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 1622878277  305 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 384
Cdd:cd14569      1 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622878277  385 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 448
Cdd:cd14569     81 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 144

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 1622878277  305 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 384
Cdd:cd14569      1 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622878277  385 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 448
Cdd:cd14569     81 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 144

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 1622878277  315 VFLGSEWNASNLEdLQNRGVRYILNVTREIDNFFPGvFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCKM 394
Cdd:pfam00782    1 LYLGSKPTASDAF-LSKLGITAVINVTREVDLYNSG-ILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQA 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1622878277  395 GVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:pfam00782   79 GISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

DEK C terminal domain; DEK is a chromatin associated protein that is linked with cancers and autoimmune disease. This domain is found at the C terminal of DEK and is of clinical importance since it can reverse the characteriztic abnormal DNA-mutagen sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients. The structure of this domain shows it to be homologous to the E2F/DP transcription factor family. This domain is also found in chitin synthase proteins like Swiss:Q8TF96, and in protein phosphatases such as Swiss:Q6NN85.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622878277  250 TERLIKTKLREIMMQKDLENITSKEIRTELEMQMVCNLREFKEFIDNEMIVIL 302
Cdd:pfam08766    2 TDEEIREAIREILRTADLETVTKKQVRKQLEERLGVDLSERKAFINALIDEIL 54

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 1622878277  305 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 384
Cdd:cd14569      1 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622878277  385 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 448
Cdd:cd14569     81 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 144

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 1622878277  305 MDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKH 384
Cdd:cd14570      1 MDKASLIFDHLYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNDAYHFINKAKKN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622878277  385 GSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 448
Cdd:cd14570     81 HSKCLVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYEGILDA 144

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 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNF-FPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGS 386
Cdd:cd14498      1 PSEILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNkFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKGG 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622878277  387 KCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEE 441
Cdd:cd14498     81 KVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

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 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSK 387
Cdd:cd14565      1 PVEILPFLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGR 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622878277  388 CLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14565     81 VLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYE 136

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 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNF-FPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGS 386
Cdd:cd14512      1 PTRILPNLYLGSQRDSLNLELMQQLGIGYVLNVSNTCPNPdFIGLFHYKRIPVNDSFCQNISPWFDEAIEFIEEAKASNG 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622878277  387 KCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEY 442
Cdd:cd14512     81 GVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRPTISPNFNFMGQLLDF 136

dual specificity phosphatase domain of dual specificity protein phosphatase 19; Dual specificity protein phosphatase 19 (DUSP19), also called low molecular weight dual specificity phosphatase 3 (LMW-DSP3) or stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP19 interacts with the MAPK kinase MKK7, a JNK activator, and inactivates the JNK MAPK pathway.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  310 QIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCL 389
Cdd:cd14523      4 VIKPWLLLSSQDVAHDLETLKKHKVTHILNVAYGVENAFPDDFTYKTISILDLPETDITSYFPECFEFIDEAKSQDGVVL 83

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622878277  390 VHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14523     84 VHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEYQ 137

dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins; This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  308 PTQIFEHVFLGSEwNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSK 387
Cdd:cd14514      1 ISQITPHLFLSGA-SAATPPLLLSRGITCIINATTELPDPSYPGIEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGR 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622878277  388 CLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEE 441
Cdd:cd14514     80 TLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSK 387
Cdd:cd14641      4 PVEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNSGGR 83

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622878277  388 CLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14641     84 VLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 139

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 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFP--GVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHG 385
Cdd:cd14644      3 PVQILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEknGDFHYKQIPISDHWSQNLSQFFPEAIEFIDEALSQN 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622878277  386 SKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14644     83 CGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFE 140

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 1622878277  310 QIFEHVFLGSEWNASNLEDLQNRGVRYILNVTRE--IDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSk 387
Cdd:cd14520      3 LVRPGLYIGNADDAADYLSLREAGITHVLTVDSEepIDAPPVGKLVRKFVPALDEESTDLLSRLDECLDFIDEGRAEGA- 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622878277  388 CLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14520     82 VLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLYE 137

dual specificity phosphatase domain of plant IBR5-like protein phosphatases; This subfamily is composed of Arabidopsis thaliana INDOLE-3-BUTYRIC ACID (IBA) RESPONSE 5 (IBR5) and similar plant proteins. IBR5 protein is also called SKP1-interacting partner 33. The IBR5 gene encodes a dual-specificity phosphatase (DUSP) which acts as a positive regulator of plant responses to auxin and abscisic acid. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. IBR5 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs. It has been shown to target MPK12, which is a negative regulator of auxin signaling.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  308 PTQIF-EHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHnirVYDEEATdllAYWNDTYKFISKAKKHGS 386
Cdd:cd18534      1 PTEILpGFLYLGSYDNASRAELLKAQGITRILNTVPDCQNLYKNSFTYH---VLSEEKT---VPFAEAVDFIEQCRKDKA 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622878277  387 KCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEY 442
Cdd:cd18534     75 RVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSPAVAKQLQEF 130

