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 2210533330   5 VDEVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAVTSRLDDYG 83
Cdd:cd14498     1 PSEILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIEDSPDEDILShFEEAIEFIEEALKKGG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2210533330  84 -VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHDALVR 133
Cdd:cd14498    81 kVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLK 131

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 2210533330   5 VDEVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAVTSRLDDYG 83
Cdd:cd14498     1 PSEILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIEDSPDEDILShFEEAIEFIEEALKKGG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2210533330  84 -VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHDALVR 133
Cdd:cd14498    81 kVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLK 131

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330    7 EVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDgVTVVDVPMVDGPRNDLAAFGRAVTA--VTSRLDDYGV 84
Cdd:smart00195   3 EILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSD-FTYLGVPIDDNTETKISPYFPEAVEfiEDAESKGGKV 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2210533330   85 LVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHDALVR 133
Cdd:smart00195  82 LVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLR 130

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 2210533330   5 VDEVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAVTSRLDDYG 83
Cdd:cd14498     1 PSEILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIEDSPDEDILShFEEAIEFIEEALKKGG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2210533330  84 -VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHDALVR 133
Cdd:cd14498    81 kVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLK 131

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 2210533330   5 VDEVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDpDGGYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAVT-SRLDDY 82
Cdd:cd14523     2 VGVIKPWLLLSSQDVAHDLETLKKHKVTHILNVAYGV-ENAFPDDFTYKTISILDLPETDITSyFPECFEFIDeAKSQDG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2210533330  83 GVLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHD 129
Cdd:cd14523    81 VVLVHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNP 127

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 2210533330   8 VASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPdGVTVVDVPMVDGPRNDLAA-FGRAVTAVTSRLDDYG-VL 85
Cdd:cd14574     4 VTDSLFISNARAACNEELLAREGVTLCVNVSRQQPFPRAP-RVSTLRVPVFDDPAEDLYRhFEQCADAIEAAVRRGGkCL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2210533330  86 VHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDP 127
Cdd:cd14574    83 VYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEP 124

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 2210533330  11 GLFIGTVADAGDGERLRRRGVGVIVSLTygDPDGGYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAV-TSRLDDYGVLVHC 88
Cdd:cd14519     7 GLYVGNFRDAKDAEQLRENGITHILSIH--DSARPLLEDIKYLCIPAADTPEQNISQhFRECINFIhEARLNGGNVLVHC 84

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2210533330  89 SAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDP 127
Cdd:cd14519    85 LAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANP 123

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330    7 EVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDgVTVVDVPMVDGPRNDLAAFGRAVTA--VTSRLDDYGV 84
Cdd:smart00195   3 EILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSD-FTYLGVPIDDNTETKISPYFPEAVEfiEDAESKGGKV 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2210533330   85 LVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHDALVR 133
Cdd:smart00195  82 LVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLR 130

dual specificity phosphatase domain of class III mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class III MKPs consist of DUSP8, DUSP10/MKP-5 and DUSP16/MKP-7, and are JNK/p38-selective phosphatases, which are found in both the cell nucleus and cytoplasm. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAVTS-RLDDYGVLVHCS 89
Cdd:cd14568     8 LYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKPDFIPDSHFLRIPVNDSYCEKLLPwLDKAVEFIEKaRASNKRVLVHCL 87

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2210533330  90 AGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDP 127
Cdd:cd14568    88 AGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISP 125

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 2210533330   7 EVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDG-VTVVDVPMVDGPRNDLAA-FGRAVTAV-TSRLDDYG 83
Cdd:cd14566     3 EILPFLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEEDGgFKYLQIPIDDHWSQNLSAfFPEAISFIdEARSKKCG 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2210533330  84 VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDP 127
Cdd:cd14566    83 VLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISP 126

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 2210533330   1 MNGDVDEVASGLFIGTVADAGDGERLRRRGVGVIVSLtYGDPDGGYPDgVTVVDVPMVDGPRNDLAA-FGRAVTAVTS-R 78
Cdd:cd14582     1 MGNGMTKVLPGLYLGNFIDAKDLEQLSRNKITHIISI-HESPQPLLQD-ITYLRIPLPDTPEAPIKKhFKECISFIHQcR 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2210533330  79 LDDYGVLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPH 128
Cdd:cd14582    79 LNGGNCLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPN 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDGVTVVD-VPMVDGPRNDLAAFGRAVTAVT--SRLDDYGVLVHC 88
Cdd:cd14567     8 LYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKGGFRYKrLPATDSNKQNLRQYFEEAFEFIeeAHQSGKGVLVHC 87

