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 1039772833 158 PQELDAFQPYPVEILPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHIC 237
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039772833 238 HFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLK 278
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLK 121

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 1039772833 158 PQELDAFQPYPVEILPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHIC 237
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039772833 238 HFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLK 278
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLK 121

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 1039772833 176 VYLGKISQACNAKMhKDLKIKAHVNISMETtpYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:pfam00782   1 LYLGSKPTASDAFL-SKLGITAVINVTREV--DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100
                  ....*....|....*....|...
gi 1039772833 256 RGISRSVAAVVALLMHYNEETLK 278
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLN 100

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 1039772833 158 PQELDAFQPYPVEILPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHIC 237
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039772833 238 HFIELHLRLHSVVLVFSTRGISRSVAAVVALLMHYNEETLK 278
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLK 121

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772833  168 PVEILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:smart00195   1 PSEILPH-LYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDF-TYLGVPIDDNTETKISPYFPEAVEFIEDAESKG 78

                           90       100
                   ....*....|....*....|....*.
gi 1039772833  248 SVVLVFSTRGISRSVAAVVALLMHYN 273
Cdd:smart00195  79 GKVLVHCQAGVSRSATLIIAYLMKTR 104

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 1039772833 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAD-KLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 246
Cdd:cd14566     1 PVEILP-FLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEEDGGfKYLQIPIDDHWSQNLSAFFPEAISFIDEARSK 79

                          90       100
                  ....*....|....*....|....*
gi 1039772833 247 HSVVLVFSTRGISRSVAAVVALLMH 271
Cdd:cd14566    80 KCGVLVHCLAGISRSVTVTVAYLMQ 104

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 1039772833 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADkLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14565     1 PVEILP-FLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQ-YKSIPVEDSHNADISSWFEEAIGFIDKVKASG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1039772833 248 SVVLVFSTRGISRSVAAVVALLMHYNE-------ETLKSRVP 282
Cdd:cd14565    79 GRVLVHCQAGISRSATICLAYLMTTRRvrlneafDYVKQRRS 120

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 1039772833 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADkLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14639     1 PVEILP-FLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQYH-YKWIPVEDSHTADISSHFQEAIDFIDCVRRAG 78

                          90       100
                  ....*....|....*....|...
gi 1039772833 248 SVVLVFSTRGISRSVAAVVALLM 270
Cdd:cd14639    79 GKVLVHCEAGISRSPTICMAYLM 101

dual specificity phosphatase domain of mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs, which are involved in gene regulation, cell proliferation, programmed cell death and stress responses, as an important feedback control mechanism that limits MAPK cascades. MKPs, also referred to as typical DUSPs, function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772833 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMET-TPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 246
Cdd:cd14512     1 PTRILP-NLYLGSQRDSLNLELMQQLGIGYVLNVSNTCpNPDFIGLF-HYKRIPVNDSFCQNISPWFDEAIEFIEEAKAS 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772833 247 HSVVLVFSTRGISRSVAAVVALLMHYNEETL 277
Cdd:cd14512    79 NGGVLVHCLAGISRSATIAIAYLMKRMRMSL 109

dual specificity phosphatase domain of dual specificity protein phosphatase 12 and similar proteins; Dual specificity protein phosphatase 12 (DUSP12), also called YVH1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP12 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It targets p38 MAPK to regulate macrophage response to bacterial infection. It also ameliorates cardiac hypertrophy in response to pressure overload through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 has been identified as a modulator of cell cycle progression, a function independent of phosphatase activity and mediated by its C-terminal zinc-binding domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772833 168 PVEILPGrVYLGKISQACNAKMHKDLKIkAHVnISMETTPYFIGNADKLLHIK---LEDSPDTLLFDYFRHICHFIElHL 244
Cdd:cd14520     1 MKLVRPG-LYIGNADDAADYLSLREAGI-THV-LTVDSEEPIDAPPVGKLVRKfvpALDEESTDLLSRLDECLDFID-EG 76

                          90       100
                  ....*....|....*....|....*..
gi 1039772833 245 RLHSVVLVFSTRGISRSVAAVVALLMH 271
Cdd:cd14520    77 RAEGAVLVHCHAGVSRSAAVVTAYLMK 103

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 1039772833 167 YPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAD-KLLHIKLEDSPDTLLFDYFRHICHFIELHLR 245
Cdd:cd14644     2 FPVQILP-NLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEKNGDfHYKQIPISDHWSQNLSQFFPEAIEFIDEALS 80

                          90       100
                  ....*....|....*....|....*.
gi 1039772833 246 LHSVVLVFSTRGISRSVAAVVALLMH 271
Cdd:cd14644    81 QNCGVLVHCLAGISRSVTVTVAYLMQ 106

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 1039772833 170 EILPGrVYLGKISQACNAKMH--KDLKIKAHVNISMETTPYFIG-NAD---KLLHIKLEDSPDTLLFDYFRHICHFIELH 243
Cdd:cd14522     7 EILPG-LYLGPYSAAMKSKLEvlLKHGITHIVCVRQNIEANFIKpNFPdhfRYLVLDVADNPTENIIRHFPTVKEFIDDC 85

                          90       100
                  ....*....|....*....|....*....
gi 1039772833 244 LRLHSVVLVFSTRGISRSVAAVVALLMHY 272
Cdd:cd14522    86 LQTGGKVLVHGNAGISRSAALVIAYIMET 114

