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Comments and Description Text from UniProtKB
ID:PDE4A_HUMAN DESCRIPTION: RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4A; EC=3.1.4.17; AltName: Full=DPDE2; AltName: Full=PDE46; FUNCTION: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. CATALYTIC ACTIVITY: Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate. COFACTOR: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. ENZYME REGULATION: Isoform 1, isoform 2, isoform 6 and isoform 7 are inhibited by rolipram and cilomilast. Isoform 1, isoform 2 and isoform 6 are inhibited by 4-[(3-butoxy-4-methoxyphenyl)-methyl]- 2-imidazolidinone (Ro 20-1724), roflumilast and denbufylline. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4.0 uM for cAMP (isoform 2); KM=3 uM for cAMP (isoform 6); PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. SUBUNIT: Isoform 1 interacts with LYN. Isoform 2 and isoform 6 interact weakly with LYN. Isoform 1, isoform 2 and isoform 6 interact with ARRB2. SUBCELLULAR LOCATION: Isoform 1: Cytoplasm, perinuclear region. SUBCELLULAR LOCATION: Isoform 2: Cytoplasm, perinuclear region. Cell projection, ruffle membrane. SUBCELLULAR LOCATION: Isoform 4: Membrane; Peripheral membrane protein. Note=Isoform 4 has propensity for association with membranes. SUBCELLULAR LOCATION: Isoform 6: Cytoplasm, perinuclear region. SUBCELLULAR LOCATION: Isoform 7: Cytoplasm. Membrane. Note=Predominantly cytoplasmic. TISSUE SPECIFICITY: Isoform 1 is widely expressed. Isoform 2 is abundant in liver, stomach, testis, thyroid and adrenal glands. It is also found in placenta, kidney, pancreas, ovary, uterus, skin, monocytes, mast cells, macrophages, as well as in bronchial smooth muscle. Isoform 6 is expressed at high levels in the heart and small intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood lymphocytes. Isoform 7 is expressed predominantly in skeletal muscle and brain and at lower levels in the testis. Isoform 7 is expressed in the brain. Found in specific neuronal subpopulations in cortex, spinal cord and cerebellum (at protein level). PTM: Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation (By similarity). Phosphorylated at Ser-686 and Ser-688 when expressed in S.frugiperda cells. Isoform 2 and isoform 7 are activated by phosphorylation at Ser-119 and Ser-123 respectively by PKA. PTM: Proteolytically cleaved by caspase-3. SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Protein Domain and Structure Information
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