Catalytic activity:ATP = 3' ,5'-cyclic AMP + diphosphate. ,cofactor:Binds 2 magnesium ions per subunit. ,Disease:Genetic variations in ADCY10 are associated with absorptive hypercalciuria type 2 (HCA2) [MIM:143870]. Absorptive hypercalciuria (AH) is a common cause of calcium oxalate nephrolithiasis. Clinically , AH is characterized by intestinal hyperabsorption of calcium in the presence of normal serum calcium and immunoreactive PTH (iPTH) . It is often accompanied by low bone mineral density (BMD) , particularly of the lumbar spine. About 50% of patients with AH present with a family history of calcium oxalate nephrolithiasis and hypercalciuria. ,enzyme regulation:Activated by manganese or magnesium ions. In the presence of magnesium ions , the enzyme is activated by bicarbonate while in the presence of manganese ions , the enzyme is inhibited by bicarbonate. In the absence of magnesium and bicarbonate , the enzyme is weakly activated by calcium. ,Function:Soluble adenylyl cyclase that has a critical role in mammalian spermatogenesis. Produces the cAMP which mediates in part the cAMP-responsive nuclear factors indispensable for maturation of sperm in the epididymis. Induces capacitation , the maturational process that sperm undergo prior to fertilization. May be the bicarbonate sensor. Involved in ciliary beat regulation. ,PTM:Cleavage may occur to generate the active 48 kDa form. ,similarity:Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. ,similarity:Contains 2 guanylate cyclase domains. ,subcellular location:Distributed to subcellular compartments containing cAMP targets. Found as a plasma membrane-associated protein , protein concentrated in the perinuclear region and protein colocalized with actin or tubulin. ,tissue specificity:Weakly expressed in multiple tissues. Expressed in brain , heart , kidney , liver , lung , pancreas , peripheral blood leukocytes , placenta , skeletal muscle , stomach , thymus , airway epithelial cells , duodenum , jejunum and ileum. Very low level of expression in bone. ,
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