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Phosphodiesterase 4A, cAMP-specific
Protein PDE4A PDB 1loi.png
PDB rendering based on 1loi.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols PDE4A ; DPDE2; PDE4; PDE46
External IDs OMIM600126 MGI99558 HomoloGene4520 ChEMBL: 254 GeneCards: PDE4A Gene
EC number
RNA expression pattern
PBB GE PDE4A 204735 at tn.png
PBB GE PDE4A 211447 s at tn.png
PBB GE PDE4A 211591 s at tn.png
More reference expression data
Species Human Mouse
Entrez 5141 18577
Ensembl ENSG00000065989 ENSMUSG00000032177
UniProt P27815 O89084
RefSeq (mRNA) NM_001111307 NM_019798
RefSeq (protein) NP_001104777 NP_062772
Location (UCSC) Chr 19:
10.42 – 10.47 Mb
Chr 9:
21.17 – 21.21 Mb
PubMed search [1] [2]

cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the PDE4A gene.[1][2]


The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second 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.[2] 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.[3]

Clinical significance[edit]

PDE4A is a target of a number of drugs including:[4][5][6]

  • rolipram (antidepressant and antiinflammatory) and cilomilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, 6, and 7
  • roflumilast (antiinflammatory) – inhibits PDE4A isoforms 1, 2, and 6


  1. ^ Milatovich A, Bolger G, Michaeli T, Francke U (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. 
  2. ^ a b "PDE4A phosphodiesterase 4A, cAMP-specific ( Homo sapiens )". Entrez Gene. NCBI. 2012-03-04. Retrieved 2012-04-02. 
  3. ^ Hansen, R. T., Conti, M., & Zhang, H.-T. (2014). Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior. Psychopharmacology. doi:10.1007/s00213-014-3480-y
  4. ^ Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD (2001). "Molecular Cloning, Genomic Positioning, Promoter Identification, and Characterization of the Novel Cyclic AMP-Specific Phosphodiesterase PDE4A10" (pdf). Molecular Pharmacology 59 (5): 996–1011. PMID 11306681. 
  5. ^ 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 (June 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. 
  6. ^ 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 (April 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. PMID 18095939. 

Further reading[edit]

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