The domain within your query sequence starts at position 1 and ends at position 59; the E-value for the DSPc domain shown below is 3e-29.

WARNING!
Some of the required catalytic sites were not detected in this domain. It is probably inactive! Check the literature (PubMed 96243129 ) for details.

Catalytic residues
Position		Amino acid	Present?
Domain	Protein
30	30	D	No
N/A	N/A	C	No
N/A	N/A	S	No

MGDNTSPISVILVSSGSRGNKLLFRYPFQRSQEHPASQTNKPRSRYAVNNTGEHADDQD

The domain was found using the schnipsel database

DSPc

Dual specificity phosphatase, catalytic domain

• SMART accession number: SM00195
• Description: -
• Interpro abstract (IPR020422):

  Dual specificity phosphatases (DUSPs) are members of the superfamily of protein tyrosine phosphatases [ (PUBMED:17057753) (PUBMED:15186772) ]. They remove the phosphate group from both phospho-tyrosine and phospho-serine/threonine residues. They are structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR [ (PUBMED:8987394) (PUBMED:7961745) (PUBMED:8154323) ]. They are characterized as VHR- [ (PUBMED:9571625) (PUBMED:8650541) ] or Cdc25-like [ (PUBMED:7601801) (PUBMED:8701088) ].

  In general, DUSPs are classified into the following subgroups [ (PUBMED:19228121) ]:

  • Slingshot phosphatases
  • Phosphatase of regenerating liver (PRL)
  • Cdc14 phosphatases
  • Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-like and myotubularin phosphatases
  • Mitogen-activated protein kinase phosphatases (MKPs)
  • Atypical DUSPs

  Tyrosine specific protein phosphatases (PTPases) contain two conserved cysteines, the second one has been shown to be absolutely required for activity. This entry represents the PTPase domain that centre on the active site cysteine. A number of conserved residues in its immediate vicinity have also been shown to be important. This domain can be found in dual specificity phosphatases.

• GO process: protein dephosphorylation (GO:0006470)
• GO function: protein tyrosine/serine/threonine phosphatase activity (GO:0008138)

There are 17170 DSPc domains in 17099 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling
Binding / catalysis: protein tyrosine phosphatase

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Ernsting BR, Dixon JE
• The PPS1 gene of Saccharomyces cerevisiae codes for a dual specificity protein phosphatase with a role in the DNA synthesis phase of the cell cycle.
• J Biol Chem. 1997; 272: 9332-43

We report the identification of the PPS1 gene of Saccharomyces cerevisiae. The deduced amino acid sequence of PPS1p shows similarity with protein-tyrosine phosphatases (PTPases) and is most closely related to a subfamily of PTPases that are capable of dephosphorylating phosphoseryl and phosphothreonyl residues as well as phosphotyrosyl residues. Analysis of the predicted amino acid sequence suggests that the protein consists of an active phosphatase domain, an inactive phosphatase-like domain, and an NH2-terminal extension. Mutation of the catalytic cysteinyl residue in the active phosphatase domain reduced the in vitro activity of the mutant protein to less than 0.5% of wild type activity, while mutation of the corresponding cysteinyl residue of the inactive phosphatase-like domain had no effect on in vitro activity. The PPS1 protein was expressed in Escherichia coli, and the protein was shown to catalyze the hydrolysis of p-nitrophenyl phosphate, dephosphorylate phosphotyrosyl, and phosphothreonyl residues in synthetic diphosphorylated peptides and to inactivate the human ERK1 protein. PPS1 transcript abundance is coregulated with that of the divergently transcribed DPB3 gene, which codes for a subunit of DNA polymerase II, with both transcripts showing peak abundance in S phase. pps1Delta mutant strains did not differ from PPS1 strains under any of the conditions tested, but overexpression of the PPS1 protein in S. cerevisiae led to synchronous growth arrest and to aberrant DNA synthesis. A screen for suppressors of this growth arrest identified the RAS2 gene as a multicopy suppressor of the PPS1p overexpression arrest. The arrest was not suppressed by the presence of multicopy RAS1, TPK2, or TPK3 genes or by the presence of 5 mM cAMP in the growth medium, suggesting that PPS1 functions in a pathway involving RAS2, but not TPK kinases or adenylate cyclase.

