Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1001184416    5 VLPGLYLGNFIDAKDLDQLGRNKITHIIS-IHESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:smart00195   4 ILPHLYLGSYSDALNLALLKKLGITHVINvTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKVLV 83

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416   84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:smart00195  84 HCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEY 135

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQ-----DITYLRIPVADTpEVPIKKHFKECINFIHCCRLNGG 79
Cdd:COG2453     3 IIPGLLAGGPLPGGGEADLKREGIDAVVSLTEEEELLLGlleeaGLEYLHLPIPDF-GAPDDEQLQEAVDFIDEALREGK 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1001184416  80 NCLVHCFAGISRSTTIVTAYVMtVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:COG2453    82 KVLVHCRGGIGRTGTVAAAYLV-LLGLSAEEALARVRAARPGAVETPAQRAFLERF 136

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLVH 84
Cdd:cd14519     4 ILPGLYVGNFRDAKDAEQLRENGITHILSIHDSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIHEARLNGGNVLVH 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1001184416  85 CFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEFGW 137
Cdd:cd14519    84 CLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 136

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 1001184416   1 MTEgVLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQ--DITYLRIPVADTPEVPIKKHFKECINFIHCCRLNG 78
Cdd:cd14498     1 PSE-ILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFpdGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKG 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1001184416  79 GNCLVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEE 134
Cdd:cd14498    80 GKVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQ-PLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14523     5 IKPWLLLSSQDVAHDLETLKKHKVTHILNVAYGVEnAFPDDFTYKTISILDLPETDITSYFPECFEFIDEAKSQDGVVLV 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14523    85 HCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEY 136

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 1001184416   9 LYLGNFIDAKDLdQLGRNKITHIISIHESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLVHCFAG 88
Cdd:pfam00782   1 LYLGSKPTASDA-FLSKLGITAVINVTREVDLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAG 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1001184416  89 ISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEFG 136
Cdd:pfam00782  80 ISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISI-HESPQPLLQDITYLR--IPVADTPEVPIKKHFKECINFIHCCRlNGGNC 81
Cdd:cd14520     4 VRPGLYIGNADDAADYLSLREAGITHVLTVdSEEPIDAPPVGKLVRkfVPALDEESTDLLSRLDECLDFIDEGR-AEGAV 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1001184416  82 LVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14520    83 LVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLY 136

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQD---ITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNC 81
Cdd:cd14567     4 ILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGkggFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSGKGV 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1001184416  82 LVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEFgwasSQKLRRQLEER 150
Cdd:cd14567    84 LVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEF----EEDLNNGVTPR 148

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHES-PQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14565     4 ILPFLYLGSAYHASRREVLKALGITAVLNVSRNcPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRVLV 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14565    84 HCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQY 135

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHII-------SIHESPQP---LLQDITYLRIPVADTPEVPIKKHFKECINFIH-C 73
Cdd:cd14515     4 VWPGIYIGDESTAKNKAKLKKLGITHVLnaaegkkNGEVNTNAkfyKGSGIIYLGIPASDLPTFDISQYFDEAADFIDkA 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1001184416  74 CRLNGGNCLVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIAnPNPGFRQQL 132
Cdd:cd14515    84 LSDPGGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRKKREIR-PNRGFLQQL 141

dual specificity protein phosphatases 18 and 21; This subfamily contains dual specificity protein phosphatase 18 (DUSP18), dual specificity protein phosphatase 21 (DUSP21), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP18, also called low molecular weight dual specificity phosphatase 20 (LMW-DSP20), is a catalytically active phosphatase with a preference for phosphotyrosine over phosphoserine/threonine oligopeptides in vitro. In vivo, it has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP21 is also called low molecular weight dual specificity phosphatase 21 (LMW-DSP21). Its gene has been identified as a potential therapeutic target in human hepatocellular carcinoma. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIH-ESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14573     5 ITESLYLSNGVAANNRTLLAANRITCVINVSlEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGGRTLL 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQL 132
Cdd:cd14573    85 HCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQL 133

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISI-HESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14639     4 ILPFLYLGSAYHASKCEFLANLHITALLNVsRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCVRRAGGKVLV 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14639    84 HCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQY 135

