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Acts as a key mediator of G protein-coupled receptor signaling by catalyzing the formation of cAMP downstream of G protein-coupled receptors (By similarity). Functions in G protein-coupled receptor signaling cascades activated by thrombin, sphingosine 1-phosphate, dopamine and anaphylatoxin C5a (By similarity). Mediates regulation of cAMP synthesis through synergistic action of the G alpha protein G(s) (GNAS) with G(13) (GNA13) (PubMed:18541530, PubMed:23178822). Also involved in inflammation by acting as a diadenylate cyclase that catalyzes the condensation of 2 ATP molecules into c-di-AMP (PubMed:40419769). Following activation by TLR9, mediates formation of c-di-AMP, which directly activates NLRP3, thereby promoting assembly and maturation of the NLRP3 inflammasome (PubMed:40419769). It is also required for the optimal functions of B- and T cells during adaptive immune responses by regulating cAMP synthesis in both B- and T-cells (PubMed:20505140)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"ATP = 3',5'-cyclic AMP + diphosphate","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:15389"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:58165"}],"ecNumber":"4.6.1.1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18205980"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40419769"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"23229509"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"2 ATP = 3',3'-c-di-AMP + 2 diphosphate","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:35655"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:71500"}],"ecNumber":"2.7.7.85","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40419769"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:35656"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40419769"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P30803"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}},{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P30803"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P30803"}],"value":"Binds 2 magnesium ions per subunit. 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Activated by TLR9, promoting synthesis of cyclic di-AMP (c-di-AMP) (PubMed:40419769)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40419769"}],"value":"Interacts with TLR9; leading to ADCY7 activation and synthesis of cyclic di-AMP (c-di-AMP)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"value":"Membrane","id":"SL-0162"},"topology":{"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7961850"}],"value":"Most abundant in heart, spleen and lung"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P26769"}],"value":"The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. 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