Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels (By similarity). May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity). ATP = 3',5'-cyclic AMP + diphosphate Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro). Activated by calcium/calmodulin. Activated by forskolin. Activated by the G protein alpha subunit GNAS. Inhibited by the G protein beta and gamma subunit complex. Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP. Interacts with CALM. Expressed in the cytoplasm of supporting cells and hair cells of the cochlea vestibule, as well as to the cochlear hair cell nuclei and stereocilia. Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Brain, retina and adrenal medulla. 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. N-glycosylated. The disease is caused by variants affecting the gene represented in this entry. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.