Adenylate cyclase type 9 (ADCY9) (ADCY9)

Adenylate cyclase type 9 (ADCY9), also known as AC9, is a membrane-bound enzyme that catalyzes the synthesis of the second messenger cyclic AMP (cAMP) from ATP in response to G protein-coupled receptor (GPCR) activation [1, 2]. It is widely expressed in tissues including the heart, lungs, and skeletal muscle, playing a pivotal role in regulating physiological functions such as heart rate, airway smooth muscle tone, and immune cell motility [2, 4, 9]. ADCY9 is distinguished from other adenylate cyclase isoforms by its relative insensitivity to the common activator forskolin and its unique regulation by the phosphatase calcineurin [5, 12, 18]. Clinically, ADCY9 has emerged as a major pharmacogenomic target in cardiovascular medicine, where the rs1967309 polymorphism determines the efficacy of the CETP inhibitor dalcetrapib; patients with the AA genotype experience significant reduction in cardiovascular events and inflammation, whereas those with the GG genotype may not benefit [10, 11, 16]. Additionally, genetic variations in ADCY9 are linked to asthma susceptibility and obesity, and the protein has been characterized as a potential tumor suppressor in lung adenocarcinoma [3, 7, 8, 15].

Other names

Adenylyl cyclase 9Adenylate cyclase type IXACIXATP pyrophosphate-lyase 9AC9KIAA0520

Adenylate cyclase type 9 catalyzes the conversion of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP) and pyrophosphate. Its activity is stimulated by the Gs alpha subunit downstream of GPCRs (such as the beta-2 adrenergic receptor) and is uniquely regulated by autoinhibition from its C-terminal domain and sensitivity to calcineurin-mediated downregulation.