PROSITE documentation PDOC00792

Protein phosphatase 2C signature


Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian serine/threonine specific protein phosphatases (EC 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 (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].


PP2C belongs [6] to a superfamily which also includes bacterial proteins such as Bacillus spoIIE, rsbU and rsbW, Synechocystis PCC 6803 icfG as well as a domain in fungal adenylate cyclases.

Last update:

May 2004 / Text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

PP2C, PS01032; Protein phosphatase 2C signature  (PATTERN)


1AuthorsWenk J., Trompeter H.-I., Pettrich K.-G., Cohen P.T.W., Campbell D.G., Mieskes G.
TitleMolecular cloning and primary structure of a protein phosphatase 2C isoform.
SourceFEBS Lett. 297:135-138(1992).
PubMed ID1312947

2AuthorsMaeda T., Tsai A.Y.M., Saito H.
TitleMutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae.
SourceMol. Cell. Biol. 13:5408-5417(1993).
PubMed ID8395005

3AuthorsStone J.M., Collinge M.A., Smith R.D., Horn M.A., Walker J.C.
TitleInteraction of a protein phosphatase with an Arabidopsis serine-threonine receptor kinase.
SourceScience 266:793-795(1994).
PubMed ID7973632

4AuthorsLawson J.E., Niu X.-D., Browning K.S., Trong H.L., Yan J., Reed L.J.
TitleMolecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C.
SourceBiochemistry 32:8987-8993(1993).
PubMed ID8396421

5AuthorsDas A.K., Helps N.R., Cohen P.T.W., Barford D.
TitleCrystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.
SourceEMBO J. 15:6798-6809(1996).
PubMed ID9003755

6AuthorsBork P., Brown N.P., Hegyi H., Schultz J.
TitleThe protein phosphatase 2C (PP2C) superfamily: detection of bacterial homologues.
SourceProtein Sci. 5:1421-1425(1996).
PubMed ID8819174

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