Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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PP2C_SIG Sigma factor PP2C-like phosphatases

SMART accession number:	SM00331
Description:
Interpro abstract (IPR001932):	This domain is found in protein phosphatase 2C, as well as other proteins eg. pyruvate dehydrogenase (lipoamide)-phosphatase (EC 3.1.3.43), adenylate cyclase (EC 4.6.1.1) and some bacterial stage II sporulation E proteins (EC 3.1.3.16). Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian serine/threonine specific protein phosphatases (EC 3.1.3.16). PP2C [(PUBMED:1312947)] 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-alpha, -beta and -gamma. In yeast, there are at least four PP2C homologues: phosphatase PTC1 [(PUBMED:8395005)], 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 A. thaliana, the kinase associated protein phosphatase (KAPP) [(PUBMED:7973632)] 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 phosphatase EC 3.1.3.43 (PDPC) [(PUBMED:8396421)], which catalyzes dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex. PDPC is a mitochondrial enzyme and, like PP2C, is magnesium-dependent.
GO function:	catalytic activity (GO:0003824)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 7422 PP2C_SIG domains in 7422 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a PP2C_SIG domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PP2C_SIG 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

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 21.43 map04010 MAPK signaling pathway 8.93 map00562 Inositol phosphate metabolism 8.93 map00760 Nicotinate and nicotinamide metabolism 8.93 map00632 Benzoate degradation via CoA ligation 8.93 map00740 Riboflavin metabolism 8.93 map00530 Aminosugars metabolism 8.93 map00730 Thiamine metabolism 8.93 map00051 Fructose and mannose metabolism 7.14 map00260 Glycine, serine and threonine metabolism 5.36 map04115 p53 signaling pathway 1.79 map00230 Purine metabolism 1.79 map02020 Two-component system - General 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 PP2C_SIG domain which could be assigned to a KEGG orthologous group, and not all proteins containing PP2C_SIG 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 PP2C_SIG 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
  2isn		Crystal structure of a phosphatase from a pathogenic strain toxoplasma gondii
  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)
  2v06		Crystal structure of the ppm ser-thr phosphatase mspp from mycobacterium smegmatis at ph 5.5
  3eq2		Structure of hexagonal crystal form of pseudomonas aeruginosa rssb
  3es2		Structure of the c-terminal phosphatase domain of p. aeruginonsa rssb
  3f79		Structure of pseudo-centered cell crystal form of the c- terminal phosphatase domain of p. aeruginosa rssb
  3f7a		Structure of orthorhombic crystal form of pseudomonas aeruginosa rssb
  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)

• INTERPRO	IPR001932

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