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 1039772833 165 QPYPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHL 244
Cdd:cd14641     1 QGGPVEILP-FLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQF-QYKSIPVEDSHMADISAWFQEAIDFIDSVK 78

                          90       100
                  ....*....|....*....|....*..
gi 1039772833 245 RLHSVVLVFSTRGISRSVAAVVALLMH 271
Cdd:cd14641    79 NSGGRVLVHCQAGISRSATICLAYLIQ 105

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772833 170 EILPGrVYLGKISQACNAKMHKDLKIKAHVNISM-------ETTPYFI-GNADKLLHIKLEDSPDTLLFDYFRHICHFIE 241
Cdd:cd14515     3 EVWPG-IYIGDESTAKNKAKLKKLGITHVLNAAEgkkngevNTNAKFYkGSGIIYLGIPASDLPTFDISQYFDEAADFID 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039772833 242 LHLRL-HSVVLVFSTRGISRSVAAVVALLM-HYN 273
Cdd:cd14515    82 KALSDpGGKVLVHCVEGVSRSATLVLAYLMiYQN 115

dual specificity phosphatase-like domain of inactive dual specificity protein phosphatase 27; Inactive dual specificity protein phosphatase 27 (DUSP27) may play a role in myofiber maturation. It is a pseudophosphatase containing a substitution of the active site cysteine into a serine. It is a large protein of more than 1000 amino acids in length with an N-terminal dual specificity phosphatase-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772833 170 EILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPY-----FIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHL 244
Cdd:cd14576    13 EVWPN-VFIAEKSVAVNKGRLKRLGITHVLNAAHGTGVYtgpefYSGMNIQYMGIEVDDFPDVDISKHFRKGAEFLDEAL 91

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039772833 245 RLH-SVVLVFSTRGISRSVAAVVALLMHYNEETL 277
Cdd:cd14576    92 LTYrGKVLVSSEMGISRSAVLVAAYLMIFHNMTI 125

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 1039772833 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 247
Cdd:cd14638     1 PVEILP-FLYLGSAYHASRKDMLDTLGITALINVSANCPNHFEGHY-QYKSIPVEDNHKADISSWFNEAIDFIDSVKNAG 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772833 248 SVVLVFSTRGISRSVAAVVALLMHYNEETLK 278
Cdd:cd14638    79 GRVFVHCQAGISRSATICLAYLMRTNRVKLD 109

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 1039772833 176 VYLGKISQACNAKMHKDLKIKAHVNISMETtPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:cd14574     8 LFISNARAACNEELLAREGVTLCVNVSRQQ-PFPRAPRVSTLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGKCLVYCK 86

                          90       100
                  ....*....|....*....|...
gi 1039772833 256 RGISRSVAAVVALLMHYNEETLK 278
Cdd:cd14574    87 NGRSRSAAVCIAYLMKHRGLSLQ 109

dual specificity phosphatase domain of slingshot homolog 1; Dual specificity protein phosphatase slingshot homolog 1 (SSH1), also called SSH-like protein 1, is part of the slingshot (SSH) family, whose members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. SSH1 links NOD1 signaling to actin remodeling, facilitating the changes that leads to NF-kappaB activation and innate immune responses. There are at least two human SSH1 isoforms reported: hSSH-1L (long) and hSSH-1S (short). As SSH family phosphatases, they contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. They also contain C-terminal tails, differing in the lengths of the tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772833 176 VYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:cd14570    11 LYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGLF-AYHNIRVYDEETTDLLAHWNDAYHFINKAKKNHSKCLVHCK 89

                          90       100
                  ....*....|....*....|...
gi 1039772833 256 RGISRSVAAVVALLMHYNEETLK 278
Cdd:cd14570    90 MGVSRSASTVIAYAMKEFGWSLE 112

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 1039772833 170 EILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNadKLLHIKLEDSPDTLLFDYFRHICHFI-ELHLRLHS 248
Cdd:cd14581     6 KVLPG-LYLGNFKDARDREQLSKNNITHILSVHDSARPMLEGM--TYLCIPAADSPSQNLTQHFKESIKFIhECRLRGEG 82

                          90       100
                  ....*....|....*....|..
gi 1039772833 249 VvLVFSTRGISRSVAAVVALLM 270
Cdd:cd14581    83 C-LVHCLAGVSRSVTLVVAYIM 103

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 1039772833 168 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGN-ADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 246
Cdd:cd14567     1 LTPILP-FLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKgGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQS 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772833 247 HSVVLVFSTRGISRSVAAVVALLMHYNEETL 277
Cdd:cd14567    80 GKGVLVHCQAGVSRSATIVIAYLMKHTRMTM 110

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 1039772833 176 VYLGKISQACNAKMHKDLKIKAHVNISMETtPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 255
Cdd:cd14572    15 LYLSRGNVASNRHLLLSRGITCIVNATIEI-PNFNWPQFEYVKVPLADMPHAPISLYFDSVADKIHSVGRKHGATLVHCA 93

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039772833 256 RGISRSVAAVVALLMHYNEETL-------KSRVP 282
Cdd:cd14572    94 AGVSRSATLCIAYLMKYHRVSLleaynwvKARRP 127