PDE4A

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

PDE4A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2QYK, 3I8V, 3TVX
Identifiers
Aliases	PDE4A, DPDE2, PDE4, PDE46, phosphodiesterase 4A
External IDs	OMIM: 600126; MGI: 99558; HomoloGene: 4520; GeneCards: PDE4A; OMA:PDE4A - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 10,416,773 bp[1] End 10,469,630 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 A3|9 7.73 cM Start 21,077,010 bp[2] End 21,124,544 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pancreatic ductal cell lateral nuclear group of thalamus parietal lobe postcentral gyrus primary visual cortex superior frontal gyrus right frontal lobe muscle of thigh cingulate gyrus anterior cingulate cortex Top expressed in superior frontal gyrus primary visual cortex dentate gyrus of hippocampal formation granule cell spermatid muscle of thigh seminiferous tubule cerebellar cortex right ventricle olfactory epithelium lumbar subsegment of spinal cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphoric diester hydrolase activity cAMP binding protein binding hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity metal ion binding 3',5'-cyclic-AMP phosphodiesterase activity Cellular component cytoplasm ruffle membrane perinuclear region of cytoplasm cytosol cell projection membrane nucleoplasm plasma membrane Biological process sensory perception of smell regulation of cAMP-mediated signaling cAMP catabolic process regulation of protein kinase A signaling signal transduction G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5141 18577 Ensembl ENSG00000065989 ENSMUSG00000032177 UniProt P27815 O89084 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 Mb Chr 9: 21.08 – 21.12 Mb PubMed search [3] [4]
Wikidata
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Function

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

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