Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921  105 FIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCK 184
Cdd:pfam00782  31 LYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERR 110

                          90
                  ....*....|....*..
gi 575771921  185 TNMRPNRAFVAQLLEWE 201
Cdd:pfam00782 111 PGISPNFGFKRQLLEYE 127

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 575771921 129 FRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEeTLKRSWAQVKKCKTNMRPNRAFVAQLLEWEK 202
Cdd:COG2453   66 LQEAVDFIDEALREGKKVLVHCRGGIGRTGTVAAAYLVLLGL-SAEEALARVRAARPGAVETPAQRAFLERFAK 138

dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in typical and atypical dual-specificity phosphatases (DUSPs), which function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Atypical DUSPs contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Also included in this family are dual specificity phosphatase-like domains of catalytically inactive members such as serine/threonine/tyrosine-interacting protein (STYX) and serine/threonine/tyrosine interacting like 1 (STYXL1), as well as active phosphatases with substrates that are not phosphoproteins such as PTP localized to the mitochondrion 1 (PTPMT1), which is a lipid phosphatase, and laforin, which is a glycogen phosphatase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 113 LHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRA 192
Cdd:cd14498   49 LRIPIEDSPDEDILSHFEEAIEFIEEALKKGGKVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPG 128

                 ....*..
gi 575771921 193 FVAQLLE 199
Cdd:cd14498  129 FLKQLKE 135

dual specificity phosphatase domain of dual specificity protein phosphatase 12 and similar proteins; Dual specificity protein phosphatase 12 (DUSP12), also called YVH1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP12 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It targets p38 MAPK to regulate macrophage response to bacterial infection. It also ameliorates cardiac hypertrophy in response to pressure overload through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 has been identified as a modulator of cell cycle progression, a function independent of phosphatase activity and mediated by its C-terminal zinc-binding domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 100 SGCPSFIGNADKLLH--IKLEDSPDTLLFDYFRHICHFIElHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSW 177
Cdd:cd14520   35 SEEPIDAPPVGKLVRkfVPALDEESTDLLSRLDECLDFID-EGRAEGAVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEAL 113

                         90       100
                 ....*....|....*....|....*
gi 575771921 178 AQVKKCKTNMRPNRAFVAQLLEWEK 202
Cdd:cd14520  114 ASLRECKPDVKPNDGFLKQLKLYEA 138

dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins; This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 113 LHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRA 192
Cdd:cd14514   47 LRVPVEDSPHADLSPHFDEVADKIHQVKRRGGRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVG 126

                 ....*..
gi 575771921 193 FVAQLLE 199
Cdd:cd14514  127 FWRQLIE 133

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921    98 RSSGCPSFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSW 177
Cdd:smart00195  33 VTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAY 112

                           90       100
                   ....*....|....*....|....*.
gi 575771921   178 AQVKKCKTNMRPNRAFVAQLLEWEKV 203
Cdd:smart00195 113 DFVKDRRPIISPNFGFLRQLIEYERK 138

dual specificity phosphatase domain of slingshot homolog 1; Dual specificity protein phosphatase slingshot homolog 1 (SSH1), also called SSH-like protein 1, is part of the slingshot (SSH) family, whose members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. SSH1 links NOD1 signaling to actin remodeling, facilitating the changes that leads to NF-kappaB activation and innate immune responses. There are at least two human SSH1 isoforms reported: hSSH-1L (long) and hSSH-1S (short). As SSH family phosphatases, they contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. They also contain C-terminal tails, differing in the lengths of the tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 114 HIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAF 193
Cdd:cd14570   52 NIRVYDEETTDLLAHWNDAYHFINKAKKNHSKCLVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGF 131

                         90
                 ....*....|.
gi 575771921 194 VAQLLEWEKVL 204
Cdd:cd14570  132 MRQLLEYEGIL 142

dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 103 PSFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHL-----------RLHSVVLVFSTRGISRSVAAVVALLMHYNEE 171
Cdd:cd14518   39 PEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIDSALfgngkdedeekKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNL 118

