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 1050392811 132 PQEIEEFLSYPIEILPGLLYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHNELHIPVMDSCESDLFQFFSRAC 211
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 212 EFIDMYMGPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRILGEQ 286
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

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 1050392811 132 PQEIEEFLSYPIEILPGLLYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHNELHIPVMDSCESDLFQFFSRAC 211
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 212 EFIDMYMGPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRILGEQ 286
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050392811  142 PIEILPGLlYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHnELHIPVMDSCESDLFQFFSRACEFIDMYMGPN 221
Cdd:smart00195   1 PSEILPHL-YLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFT-YLGVPIDDNTETKISPYFPEAVEFIEDAESKG 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050392811  222 SAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENR 281
Cdd:smart00195  79 GKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

N-terminal regulatory rhodanese domain of dual specificity phosphatases (DSP), such as Mapk Phosphatase. This domain is believed to determine substrate specificity by binding the substrate, such as ERK2, and activating the C-terminal catalytic domain by inducing a conformational change. This domain has homology to the Rhodanese Homology Domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050392811  33 LLDARSKREYNESHIVTA----------RRAKQDK-DENFLLP-----ESVELECVRYCVVYDGNTSSLNETGPAIKCAR 96
Cdd:cd01446    20 LLDCRPFLEYSSSHIRGAvnvccptilrRRLQGGKiLLQQLLScpedrDRLRRGESLAVVVYDESSSDRERLREDSTAES 99

                          90       100
                  ....*....|....*....|....*....
gi 1050392811  97 VMAQVCR-----YTVLVLEGGYERFSAYY 120
Cdd:cd01446   100 VLGKLLRklqegCSVYLLKGGFEQFSSEF 128

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050392811 150 LYLGDQRQANDRHIQKDLKIKAQINVSLDPDkSLSSAVHNE----LHIPVMDSCESDLFQFfSRACEFIDMYMGPNSAVL 225
Cdd:PRK12361  102 LYLGCRLFPADLEKLKSNKITAILDVTAEFD-GLDWSLTEEdidyLNIPILDHSVPTLAQL-NQAINWIHRQVRANKSVV 179

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050392811 226 VFSKLGISRSSTVVIAYLIYC-KQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRilGEQRTD-----IADP 293
Cdd:PRK12361  180 VHCALGRGRSVLVLAAYLLCKdPDLTVEEVLQQIKQIRKTARLNKRQLRALEKMLEQ--GKLNIHkrawlIANP 251

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 1050392811 132 PQEIEEFLSYPIEILPGLLYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHNELHIPVMDSCESDLFQFFSRAC 211
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 212 EFIDMYMGPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRILGEQ 286
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

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 1050392811 142 PIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSLD-PDKSLSSAVHNELHIPVMDSCESDLFQFFSRACEFIDMYMGP 220
Cdd:cd14566     1 PVEILP-FLYLGNAKDSANIDLLKKYNIKYILNVTPNlPNTFEEDGGFKYLQIPIDDHWSQNLSAFFPEAISFIDEARSK 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 221 NSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQL 275
Cdd:cd14566    80 KCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQL 134

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 1050392811 142 PIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSldpdKSLSSAVHNELH---IPVMDSCESDLFQFFSRACEFIDMYM 218
Cdd:cd14565     1 PVEILP-FLYLGSAYHASRREVLKALGITAVLNVS----RNCPNHFEDHFQyksIPVEDSHNADISSWFEEAIGFIDKVK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1050392811 219 GPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENR 281
Cdd:cd14565    76 ASGGRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYESQ 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 1050392811 144 EILPGLlYLGDQRQANDRHIqKDLKIKAQINVSLD-PDKSLSSAVHneLHIPVMDSCESDLFQFFSRACEFIDMYMGPNS 222
Cdd:cd14514     3 QITPHL-FLSGASAATPPLL-LSRGITCIINATTElPDPSYPGIEY--LRVPVEDSPHADLSPHFDEVADKIHQVKRRGG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1050392811 223 AVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQL 275
Cdd:cd14514    79 RTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQL 131

