Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548    68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:smart00195   4 ILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKVLV 83

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 219275548   148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTYR 200
Cdd:smart00195  84 HCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYE 136

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  72 LLLGSQDAAHDLELLRQHKVTHILNVA----YGVENVFLSEFTYKTISILD--VPETNIlsyFPECFEFIEQAKLKDGVV 145
Cdd:COG2453    7 LLAGGPLPGGGEADLKREGIDAVVSLTeeeeLLLGLLEEAGLEYLHLPIPDfgAPDDEQ---LQEAVDFIDEALREGKKV 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 219275548 146 LVHCNAGVSRAAAVVIGFLMsSEELAFTNALSLVKEARPSICLNPGFMEQLRTYR 200
Cdd:COG2453   84 LVHCRGGIGRTGTVAAAYLV-LLGLSAEEALARVRAARPGAVETPAQRAFLERFA 137

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENV-FLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVL 146
Cdd:cd14498    4 ILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNkFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKGGKVL 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 219275548 147 VHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLR 197
Cdd:cd14498   84 VHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLK 134

dual specificity phosphatase domain of slingshot family phosphatases; The slingshot (SSH) family of dual specificity protein phosphatases is composed of Drosophila slingshot phosphatase and its vertebrate homologs: SSH1, SSH2 and SSH3. Its members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. In Drosophila, loss of ssh gene function causes prominent elevation in the levels of P-cofilin and filamentous actin and disorganized epidermal cell morphogenesis, including bifurcation phenotypes of bristles and wing hairs. SSH family phosphatases 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, many members contain a C-terminal tail. The SSH-N domain plays critical roles in P-cofilin recognition, F-actin-mediated activation, and subcellular localization of SSHs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:cd14513    4 IFDHLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGSKVLV 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 219275548 148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14513   84 HCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITY 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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYgvENV----FLSEFTYKTISILDVPETNILSYFPECFEFIEQAkLKDG 143
Cdd:cd14520    4 VRPGLYIGNADDAADYLSLREAGITHVLTVDS--EEPidapPVGKLVRKFVPALDEESTDLLSRLDECLDFIDEG-RAEG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 219275548 144 VVLVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14520   81 AVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLY 136

dual specificity phosphatase domain of class II 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 II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic 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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFL--SEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVV 145
Cdd:cd14566    4 ILPFLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEedGGFKYLQIPIDDHWSQNLSAFFPEAISFIDEARSKKCGV 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 219275548 146 LVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQL 196
Cdd:cd14566   84 LVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQL 134

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENV-FLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVL 146
Cdd:cd14512    4 ILPNLYLGSQRDSLNLELMQQLGIGYVLNVSNTCPNPdFIGLFHYKRIPVNDSFCQNISPWFDEAIEFIEEAKASNGGVL 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 219275548 147 VHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14512   84 VHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRPTISPNFNFMGQLLDF 136

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:cd14565    4 ILPFLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRVLV 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 219275548 148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14565   84 HCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQY 135

dual specificity phosphatase domain of dual specificity protein phosphatase 22, 15, and similar proteins; Dual specificity protein phosphatase 22 (DUSP22, also known as VHX) and 15 (DUSP15, also known as VHY) function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). They 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. The both contain N-terminal myristoylation recognition sequences and myristoylation regulates their subcellular location. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. DUSP15 has been identified as a regulator of oligodendrocyte differentiation. DUSP22 is a single domain protein containing only the catalytic dual specificity phosphatase domain while DUSP15 contains a short C-terminal tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVaYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:cd14519    4 ILPGLYVGNFRDAKDAEQLRENGITHILSI-HDSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIHEARLNGGNVLV 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 219275548 148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14519   83 HCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEF 134

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family 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. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  70 PWLLLGSQDAAHDLELLRQHKVTHILNVAYG---VENVFLSEF------TYKTISILDVPETNILSYFPECFEFIEQA-K 139
Cdd:cd14515    6 PGIYIGDESTAKNKAKLKKLGITHVLNAAEGkknGEVNTNAKFykgsgiIYLGIPASDLPTFDISQYFDEAADFIDKAlS 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 219275548 140 LKDGVVLVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARpSICLNPGFMEQLR 197
Cdd:cd14515   86 DPGGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRKKR-EIRPNRGFLQQLC 142

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVaYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:cd14582    8 VLPGLYLGNFIDAKDLEQLSRNKITHIISI-HESPQPLLQDITYLRIPLPDTPEAPIKKHFKECISFIHQCRLNGGNCLV 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 219275548 148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14582   87 HCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  66 GVIKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISilDVPETNilsyFPECFEFIEQAKLKDGVV 145
Cdd:cd18534    3 EILPGFLYLGSYDNASRAELLKAQGITRILNTVPDCQNLYKNSFTYHVLS--EEKTVP----FAEAVDFIEQCRKDKARV 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 219275548 146 LVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd18534   77 LVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSPAVAKQLQEF 130

