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.,disease:Genetic variations in PDE4D might be associated with susceptibility to stroke type 1 (STRK1) [MIM:606799]. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. PubMed:17006457 states that association with stroke has to be considered with caution.,enzyme regulation:Inhibited by rolipram. Activated by phosphatidic acid.,function:Regulates the levels of cAMP in the cell.,pathway:Purine metabolism; cAMP degradation; AMP from cAMP: step 1/1.,PTM:Isoform 2 and isoform 11 are activated by phosphorylation (in vitro), but not isoform 8. Isoform 7 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.,similarity:Belongs to the cyclic nucleotide phosphodiesterase family.,subcellular location:Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome.,subunit:Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 2 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP (By similarity). Isoform 5 binds GNB2L1 via its unique N-terminus. Binds ARRB2.,tissue specificity:Widespread; most abundant in skeletal muscle. Isoform 8 is detected in brain. Isoform 9 is detected in brain, placenta, lung and kidney. Isoform 11 is detected in heart and skeletal muscle.,
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