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 6005812  322 LTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCG 401
Cdd:cd14567   1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKGGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6005812  402 KGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTP 473
Cdd:cd14567  81 KGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTP 152

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 6005812  322 LTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCG 401
Cdd:cd14567   1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKGGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6005812  402 KGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTP 473
Cdd:cd14567  81 KGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTP 152

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812     325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHyeKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGL 404
Cdd:smart00195   4 ILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYN--GSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKV 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 6005812     405 LIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEED 461
Cdd:smart00195  82 LVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  328 FLFLGNEQDAQDLDtMQRLNIGYVINVTTHLPLY--HYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQcGKGLL 405
Cdd:COG2453   7 LLAGGPLPGGGEAD-LKREGIDAVVSLTEEEELLlgLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDFIDEALRE-GKKVL 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6005812  406 IHCQAGVSRSATIVIAYLMKHTrMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:COG2453  85 VHCRGGIGRTGTVAAAYLVLLG-LSAEEALARVRAARPGAVETPAQRAFLERFAKRL 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 6005812     170 QGPVIIDCRPFMEYNKSHIQGAVHINCADKISRRRLQQGKITVLDLISCREGKDsfkrifsKEIIVYDENTNEpsrvmps 249
Cdd:smart00450   3 EKVVLLDVRSPEEYEGGHIPGAVNIPLSELLDRRGELDILEFEELLKRLGLDKD-------KPVVVYCRSGNR------- 68

                           90       100       110
                   ....*....|....*....|....*....|..
gi 6005812     250 qpLHIVLESLKREG-KEPLVLKGGLSSFKQNH 280
Cdd:smart00450  69 --SAKAAWLLRELGfKNVYLLDGGYKEWSAAG 98

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812   325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTH---LPLYHYEKGlFNYKRLPATDSNKQNLRQyfeeafefieeAHQ-- 399
Cdd:PRK12361  98 IDENLYLGCRLFPADLEKLKSNKITAILDVTAEfdgLDWSLTEED-IDYLNIPILDHSVPTLAQ-----------LNQai 165

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 6005812   400 --------CGKGLLIHCQAGVSRSATIVIAYLM-KHTRMTMTDAYKFVKGKRPIISPN 448
Cdd:PRK12361 166 nwihrqvrANKSVVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRKTARLN 223

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 6005812  322 LTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCG 401
Cdd:cd14567   1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKGGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6005812  402 KGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTP 473
Cdd:cd14567  81 KGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTP 152

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 6005812  322 LTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEkGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCG 401
Cdd:cd14568   1 PTRILPHLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKPDFI-PDSHFLRIPVNDSYCEKLLPWLDKAVEFIEKARASN 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6005812  402 KGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:cd14568  80 KRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFEKKL 140

N-terminal regulatory rhodanese domain of dual specificity phosphatases (DSP), such as Mapk Phosphatase. This domain is believed to determine substrate specificity by binding the substrate, such as ERK2, and activating the C-terminal catalytic domain by inducing a conformational change. This domain has homology to the Rhodanese Homology Domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  149 IIYPNDLAKKMTKCSKshlpsqGPVIIDCRPFMEYNKSHIQGAVHINCAdKISRRRLQQGKITVLDLISCREGKDSFKRI 228
Cdd:cd01446   1 TIDCAWLAALLREGGE------RLLLLDCRPFLEYSSSHIRGAVNVCCP-TILRRRLQGGKILLQQLLSCPEDRDRLRRG 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6005812  229 FSKEIIVYDENTNEPSRVMPSQPLHIVLESLKR---EGKEPLVLKGGLSSFKQNHENLC 284
Cdd:cd01446  74 ESLAVVVYDESSSDRERLREDSTAESVLGKLLRklqEGCSVYLLKGGFEQFSSEFPELC 132

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYekGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGL 404
Cdd:cd14565   4 ILPFLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFE--DHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRV 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 6005812  405 LIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEE 460
Cdd:cd14565  82 LVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYES 137

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKGLFNYKRLPATDSNKQNLRQYFEEAFE--FIEEAHQCGk 402
Cdd:cd14644   6 ILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEKNGDFHYKQIPISDHWSQNLSQFFPEAIEfiDEALSQNCG- 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  403 gLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:cd14644  85 -VLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSL 143

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGL 404
Cdd:cd14643   9 ILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCGI 88

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6005812  405 LIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:cd14643  89 LVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPlyHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGL 404
Cdd:cd14641   7 ILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCP--NYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNSGGRV 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6005812  405 LIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:cd14641  85 LVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQV 142

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), 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. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPlYHYEkGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGL 404
Cdd:cd14640   4 ILPFLYLGSAYHAARRDMLDALGITALLNVSSDCP-NHFE-GHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRV 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6005812  405 LIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFE 459
Cdd:cd14640  82 LVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 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 6005812  322 LTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVtthlplYHYEKGLF---NYKRLPATDSNKQNLRQYFEEAFEFIeeaH 398
Cdd:cd14519   1 MNKILPGLYVGNFRDAKDAEQLRENGITHILSI------HDSARPLLediKYLCIPAADTPEQNISQHFRECINFI---H 71

