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 4758206  170 QGGPVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNS 249
Cdd:cd14641   1 QGGPVEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4758206  250 GGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVLC 313
Cdd:cd14641  81 GGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVLC 144

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 4758206  170 QGGPVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNS 249
Cdd:cd14641   1 QGGPVEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4758206  250 GGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVLC 313
Cdd:cd14641  81 GGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVLC 144

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206     173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGR 252
Cdd:smart00195   1 PSEILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGK 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 4758206     253 VLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQ 310
Cdd:smart00195  81 VLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206  175 EILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGL----FRYKSIPVEDNQMVEISAWfQEAIGFIDWVKNSG 250
Cdd:COG2453   2 WIIPGLLAGGPLPGGGEADLKREGIDAVVSLTEEEELLLGLLeeagLEYLHLPIPDFGAPDDEQL-QEAVDFIDEALREG 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQsRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQV 311
Cdd:COG2453  81 KKVLVHCRGGIGRTGTVAAAYLVL-LGLSAEEALARVRAARPGAVETPAQRAFLERFAKRL 140

Rhodanese Homology Domain; An alpha beta fold found duplicated in the Rhodanese protein. The the Cysteine containing enzymatically active version of the domain is also found in the CDC25 class of protein phosphatases and a variety of proteins such as sulfide dehydrogenases and stress proteins such as Senesence specific protein 1 in plants, PspE and GlpE in bacteria and cyanide and arsenate resistance proteins. Inactive versions with a loss of the cysteine are also seen in Dual specificity phosphatases, ubiquitin hydrolases from yeast and in sulfuryltransferases. These are likely to play a role in protein interactions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206      23 EAERTLLLDCRPFLAFCRRHVRAARPVPWNALLRRRARGPPaavlaclLPDRALRTRLVRGELARAVVLDEGSASVAElr 102
Cdd:smart00450   1 NDEKVVLLDVRSPEEYEGGHIPGAVNIPLSELLDRRGELDI-------LEFEELLKRLGLDKDKPVVVYCRSGNRSAK-- 71

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 4758206     103 pdspahvlLAALLHEtrAGPTAVYFLRGGFDGFQGCCPD 141
Cdd:smart00450  72 --------AAWLLRE--LGFKNVYLLDGGYKEWSAAGPP 100

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 4758206  170 QGGPVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNS 249
Cdd:cd14641   1 QGGPVEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4758206  250 GGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVLC 313
Cdd:cd14641  81 GGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVLC 144

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPN-HFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGG 251
Cdd:cd14512   1 PTRILPNLYLGSQRDSLNLELMQQLGIGYVLNVSNTCPNpDFIGLFHYKRIPVNDSFCQNISPWFDEAIEFIEEAKASNG 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4758206  252 RVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQF 307
Cdd:cd14512  81 GVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRPTISPNFNFMGQLLDF 136

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGR 252
Cdd:cd14638   1 PVEILPFLYLGSAYHASRKDMLDTLGITALINVSANCPNHFEGHYQYKSIPVEDNHKADISSWFNEAIDFIDSVKNAGGR 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206  253 VLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVL 312
Cdd:cd14638  81 VFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFESQVL 140

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFE--GLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSG 250
Cdd:cd14566   1 PVEILPFLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEedGGFKYLQIPIDDHWSQNLSAFFPEAISFIDEARSKK 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQF 307
Cdd:cd14566  81 CGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLDF 137

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 4758206    180 LFLGSCSHSSDLQgLQACGITAVLNVSASCPNHFEGlFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGRVLVHCQA 259
Cdd:pfam00782   1 LYLGSKPTASDAF-LSKLGITAVINVTREVDLYNSG-ILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQA 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 4758206    260 GISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 308
Cdd:pfam00782  79 GISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPN-HFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGG 251
Cdd:cd14568   1 PTRILPHLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKpDFIPDSHFLRIPVNDSYCEKLLPWLDKAVEFIEKARASNK 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4758206  252 RVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 308
Cdd:cd14568  81 RVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFE 137

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFE--GLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSG 250
Cdd:cd14643   6 PVQILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEhdGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKK 85

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 308
Cdd:cd14643  86 CGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFE 143

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFE--GLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSG 250
Cdd:cd14644   3 PVQILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEknGDFHYKQIPISDHWSQNLSQFFPEAIEFIDEALSQN 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 308
Cdd:cd14644  83 CGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFE 140

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFE--GLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSG 250
Cdd:cd14642   3 PVEILPYLYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFEnaGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARGKN 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 308
Cdd:cd14642  83 CGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 140

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 4758206  175 EILPYLFLGSCSHSSDLqGLQACGITAVLNVSASCPN-HFEGLfRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGRV 253
Cdd:cd14514   3 QITPHLFLSGASAATPP-LLLSRGITCIINATTELPDpSYPGI-EYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGRT 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 4758206  254 LVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQ 306
Cdd:cd14514  81 LVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

dual specificity phosphatase domain of dual specificity protein phosphatase 16; Dual specificity protein phosphatase 16 (DUSP16), also called mitogen-activated protein kinase (MAPK) phosphatase 7 (MKP-7), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP16/MKP-7 plays an essential role in perinatal survival and selectively controls the differentiation and cytokine production of myeloid cells. It is acetylated by Mycobacterium tuberculosis Eis protein, which leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation, and thus, initiating suppression of host immune responses. DUSP16/MKP-7 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206  172 GPVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPN-HFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSG 250
Cdd:cd14646   2 GPTRILPHLYLGCQRDVLNKELMQQNGIGYVLNASNTCPKpDFIPESHFLRVPVNDSFCEKILPWLDKSVDFIEKAKASN 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQV 311
Cdd:cd14646  82 GRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKI 142

