Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors. Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and by beta-adrenergic receptors. ATP = 3',5'-cyclic AMP + diphosphate Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro). Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation. Activity is down-regulated by calcium/calcineurin. Detected in brain, spleen, lung, liver and testis (at protein level). Detected in brain, especially in hippocampus, cerebellum and neocortex. Found in decreasing order in skeletal muscle, heart, adrenal gland, ovary and brain; and to a lesser extent, in kidney, liver, testis, lung, thymus and spleen. The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.