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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPS-KEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGL-HHGSVLVHC 78
Cdd:cd14498    7 GLYLGSLDAAQDKELLKKLGITHILNVAGEpPPNKFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALkKGGKVLVHC 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  79 QRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKE 127
Cdd:cd14498   87 QAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPS-KEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGL-HHGSVLVHC 78
Cdd:cd14498    7 GLYLGSLDAAQDKELLKKLGITHILNVAGEpPPNKFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALkKGGKVLVHC 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  79 QRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKE 127
Cdd:cd14498   87 QAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

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 223993053    2 LYLGGKIDArSLSTLQQRNVRRILNVTPSKEAgITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLH-HGSVLVHCQR 80
Cdd:pfam00782   1 LYLGSKPTA-SDAFLSKLGITAVINVTREVDL-YNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQkGGKVLVHCQA 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 223993053   81 GVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:pfam00782  79 GISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSKEA----GITAGIQYKRIPVYDASTSDLrayaEEIVSFIsNGLHHG---- 72
Cdd:PRK12361 101 NLYLGCRLFPADLEKLKSNKITAILDVTAEFDGldwsLTEEDIDYLNIPILDHSVPTL----AQLNQAI-NWIHRQvran 175

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 223993053  73 -SVLVHCQRGVSRSASAVMMFLI-RKTNMTLQQSLQLCQRRRE 113
Cdd:PRK12361 176 kSVVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRK 218

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPS-KEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGL-HHGSVLVHC 78
Cdd:cd14498    7 GLYLGSLDAAQDKELLKKLGITHILNVAGEpPPNKFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALkKGGKVLVHC 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  79 QRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKE 127
Cdd:cd14498   87 QAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053     1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGL-HHGSVLVHCQ 79
Cdd:smart00195   7 HLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAEsKGGKVLVHCQ 86

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 223993053    80 RGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:smart00195  87 AGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYE 136

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNV--TPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHHGSVLVHC 78
Cdd:cd14520    7 GLYIGNADDAADYLSLREAGITHVLTVdsEEPIDAPPVGKLVRKFVPALDEESTDLLSRLDECLDFIDEGRAEGAVLVHC 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 223993053  79 QRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14520   87 HAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLYE 137

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTP-SKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGL---------- 69
Cdd:cd14518    7 GLYLGGIEPLNRNRLLKAENITHILSVIPgDVPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIDSALfgngkdedee 86

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 223993053  70 --HHGSVLVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14518   87 kkHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYH 148

dual specificity phosphatase domain of slingshot homolog 2; Dual specificity protein phosphatase slingshot homolog 2 (SSH2), also called SSH-like protein 2, 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. SSH2 has been identified as a target of protein kinase D1 that regulates cofilin phosphorylation and remodeling of the actin cytoskeleton during neutrophil chemotaxis. There are at least two human SSH2 isoforms reported: hSSH-2L (long) and hSSH-2. 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. In addition, hSSH-2L contains a long C-terminal tail while hSSH-2 does not.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHHGS-VLVHCQ 79
Cdd:cd14569   10 HVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSkCLVHCK 89

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 223993053  80 RGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14569   90 MGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 139

dual specificity phosphatase domain of slingshot homolog 3; Dual specificity protein phosphatase slingshot homolog 3 (SSH3), also called SSH-like protein 3, 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. The Xenopus homolog (xSSH) is involved in the gastrulation movement. Mouse SSH3 dephosphorylates actin-depolymerizing factor (ADF) and cofilin but is dispensable for development. There are at least two human SSH3 isoforms reported: hSSH-3L (long) and hSSH-3. 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. In addition, hSSH-3L contains a C-terminal tail while hSSH-3 does not.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHHGS-VLVHCQR 80
Cdd:cd14571   11 LYLGSEWNAANLEELQRNRVSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTrVLVHCKM 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  81 GVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14571   91 GVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQ 139

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNG-LHHGSVLVHCQ 79
Cdd:cd14570   10 HLYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNDAYHFINKAkKNHSKCLVHCK 89

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 223993053  80 RGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14570   90 MGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYE 139

dual specificity phosphatase domain of dual specificity protein phosphatase 19; Dual specificity protein phosphatase 19 (DUSP19), also called low molecular weight dual specificity phosphatase 3 (LMW-DSP3) or stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It 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. DUSP19 interacts with the MAPK kinase MKK7, a JNK activator, and inactivates the JNK MAPK pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNG-LHHGSVLVHCQR 80
Cdd:cd14523    9 LLLSSQDVAHDLETLKKHKVTHILNVAYGVENAFPDDFTYKTISILDLPETDITSYFPECFEFIDEAkSQDGVVLVHCNA 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  81 GVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14523   89 GVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEYQ 137

dual specificity phosphatase domain of class III 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 III MKPs consist of DUSP8, DUSP10/MKP-5 and DUSP16/MKP-7, and are JNK/p38-selective phosphatases, which are found in both the cell nucleus and cytoplasm. 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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVT-----PSKEAGItagiQYKRIPVYDASTSDLRAYAEEIVSFISNGLHHG-SV 74
Cdd:cd14568    7 HLYLGSQRDVLDKDLMQRNGISYVLNVSntcpkPDFIPDS----HFLRIPVNDSYCEKLLPWLDKAVEFIEKARASNkRV 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 223993053  75 LVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14568   83 LVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFE 137

