Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:1409703, PubMed:15385642, PubMed:17110384, PubMed:21606183). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:21606183). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA (PubMed:21606183). This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (By similarity). Contributes to bone cell responses to mechanical stimuli (By similarity). ATP = 3',5'-cyclic AMP + diphosphate Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro). Activated by forskolin (PubMed:9391159). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:9391159, PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (PubMed:15385642). Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity). Interacts with RAF1 (PubMed:15385642). Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (By similarity). Detected in brain and kidney (PubMed:1409703). Detected in vascular smooth muscle cells (PubMed:21606183). 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. Phosphorylation by RAF1 increases enzyme activity (PubMed:15385642). Phosphorylation by PKA on Ser-660 inhibits the GNAS-mediated increase in catalytic activity (PubMed:9391159). Phosphorylation by PKC on Ser-554, Ser-660 and Thr-917 inhibits catalytic activity (PubMed:11877398). Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Extended N-terminus.