cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the PDE4A gene.[5][6]

PDE4A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPDE4A, DPDE2, PDE4, PDE46, phosphodiesterase 4A
External IDsOMIM: 600126; MGI: 99558; HomoloGene: 4520; GeneCards: PDE4A; OMA:PDE4A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001111307
NM_001111308
NM_001111309
NM_001243121
NM_006202

NM_019798
NM_183408
NM_001310750

RefSeq (protein)

NP_001104777
NP_001104778
NP_001104779
NP_001230050
NP_006193

NP_001297679
NP_062772
NP_899668

Location (UCSC)Chr 19: 10.42 – 10.47 MbChr 9: 21.08 – 21.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

edit

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the secondary messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes.[6] Recently, it has been shown through the use of PDE4A knock out mice that PDE4A may play a role in the regulation of anxiety and emotional memory.[7]

Clinical significance

edit

PDE4A inhibition is a target of a number of drugs including:[8][9][10]

  • rolipram (antidepressant and antiinflammatory) and cilomilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, 6, and 7
  • roflumilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, and 6
  • tofisopam (anxiolytic with alleged antiinflammatory properties) – inhibits PDE4A isoform 1, PDE-10A1, PDE-3, and PDE-2A3

References

edit
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000065989Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032177Ensembl, 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. ^ Milatovich A, Bolger G, Michaeli T, Francke U (Mar 1994). "Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse". Somatic Cell and Molecular Genetics. 20 (2): 75–86. doi:10.1007/BF02290677. PMID 8009369. S2CID 19182571.
  6. ^ a b "PDE4A phosphodiesterase 4A, cAMP-specific ( Homo sapiens )". Entrez Gene. 2012-03-04. Retrieved 2012-04-02.
  7. ^ Hansen RT, Conti M, Zhang H-T (2014). "Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior". Psychopharmacology. 231 (15): 2941–2954. doi:10.1007/s00213-014-3480-y. PMID 24563185. S2CID 13542300.
  8. ^ Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD (May 2001). "Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10" (PDF). Molecular Pharmacology. 59 (5): 996–1011. doi:10.1124/mol.59.5.996. PMID 11306681.
  9. ^ Wallace DA, Johnston LA, Huston E, MacMaster D, Houslay TM, Cheung YF, Campbell L, Millen JE, Smith RA, Gall I, Knowles RG, Sullivan M, Houslay MD (Jun 2005). "Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene". Molecular Pharmacology. 67 (6): 1920–34. doi:10.1124/mol.104.009423. PMID 15738310. S2CID 1758221.
  10. ^ Mackenzie KF, Topping EC, Bugaj-Gaweda B, Deng C, Cheung YF, Olsen AE, Stockard CR, High Mitchell L, Baillie GS, Grizzle WE, De Vivo M, Houslay MD, Wang D, Bolger GB (Apr 2008). "Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change". The Biochemical Journal. 411 (2): 361–9. doi:10.1042/BJ20071251. PMC 4337886. PMID 18095939.

Further reading

edit

This article incorporates text from the United States National Library of Medicine, which is in the public domain.