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISI-HESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14571     7 IFPYLYLGSEWNAANLEELQRNRVSHILNVtREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTRVLV 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14571    87 HCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTY 138

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHES-PQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14641     7 ILPFLFLGSAHHSSRRETLESLGITAVLNVSSScPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNSGGRVLV 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14641    87 HCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQF 138

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQ---DITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNC 81
Cdd:cd14643     9 ILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEhdgEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCGI 88

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1001184416  82 LVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14643    89 LVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDF 142

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHES-PQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14638     4 ILPFLYLGSAYHASRKDMLDTLGITALINVSANcPNHFEGHYQYKSIPVEDNHKADISSWFNEAIDFIDSVKNAGGRVFV 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14638    84 HCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQF 135

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIH-ESPQPLLQDITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLV 83
Cdd:cd14572    11 ITPSLYLSRGNVASNRHLLLSRGITCIVNATiEIPNFNWPQFEYVKVPLADMPHAPISLYFDSVADKIHSVGRKHGATLV 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1001184416  84 HCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14572    91 HCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDY 142

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1001184416   4 GVLPG-LYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQD-ITYLriPVADTPEVPikkhFKECINFIHCCRLNGGNC 81
Cdd:cd18534     3 EILPGfLYLGSYDNASRAELLKAQGITRILNTVPDCQNLYKNsFTYH--VLSEEKTVP----FAEAVDFIEQCRKDKARV 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1001184416  82 LVHCFAGISRSTTIVTAYVMTVTglGWR--DVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd18534    77 LVHCMSGQSRSPAVVIAYLMKHK--GWRlaESYQWVKERRPSINLSPAVAKQLQEF 130

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 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQ---DITYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNC 81
Cdd:cd14644     6 ILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEkngDFHYKQIPISDHWSQNLSQFFPEAIEFIDEALSQNCGV 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1001184416  82 LVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14644    86 LVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDF 139

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 1001184416   9 LYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQDI-TYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLVHCFA 87
Cdd:cd14570    11 LYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGLfAYHNIRVYDEETTDLLAHWNDAYHFINKAKKNHSKCLVHCKM 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1001184416  88 GISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14570    91 GVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEY 138

dual specificity phosphatase domain of dual specificity protein phosphatase 6; Dual specificity protein phosphatase 6 (DUSP6), also called mitogen-activated protein kinase (MAPK) phosphatase 3 (MKP-3) or dual specificity protein phosphatase PYST1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP6/MKP-3 plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output. MKP-3 deficiency attenuates body weight gain induced by a high-fat diet, protects mice from developing obesity-related hepatosteatosis, and reduces adiposity, possibly by repressing adipocyte differentiation. It also contributes to p53-controlled cellular senescence. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1001184416   5 VLPGLYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQ---DITYLRIPVADTPEVPIKKHFKECINFIHCCRlnGGNC 81
Cdd:cd14642     6 ILPYLYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFEnagEFKYKQIPISDHWSQNLSQFFPEAISFIDEAR--GKNC 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1001184416  82 --LVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14642    84 gvLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDF 139

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 1001184416   5 VLPG-LYLGNFIDA------KDLdqlgrnKITHIISIHESPQPLLQ--DITYLRIPVADTPEVPIKKHFKECINFIHCCR 75
Cdd:cd14517    14 ILPGfLYMGNYKQAcdkkiqKDL------KIKAHINVSMDADELFKsgNDQVLHIPVEDSVEADLLSFFERACSFIDKHK 87

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1001184416  76 LNGGNCLVHCFAGISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14517    88 NNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEW 147

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 1001184416   9 LYLGNFIDAKDLDQLGRNKITHIISIHESPQPLLQDI-TYLRIPVADTPEVPIKKHFKECINFIHCCRLNGGNCLVHCFA 87
Cdd:cd14569    11 VFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLfEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCKM 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1001184416  88 GISRSTTIVTAYVMTVTGLGWRDVLEAIKATRPIANPNPGFRQQLEEF 135
Cdd:cd14569    91 GVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEY 138