The domain within your query sequence starts at position 1463 and ends at position 1555; the E-value for the PP2Cc domain shown below is 2e-39.

SPAYPNEQRCMLHPVCLSNSFQRQLSSATFSSAFSDNGLDSDDEEPIEGVFSNGSRVEVE
VDIHCSRAKEKERQQHLLQVPAEASDEGIVISA

The domain was found using the schnipsel database

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.

There are 66722 PP2Cc domains in 66644 proteins in SMART's nrdb database.

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

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

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

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

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

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)

% 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	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 2 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 PP2C 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
2xzv	The cyanobacterial PP2C-like phosphatase tPphA requires three metals in the catalytic center for efficient catalysis
2y09	The cyanobacterial PP2C-like phosphatase tPphA requires three metals in the catalytic center for efficient catalysis
3d8k	Crsytal structure of a phosphatase from a toxoplasma gondii
3fxj	Crystal Structure of Human Protein phosphatase 1A (PPM1A) Bound with Phosphate at 3 mM of Mn2+
3fxk	Crystal Structure of Human Protein phosphatase 1A (PPM1A) Bound with Phosphate at 10 mM of Mn2+
3fxl	Crystal Structure of Human Protein phosphatase 1A (PPM1A) Bound with Citrate at 1 mM of Mn2+
3fxm	Crystal Structure of Human Protein phosphatase 1A (PPM1A) Bound with Citrate at 10 mM of Mn2+
3fxo	Crystal Structure of Human Protein phosphatase 1A (PPM1A) Bound with Phosphate at 1 mM of Mn2+
3jrq	Crystal structure of (+)-ABA-bound PYL1 in complex with ABI1
3kb3	Crystal structure of abscisic acid-bound PYL2 in complex with HAB1
3kdj	Complex structure of (+)-ABA-bound PYL1 and ABI1
3mq3	Crystal structure of native bovine PDP1c
3n3c	Crystal structure of native bovine PDP1c
3nmn	Crystal structure of pyrabactin-bound abscisic acid receptor PYL1 in complex with type 2C protein phosphatase ABI1
3nmt	Crystal structure of pyrabactin bound abscisic acid receptor PYL2 mutant A93F in complex with type 2C protein phosphatase HAB1
3nmv	Crystal structure of pyrabactin-bound abscisic acid receptor PYL2 mutant A93F in complex with type 2C protein phosphatase ABI2
3qn1	Crystal structure of the PYR1 Abscisic Acid receptor in complex with the HAB1 type 2C phosphatase catalytic domain
3rnr	Crystal Structure of Stage II Sporulation E Family Protein from Thermanaerovibrio acidaminovorans
3rt0	Crystal structure of PYL10-HAB1 complex in the absence of abscisic acid (ABA)
3t91	Structure of the Phosphatase Domain of the Cell Fate Determinant SpoIIE from Bacillus subtilis
3t9q	Structure of the Phosphatase Domain of the Cell Fate Determinant SpoIIE from Bacillus subtilis (Mn presoaked)
3ujg	Crystal structure of SnRK2.6 in complex with HAB1
3ujk	Crystal structure of protein phosphatase ABI2
3ujl	Crystal structure of abscisic acid bound PYL2 in complex with type 2C protein phosphatase ABI2
3w40	Crystal structure of RsbX in complex with magnesium in space group P1
3w41	Crystal structure of RsbX in complex with magnesium in space group P21
3w42	Crystal structure of RsbX in complex with manganese in space group P1
3w43	Crystal structure of RsbX in complex with manganese in space group P21
3w44	Crystal structure of RsbX, selenomethionine derivative
3w45	Crystal structure of RsbX in complex with cobalt in space group P1
3zt9	The bacterial stressosome: a modular system that has been adapted to control secondary messenger signaling
3zvu	Structure of the PYR1 His60Pro mutant in complex with the HAB1 phosphatase and Abscisic acid
4da1	Crystal structure of branched-chain alpha-ketoacid dehydrogenase phosphatase with Mg (II) ions at the active site
4ds8	Complex structure of abscisic acid receptor PYL3-(+)-ABA-HAB1 in the presence of Mn2+
4jnd	Structure of a C.elegans sex determining protein
4la7	X-ray crystal structure of the PYL2-quinabactin-Hab1 ternary complex
4lg5	ABA-mimicking ligand QUINABACTIN in complex with ABA receptor PYL2 and PP2C HAB1
4lga	ABA-mimicking ligand N-(2-OXO-1-PROPYL-1,2,3,4-TETRAHYDROQUINOLIN-6-YL)-1-PHENYLMETHANESULFONAMIDE in complex with ABA receptor PYL2 and PP2C HAB1
4lgb	ABA-mimicking ligand N-(1-METHYL-2-OXO-1,2,3,4-TETRAHYDROQUINOLIN-6-YL)-1-(4-METHYLPHENYL)METHANESULFONAMIDE in complex with ABA receptor PYL2 and PP2C HAB1
4n0g	Crystal Structure of PYL13-PP2CA complex
4oic	4OIC
4ra2	4RA2
4raf	4RAF
4rag	4RAG
4wvo	4WVO
4yzg	4YZG
4yzh	4YZH
5d2u	5D2U
5f1m	5F1M
5iti	5ITI
5jo1	5JO1
5jo2	5JO2

Links (links to other resources describing this domain)

• PROSITE: PP2C
• PFAM: PP2C