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6005812  399 QC---GKGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEE 460
Cdd:cd14519  72 EArlnGGNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 136

dual specificity phosphatase domain of slingshot family phosphatases; The slingshot (SSH) family of dual specificity protein phosphatases is composed of Drosophila slingshot phosphatase and its vertebrate homologs: SSH1, SSH2 and SSH3. Its members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. In Drosophila, loss of ssh gene function causes prominent elevation in the levels of P-cofilin and filamentous actin and disorganized epidermal cell morphogenesis, including bifurcation phenotypes of bristles and wing hairs. SSH family phosphatases 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, many members contain a C-terminal tail. The SSH-N domain plays critical roles in P-cofilin recognition, F-actin-mediated activation, and subcellular localization of SSHs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  323 TPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPlyHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGK 402
Cdd:cd14513   2 SKIFDHLYLGSEWNASNLEELQNNGVKYILNVTREID--NFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGS 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6005812  403 GLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFE 459
Cdd:cd14513  80 KVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  312 PTTPdIENAELTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKGlFNYKRLPATDSNKQNLRQYFEEAF 391
Cdd:cd14645   3 PCLP-VANVGPTRILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKPDFICE-SHFMRIPVNDNYCEKLLPWLDKSI 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6005812  392 EFIEEAHQCGKGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:cd14645  81 EFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 6005812  327 PFLFLGNEQDAQDLDTMQRLNIGYVINV--------TTHLPLYHYEKGLfNYKRLPATDSNKQNLRQYFEEAFEFIeeaH 398
Cdd:cd14515   6 PGIYIGDESTAKNKAKLKKLGITHVLNAaegkkngeVNTNAKFYKGSGI-IYLGIPASDLPTFDISQYFDEAADFI---D 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6005812  399 QC-----GKgLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIIsPNLNFMGQLLEFEEDL 462
Cdd:cd14515  82 KAlsdpgGK-VLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRKKREIR-PNRGFLQQLCELNDKL 148

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINV-TTHLPLYHYEKglfnYKRLPATDSNKQNLRQYFEEAFEFIeeaHQC--- 400
Cdd:cd14581   7 VLPGLYLGNFKDARDREQLSKNNITHILSVhDSARPMLEGMT----YLCIPAADSPSQNLTQHFKESIKFI---HECrlr 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6005812  401 GKGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFE 459
Cdd:cd14581  80 GEGCLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFE 138

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEkgLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGL 404
Cdd:cd14571   7 IFPYLYLGSEWNAANLEELQRNRVSHILNVTREIDNFFPE--RFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTRV 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 6005812  405 LIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDLN 463
Cdd:cd14571  85 LVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQGILT 143

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPLYHYEKglFNYKRLPATDSNKQNLRQYFEEAFEFIeeaHQCGK-- 402
Cdd:cd14572  11 ITPSLYLSRGNVASNRHLLLSRGITCIVNATIEIPNFNWPQ--FEYVKVPLADMPHAPISLYFDSVADKI---HSVGRkh 85

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6005812  403 -GLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDL 462
Cdd:cd14572  86 gATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYERKL 146

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 6005812  323 TPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPlyHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGK 402
Cdd:cd14569   5 TQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREID--NFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGS 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 6005812  403 GLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFE 459
Cdd:cd14569  83 KCLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQ 139

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 6005812  325 ILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHL----PLYHYEKGLFNYKRLPATDSNKQN------------------ 382
Cdd:cd14516  10 ILPHLYLGSLNHASNATLLESLGITHIVSVGESPswfsNLKIKYIFDFSLQDLSNLDSNSEGslwaaeykglisvlyihn 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  383 --------LRQYFEEAFEFIEEAHQCGKGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKR--PIISPNLNFM 452
Cdd:cd14516  90 lkddgidsLLPQLTDALDFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRRlnIIIQPNLRFF 169

                ....*...
gi 6005812  453 GQLLEFEE 460
Cdd:cd14516 170 YELFKWEE 177

dual specificity phosphatase domain of dual specificity protein phosphatase 15; Dual specificity protein phosphatase 15 (DUSP15), also called Vaccinia virus VH1-related dual-specific protein phosphatase Y (VHY) or VH1-related member Y, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). DUSP15 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 highly expressed in the testis and is located in the plasma membrane in a myristoylation-dependent manner. It may be involved in the regulation of meiotic signal transduction in testis cells. It is also expressed in the brain and has been identified as a regulator of oligodendrocyte differentiation. DUSP15 contains an N-terminal catalytic dual specificity phosphatase domain and a short C-terminal tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6005812  322 LTPILPFLFLGNEQDAQDLDTMQRLNIGYVINV-TTHLPLYHYekglFNYKRLPATDSNKQNLRQYFEEAFEFIeeaHQC 400
Cdd:cd14582   5 MTKVLPGLYLGNFIDAKDLEQLSRNKITHIISIhESPQPLLQD----ITYLRIPLPDTPEAPIKKHFKECISFI---HQC 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6005812  401 ---GKGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEF 458
Cdd:cd14582  78 rlnGGNCLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

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 6005812  321 ELTPILPFLFLGNEQDAQ--DLDTMQRLNIGYVINVTTHL------PLYhyeKGLFNYKRLPATDSNKQNLRQYFEEAFE 392
Cdd:cd14522   4 EMQEILPGLYLGPYSAAMksKLEVLLKHGITHIVCVRQNIeanfikPNF---PDHFRYLVLDVADNPTENIIRHFPTVKE 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6005812  393 FIEEAHQCGKGLLIHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFE 459
Cdd:cd14522  81 FIDDCLQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147