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 Contents Inhibitors ; See also ; References ; Further reading ;
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)
End	42,775,509 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	31,476,310 bp
RNA expression pattern
	Top expressed in
	ganglionic eminence; ; oocyte; ; sural nerve; ; prostate; ; rectum; ; optic nerve; ; secondary oocyte; ; putamen; ; renal medulla; ; caudate nucleus;
	Top expressed in
	colon; ; duodenum; ; left colon; ; jejunum; ; cerebellar vermis; ; ileum; ; crypt of lieberkuhn of small intestine; ; olfactory tubercle; ; yolk sac; ; proximal tubule;
	More reference expression data
	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
	5152
	18585
	ENSG00000160191
	ENSMUSG00000041119
	O76083
	O70628
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
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
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 03, 2023

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

Related Research Articles

Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A is an enzyme that in humans is encoded by the PDE11A gene.

Sialic acid-binding Ig-like lectin 12, or Siglec-XII, is a protein that in humans, is encoded by the SIGLEC12 gene.

Guanine nucleotide-binding protein G(t) subunit alpha-2 is a protein that in humans is encoded by the GNAT2 gene.

Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma is an enzyme that in humans is encoded by the PDE6G gene.

Guanine nucleotide-binding protein G(t) subunit alpha-1 is a protein that in humans is encoded by the GNAT1 gene.

Thiamin pyrophosphokinase 1 is an enzyme that in humans is encoded by the TPK1 gene.

ATP-binding cassette sub-family B member 9 is a protein that in humans is encoded by the ABCB9 gene.

Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A is an enzyme that in humans is encoded by the PDE1A gene.

High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A is an enzyme that in humans is encoded by the PDE7A gene. Mammals possess 21 cyclic nucleotide phosphodiesterase (PDE) genes that are pharmacologically grouped into 11 families. PDE7A is one of two genes in the PDE7 family, the other being PDE7B. The PDE7 family, along with the PDE4 and PDE8 families, are cAMP-specific, showing little to no activity against 3', 5'-cyclic guanosine monophosphate (cGMP).

Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha is an enzyme that in humans is encoded by the PDE6A gene.

Probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase is an enzyme that in humans is encoded by the ALG8 gene.

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

Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B is an enzyme that in humans is encoded by the PDE1B gene.

Choline transporter-like protein 2 is a protein that in humans is encoded by the SLC44A2 gene.

Large ribosomal subunit protein uL22 is a protein that in humans is encoded by the RPL17 gene.

Kv channel-interacting protein 4 is a protein that in humans is encoded by the KCNIP4 gene.

Long-chain fatty acid transport protein 6 is a protein that in humans is encoded by the SLC27A6 gene.

cGMP-dependent 3',5'-cyclic phosphodiesterase is an enzyme that in humans is encoded by the PDE2A gene.

Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' is an enzyme that in humans is encoded by the PDE6C gene.

Tropomodulin 4 (muscle) also known as TMOD4 is a protein which in humans is encoded by the TMOD4 gene.

References

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

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. 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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000160191 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid9624146-5] 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.

[entrez-6] 1 2 "Entrez Gene: PDE9A phosphodiesterase 9A".

[pmid22780914-7] 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.

[pmid21619887-8] 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.

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PDE9A

Contents

Inhibitors

See also

Related Research Articles

References

Further reading