PP2CcSerine/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.|
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- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a PP2Cc domain in a specific node, click on it.
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)
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% proteins involved KEGG pathway ID Description 24.68 map04010 MAPK signaling pathway 10.39 map04115 p53 signaling pathway 10.39 map00230 Purine metabolism 9.09 map04620 Toll-like receptor signaling pathway 6.49 map00760 Nicotinate and nicotinamide metabolism 6.49 map00740 Riboflavin metabolism 6.49 map00530 Aminosugars metabolism 6.49 map00730 Thiamine metabolism 6.49 map00051 Fructose and mannose metabolism 5.19 map00562 Inositol phosphate metabolism 5.19 map00632 Benzoate degradation via CoA ligation 2.60 map00260 Glycine, serine and threonine metabolism
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PP2Cc domain which could be assigned to a KEGG orthologous group, and not all proteins containing PP2Cc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of PP2Cc domains in PDB
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
- Links (links to other resources describing this domain)
PFAM PP2C PROSITE PP2C