Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:18071070, PubMed:24363043). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:18071070). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption (PubMed:20466003, PubMed:20864687). Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion (PubMed:24854272). Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (PubMed:23753526). Signaling mediates cAMP-dependent activation of protein kinase PKA and promotes increased phosphorylation of various proteins, including AKT (PubMed:18071070, PubMed:23753526). Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility (PubMed:18071070). May contribute to normal heart function (PubMed:18071070, PubMed:20359598). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (By similarity). Contributes to bone cell responses to mechanical stimuli (PubMed:20371630, PubMed:24277577). ATP = 3',5'-cyclic AMP + diphosphate Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro). Activated by forskolin (PubMed:18071070, PubMed:20466003, PubMed:20864687, PubMed:23753526, PubMed:24363043). Inhibited by calcium ions, already at micromolar concentrations (PubMed:1379717, PubMed:18071070). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS. Is further activated by the complex formed by GNB1 and GNG2 (By similarity). Phosphorylation by RAF1 results in its activation (By similarity). Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (PubMed:21670265). Interacts with RAF1. Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (By similarity). Detected in kidney tubules (PubMed:20466003). Detected in primary bone cells with osteocyte morphology (PubMed:24277577). Detected in heart (at protein level) (PubMed:18071070). Highly expressed in heart (PubMed:1379717, PubMed:18071070). Detected in kidney, pancreas acini and ducts (PubMed:23753526). Expressed in cochlear outer and inner hair cells (PubMed:17567809). Weakly detectable in brain, intestine, lung and spleen (PubMed:1379717). In the inner ear, between 16 dpc and P1, present along the sterocilia of outer hair cells, but almost undetectable in inner hair cell hair bundle. From P3 onward, expression in outer hair cell bundles is restricted to their base and it is also expressed at the base of inner hair cell stereocilia. 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. Phosphorylation by PKA on Ser-659 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC on Ser-553, Ser-659 and Thr-916 inhibits catalytic activity. Mutant mice are born at the expected Mendelian rate, present no obvious phenotype and are fertile (PubMed:18071070, PubMed:20466003, PubMed:23753526, PubMed:24277577). Their hearts display a decrease in left ventricular pressure, both at the basal level and after activation of beta-adrenergic receptors (PubMed:18071070). Besides, their hearts show defects in sarcoplasmic Ca(2+) uptake and storage, and decreased levels of protein phosphorylation (PubMed:18071070). Male mice show increased mortality after transversal aortic constriction (PubMed:20359598). In contrast, female mice do not show increased mortality after transversal aortic constriction, and develop less heart hypertrophy and fibrosis than wild-type (PubMed:20359598). Compared to wild-type, mutant mice drink more and produce greater volumes of urine with decreased osmolarity, but there is no difference in the total quantity of excreted urinary solutes and no difference in blood plasma composition (PubMed:20466003, PubMed:20864687). The impaired urinary water homeostasis is due to retention of AQP2 in intracellular vesicles and decreased AQP2 levels at the cell membrane (PubMed:20466003). Mutant mice display increased urinary inorganic phosphate excretion, but normal plasma phosphate levels (PubMed:24854272). Mutant mice display increased plasma levels of PTH and FGF23, the two principal regulators of urinary phosphate excretion (PubMed:24854272). Mutant mice display no obvious skeleton defects, but display less bone formation after load stress than wild-type (PubMed:24277577). Mutant mice lacking both Adcy6 and Pkd1 survive longer and have less severe polycystic kidney disease than mice lacking only Pkd1 (PubMed:24158982). Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.