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 1050392811 144 EILPGLlYLGDQRQANDRHIQKDLKIKAQIN---------VSLDPDKSLSSAVHNeLHIPVMDSCESDLFQFFSRACEFI 214
Cdd:cd14515     3 EVWPGI-YIGDESTAKNKAKLKKLGITHVLNaaegkkngeVNTNAKFYKGSGIIY-LGIPASDLPTFDISQYFDEAADFI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050392811 215 DMYMG-PNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKcKPNMRPNRGFVKQLSEWENRI 282
Cdd:cd14515    81 DKALSdPGGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRK-KREIRPNRGFLQQLCELNDKL 148

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 1050392811 142 PIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSLD-PDkslssavHNELH-----IPVMDSCESDLFQFFSRACEFID 215
Cdd:cd14640     1 PVEILP-FLYLGSAYHAARRDMLDALGITALLNVSSDcPN-------HFEGHyqykcIPVEDNHKADISSWFMEAIEYID 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1050392811 216 MYMGPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRIL 283
Cdd:cd14640    73 SVKDCNGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVL 140

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 1050392811 142 PIEILPGLlYLGDqrqANDRHIQKDLKiKAQIN--VSLDPDKSLSSAVHNELH---IPVMDSCESDLFQFFSRACEFIDM 216
Cdd:cd14520     1 MKLVRPGL-YIGN---ADDAADYLSLR-EAGIThvLTVDSEEPIDAPPVGKLVrkfVPALDEESTDLLSRLDECLDFIDE 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1050392811 217 YMGpNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWEN 280
Cdd:cd14520    76 GRA-EGAVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLYEA 138

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 1050392811 140 SYPIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSLD-PDKSLSSAVHNELHIPVMDSCESDLFQFFSRACEFIDMYM 218
Cdd:cd14642     1 SFPVEILP-YLYLGCAKDSTNLDVLEEFGIKYILNVTPNlPNLFENAGEFKYKQIPISDHWSQNLSQFFPEAISFIDEAR 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1050392811 219 GPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWE 279
Cdd:cd14642    80 GKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 140

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 1050392811 150 LYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHnELHIPVMDSCESDLFQFFSRACEFIDMYMGPNSAVLVFSK 229
Cdd:cd14573     9 LYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIE-YLHVPVADSPDTRLRDYFDPIADKIHTVEARGGRTLLHCV 87

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1050392811 230 LGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRILGE 285
Cdd:cd14573    88 AGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFELFGK 143

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 1050392811 142 PIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSS--AVHNelhIPVMDSCESDLFQFFSRACEFIDMYMG 219
Cdd:cd14513     1 ASKIFD-HLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGrfTYHN---IRVWDEESTNLLPYWNETYRFIKEARR 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1050392811 220 PNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWE 279
Cdd:cd14513    77 KGSKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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 1050392811 142 PIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSldpdKSLSSAVHNELH---IPVMDSCESDLFQFFSRACEFIDMYM 218
Cdd:cd14641     4 PVEILP-FLFLGSAHHSSRRETLESLGITAVLNVS----SSCPNYFEGQFQyksIPVEDSHMADISAWFQEAIDFIDSVK 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 219 GPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRIL 283
Cdd:cd14641    79 NSGGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVL 143

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 1050392811 145 ILPGLlYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAvhNELHIPVMDSCESDLFQFFSRACEFIDMYMGPNSAV 224
Cdd:cd14519     4 ILPGL-YVGNFRDAKDAEQLRENGITHILSIHDSARPLLEDI--KYLCIPAADTPEQNISQHFRECINFIHEARLNGGNV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1050392811 225 LVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWEN 280
Cdd:cd14519    81 LVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 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 1050392811 142 PIEILPgLLYLGDQRQANDRHIQKDLKIKAQINVSLD-PDkslssavHNELH-----IPVMDSCESDLFQFFSRACEFID 215
Cdd:cd14638     1 PVEILP-FLYLGSAYHASRKDMLDTLGITALINVSANcPN-------HFEGHyqyksIPVEDNHKADISSWFNEAIDFID 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050392811 216 MYMGPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRILG 284
Cdd:cd14638    73 SVKNAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

