieberkuhn of small intestine olfactory tubercle yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function 3',5'-cyclic-nucleotide phosphodiesterase activity metal ion binding protein binding phosphoric diester hydrolase activity hydrolase activity 3',5'-cyclic-GMP phosphodiesterase activity Cellular component cytoplasm cytosol perikaryon Golgi apparatus cell projection membrane plasma 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

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

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]}

See also

• Phosphodiesterase

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. Bibcode:2002PNAS...9916899M. 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. Bibcode:2003BBRC..301..686R. 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.