• Fauman EB, Saper MA
• Structure and function of the protein tyrosine phosphatases.
• Trends Biochem Sci. 1996; 21: 413-7

The tyrosine and dual-specificity phosphatases are involved in signaling, cell growth and differentiation, and the cell cycle. The enzymes share a common catalytic mechanism mediated by an active site cysteine, arginine and aspartic acid. Supplementary domains assist in targeting and substrate specificity.

• Yuvaniyama J, Denu JM, Dixon JE, Saper MA
• Crystal structure of the dual specificity protein phosphatase VHR.
• Science. 1996; 272: 1328-31

Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. Here, the crystal structure of a human DSP, vaccinia H1-related phosphatase (or VHR), was determined at 2.1 angstrom resolution. A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. Positively charged crevices near the active site may explain the enzyme's preference for substrates with two phosphorylated residues. The VHR structure defines a conserved structural scaffold for both DSPs and PTPs. A "recognition region," connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs.

• Rohan PJ et al.
• PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase.
• Science. 1993; 259: 1763-6

Tyrosine phosphorylation of proteins is required for signal transduction in cells and for growth regulation. A mitogen-induced gene (PAC-1) has been cloned from human T cells and encodes a 32-kilodalton protein that contains a sequence that defines the enzymatic site of known protein phosphotyrosine phosphatases (PTPases). Other than this sequence, PAC-1 is different from several other known related PTPases exemplified by PTP-1b. PAC-1 is similar to a phosphatase induced by mitogens or heat shock in fibroblasts, a yeast gene, and a vaccinia virus-encoded serine-tyrosine phosphatase (VH1). PAC-1 was predominantly expressed in hematopoietic tissues and localized to the nucleus in transfected COS-7 cells and in mitogen-stimulated T cells.

• Sun H, Charles CH, Lau LF, Tonks NK
• MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo.
• Cell. 1993; 75: 487-93

Mitogenic stimulation of cells induces rapid and transient activation of MAP kinases. Here we report that a growth factor-inducible gene, 3CH134, encodes a dual specificity phosphatase that dephosphorylates and inactivates p42MAPK both in vitro and in vivo. In vitro, 3CH134 protein dephosphorylates both T183 and Y185 in p42MAPK. In serum-stimulated normal fibroblasts, the kinetics of inactivation of p42MAPK coincides with the appearance of newly synthesized 3CH134 protein, and the protein synthesis inhibitor cycloheximide leads to persistent activation of MAP kinase. Expression of 3CH134 in COS cells leads to selective dephosphorylation of p42MAPK from the spectrum of phosphotyrosyl proteins. 3CH134 blocks phosphorylation and activation of p42MAPK mediated by serum, oncogenic Ras, or activated Raf, whereas the catalytically inactive mutant of the phosphatase, Cys-258-->Ser, augments MAP kinase phosphorylation under similar conditions. The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK. These findings suggest that 3CH134 is a physiological MAP kinase phosphatase; we propose the name MKP-1 for this phosphatase.

• Keyse SM, Emslie EA
• Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase.
• Nature. 1992; 359: 644-7

Reactive oxygen species have been implicated both in the ageing process and in degenerative diseases, including arthritis and cancer. Bacteria adapt to the lethal effects of oxidants such as hydrogen peroxide by inducing the expression of protective stress genes. Analogous responses have been identified in human cells. For example, haem oxygenase is a major stress protein in human cells treated with oxidants, and reactive oxygen intermediates activate NF-kappa B, a transcriptional regulator of genes involved in inflammatory and acute-phase responses. We report here the isolation and characterization of a novel complementary DNA (CL100) corresponding to a messenger RNA that is highly inducible by oxidative stress and heat shock in human skin cells. The cDNA contains an open reading frame specifying a protein of M(r) 39.3K with the structural features of a non-receptor-type protein-tyrosine phosphatase and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The purified protein encoded by the CL100 open reading frame expressed in bacteria has intrinsic phosphatase activity. Given the relationship between the levels of protein-tyrosine phosphorylation, receptor activity, cellular proliferation and cell-cycle control, the induction of this gene may play an important regulatory role in the human cellular response to environmental stress.

