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 413004833  11 MSEINDHLYLSGAGVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKT 90
Cdd:cd14514    1 ISQITPHLFLSGASAATPPLLLSRGITCIINATTELPDPSYPGIEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGRT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 413004833  91 LVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVD 143
Cdd:cd14514   81 LVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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 413004833  11 MSEINDHLYLSGAGVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKT 90
Cdd:cd14514    1 ISQITPHLFLSGASAATPPLLLSRGITCIINATTELPDPSYPGIEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGRT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 413004833  91 LVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVD 143
Cdd:cd14514   81 LVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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 413004833   18 LYLSGAGVLKPDKIKQRKINMIVNATTEEPsTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTLVHCMAG 97
Cdd:pfam00782   1 LYLGSKPTASDAFLSKLGITAVINVTREVD-LYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAG 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 413004833   98 VSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYE 145
Cdd:pfam00782  80 ISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833  11 MSEINDHLYLsgAGVLKP---DKIKQRKINMIVNATTE----EPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNV 83
Cdd:PRK12361  95 IQKIDENLYL--GCRLFPadlEKLKSNKITAILDVTAEfdglDWSLTEEDIDYLNIPILDHSVPTLAQLNQAINWIHRQV 172

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 413004833  84 KeRGGKTLVHCMAGVSRSASLVMIYLV-KHEHMTLRQAYHYVKAARPIIRPN 134
Cdd:PRK12361 173 R-ANKSVVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRKTARLN 223

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 413004833  11 MSEINDHLYLSGAGVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKT 90
Cdd:cd14514    1 ISQITPHLFLSGASAATPPLLLSRGITCIINATTELPDPSYPGIEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGRT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 413004833  91 LVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVD 143
Cdd:cd14514   81 LVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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 413004833  11 MSEINDHLYLSGAGVLK-PDKIKQRKINMIVNATTEEPSTY-MQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGG 88
Cdd:cd14498    1 PSEILPGLYLGSLDAAQdKELLKKLGITHILNVAGEPPPNKfPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKGG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 413004833  89 KTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQ 140
Cdd:cd14498   81 KVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQ 132

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833    11 MSEINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGK 89
Cdd:smart00195   1 PSEILPHLYLGSYsDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGK 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 413004833    90 TLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKR 147
Cdd:smart00195  81 VLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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 413004833  11 MSEINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGK 89
Cdd:cd14574    1 LCRVTDSLFISNArAACNEELLAREGVTLCVNVSRQQPFPRAPRVSTLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833  90 TLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRLR 149
Cdd:cd14574   81 CLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEELQ 140

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 413004833  13 EINDHLYL-SGAGVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTL 91
Cdd:cd14565    3 EILPFLYLgSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRVL 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 413004833  92 VHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKR 147
Cdd:cd14565   83 VHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYESQ 138

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 413004833  12 SEINDHLYLS---GAGVLkpDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGG 88
Cdd:cd14513    2 SKIFDHLYLGsewNASNL--EELQNNGVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGS 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 413004833  89 KTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYE 145
Cdd:cd14513   80 KVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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 413004833  10 QMSEINDHLYLSGAGVL-KPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGG 88
Cdd:cd14523    1 QVGVIKPWLLLSSQDVAhDLETLKKHKVTHILNVAYGVENAFPDDFTYKTISILDLPETDITSYFPECFEFIDEAKSQDG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 413004833  89 KTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYE 145
Cdd:cd14523   81 VVLVHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEYQ 137

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 413004833  13 EINDHLYLSGAGVLKP-DKIKQRKINMIVNATTEEPSTYMQ--GVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGK 89
Cdd:cd14566    3 EILPFLYLGNAKDSANiDLLKKYNIKYILNVTPNLPNTFEEdgGFKYLQIPIDDHWSQNLSAFFPEAISFIDEARSKKCG 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 413004833  90 TLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDY 144
Cdd:cd14566   83 VLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLDF 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 413004833  11 MSEINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEE-PSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKI-------- 80
Cdd:cd14518    1 LSRILGGLYLGGIePLNRNRLLKAENITHILSVIPGDvPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIdsalfgng 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 413004833  81 ---RNVKERGGKTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEK 146
Cdd:cd14518   81 kdeDEEKKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYHE 149

dual specificity phosphatase domain of dual specificity protein phosphatase 5; Dual specificity protein phosphatase 5 (DUSP5) 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. DUSP5 preferentially dephosphorylates extracellular signal-regulated kinase (ERK), and is involved in ERK signaling and ERK-dependent inflammatory gene expression in adipocytes. It also plays a role in regulating pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain. DUSP5 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 413004833  13 EINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTL 91
Cdd:cd14639    3 EILPFLYLGSAyHASKCEFLANLHITALLNVSRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCVRRAGGKVL 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 413004833  92 VHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYE 145
Cdd:cd14639   83 VHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYE 136