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2210533330  89 SAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDP 127
Cdd:cd14567    88 QAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISP 126

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 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYgDPDGGYPDGVTVVDVPMVDGPRNDLAAFGRAVTAV--TSRLDDYGVLVHCS 89
Cdd:cd14571    11 LYLGSEWNAANLEELQRNRVSHILNVTR-EIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFieAARAQGTRVLVHCK 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2210533330  90 AGASRSpavAATALALS---EGIGLDDAFRRVAAARDAVDPHDALVRR 134
Cdd:cd14571    90 MGVSRS---ASTVIAYAmkqYGWTLEQALRHVRERRPIVQPNPGFLRQ 134

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 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYgDPDGGYPDGVTVVDVPMVDGPRNDLAAFGRAVTAVTSRLDDYG--VLVHCS 89
Cdd:cd14569    11 VFLGSEWNASNLEDLQNRGVRYILNVTR-EIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGskCLVHCK 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2210533330  90 AGASRSpAVAATALALSE-GIGLDDAFRRVAAARDAVDPHDALVRR 134
Cdd:cd14569    90 MGVSRS-ASTVIAYAMKEyGWNLDRAYDYVKERRTVTKPNPSFMRQ 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 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYgDPDGGYPDGVTVVDVPMVDGPRNDLAAFGRAVTAVTSRLDDYG--VLVHCS 89
Cdd:cd14513     8 LYLGSEWNASNLEELQNNGVKYILNVTR-EIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGskVLVHCK 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2210533330  90 AGASRSPAVAAtALALSE-GIGLDDAFRRVAAARDAVDPHDALVRR 134
Cdd:cd14513    87 MGVSRSASTVI-AYAMKEyGWSLEQALEHVKERRSCIKPNPGFLRQ 131

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  22 DGERLRRRGVGVIVSL-------TYGDPDggYPD-----GVTVVDVPMVDG-PRNDLAAFGRAVTAVTSRLDDY-GVLVH 87
Cdd:cd14505    35 DLEELKDQGVDDVVTLctdgeleELGVPD--LLEqyqqaGITWHHLPIPDGgVPSDIAQWQELLEELLSALENGkKVLIH 112

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2210533330  88 CSAGASRSPAVAA-TALALSEGIGLDDAFRRVAAAR 122
Cdd:cd14505   113 CKGGLGRTGLIAAcLLLELGDTLDPEQAIAAVRALR 148

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 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDG-VTVVDVPMVDGPRNDLAAF-GRAVTAV-TSRLDDYGVLVHC 88
Cdd:cd14643    13 LYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGeFKYKQIPISDHWSQNLSQFfPEAISFIdEARSKKCGILVHC 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2210533330  89 SAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPH 128
Cdd:cd14643    93 LAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPN 132

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 2210533330   7 EVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGgYPDGVTVVDVPMVDGPRNDLAA-FGRAVTAVTSRLDDYG-V 84
Cdd:cd14641     6 EILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNY-FEGQFQYKSIPVEDSHMADISAwFQEAIDFIDSVKNSGGrV 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2210533330  85 LVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPH 128
Cdd:cd14641    85 LVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPN 128

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 2210533330   6 DEVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPD-------GGYPD-GVTVVDVPMVDGPRNDLAA-FGRAVTAVT 76
Cdd:cd14579    22 NEVYPRIYVGNASVAQNIMRLQRLGITHVLNAAEGKSFmhvntnaEFYEDtGITYHGIKANDTQHFNLSAyFEEAADFID 101

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  77 SRLDDYG--VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDaVDPHDALVRR 134
Cdd:cd14579   102 KALAQKNgrVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKRE-IGPNDGFLKQ 160

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 2210533330  12 LFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDGVTVVDVPMVDG-PRNDLAAFGRAVTAV-TSRLDDYGVLVHCS 89
Cdd:cd14646    10 LYLGCQRDVLNKELMQQNGIGYVLNASNTCPKPDFIPESHFLRVPVNDSfCEKILPWLDKSVDFIeKAKASNGRVLVHCL 89

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2210533330  90 AGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPH 128
Cdd:cd14646    90 AGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPN 128

