SMART: PP2Cc domain annotation

PP2Cc Serine/threonine phosphatases, family 2C, catalytic domain

SMART accession number:	SM00332
Description:	The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence similarity.
Family alignment:	View or

There are 5531 PP2Cc domains in 5530 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PP2Cc domain is also avaliable.

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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Cellular role (predicted cellular role)
Cellular role: signalling
Binding / catalysis: protein phosphatase, serine-specific phosphatase, threonine-specific phosphatase
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Adler E, Donella-Deana A, Arigoni F, Pinna LA, Stragler P
- Structural relationship between a bacterial developmental protein and eukaryotic PP2C protein phosphatases.
- Mol Microbiol. 1997; 23: 57-62
- Display abstract
- Bacillus subtilis SpoIIE is a Ser protein phosphatase whose action on the phosphoprotein SpoIIAA triggers the cell type-specific activation of a sporulation transcription factor. Here we report that SpoIIE displays sequence similarity to the PP2C family of eukaryotic Ser/Thr protein phosphatases, and that residues common to these proteins are required for the function of both SpoIIE and TPD1, a yeast PP2C. These findings suggest that SpoIIE and the PP2C protein phosphatases are structurally related, and reveal a striking formal similarity between the SpoIIAA regulatory circuit and that of mammalian mitochondrial pyruvate dehydrogenase. This similarity may reflect an evolutionarily conserved mechanism of biological regulation based on the interplay of His protein kinase-like Ser kinases and PP2C-like protein phosphatases.
- Cohen PT
- Novel protein serine/threonine phosphatases: variety is the spice of life.
- Trends Biochem Sci. 1997; 22: 245-51
- Display abstract
- The dephosphorylation of proteins on serine and threonine residues is a major mechanism of cellular regulation. Many novel protein serine/threonine phosphatases in the PPP family have recently been discovered and the insights that have been gained into their different functions are summarised in this review.
- Bork P, Brown NP, Hegyi H, Schultz J
- The protein phosphatase 2C (PP2C) superfamily: detection of bacterial homologues.
- Protein Sci. 1996; 5: 1421-5
- Display abstract
- A thorough sequence analysis of the various members of the eukaryotic protein serine/threonine phosphatase 2C (PP2C) family revealed the conservation of 11 motifs. These motifs could be identified in numerous other sequences, including fungal adenylate cyclases that are predicted to contain a functionally active PP2C domain, and a family of prokaryotic serine/threonine phosphatases including SpoIIE. Phylogenetic analysis of all the proteins indicates a widespread sequence family for which a considerable number of isoenzymes can be inferred.
- Das AK, Helps NR, Cohen PT, Barford D
- Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.
- EMBO J. 1996; 15: 6798-809
- Display abstract
- Protein phosphatase 2C (PP2C) is a Mn2+- or Mg2+-dependent protein Ser/Thr phosphatase that is essential for regulating cellular stress responses in eukaryotes. The crystal structure of human PP2C reveals a novel protein fold with a catalytic domain composed of a central beta-sandwich that binds two manganese ions, which is surrounded by alpha-helices. Mn2+-bound water molecules at the binuclear metal centre coordinate the phosphate group of the substrate and provide a nucleophile and general acid in the dephosphorylation reaction. Our model presents a framework for understanding not only the classical Mn2+/Mg2+-dependent protein phosphatases but also the sequence-related domains of mitochondrial pyruvate dehydrogenase phosphatase, the Bacillus subtilus phosphatase SpoIIE and a 300-residue domain within yeast adenyl cyclase. The protein architecture and deduced catalytic mechanism are strikingly similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence similarity, suggestive of convergent evolution of protein Ser/Thr phosphatases.
- Mumby MC, Walter G
- Protein serine/threonine phosphatases: structure, regulation, and functions in cell growth.
- Physiol Rev. 1993; 73: 673-99
- Display abstract
- It is clear that much remains to be discovered regarding the roles of protein phosphatases in mitogenic signaling pathways. The ability of okadaic acid to activate MAPK/ERKs demonstrates that alteration in serine/threonine dephosphorylation can have significant effects on common steps in growth stimulation induced by different types of mitogens. As in the case of cell cycle control, protein serine/threonine phosphatase plays a central role in the reentry of quiescent cells into the cycle. Because the only known targets of okadaic acid are the catalytic subunits PP1 and PP2A, these enzymes are crucial components of two basic functions carried out by cells: growth and division. Important and obligatory roles for PP2B, PP2C, and newly discovered serine/threonine phosphatases are also likely. However, the limited tissue distribution, unique regulatory properties, and limited substrate specificities of these forms suggest more specialized functions in restricted cell types. The available information on the specific functions of different forms of protein serine/threonine phosphatases, let alone their individual isoforms and different multimeric holoenzymes, is still severely limited. Years of biochemical characterization and cDNA cloning have left us with far more forms than functions. This has led to the gratifying situation, at least for the biochemists, in which genetics and cell biology identify protein phosphatases for which a wealth of biochemical information is already available. The appreciation of the importance of these enzymes in the coming years can only increase as the functions for individual forms are discovered.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Links (links to other resources describing this domain)
PFAM PP2C
PROSITE PP2C

PDB code	Main view	Title
1a6q		Crystal structure of the protein serine/threonine phosphatase 2c at 2 a resolution
1txo		Crystal structure of the mycobacterium tuberculosis serine/threonine phosphatase pstp/ppp at 1.95 a.
2cm1		Crystal structure of the catalytic domain of serine threonine protein phosphatase pstp in complex with manganese ions.
2i0o		Crystal structure of anopheles gambiae ser/thr phosphatase complexed with zn2+
2i44		Crystal structure of serine-threonine phosphatase 2c from toxoplasma gondii
2iq1		Crystal structure of human ppm1k
2irm		Crystal structure of mitogen-activated protein kinase kinase kinase 7 interacting protein 1 from anopheles gambiae
2isn		Crystal structure of a phosphatase from a pathogenic strain toxoplasma gondii
2j4o		Structure of tab1
2j82		Structural analysis of the pp2c family phosphatase tppha from thermosynechococcus elongatus
2j86		Structural analysis of the pp2c family phosphatase tppha of thermosynechococcus elongatus
2jfr		Crystal structure of the ppm ser-thr phosphatase mspp from mycobacterium smegmatis in complex with phosphate at 0.83 a resolution
2jfs		Crystal structure of the ppm ser-thr phosphatase mspp from mycobacterium smegmatis in complex with cacodylate
2jft		Crystal structure of the ppm ser-thr phosphatase mspp from mycobacterium smegmatis in complex with sulfate
2p8e		Crystal structure of the serine/threonine phosphatase domain of human ppm1b
2pk0		Structure of the s. agalactiae serine/threonine phosphatase at 2.65 resolution
2pnq		Crystal structure of pyruvate dehydrogenase phosphatase 1 (pdp1)
2pom		Tab1 with manganese ion
2pop		The crystal structure of tab1 and bir1 complex
2v06		Crystal structure of the ppm ser-thr phosphatase mspp from mycobacterium smegmatis at ph 5.5
3d8k		Crsytal structure of a phosphatase from a toxoplasma gondii
3jrq		Crystal structure of (+)-aba-bound pyl1 in complex with abi1
3kdj		Complex structure of (+)-aba-bound pyl1 and abi1

PFAM	PP2C
PROSITE	PP2C

PP2Cc

3D Structures of PP2Cc domains in PDB