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFL--SEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVV 145
Cdd:cd14643    9 ILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEhdGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCGI 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 219275548 146 LVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQL 196
Cdd:cd14643   89 LVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQL 139

dual specificity protein phosphatases 18 and 21; This subfamily contains dual specificity protein phosphatase 18 (DUSP18), dual specificity protein phosphatase 21 (DUSP21), 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. DUSP18, also called low molecular weight dual specificity phosphatase 20 (LMW-DSP20), is a catalytically active phosphatase with a preference for phosphotyrosine over phosphoserine/threonine oligopeptides in vitro. In vivo, it has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP21 is also called low molecular weight dual specificity phosphatase 21 (LMW-DSP21). Its gene has been identified as a potential therapeutic target in human hepatocellular carcinoma. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:cd14573    5 ITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGGRTLL 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 219275548 148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTY 199
Cdd:cd14573   85 HCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHY 136

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLV 147
Cdd:cd14640    4 ILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVLV 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 219275548 148 HCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQL 196
Cdd:cd14640   84 HCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQL 132

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 219275548  72 LLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLVHCNA 151
Cdd:cd14569   11 VFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCKM 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 219275548 152 GVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTYR 200
Cdd:cd14569   91 GVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 139

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVF--LSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVV 145
Cdd:cd14642    6 ILPYLYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFenAGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARGKNCGV 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 219275548 146 LVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQL 196
Cdd:cd14642   86 LVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQL 136

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 219275548  70 PWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEFTYKTISIL-------DVPETNILSYFPECFEFIEQA-KLK 141
Cdd:cd14577   23 PNLYLGDAYAARDKSVLIQLGITHIVNAASGKFHVNTGPKFYRDMNIDyygveadDNPFFDLSVYFYPVARFIRAAlSSP 102

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 219275548 142 DGVVLVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARpSICLNPGFMEQLR 197
Cdd:cd14577  103 NGRVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHR-DICPNSGFLRQLR 157

dual specificity phosphatase-like domain of serine/threonine/tyrosine interacting like 1; Serine/threonine/tyrosine interacting like 1 (STYXL1), also known as DUSP24 and MK-STYX, is a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). STYXL1 plays a role in regulating pathways by competing with active phosphatases for binding to MAPKs. Similar to MKPs, STYXL1 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, however its C-terminal dual specificity phosphatase-like domain is a pseudophosphatase missing the catalytic cysteine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 219275548  72 LLLGSQDAAHDLELLRQHKVTHILNVAYGVENVFLSEF-TYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVLVHCN 150
Cdd:cd14517   19 LYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNdQVLHIPVEDSVEADLLSFFERACSFIDKHKNNGSRVLVFST 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 219275548 151 AGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQL 196
Cdd:cd14517   99 LGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQL 144

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 219275548  70 PWLLLGSQDAAHDLELLRQHKVTHILNVAYGveNVFL-----SEF------TYKTISILDVPETNILSYFPECFEFIEQA 138
Cdd:cd14579   26 PRIYVGNASVAQNIMRLQRLGITHVLNAAEG--KSFMhvntnAEFyedtgiTYHGIKANDTQHFNLSAYFEEAADFIDKA 103

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 219275548 139 -KLKDGVVLVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARpSICLNPGFMEQL 196
Cdd:cd14579  104 lAQKNGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKR-EIGPNDGFLKQL 161

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 219275548  68 IKPWLLLGSQDAAHDLELLRQHKVTHILNVAYGVENV-FLSEFTYKTISILDVPETNILSYFPECFEFIEQAKLKDGVVL 146
Cdd:cd14645   15 ILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKPdFICESHFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVSNCRVI 94

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 219275548 147 VHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARPSICLNPGFMEQLRTYRVG 202
Cdd:cd14645   95 VHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKS 150

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 219275548  70 PWLLLGSQDAAHDLELLRQHKVTHILNVAY-----GVENVFLSEFTYKTISILDVPETNILSYFPECFEFIEQAkLKD-- 142
Cdd:cd14578    6 PGLYLGDQDIAANRRELRRLGITHILNASHskwrgGAEYYEGLNIRYLGIEAHDSPAFDMSIHFYPAADFIHRA-LSQpg 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 219275548 143 GVVLVHCNAGVSRAAAVVIGFLMSSEELAFTNALSLVKEARpSICLNPGFMEQL 196
Cdd:cd14578   85 GKILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDHR-GIIPNRGFLRQL 137