                         90       100       110
                 ....*....|....*....|....*....|.
gi 575771921 172 TLKRSWAQVKKCKTNMRPNRAFVAQLLEWEK 202
Cdd:cd14518  119 SVSQALHAVRRKRPIAEPNDGFMEQLELYHE 149

dual specificity phosphatase domain of mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs, which are involved in gene regulation, cell proliferation, programmed cell death and stress responses, as an important feedback control mechanism that limits MAPK cascades. MKPs, also referred to as typical DUSPs, function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921  96 LRRSSGCPSFIGNAD-KLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLK 174
Cdd:cd14512   31 LNVSNTCPNPDFIGLfHYKRIPVNDSFCQNISPWFDEAIEFIEEAKASNGGVLVHCLAGISRSATIAIAYLMKRMRMSLD 110

                         90       100
                 ....*....|....*....|....*.
gi 575771921 175 RSWAQVKKCKTNMRPNRAFVAQLLEW 200
Cdd:cd14512  111 EAYDFVKEKRPTISPNFNFMGQLLDF 136

dual specificity phosphatase domain of dual specificity protein phosphatase 9; Dual specificity protein phosphatase 9 (DUSP9), also called mitogen-activated protein kinase (MAPK) phosphatase 4 (MKP-4), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP9 is a mediator of bone morphogenetic protein (BMP) signaling to control the appropriate ERK activity critical for the determination of embryonic stem cell fate. Down-regulation of DUSP9 expression has been linked to severe pre-eclamptic placenta as well as cancers such as hepatocellular carcinoma. DUSP9 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 114 HIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAF 193
Cdd:cd14644   53 QIPISDHWSQNLSQFFPEAIEFIDEALSQNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNF 132

                         90
                 ....*....|.
gi 575771921 194 VAQLLEWEKVL 204
Cdd:cd14644  133 MGQLLDFEKSL 143

dual specificity phosphatase domain of dual specificity protein phosphatase 7; Dual specificity protein phosphatase 7 (DUSP7), also called mitogen-activated protein kinase (MAPK) phosphatase X (MKP-X) or dual specificity protein phosphatase PYST2, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP7 has been shown as an essential regulator of multiple steps in oocyte meiosis. Due to alternative promoter usage, the PYST2 gene gives rise to two isoforms, PYST2-S and PYST2-L. PYST2-L is over-expressed in leukocytes derived from AML and ALL patients as well as in some solid tumors and lymphoblastoid cell lines; it plays a role in cell-crowding. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 111 KLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPN 190
Cdd:cd14643   53 KYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPN 132

                         90
                 ....*....|....
gi 575771921 191 RAFVAQLLEWEKVL 204
Cdd:cd14643  133 FNFMGQLLDFERTL 146

dual specificity phosphatase domain of dual specificity protein phosphatase 10; Dual specificity protein phosphatase 10 (DUSP10), also called mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP-5), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP10/MKP-5 coordinates skeletal muscle regeneration by negatively regulating mitochondria-mediated apoptosis. It is also an important regulator of intestinal epithelial barrier function and a suppressor of colon tumorigenesis. DUSP10/MKP-5 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 119 DSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLL 198
Cdd:cd14567   56 DSNKQNLRQYFEEAFEFIEEAHQSGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLL 135

                 ....*.
gi 575771921 199 EWEKVL 204
Cdd:cd14567  136 EFEEDL 141

dual specificity phosphatase domain of dual specificity protein phosphatase 6; Dual specificity protein phosphatase 6 (DUSP6), also called mitogen-activated protein kinase (MAPK) phosphatase 3 (MKP-3) or dual specificity protein phosphatase PYST1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP6/MKP-3 plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output. MKP-3 deficiency attenuates body weight gain induced by a high-fat diet, protects mice from developing obesity-related hepatosteatosis, and reduces adiposity, possibly by repressing adipocyte differentiation. It also contributes to p53-controlled cellular senescence. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 103 PSFIGNAD--KLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQV 180
Cdd:cd14642   40 PNLFENAGefKYKQIPISDHWSQNLSQFFPEAISFIDEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIV 119

