ADCY6

This gene encodes a member of the adenylyl cyclase family of proteins, which are required for the synthesis of cyclic AMP. All members of this family have an intracellular N-terminus, a tandem repeat of six transmembrane domains separated by a cytoplasmic loop, and a C-terminal cytoplasmic domain. The two cytoplasmic regions bind ATP and form the catalytic core of the protein. Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. A mutation in this gene is associated with arthrogryposis multiplex congenita. [provided by RefSeq, May 2015]

Full Name

Adenylate Cyclase 6

Function

Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors. Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells. Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca2+ uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol. Contributes to bone cell responses to mechanical stimuli (By similarity).

Biological Process

Activation of adenylate cyclase activity
Activation of protein kinase A activity
Adenylate cyclase-activating G protein-coupled receptor signaling pathway
Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Blood vessel diameter maintenance
cAMP biosynthetic process
Cellular response to catecholamine stimulus
Cellular response to forskolin
Cellular response to glucagon stimulus
Cellular response to prostaglandin E stimulus
Cellular response to vasopressin
Dopamine receptor signaling pathway
G protein-coupled receptor signaling pathway
Negative regulation of inflammatory response to antigenic stimulus
Negative regulation of neuron projection development
Negative regulation of urine volume
Renal water homeostasis

Cellular Location

Cell membrane; Cilium

Involvement in disease

Lethal congenital contracture syndrome 8 (LCCS8): A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS8 is an axoglial form of arthrogryposis multiplex congenita, characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period.

PTM

Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA at Ser-662 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC at Ser-556, Ser-662 and Thr-919 inhibits catalytic activity.