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 1050392811 150 LYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVhNELHIPVMDSCESDLFQFFSRACEFIDMYMGPNSAVLVFSK 229
Cdd:cd14574     8 LFISNARAACNEELLAREGVTLCVNVSRQQPFPRAPRV-STLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGKCLVYCK 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1050392811 230 LGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWE 279
Cdd:cd14574    87 NGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYE 136

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 1050392811 150 LYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSS--AVHNelhIPVMDSCESDLFQFFSRACEFIDMYMGPNSAVLVF 227
Cdd:cd14570    11 LYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGlfAYHN---IRVYDEETTDLLAHWNDAYHFINKAKKNHSKCLVH 87

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1050392811 228 SKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWE 279
Cdd:cd14570    88 CKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYE 139

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 1050392811 144 EILPGLlYLGDQRQANDRHIQKDLKIKAQINVSL-------DPDKSLSSAVHneLHIPVMDSCESDLFQFFSRACEFI-D 215
Cdd:cd14580     3 EVWPNL-FLGDLATAHNRFGLWKLGITHVLNAAHgklfcqgGDDFYGTSVDY--YGVPANDLPDFDISPYFYSAAEFIhR 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1050392811 216 MYMGPNSAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAwthILKCKPNMR--PNRGFVKQLSEWENRI 282
Cdd:cd14580    80 ALNTPGAKVLVHCAVGVSRSATLVLAYLMIYHQLSLVQA---IKTVKERRWifPNRGFLKQLRKLDQQL 145

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 1050392811 144 EILPGLlYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHneLHIPVMDSCESDLFQFFSRACEFIDMYMGPNSA 223
Cdd:cd14581     6 KVLPGL-YLGNFKDARDREQLSKNNITHILSVHDSARPMLEGMTY--LCIPAADSPSQNLTQHFKESIKFIHECRLRGEG 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 224 VLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWENRILGEQRT 288
Cdd:cd14581    83 CLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFEKHEVHQYRQ 147

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 1050392811 144 EILPGLlYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHneLHIPVMDSCESDLFQFFSRACEFIDMYMGPNSA 223
Cdd:cd14582     7 KVLPGL-YLGNFIDAKDLEQLSRNKITHIISIHESPQPLLQDITY--LRIPLPDTPEAPIKKHFKECISFIHQCRLNGGN 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1050392811 224 VLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEW 278
Cdd:cd14582    84 CLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 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 1050392811 142 PIEILPGLlYLGDQRQANDRHIQKDLKIKAQINVSLDPDKSLSSAVHNELHIPVMDSCESDLFQFFSRACEFIDMYMGPN 221
Cdd:cd14645    12 PTRILPHL-YLGSQKDVLNKDLMAQNGITYVLNASNSCPKPDFICESHFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVSN 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1050392811 222 SAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPNMRPNRGFVKQLSEWE 279
Cdd:cd14645    91 CRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 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 1050392811 191 LHIPVMDSCESDLFQFFSRACEFID----MYMGpnsAVLVFSKLGISRSSTVVIAYLIYCKQYSLKEAWTHILKCKPnMR 266
Cdd:cd14576    64 MGIEVDDFPDVDISKHFRKGAEFLDeallTYRG---KVLVSSEMGISRSAVLVAAYLMIFHNMTIMEALMTLRKKRA-IY 139

                          90       100
                  ....*....|....*....|
gi 1050392811 267 PNRGFVKQLSEWENRILGEQ 286
Cdd:cd14576   140 PNEGFLKQLRELNEKLLEER 159