PP6

Protein phosphatase 6 (PP6) is a serine/threonine protein phosphatase belonging to the PPP family of phosphatases. Like other PPP enzymes (PP1, PP2A, PP4), PP6 is a metal-dependent phosphatase that removes phosphate groups from serine or threonine residues in proteins, counteracting kinase signaling.

PP6 functions as a holoenzyme rather than a single polypeptide. The catalytic core is the PPP6C subunit; regulatory subunits PPP6R1, PPP6R2, and PPP6R3, along with small acidic subunits SAPS1-3, assemble to form active complexes. The regulatory subunits determine substrate selection, localization, and catalytic activity.

In humans, PPP6C encodes the catalytic subunit; PPP6R1-3 and SAPS1-3 encode regulatory subunits. The enzyme participates in several cellular processes including cell cycle control, mitosis, DNA damage response, and signaling pathway regulation. Through its regulatory subunits, PP6 is implicated in dephosphorylating key targets involved in spindle assembly, DNA repair, and NF-κB signaling, among others.

Alterations in PP6 components have been reported in various cancers, indicating a potential role in tumor suppression and genomic stability, though the exact mechanisms are still being studied.

PP6 is conserved in eukaryotes and is characterized by conserved catalytic motifs typical of the PPP family and a requirement for divalent metal ions for catalysis.