Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2)

Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2) is a protein kinase subunit that forms part of the phosphorylase b kinase complex, essential for regulating glycogen degradation in the liver. PHKA2 encodes the liver-specific alpha subunit, which serves a regulatory function, modulating enzyme activation in response to phosphorylation and calcium/calmodulin signals. The holoenzyme is a hexadecamer consisting of four copies each of alpha, beta, gamma, and delta subunits; the gamma subunit harbors kinase activity, while alpha and beta subunits control regulation, and delta acts as calmodulin, mediating calcium response. Mutations in PHKA2 result in X-linked hepatic glycogen storage disease type IX, leading to inadequate glycogen breakdown, hepatomegaly, and hypoglycemia. The PHKA2 subunit also supports integration of hormonal and metabolic signals necessary for glucose homeostasis, and its dysfunction has been linked to cancer progression through caspase-3-mediated cleavage and regulatory imbalances. There are no direct pharmacological agents targeting PHKA2, but genetic analysis and metabolic/biochemical biomarkers are used for diagnosis and monitoring.

Other names

PHKA2PHKLAPYKXLGXLG2GSD9APhosphorylase kinase alpha L subunitPhosphorylase kinase alpha-subunitphosphorylase b kinase regulatory subunit alpha, liver isoformphosphorylase kinase alpha L subunit

Not directly targeted by drugs; therapeutic interventions act by modulating upstream signals, or addressing metabolic consequences of deficiency (e.g., dietary management, monitoring liver function). Indirect interactions: agents affecting cAMP/PKA pathways or calcium signaling may modulate activity.