dual specificity phosphatase domain of dual specificity protein phosphatase 2; Dual specificity protein phosphatase 2 (DUSP2), also called dual specificity protein phosphatase PAC-1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other mitogen-activated protein kinase (MAPK) phosphatases (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. DUSP2 can preferentially dephosphorylate ERK1/2 and p38, but not JNK in vitro. It is predominantly expressed in hematopoietic tissues with high T-cell content, such as thymus, spleen, lymph nodes, peripheral blood and other organs such as the brain and liver. It has a critical and positive role in inflammatory responses. DUSP2 mRNA and protein are significantly reduced in most solid cancers including breast, colon, lung, ovary, kidney and prostate, and the suppression of DUSP2 is associated with tumorigenesis and malignancy. DUSP2 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 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFI----SNGlhhGSVLVH 77
Cdd:cd14641   11 LFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIdsvkNSG---GRVLVH 87

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 223993053  78 CQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14641   88 CQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 139

dual specificity phosphatase domain of dual specificity protein phosphatase 15; Dual specificity protein phosphatase 15 (DUSP15), also called Vaccinia virus VH1-related dual-specific protein phosphatase Y (VHY) or VH1-related member Y, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). DUSP15 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 highly expressed in the testis and is located in the plasma membrane in a myristoylation-dependent manner. It may be involved in the regulation of meiotic signal transduction in testis cells. It is also expressed in the brain and has been identified as a regulator of oligodendrocyte differentiation. DUSP15 contains an N-terminal catalytic dual specificity phosphatase domain and a short C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAgITAGIQYKRIPVYDASTSDLRAYAEEIVSFI-SNGLHHGSVLVHCQR 80
Cdd:cd14582   12 LYLGNFIDAKDLEQLSRNKITHIISIHESPQP-LLQDITYLRIPLPDTPEAPIKKHFKECISFIhQCRLNGGNCLVHCLA 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 223993053  81 GVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEY 128
Cdd:cd14582   91 GISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

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 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFI-SNGLHHGSVLVHCQR 80
Cdd:cd14640    8 LYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIdSVKDCNGRVLVHCQA 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  81 GVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14640   88 GISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 136

dual specificity phosphatase domain of dual specificity protein phosphatase 1; Dual specificity protein phosphatase 1 (DUSP1), also called mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1), 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. Human MKP-1 dephosphorylates MAPK1/ERK2, regulating its activity during the meiotic cell cycle. Although initially MKP-1 was considered to be ERK-specific, it has been shown that MKP-1 also dephosphorylates both JNK and p38 MAPKs. DUSP1/MKP-1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. It is a central regulator of a variety of functions in the immune, metabolic, cardiovascular, and nervous systems. 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 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHHGS-VLVHCQR 80
Cdd:cd14638    8 LYLGSAYHASRKDMLDTLGITALINVSANCPNHFEGHYQYKSIPVEDNHKADISSWFNEAIDFIDSVKNAGGrVFVHCQA 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223993053  81 GVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14638   88 GISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFE 136

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 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPS-----KEAGitaGIQYKRIPVYDASTSDLRAYAEEIVSFI--SNGLHHGsV 74
Cdd:cd14642   10 LYLGCAKDSTNLDVLEEFGIKYILNVTPNlpnlfENAG---EFKYKQIPISDHWSQNLSQFFPEAISFIdeARGKNCG-V 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 223993053  75 LVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14642   86 LVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 140

dual specificity protein phosphatase 28; Dual specificity protein phosphatase 28 (DUSP28), also called VHP, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP that 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 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells. DUSP28 has an exceptionally low phosphatase activity due to the presence of bulky residues in the active site pocket resulting in low accessibility.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   2 LYLGGKIDARSLSTLQQRNVRRILNVTPSKEAGITAGIQYKRIPVYDASTSDLRAY----AEEIVSFISNGlhhGSVLVH 77
Cdd:cd14574    8 LFISNARAACNEELLAREGVTLCVNVSRQQPFPRAPRVSTLRVPVFDDPAEDLYRHfeqcADAIEAAVRRG---GKCLVY 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 223993053  78 CQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14574   85 CKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYE 136

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), 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. DUSP3 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 favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILN---------VTPSKEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHH 71
Cdd:cd14579   27 RIYVGNASVAQNIMRLQRLGITHVLNaaegksfmhVNTNAEFYEDTGITYHGIKANDTQHFNLSAYFEEAADFIDKALAQ 106

