Adenylyl cyclase 7 (ADCY7)

Adenylyl cyclase 7 is a membrane-bound enzyme that catalyzes the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP)[1][2]. The enzyme is characterized by twelve membrane-spanning domains and belongs to the adenylyl cyclase class-4/guanylyl cyclase enzyme family[1]. ADCY7 is inhibitable by calcium and plays a critical role in G protein-coupled receptor signaling cascades[1][3]. Function and Signaling ADCY7 functions as a key regulator in cAMP-mediated signaling pathways, responding to activation of G protein-coupled receptors[3]. The enzyme mediates signaling cascades activated by various molecules including thrombin, sphingosine 1-phosphate, dopamine, and C5 alpha chain through synergistic actions with stimulatory G proteins[3]. During inflammatory responses, ADCY7 mediates zymosan-induced increases in intracellular cAMP, leading to protein kinase A pathway activation to modulate innate immune responses[3]. Immune System Role In the immune system, ADCY7 is highly expressed in B and T lymphocytes where it orchestrates cAMP synthesis[2]. This regulation is critical for controlling innate and adaptive immune responses, as loss of ADCY7 activity leads to exaggerated proinflammatory cytokine production and heightened sensitivity to bacterial endotoxins[2]. The enzyme functions to keep inflammation under control during bacterial infection by sensing serum factors such as lysophospholipid that regulate lipopolysaccharide-induced tumor necrosis factor-alpha production[3]. Disease Associations ADCY7 has been implicated in multiple disease contexts. A rare missense variant in ADCY7 doubles the risk for ulcerative colitis, linking altered ADCY7 activity to inflammatory bowel disease[2]. In the central nervous system, altered ADCY7-mediated cAMP signaling has been associated with mood and emotional reactivity modulation, with evidence supporting a sex-specific influence on major depressive disorder risk[2]. Cancer Biology In cancer research, ADCY7 shows abnormal expression patterns across multiple human cancers and correlates with mismatch repair genes and DNA methyltransferase expression[4]. The enzyme's expression influences overall survival in six cancer types, disease-specific survival in eight types, and progression-free interval in three types[4]. High ADCY7 expression is strongly associated with poor outcomes in breast cancer and lung squamous cell carcinoma patients[4]. In hematologic malignancies, reduced ADCY7 expression in acute myeloid leukemia is associated with diminished cell growth and increased apoptosis[2]. Metabolic and Behavioral Functions ADCY7 contributes to alcohol consumption and dependence regulation, particularly in females, where genetic polymorphisms modulate drinking behavior and ADCY7 expression[2]. Novel studies have identified compound heterozygous variants in ADCY7 in patients with congenital hyperinsulinism, highlighting its emerging role in metabolic regulation[2].

Other names

AC7adenylate cyclase 7adenylate cyclase type 7adenylate cyclase type VIIadenylyl cyclase 7ATP pyrophosphate-lyase 7KIAA0037

cAMP synthesis inhibition, G protein-coupled receptor signaling modulation