Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10359840). Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10359840). May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:10359840, PubMed:14751289, PubMed:27058446). a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate + H(+) 3',5'-cyclic AMP + H2O = AMP + H(+) 3',5'-cyclic GMP + H2O = GMP + H(+) 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. Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. Purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1. Homodimer. Detected in striatum (at protein level). Detected in testis and brain. Down-regulated by the expression of a huntingtin (HD) gene with an expanded polyglutamine repeat prior to the onset of neurological symptoms related to Huntington disease. The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity (By similarity). Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region. Belongs to the cyclic nucleotide phosphodiesterase family.