• Guan KL, Broyles SS, Dixon JE
• A Tyr/Ser protein phosphatase encoded by vaccinia virus.
• Nature. 1991; 350: 359-62

Protein tyrosine phosphorylation is associated with alterations in receptor activity, cellular proliferation and modulation of the cell cycle. Inappropriate tyrosine phosphorylation can lead to unrestrained cell growth and oncogenesis. Enzymes important in tyrosine dephosphorylation have also been described. Protein tyrosine phosphatases (PTPases) consist of two families. There is a receptor-like family of PTPases with an extracellular domain, transmembrane-spanning region and typically two repeated phosphatase domains. Proteins of the non-receptor-like family have a single catalytic phosphatase domain, show a substrate specificity for Tyr phosphate and will not hydrolyse Ser or Thr phosphate. Here we report that the vaccinia virus genome contains an open reading frame which shares amino-acid sequence identity with the PTPases. The purified protein encoded by the vaccinia virus H1 open reading frame expressed in bacteria hydrolyses substrates containing phosphotyrosine and phosphoserine. Mutagenesis of an essential Cys in the vaccinia phosphatase abolishes catalytic activity directed towards both substrates, suggesting that hydrolysis proceeds by a common mechanism. Understanding the function of the H1-encoded protein will help to define the role of the phosphatase in viral replication and pathogenesis.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
72.50	map04010	MAPK signaling pathway
15.83	map04810	Regulation of actin cytoskeleton
3.33	map04111	Cell cycle - yeast
3.33	map04110	Cell cycle
0.83	map04310	Wnt signaling pathway
0.83	map04660	T cell receptor signaling pathway
0.83	map04370	VEGF signaling pathway
0.83	map04360	Axon guidance
0.83	map04662	B cell receptor signaling pathway
0.83	map04650	Natural killer cell mediated cytotoxicity

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 DSPc domain which could be assigned to a KEGG orthologous group, and not all proteins containing DSPc 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 DSPc domains in PDB

PDB code	Title
1j4x	HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX
1m3g	SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF MAPK PHOSPHATASE PAC-1: INSIGHTS INTO SUBSTRATE-INDUCED ENZYMATIC ACTIVATION
1mkp	CRYSTAL STRUCTURE OF PYST1 (MKP3)
1vhr	HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE
1wrm	Crystal structure of JSP-1
1yz4	Crystal structure of DUSP15
1zzw	Crystal Structure of catalytic domain of Human MAP Kinase Phosphatase 5
2e0t	Crystal structure of catalytic domain of dual specificity phosphatase 26, MS0830 from Homo sapiens
2esb	Crystal structure of human DUSP18
2g6z	Crystal structure of human DUSP5
2gwo	crystal structure of TMDP
2hcm	Crystal structure of mouse putative dual specificity phosphatase complexed with zinc tungstate, New York Structural Genomics Consortium
2hxp	Crystal Structure of the human phosphatase (DUSP9)
2j16	Apo & Sulphate bound forms of SDP-1
2j17	pTyr bound form of SDP-1
2nt2	Crystal Structure of Slingshot phosphatase 2
2oud	Crystal structure of the catalytic domain of human MKP5
2p4d	Structure-assisted discovery of Variola major H1 phosphatase inhibitors
2pq5	Crystal structure of Dual specificity protein phosphatase 13 (DUSP13)
2q05	Crystal structure of tyr/ser protein phosphatase from Vaccinia virus WR
2r0b	Crystal structure of human tyrosine phosphatase-like serine/threonine/tyrosine-interacting protein
2rf6	Crystal Structure of the Vaccinia Virus Dual-Specificity Phosphatase VH1
2wgp	Crystal structure of human dual specificity phosphatase 14
2y96	Structure of human dual-specificity phosphatase 27
3cm3	High Resolution Crystal Structure of the Vaccinia Virus Dual-Specificity Phosphatase VH1
3ezz	Crystal Structure of human MKP-2
3f81	Interaction of VHR with SA3
3lj8	Crystal Structure of MKP-4
3s4e	Crystal Structrue of a Novel Mitogen-activated Protein Kinase Phosphatase, SKRP1
4b04	Crystal structure of the Catalytic Domain of Human DUSP26 (C152S)
4d3p	4D3P
4d3q	4D3Q
4d3r	4D3R
4hrf	Atomic structure of DUSP26
4jmk	Structure of dusp8
4jnb	Crystal structure of the Catalytic Domain of Human DUSP12
4ki9	Crystal structure of the catalytic domain of human DUSP12 at 2.0 A resolution
4woh	4WOH
4y2e	4Y2E
4yr8	4YR8
5gtj	5GTJ
5m43	5M43

Links (links to other resources describing this domain)

• INTERPRO: IPR020422
• PFAM: DSPc
• PROSITE: TYR_PHOSPHATASE_DUAL