PP2A

Protein Phosphatase 2A (PP2A), a heterotrimeric protein phosphatase, is a ubiquitous and conserved Serine/Threonine phosphatase with broad substrate specificity and diverse cellular functions. PP2A comprises A and B subunits which are regulatory and a catalytic C subunit. When the PP2A catalytic C subunit associates with the regulatory A and B subunits several species of holoenzymes are produced with distinct functions and characteristics. The A subunit, a founding member of the HEAT repeat protein family (huntington-elongation-A subunit-TOR), is the scaffold required for the formation of the heterotrimeric complex. When the A subunit binds it alters the enzymatic activity of the catalytic subunit, even if the B subunit is absent. While C and A subunit sequences show remarkable sequence conservation throughout eukaryotes, regulatory B subunits are more heterogeneous and are believed to play key roles in controlling the localization and specific activity of different holoenzymes. Multicellular eukaryotes express four classes of variable regulatory subunits: B (PR55), Bˈ (B56 or PR61), Bˈˈ (PR72), and Bˈˈˈ (PR93/PR110), with at least 16 members in these subfamilies. In Addition, accessory proteins and posttranslational modifications (such as methylation) control PP2A subunit associations and activities.

The two catalytic metal ions located at bottom of PP2A's active site have been recently identified as manganese, which had previously been suggested as potential candidates.