PRKAR2A

PRKAR2A is a human gene that encodes the regulatory subunit II-alpha of the cAMP-dependent protein kinase A (PKA). The encoded protein is one of the regulatory subunits that assemble with catalytic subunits to form the PKA holoenzyme. In the absence of cyclic AMP, RII-alpha binds and inhibits the catalytic subunits, maintaining PKA in an inactive state.

Binding of cyclic AMP to RII-alpha relieves inhibition by causing dissociation of the catalytic subunits, thereby activating PKA signaling. RII-alpha has distinct cAMP-binding properties and contributes to isoform-specific regulation of PKA. Through interactions with A-kinase anchoring proteins (AKAPs), RII-alpha localizes PKA to particular subcellular compartments for targeted phosphorylation of substrates.

PRKAR2A is broadly expressed, with transcripts detected in multiple tissues, consistent with a general role in cAMP signaling. The regulated activity of PKA influences diverse cellular processes, including metabolism, transcription, and neuronal signaling, depending on cellular context and localization.

Clinical significance: There are no widely established disease-causing mutations in PRKAR2A. Alterations in PKA signaling are implicated in various conditions, but PRKAR2A-specific disease associations are less clear and require further study. By contrast, other regulatory subunits of PKA, such as PRKAR1A, have well-characterized disease links.

Interactions: The RII-alpha regulatory subunit forms a holoenzyme complex with catalytic subunits PRKACA and PRKACB and interacts with AKAPs to anchor PKA to specific cellular sites, enabling localized and time-dependent phosphorylation of target proteins.