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 4758206  175 EILPYLFLG--SCSHSSDLQGLQACGITAVLNVSASC------PNhFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWV 246
Cdd:cd14522   7 EILPGLYLGpySAAMKSKLEVLLKHGITHIVCVRQNIeanfikPN-FPDHFRYLVLDVADNPTENIIRHFPTVKEFIDDC 85

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4758206  247 KNSGGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFET 309
Cdd:cd14522  86 LQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYEA 148

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGR 252
Cdd:cd14570   4 ASLIFDHLYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNDAYHFINKAKKNHSK 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4758206  253 VLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 308
Cdd:cd14570  84 CLVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYE 139

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 4758206  173 PVEILP-YLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEdnQMVEisawFQEAIGFIDWVKNSGG 251
Cdd:cd18534   1 PTEILPgFLYLGSYDNASRAELLKAQGITRILNTVPDCQNLYKNSFTYHVLSEE--KTVP----FAEAVDFIEQCRKDKA 74

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 4758206  252 RVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQF 307
Cdd:cd18534  75 RVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSPAVAKQLQEF 130

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 4758206  173 PVEILP-YLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHF-EGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSG 250
Cdd:cd14517  11 PVEILPgFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFkSGNDQVLHIPVEDSVEADLLSFFERACSFIDKHKNNG 90

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4758206  251 GRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVL 312
Cdd:cd14517  91 SRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLL 152

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLFRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGR 252
Cdd:cd14571   4 PSRIFPYLYLGSEWNAANLEELQRNRVSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTR 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 4758206  253 VLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQL 304
Cdd:cd14571  84 VLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQL 135

dual specificity protein phosphatase 26; Dual specificity protein phosphatase 26 (DUSP26), also called mitogen-activated protein kinase (MAPK) phosphatase 8 (MKP-8) or low-molecular-mass dual-specificity phosphatase 4 (LDP-4), 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. DUSP26 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It is a brain phosphatase highly overexpressed in neuroblastoma and has also been identified as a p53 phosphatase, dephosphorylating phospho-Ser20 and phospho-Ser37 in the p53 transactivation domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206  175 EILPYLFLGSCSHSSDLQGLQACGITAVLNVSAS----CPNHFEGL-FRYKSIPVEDNQMVEISAWFQEAIGFI-DWVKN 248
Cdd:cd14578   3 EVWPGLYLGDQDIAANRRELRRLGITHILNASHSkwrgGAEYYEGLnIRYLGIEAHDSPAFDMSIHFYPAADFIhRALSQ 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 4758206  249 SGGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVIsPNFSFMGQLL 305
Cdd:cd14578  83 PGGKILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDHRGII-PNRGFLRQLL 138

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 4758206  173 PVEILPYLFLGSCSHSSDLQGLQACGITAVLNV--SASCPNHFEGLFR-----------------------YKSI----- 222
Cdd:cd14516   7 PSRILPHLYLGSLNHASNATLLESLGITHIVSVgeSPSWFSNLKIKYIfdfslqdlsnldsnsegslwaaeYKGLisvly 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758206  223 --PVEDNQMVEISAWFQEAIGFIDWVKNSGGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRR--GVISPNF 298
Cdd:cd14516  87 ihNLKDDGIDSLLPQLTDALDFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRRlnIIIQPNL 166

                       170
                ....*....|.
gi 4758206  299 SFMGQLLQFET 309
Cdd:cd14516 167 RFFYELFKWEE 177

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 4758206  175 EILPYLFLGSCSHSSDLQGLQACGITAVLNVSA--------SCPNHFEGL-FRYKSIPVEDNQMVEISAWFQEAIGFID- 244
Cdd:cd14579  23 EVYPRIYVGNASVAQNIMRLQRLGITHVLNAAEgksfmhvnTNAEFYEDTgITYHGIKANDTQHFNLSAYFEEAADFIDk 102

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4758206  245 WVKNSGGRVLVHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGvISPNFSFMGQLLQF 307
Cdd:cd14579 103 ALAQKNGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKRE-IGPNDGFLKQLCQL 164

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 4758206  175 EILPYLFLGSCSHSSDLQGLQACGITAVLNVSASCPNHFEGLfRYKSIPVEDNQMVEISAWFQEAIGFIDWVKNSGGRVL 254
Cdd:cd14581   6 KVLPGLYLGNFKDARDREQLSKNNITHILSVHDSARPMLEGM-TYLCIPAADSPSQNLTQHFKESIKFIHECRLRGEGCL 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 4758206  255 VHCQAGISRSATICLAYLMQSRRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFET 309
Cdd:cd14581  85 VHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFEK 139