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 223993053  72 --GSVLVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREmVDPIPAFIDQL 125
Cdd:cd14579  107 knGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKRE-IGPNDGFLKQL 161

dual specificity phosphatase domain of dual specificity protein phosphatase 16; Dual specificity protein phosphatase 16 (DUSP16), also called mitogen-activated protein kinase (MAPK) phosphatase 7 (MKP-7), 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. DUSP16/MKP-7 plays an essential role in perinatal survival and selectively controls the differentiation and cytokine production of myeloid cells. It is acetylated by Mycobacterium tuberculosis Eis protein, which leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation, and thus, initiating suppression of host immune responses. DUSP16/MKP-7 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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPS-KEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNG-LHHGSVLVHC 78
Cdd:cd14646    9 HLYLGCQRDVLNKELMQQNGIGYVLNASNTcPKPDFIPESHFLRVPVNDSFCEKILPWLDKSVDFIEKAkASNGRVLVHC 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 223993053  79 QRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14646   89 LAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFE 139

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSKEAgITAG--------IQYKRIPVYDASTSDLRAYAEEIVSFISNGLH-- 70
Cdd:cd14577   24 NLYLGDAYAARDKSVLIQLGITHIVNAASGKFH-VNTGpkfyrdmnIDYYGVEADDNPFFDLSVYFYPVARFIRAALSsp 102

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 223993053  71 HGSVLVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVdPIPAFIDQLKE 127
Cdd:cd14577  103 NGRVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHRDIC-PNSGFLRQLRE 158

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSK-----EAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHH--GS 73
Cdd:cd14578    7 GLYLGDQDIAANRRELRRLGITHILNASHSKwrggaEYYEGLNIRYLGIEAHDSPAFDMSIHFYPAADFIHRALSQpgGK 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 223993053  74 VLVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVdPIPAFIDQL 125
Cdd:cd14578   87 ILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDHRGII-PNRGFLRQL 137

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSK---EAG---ITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNGLHH--G 72
Cdd:cd14580    7 NLFLGDLATAHNRFGLWKLGITHVLNAAHGKlfcQGGddfYGTSVDYYGVPANDLPDFDISPYFYSAAEFIHRALNTpgA 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 223993053  73 SVLVHCQRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRReMVDPIPAFIDQL 125
Cdd:cd14580   87 KVLVHCAVGVSRSATLVLAYLMIYHQLSLVQAIKTVKERR-WIFPNRGFLKQL 138

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 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPS-KEAGITAGIQYKRIPVYDASTSDLRAYAEEIVSFISNG-LHHGSVLVHC 78
Cdd:cd14645   18 HLYLGSQKDVLNKDLMAQNGITYVLNASNScPKPDFICESHFMRIPVNDNYCEKLLPWLDKSIEFIDKAkVSNCRVIVHC 97

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 223993053  79 QRGVSRSASAVMMFLIRKTNMTLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14645   98 LAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 148

dual specificity phosphatase-like domain of inactive dual specificity protein phosphatase 27; Inactive dual specificity protein phosphatase 27 (DUSP27) may play a role in myofiber maturation. It is a pseudophosphatase containing a substitution of the active site cysteine into a serine. It is a large protein of more than 1000 amino acids in length with an N-terminal dual specificity phosphatase-like domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053  39 IQYKRIPVYDASTSDLRAYAEEIVSFISNGL--HHGSVLVHCQRGVSRSASAVMMFLIRKTNMTLQQSLqLCQRRREMVD 116
Cdd:cd14576   61 IQYMGIEVDDFPDVDISKHFRKGAEFLDEALltYRGKVLVSSEMGISRSAVLVAAYLMIFHNMTIMEAL-MTLRKKRAIY 139

                         90
                 ....*....|.
gi 223993053 117 PIPAFIDQLKE 127
Cdd:cd14576  140 PNEGFLKQLRE 150

unknown subfamily of bacterial and plant dual specificity protein phosphatases; This subfamily is composed of uncharacterized bacterial and plant dual-specificity protein phosphatases. DUSPs function as a protein-serine/threonine phosphatases (EC 3.1.3.16) and a protein-tyrosine-phosphatases (EC 3.1.3.48).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   1 NLYLGGKIDARSLstlqQRNVRRILNVTpsKEAGITAGIQ-YKRIPVYDA---STSDLRAYAEEIVSFISNglhHGSVLV 76
Cdd:cd14527   11 GLYLGRWPSADEL----PPGVPAVLDLT--AELPRPRKRQaYRCVPLLDLvapTPEQLERAVAWIEELRAQ---GGPVLV 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 223993053  77 HCQRGVSRSASAVMMFLIRKTNM-TLQQSLQLCQRRREMVDPIPAFIDQLKEYE 129
Cdd:cd14527   82 HCALGYGRSATVVAAWLLAYGRAkSVAEAEALIRAARPQVVLNPAQRKALEAWS 135

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 223993053   1 NLYLGGKIDARSLSTLQQRNVRRILNVTPSKEA----GITAGIQYKRIPVYDASTSDLrayaEEIVSFIsNGLHHG---- 72
Cdd:PRK12361 101 NLYLGCRLFPADLEKLKSNKITAILDVTAEFDGldwsLTEEDIDYLNIPILDHSVPTL----AQLNQAI-NWIHRQvran 175

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 223993053  73 -SVLVHCQRGVSRSASAVMMFLI-RKTNMTLQQSLQLCQRRRE 113
Cdd:PRK12361 176 kSVVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRK 218