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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030 158 PQELDAFQPYPVEILPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHIC 237
Cdd:cd14517    1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308082030 238 HFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVLHGE 311
Cdd:cd14517   81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGT 154

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 308082030 158 PQELDAFQPYPVEILPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHIC 237
Cdd:cd14517    1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308082030 238 HFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVLHGE 311
Cdd:cd14517   81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGT 154

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 308082030  176 VYLGKISQACNAKMhKDLKIKAHVNISMETtpYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:pfam00782   1 LYLGSKPTASDAFL-SKLGITAVINVTREV--DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 308082030  256 RGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 305
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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 308082030 158 PQELDAFQPYPVEILPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHIC 237
Cdd:cd14517    1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308082030 238 HFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVLHGE 311
Cdd:cd14517   81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGT 154

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030   168 PVEILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:smart00195   1 PSEILPH-LYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDF-TYLGVPIDDNTETKISPYFPEAVEFIEDAESKG 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030   248 SVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKV 307
Cdd:smart00195  79 GKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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 308082030  176 VYLGKISQACNAKMhKDLKIKAHVNISMETtpYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:pfam00782   1 LYLGSKPTASDAFL-SKLGITAVINVTREV--DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 308082030  256 RGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 305
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

dual specificity phosphatase domain of dual specificity protein phosphatase 9; Dual specificity protein phosphatase 9 (DUSP9), also called mitogen-activated protein kinase (MAPK) phosphatase 4 (MKP-4), 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. DUSP9 is a mediator of bone morphogenetic protein (BMP) signaling to control the appropriate ERK activity critical for the determination of embryonic stem cell fate. Down-regulation of DUSP9 expression has been linked to severe pre-eclamptic placenta as well as cancers such as hepatocellular carcinoma. DUSP9 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 308082030 167 YPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAD-KLLHIKLEDSPDTLLFDYFRHICHFIELHLR 245
Cdd:cd14644    2 FPVQILP-NLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEKNGDfHYKQIPISDHWSQNLSQFFPEAIEFIDEALS 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 308082030 246 LHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14644   81 QNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSL 143

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 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADkLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14565    1 PVEILP-FLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQ-YKSIPVEDSHNADISSWFEEAIGFIDKVKASG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 308082030 248 SVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 305
Cdd:cd14565   79 GRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYE 136

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 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADkLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14639    1 PVEILP-FLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQYH-YKWIPVEDSHTADISSHFQEAIDFIDCVRRAG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 308082030 248 SVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 305
Cdd:cd14639   79 GKVLVHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYE 136

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 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISME-TTPYFIGNaDKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 246
Cdd:cd14568    1 PTRILP-HLYLGSQRDVLDKDLMQRNGISYVLNVSNTcPKPDFIPD-SHFLRIPVNDSYCEKLLPWLDKAVEFIEKARAS 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 308082030 247 HSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14568   79 NKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFEKKL 140

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 308082030 165 QP-YPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAD-KLLHIKLEDSPDTLLFDYFRHICHFIEL 242
Cdd:cd14643    2 QPaFPVQILP-YLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGEfKYKQIPISDHWSQNLSQFFPEAISFIDE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 308082030 243 HLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14643   81 ARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

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 308082030 167 YPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISmETTPYFIGNAD--KLLHIKLEDSPDTLLFDYFRHICHFIELHL 244
Cdd:cd14642    2 FPVEILP-YLYLGCAKDSTNLDVLEEFGIKYILNVT-PNLPNLFENAGefKYKQIPISDHWSQNLSQFFPEAISFIDEAR 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308082030 245 RLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14642   80 GKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 143

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 308082030 165 QPYPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHL 244
Cdd:cd14641    1 QGGPVEILP-FLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQF-QYKSIPVEDSHMADISAWFQEAIDFIDSVK 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 308082030 245 RLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 305
Cdd:cd14641   79 NSGGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 139

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 308082030 172 LPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHL------- 244
Cdd:cd14518    4 ILGGLYLGGIEPLNRNRLLKAENITHILSVIPGDVPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIDSALfgngkde 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 308082030 245 ----RLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEK 306
Cdd:cd14518   84 deekKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYHE 149