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 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFP--GVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHG 385
Cdd:cd14643      6 PVQILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEhdGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKK 85

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622878277  386 SKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGIL 446
Cdd:cd14643     86 CGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

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 1622878277  303 GQMDSPTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFI-SKA 381
Cdd:cd14572      3 GDLGGIAQITPSLYLSRGNVASNRHLLLSRGITCIVNATIEIPNFNWPQFEYVKVPLADMPHAPISLYFDSVADKIhSVG 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622878277  382 KKHGSkCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14572     83 RKHGA-TLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYE 143

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 1622878277  311 IFEHVFLGSEWNASNLEDLQNRGVRYILNVTREidNFFPGVFEYHNIR--VYDEEATDLLAYWNDTYKFISKAKKHGSKC 388
Cdd:cd14574      4 VTDSLFISNARAACNEELLAREGVTLCVNVSRQ--QPFPRAPRVSTLRvpVFDDPAEDLYRHFEQCADAIEAAVRRGGKC 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622878277  389 LVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14574     82 LVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYE 136

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  306 DSPTQIFE-HVFLGSEwnaSNLEDLQNRGVryILNVTREIDNFFP------------------GVFEYHNIRvyDEEATD 366
Cdd:cd14521      3 DGPVCVLPpNIYLYSE---PTLEEASSFDV--VINVAKEVKNPFLsdaslaekektilpgqqvKNPEYIHVP--WDHNSQ 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  367 LLAYWNDTYKFISKAKKHGSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGIL 446
Cdd:cd14521     76 IQKDLPKLTSIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLIFQLMEFEKVL 155

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 1622878277  309 TQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKC 388
Cdd:cd14573      3 SRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGGRT 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622878277  389 LVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 443
Cdd:cd14573     83 LLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYE 137

dual specificity phosphatase domain of fungal dual specificity protein phosphatase PPS1-like; This subfamily contains fungal proteins with similarity to dual specificity protein phosphatase PPS1 from Saccharomyces cerevisiae, which has a role in the DNA synthesis phase of the cell cycle. As a dual specificity protein phosphatase, PPS1 functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It contains a C-terminal catalytic dual specificity phosphatase domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  308 PTQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTrEIDNFFPGVF--EYHNIRVYDEEATDLL---AYWNDTYK------ 376
Cdd:cd14516      7 PSRILPHLYLGSLNHASNATLLESLGITHIVSVG-ESPSWFSNLKikYIFDFSLQDLSNLDSNsegSLWAAEYKglisvl 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622878277  377 ----------------------FISKAKKHGSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERR--TVTKPN 432
Cdd:cd14516     86 yihnlkddgidsllpqltdaldFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRRlnIIIQPN 165

                          170
                   ....*....|
gi 1622878277  433 PSFMRQLEEY 442
Cdd:cd14516    166 LRFFYELFKW 175

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 1622878277  303 GQMDSPTQ----IFEHVFLGSEWNASNLEDLQNRGVRYILNVTREID--------NFFPGV-FEYHNIRVYDEEATDLLA 369
Cdd:cd14579     12 GCYSLPSQhcneVYPRIYVGNASVAQNIMRLQRLGITHVLNAAEGKSfmhvntnaEFYEDTgITYHGIKANDTQHFNLSA 91

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622878277  370 YWNDTYKFISKA-KKHGSKCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVtKPNPSFMRQL 439
Cdd:cd14579     92 YFEEAADFIDKAlAQKNGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKREI-GPNDGFLKQL 161

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 1622878277  309 TQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGVfEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKC 388
Cdd:cd14519      2 NKILPGLYVGNFRDAKDAEQLRENGITHILSIHDSARPLLEDI-KYLCIPAADTPEQNISQHFRECINFIHEARLNGGNV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622878277  389 LVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQG 444
Cdd:cd14519     81 LVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 136