Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian serine/threonine specific protein phosphatases (EC 3.1.3.16). PP2C [1] is a monomeric enzyme of about 42 Kd which shows broad substrate specificity and is dependent on divalent cations (mainly manganese and magnesium) for its activity. Its exact physiological role is still unclear. Three isozymes are currently known in mammals: PP2C-α, -β and -γ. In yeast, there are at least four PP2C homologs: phosphatase PTC1 [2] which has weak tyrosine phosphatase activity in addition to its activity on serines, phosphatases PTC2 and PTC3, and hypothetical protein YBR125c. Isozymes of PP2C are also known from Arabidopsis thaliana (ABI1, PPH1), Caenorhabditis elegans (FEM-2, F42G9.1, T23F11.1), Leishmania chagasi and Paramecium tetraurelia.

In Arabidopsis thaliana, the kinase associated protein phosphatase (KAPP) [3] is an enzyme that dephosphorylates the Ser/Thr receptor-like kinase RLK5 and which contains a C-terminal PP2C domain.

PP2C does not seem to be evolutionary related to the main family of serine/ threonine phosphatases: PP1, PP2A and PP2B . However, it is significantly similar to the catalytic subunit of pyruvate dehydrogenase (lipoamide)-phosphatase (EC 3.1.3.43) (PDPC) [4], which catalyzes dephosphorylation and concomitant reactivation of the α subunit of the E1 component of the pyruvate dehydrogenase complex. PDPC is a mitochondrial enzyme and, like PP2C, is magnesium-dependent.

As a signature pattern, we selected the best conserved region which is located in the N-terminal part and contains a perfectly conserved tripeptide. This region includes a conserved aspartate residue involved in divalent cation binding [5].