                         90       100
                 ....*....|....*....|....
gi 575771921 181 KKCKTNMRPNRAFVAQLLEWEKVL 204
Cdd:cd14642  120 KMKKSNISPNFNFMGQLLDFERTL 143

dual specificity phosphatase-like domain of serine/threonine/tyrosine-interacting protein; Serine/threonine/tyrosine-interacting protein (STYX), also called protein tyrosine phosphatase-like protein, is a catalytically inactive member of the protein tyrosine phosphatase family that plays an integral role in regulating pathways by competing with active phosphatases for binding to MAPKs. It acts as a nuclear anchor for MAPKs, affecting their nucleocytoplasmic shuttling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 111 KLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPN 190
Cdd:cd14522   57 RYLVLDVADNPTENIIRHFPTVKEFIDDCLQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPN 136

                         90
                 ....*....|.
gi 575771921 191 RAFVAQLLEWE 201
Cdd:cd14522  137 EGFVHQLKEYE 147

dual specificity phosphatase domain of class I mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class I MKPs consist of DUSP1/MKP-1, DUSP2 (PAC1), DUSP4/MKP-2 and DUSP5. They are all mitogen- and stress-inducible nuclear MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921  89 ACTTSSGLRRSSGCPSFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHY 168
Cdd:cd14565   24 ALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRVLVHCQAGISRSATICLAYLMTT 103

                         90       100       110
                 ....*....|....*....|....*....|...
gi 575771921 169 NEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 201
Cdd:cd14565  104 RRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYE 136

dual specificity protein phosphatase 22; Dual specificity protein phosphatase 22 (DUSP22), also called JNK-stimulatory phosphatase-1 (JSP-1), low molecular weight dual specificity phosphatase 2 (LMW-DSP2), mitogen-activated protein kinase phosphatase x (MKP-x) or VHR-related MKPx (VHX), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP22 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. It also regulates cell death by acting as a scaffold protein for the ASK1-MKK7-JNK signal transduction pathway independently of its phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 111 KLLHIKLEDSPDTLLFDYFRHICHFI-ELHLRLHSVvLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRP 189
Cdd:cd14581   48 TYLCIPAADSPSQNLTQHFKESIKFIhECRLRGEGC-LVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANP 126

                         90
                 ....*....|...
gi 575771921 190 NRAFVAQLLEWEK 202
Cdd:cd14581  127 NMGFQRQLQEFEK 139

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921  96 LRRSSGCPSFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKR 175
Cdd:cd14640   31 LNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVLVHCQAGISRSATICLAYLMMKKRVRLEE 110

                         90       100
                 ....*....|....*....|....*.
gi 575771921 176 SWAQVKKCKTNMRPNRAFVAQLLEWE 201
Cdd:cd14640  111 AFEFVKQRRSIISPNFSFMGQLLQFE 136

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP13A is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921  95 GLRRSSGCPSFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIelHLRLHSV---VLVFSTRGISRSVAAVVALLMHYNEE 171
Cdd:cd14580   36 GKLFCQGGDDFYGTSVDYYGVPANDLPDFDISPYFYSAAEFI--HRALNTPgakVLVHCAVGVSRSATLVLAYLMIYHQL 113

                         90       100
                 ....*....|....*....|....*..
gi 575771921 172 TLKRSWAQVKKcKTNMRPNRAFVAQLL 198
Cdd:cd14580  114 SLVQAIKTVKE-RRWIFPNRGFLKQLR 139

dual specificity phosphatase and pro isomerase domain containing 1; Dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1) was initially named as such because computational prediction appeared to encode a protein of 446 amino acids in length that included two catalytic domains: a proline isomerase and a dual specificity phosphatase (DUSP). However, it was subsequently shown that the true open reading frame only encompassed the DUSP domain and the gene product was therefore renamed DUSP27. This is distinct from inactive DUSP27. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). DUPD1/DUSP27 has been shown to have catalytic activity with preference for phosphotyrosine over phosphothreonine and phosphoserine residues. It associates with the short form of the prolactin (PRL) receptor and plays a role in PRL-mediated MAPK inhibition in ovarian cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 115 IKLEDSPDTLLFDYFRHICHFIELHLRL-HSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKcKTNMRPNRAF 193
Cdd:cd14575   67 VEADDLPTFNLSQFFYSAAEFIHQALSDpHNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQVAQ-RRCILPNRGF 145