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 413004833  12 SEINDHLYL-SGAGVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKT 90
Cdd:cd14571    5 SRIFPYLYLgSEWNAANLEELQRNRVSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTRV 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 413004833  91 LVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYE 145
Cdd:cd14571   85 LVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQ 139

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 413004833  12 SEINDHLYLS-GAGVLKPDKIKQRKINMIVNATTEEPS-TYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGK 89
Cdd:cd14646    4 TRILPHLYLGcQRDVLNKELMQQNGIGYVLNASNTCPKpDFIPESHFLRVPVNDSFCEKILPWLDKSVDFIEKAKASNGR 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833  90 TLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRLR 149
Cdd:cd14646   84 VLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKIK 143

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 413004833  32 KQRKINMIVNATTEEPSTYMQGVDT-MKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTLVHCMAGVSRSASLVMIYLV 110
Cdd:cd14517   34 KDLKIKAHINVSMDADELFKSGNDQvLHIPVEDSVEADLLSFFERACSFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLM 113

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 413004833 111 KHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRLRGT 151
Cdd:cd14517  114 YHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGT 154

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 413004833  13 EINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTL 91
Cdd:cd14640    3 EILPFLYLGSAyHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVL 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 413004833  92 VHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:cd14640   83 VHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQV 139

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 413004833  13 EINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEEPSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTL 91
Cdd:cd14638    3 EILPFLYLGSAyHASRKDMLDTLGITALINVSANCPNHFEGHYQYKSIPVEDNHKADISSWFNEAIDFIDSVKNAGGRVF 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 413004833  92 VHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:cd14638   83 VHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFESQV 139

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 413004833  11 MSEINDHLYL-SGAGVLKPDKIKQRKINMIVNATTEEPS-TYMQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGG 88
Cdd:cd14645   12 PTRILPHLYLgSQKDVLNKDLMAQNGITYVLNASNSCPKpDFICESHFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVSNC 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833  89 KTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:cd14645   92 RVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833  13 EINDHLYLSGAGVLKPDKIKQRKINMIVNATTEEPSTYMQ----GVDTMKIRIEDHPYARLsEHFDVVADKIRNVKERGG 88
Cdd:COG2453    3 IIPGLLAGGPLPGGGEADLKREGIDAVVSLTEEEELLLGLleeaGLEYLHLPIPDFGAPDD-EQLQEAVDFIDEALREGK 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 413004833  89 KTLVHCMAGVSRSASLVMIYLVKHEhMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:COG2453   82 KVLVHCRGGIGRTGTVAAAYLVLLG-LSAEEALARVRAARPGAVETPAQRAFLERFAKRL 140

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 413004833  51 MQGVDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPI 130
Cdd:cd14581   44 LEGMTYLCIPAADSPSQNLTQHFKESIKFIHECRLRGEGCLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSC 123

                         90
                 ....*....|....*.
gi 413004833 131 IRPNVGFWKQMVDYEK 146
Cdd:cd14581  124 ANPNMGFQRQLQEFEK 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 413004833  47 PSTYMQGVDTMKIRIEDHPYARLSEHFDVVADKI-RNVKERGGKTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVK 125
Cdd:cd14580   44 DDFYGTSVDYYGVPANDLPDFDISPYFYSAAEFIhRALNTPGAKVLVHCAVGVSRSATLVLAYLMIYHQLSLVQAIKTVK 123

                         90       100
                 ....*....|....*....|...
gi 413004833 126 AARPIIrPNVGFWKQMVDYEKRL 148
Cdd:cd14580  124 ERRWIF-PNRGFLKQLRKLDQQL 145

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 413004833  29 DKIKQRKINMIVNATTEEPSTYMQGVD--TMKIRIEDHPYARLSEHFDVVADKIRNVKERGGKTLVHCMAGVSRSASLVM 106
Cdd:cd14643   25 DVLGKYGIKYILNVTPNLPNMFEHDGEfkYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCGILVHCLAGISRSVTVTV 104

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 413004833 107 IYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:cd14643  105 AYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 413004833  78 DKIRNVKERGGKTLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:cd14521   85 SIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLIFQLMEFEKVL 155

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 413004833  13 EINDHLYLSGA-GVLKPDKIKQRKINMIVNATTEEPSTYMQG--VDTMKIRIEDHPYARLSEHFDVVADKIRNVKERGGK 89
Cdd:cd14642    5 EILPYLYLGCAkDSTNLDVLEEFGIKYILNVTPNLPNLFENAgeFKYKQIPISDHWSQNLSQFFPEAISFIDEARGKNCG 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 413004833  90 TLVHCMAGVSRSASLVMIYLVKHEHMTLRQAYHYVKAARPIIRPNVGFWKQMVDYEKRL 148
Cdd:cd14642   85 VLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 143