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 308082030 171 ILPGrVYLGKIsqaCNAKMHKDLKIK--AHVnISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIElHLRLHS 248
Cdd:cd14519    4 ILPG-LYVGNF---RDAKDAEQLRENgiTHI-LSIHDSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIH-EARLNG 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 308082030 249 -VVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEK 306
Cdd:cd14519   78 gNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 136

dual specificity phosphatase-like domain of serine/threonine/tyrosine-interacting protein; Serine/threonine/tyrosine-interacting protein (STYX), also called protein tyrosine phosphatase-like protein, is a catalytically inactive member of the protein tyrosine phosphatase family that plays an integral role in regulating pathways by competing with active phosphatases for binding to MAPKs. It acts as a nuclear anchor for MAPKs, affecting their nucleocytoplasmic shuttling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030 170 EILPGrVYLGKISQACNAKMH--KDLKIKAHVNISMETTPYFIG-NAD---KLLHIKLEDSPDTLLFDYFRHICHFIELH 243
Cdd:cd14522    7 EILPG-LYLGPYSAAMKSKLEvlLKHGITHIVCVRQNIEANFIKpNFPdhfRYLVLDVADNPTENIIRHFPTVKEFIDDC 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 308082030 244 LRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWE 305
Cdd:cd14522   86 LQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147

dual specificity protein phosphatase 14; dual specificity protein phosphatase 14 (DUSP14), also called mitogen-activated protein kinase (MAPK) phosphatase 6 (MKP-6) or MKP-1-like protein tyrosine phosphatase (MKP-L), 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. DUSP14 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. DUSP14 dephosphorylates JNK, ERK, and p38 in vitro. It also 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030 176 VYLGKISQACNAKMHKDLKIKAHVNISMETtPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:cd14572   15 LYLSRGNVASNRHLLLSRGITCIVNATIEI-PNFNWPQFEYVKVPLADMPHAPISLYFDSVADKIHSVGRKHGATLVHCA 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 308082030 256 RGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVLHGE 311
Cdd:cd14572   94 AGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYERKLFGK 149

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 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGnADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14569    4 PTQIFE-HVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPG-LFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHG 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 308082030 248 SVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14569   82 SKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGIL 142

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 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFiGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14571    4 PSRIFP-YLYLGSEWNAANLEELQRNRVSHILNVTREIDNFF-PERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQG 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 308082030 248 SVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14571   82 TRVLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQGIL 142

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 308082030 170 EILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNadKLLHIKLEDSPDTLLFDYFRHICHFI-ELHLRLHS 248
Cdd:cd14581    6 KVLPG-LYLGNFKDARDREQLSKNNITHILSVHDSARPMLEGM--TYLCIPAADSPSQNLTQHFKESIKFIhECRLRGEG 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 308082030 249 VvLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEK 306
Cdd:cd14581   83 C-LVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFEK 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 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMET-TPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 246
Cdd:cd14646    3 PTRILP-HLYLGCQRDVLNKELMQQNGIGYVLNASNTCpKPDFIPES-HFLRVPVNDSFCEKILPWLDKSVDFIEKAKAS 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 308082030 247 HSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVLHGE 311
Cdd:cd14646   81 NGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKIKNQ 145

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 308082030 170 EILPGrVYLGKISQACNAKMHKDLKI-----KAHVNISMETTP-YFignADKLLH---IKLEDSPDTLLFDYFRHICHFI 240
Cdd:cd14575   13 EVWPG-LYIGDEKTALDRYSLQKLGIthilnAAHGKWNVDTGAeYY---KDMTIHyygVEADDLPTFNLSQFFYSAAEFI 88

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 308082030 241 ELHLRL-HSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKcKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14575   89 HQALSDpHNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQVAQ-RRCILPNRGFLKQLRELDIQL 156

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308082030 234 RHICHFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHY-NEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEK 306
Cdd:cd14527   63 ERAVAWIEELRAQGGPVLVHCALGYGRSATVVAAWLLAYgRAKSVAEAEALIRAARPQVVLNPAQRKALEAWSG 136

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP3 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030 170 EILPgRVYLGKISQACNAKMHKDLKIK-----------AHVNISMEttpYFIGNADKLLHIKLEDSPDTLLFDYFRHICH 238
Cdd:cd14579   23 EVYP-RIYVGNASVAQNIMRLQRLGIThvlnaaegksfMHVNTNAE---FYEDTGITYHGIKANDTQHFNLSAYFEEAAD 98

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 308082030 239 FIELHLRLHS-VVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKcKTNMRPNRAFVAQL 301
Cdd:cd14579   99 FIDKALAQKNgRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQ-KREIGPNDGFLKQL 161

dual specificity phosphatase domain of dual specificity protein phosphatase 8; Dual specificity protein phosphatase 8 (DUSP8), also called DUSP hVH-5 or M3/6, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP8 controls basal and acute stress-induced ERK1/2 signaling in adult cardiac myocytes, which impacts contractility, ventricular remodeling, and disease susceptibility. It also plays a role in decreasing ureteric branching morphogenesis by inhibiting p38MAPK. DUSP8 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308082030 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMET-TPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 246
Cdd:cd14645   12 PTRILP-HLYLGSQKDVLNKDLMAQNGITYVLNASNSCpKPDFICES-HFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVS 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 308082030 247 HSVVLVFSTRGISRSVAAVVALLMHYNEETLKRSWAQVKKCKTNMRPNRAFVAQLLEWEKVL 308
Cdd:cd14645   90 NCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151