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2210533330  77 SRLDDYGVLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPH 128
Cdd:cd14645    86 AKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPN 137

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2210533330  76 TSRLDDYGVLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPHDALVRR 134
Cdd:cd18534    68 QCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSPAVAKQ 126

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2210533330  84 VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDP 127
Cdd:cd14494    59 VLVHCKAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGIP 102

protein-tyrosine phosphatase mitochondrial 1; Protein-tyrosine phosphatase mitochondrial 1 or PTP localized to the mitochondrion 1 (PTPMT1), also called phosphoinositide lipid phosphatase (PLIP), phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1, or PTEN-like phosphatase, is a lipid phosphatase or phosphatidylglycerophosphatase (EC 3.1.3.27) which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. It is essential for the biosynthesis of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. PTPMT1 also plays a crucial role in hematopoietic stem cell (HSC) function, and has been shown to display activity toward phosphoprotein substrates.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  49 GVTVVDVPMVD---GPrnDLAAFGRAVT-AVTSRLDDYGVLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDA 124
Cdd:cd14524    55 GVEQLRLPTVDftgVP--SLEDLEKGVDfILKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPH 132

                  ....
gi 2210533330 125 VDPH 128
Cdd:cd14524   133 ILLR 136

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330   5 VDEVASGLFIGTVADAGDGERLRRRGVGVIVSLTYG--DPDGG---YPD------GVTVVDVPMVdgprNDLAAFGRAVT 73
Cdd:cd14575    11 VNEVWPGLYIGDEKTALDRYSLQKLGITHILNAAHGkwNVDTGaeyYKDmtihyyGVEADDLPTF----NLSQFFYSAAE 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2210533330  74 AVTSRLDD--YGVLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAAR 122
Cdd:cd14575    87 FIHQALSDphNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQVAQRR 137

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 2210533330   7 EVASGLFIGTVADAGDGERLRRRGVGVIVSLTYGDPDGGYPDG-VTVVDVPMVDGPRNDLAAF-GRAVTAV-TSRLDDYG 83
Cdd:cd14642     5 EILPYLYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFENAGeFKYKQIPISDHWSQNLSQFfPEAISFIdEARGKNCG 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2210533330  84 VLVHCSAGASRSPAVAATALALSEGIGLDDAFRRVAAARDAVDPH 128
Cdd:cd14642    85 VLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPN 129

protein tyrosine phosphatase type IVA 1; Protein tyrosine phosphatase type IVA 1 (PTP-IVa1), also known as protein-tyrosine phosphatase of regenerating liver 1 (PRL-1), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It may play a role in the development and maintenance of differentiating epithelial tissues. PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways. It is a member of the PTP-IVa/PRL family of small, prenylated phosphatases that are the most oncogenic of all PTPs. PRLs associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  24 ERLRRRGVGVIVSLTYGDPDGGY--PDGVTVVDVPMVDG--PRNDLAAFGRAVTAVTSRlDDYG--VLVHCSAGASRSPA 97
Cdd:cd18537    35 EELKKYGVTTVVRVCEATYDTTLveKEGIQVLDWPFDDGapPSNQIVDDWLNLLKVKFR-EEPGccIAVHCVAGLGRAPV 113

                          90       100
                  ....*....|....*....|....*
gi 2210533330  98 VAATALaLSEGIGLDDAFRRVAAAR 122
Cdd:cd18537   114 LVALAL-IECGMKYEDAVQFIRQKR 137

bacterial protein tyrosine and dual-specificity phosphatases related to Pseudomonas aeruginosa TpbA; This subfamily contains bacterial protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DUSPs) related to Pseudomonas aeruginosa TpbA, a DUSP that negatively regulates biofilm formation by converting extracellular quorum sensing signals and to Mycobacterium tuberculosis PtpB, a PTP virulence factor that attenuates host immune defenses by interfering with signal transduction pathways in macrophages. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides, while DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and PTPs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2210533330  20 AGDGERLRRRGVGVIVSLTYGDPDGGYP------DGVTVVDVPMVDGPRNDLAAfgRAVTAVTSRLDDYG-VLVHCSAGA 92
Cdd:cd14529    23 DEDRALLKKLGIKTVIDLRGADERAASEeaaakiDGVKYVNLPLSATRPTESDV--QSFLLIMDLKLAPGpVLIHCKHGK 100