                         90
                 ....*....|.
gi 575771921 194 VAQLLEWEKVL 204
Cdd:cd14575  146 LKQLRELDIQL 156

dual specificity protein phosphatase 26; Dual specificity protein phosphatase 26 (DUSP26), also called mitogen-activated protein kinase (MAPK) phosphatase 8 (MKP-8) or low-molecular-mass dual-specificity phosphatase 4 (LDP-4), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP26 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It is a brain phosphatase highly overexpressed in neuroblastoma and has also been identified as a p53 phosphatase, dephosphorylating phospho-Ser20 and phospho-Ser37 in the p53 transactivation domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 115 IKLEDSPdtlLFD---YFRHICHFIELHLR-LHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKtNMRPN 190
Cdd:cd14578   55 IEAHDSP---AFDmsiHFYPAADFIHRALSqPGGKILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDHR-GIIPN 130

                         90
                 ....*....|....
gi 575771921 191 RAFVAQLLEWEKVL 204
Cdd:cd14578  131 RGFLRQLLALDRRL 144

dual specificity phosphatase domain of fungal dual specificity protein phosphatase SDP1, MSG5, and similar proteins; This family is composed of fungal dual specificity protein phosphatases (DUSPs) including Saccharomyces cerevisiae SDP1 and MSG5, and Schizosaccharomyces pombe Pmp1. function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. SDP1 is oxidative stress-induced and dephosphorylates MAPK substrates such as SLT2. MSG5 dephosphorylates the Fus3 and Slt2 MAPKs operating in the mating and cell wall integrity (CWI) pathways, respectively. Pmp1 is responsible for dephosphorylating the CWI MAPK Pmk1. These phosphatases bind to their target MAPKs through a conserved IYT motif located outside of the dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 115 IKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFV 194
Cdd:cd14521   66 IHVPWDHNSQIQKDLPKLTSIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLI 145

                         90
                 ....*....|
gi 575771921 195 AQLLEWEKVL 204
Cdd:cd14521  146 FQLMEFEKVL 155

dual specificity phosphatase domain of plant IBR5-like protein phosphatases; This subfamily is composed of Arabidopsis thaliana INDOLE-3-BUTYRIC ACID (IBA) RESPONSE 5 (IBR5) and similar plant proteins. IBR5 protein is also called SKP1-interacting partner 33. The IBR5 gene encodes a dual-specificity phosphatase (DUSP) which acts as a positive regulator of plant responses to auxin and abscisic acid. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. IBR5 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs. It has been shown to target MPK12, which is a negative regulator of auxin signaling.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 575771921 135 FIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVK--KCKTNMRPnrAFVAQLLEW 200
Cdd:cd18534   65 FIEQCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKerRPSINLSP--AVAKQLQEF 130

dual specificity protein phosphatase 13 isoform B; Dual specificity protein phosphatase 13 isoform B (DUSP13B), also called testis- and skeletal-muscle-specific DSP (TMDP) or dual specificity phosphatase SKRP4, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP13B is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP13B inactivates MAPK activation in the order of selectivity, JNK = p38 > ERK in cells. It may play a role in protection from external stress during spermatogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921 115 IKLEDSPDTLLFDYFRHICHFIELHLRL-HSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKtNMRPNRAF 193
Cdd:cd14577   74 VEADDNPFFDLSVYFYPVARFIRAALSSpNGRVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHR-DICPNSGF 152

                         90
                 ....*....|.
gi 575771921 194 VAQLLEWEKVL 204
Cdd:cd14577  153 LRQLRELDNRL 163

dual specificity phosphatase domain of dual specificity protein phosphatase 8; Dual specificity protein phosphatase 8 (DUSP8), also called DUSP hVH-5 or M3/6, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP8 controls basal and acute stress-induced ERK1/2 signaling in adult cardiac myocytes, which impacts contractility, ventricular remodeling, and disease susceptibility. It also plays a role in decreasing ureteric branching morphogenesis by inhibiting p38MAPK. DUSP8 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 575771921  96 LRRSSGCPS--FIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETL 173
Cdd:cd14645   42 LNASNSCPKpdFICES-HFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSS 120

                         90       100       110
                 ....*....|....*....|....*....|.
gi 575771921 174 KRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 204
Cdd:cd14645  121 DDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151