Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP (PubMed:11502204). Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively (PubMed:11502204). 3',5'-cyclic GMP + H2O = GMP + H(+) 3',5'-cyclic AMP + H2O = AMP + 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. Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator. Isoform 1 is expressed in brain, heart, kidney and liver, but not in prostate. Isoform 2 is specifically expressed in testis. Isoform 3 is expressed in various tissues including brain, lung, skeletal muscle, spleen, testis and prostate. The tandem GAF domains bind cGMP, and regulate enzyme activity. The binding of cGMP stimulates enzyme activity. Belongs to the cyclic nucleotide phosphodiesterase family.