Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772821  181 PVEILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 260
Cdd:smart00195   1 PSEILPH-LYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDF-TYLGVPIDDNTETKISPYFPEAVEFIEDAESKG 78

                           90       100
                   ....*....|....*....|....*.
gi 1039772821  261 SVVLVFSTRGISRSVAAVVALLMHYN 286
Cdd:smart00195  79 GKVLVHCQAGVSRSATLIIAYLMKTR 104

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 1039772821 181 PVEILPGrVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 260
Cdd:cd14498     1 PSEILPG-LYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKG 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772821 261 SVVLVFSTRGISRSVAAVVALLMHYNEETLK 291
Cdd:cd14498    80 GKVLVHCQAGVSRSATIVIAYLMKKYGWSLE 110

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 1039772821 189 VYLGKISQACNAKMhKDLKIKAHVNISMETtpYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSVVLVFST 268
Cdd:pfam00782   1 LYLGSKPTASDAFL-SKLGITAVINVTREV--DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100
                  ....*....|....*....|...
gi 1039772821 269 RGISRSVAAVVALLMHYNEETLK 291
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLN 100

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 1039772821 181 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 260
Cdd:cd14513     1 ASKIFD-HLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGRF-TYHNIRVWDEESTNLLPYWNETYRFIKEARRKG 78

                          90       100
                  ....*....|....*....|...
gi 1039772821 261 SVVLVFSTRGISRSVAAVVALLM 283
Cdd:cd14513    79 SKVLVHCKMGVSRSASTVIAYAM 101

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 1039772821 184 ILPGrVYLGKIsqaCNAKMHKDLKIK--AHVnISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIElHLRLHS 261
Cdd:cd14519     4 ILPG-LYVGNF---RDAKDAEQLRENgiTHI-LSIHDSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIH-EARLNG 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1039772821 262 -VVLVFSTRGISRSVAAVVALLM---HYN-EETLKSRVPARGWSCP 302
Cdd:cd14519    78 gNVLVHCLAGVSRSVTIVAAYLMtvtDLGwRDALKAVRAARPCANP 123

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 1039772821 183 EILPGrVYLGKISQACNAKMhKDLKIKAHVNISMETTPYFIGNADkLLHIKLEDSPDTLLFDYFRHICHFIELHLRLHSV 262
Cdd:cd14514     3 QITPH-LFLSGASAATPPLL-LSRGITCIINATTELPDPSYPGIE-YLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGR 79

                          90       100
                  ....*....|....*....|....*....
gi 1039772821 263 VLVFSTRGISRSVAAVVALLMHYNEETLK 291
Cdd:cd14514    80 TLVHCVAGVSRSATLCLAYLMKYEGMTLR 108

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 1039772821 181 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISME-TTPYFIGNaDKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 259
Cdd:cd14568     1 PTRILP-HLYLGSQRDVLDKDLMQRNGISYVLNVSNTcPKPDFIPD-SHFLRIPVNDSYCEKLLPWLDKAVEFIEKARAS 78

                          90       100
                  ....*....|....*....|....*.
gi 1039772821 260 HSVVLVFSTRGISRSVAAVVALLMHY 285
Cdd:cd14568    79 NKRVLVHCLAGISRSATIAIAYIMKH 104

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 1039772821 181 PVEILPGrVYLGKISQACNAKMHKDLKIkAHVnISMETTPYFIGNADKLLHIK---LEDSPDTLLFDYFRHICHFIElHL 257
Cdd:cd14520     1 MKLVRPG-LYIGNADDAADYLSLREAGI-THV-LTVDSEEPIDAPPVGKLVRKfvpALDEESTDLLSRLDECLDFID-EG 76

                          90       100
                  ....*....|....*....|....*..
gi 1039772821 258 RLHSVVLVFSTRGISRSVAAVVALLMH 284
Cdd:cd14520    77 RAEGAVLVHCHAGVSRSAAVVTAYLMK 103

dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772821 185 LPGRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHL------- 257
Cdd:cd14518     4 ILGGLYLGGIEPLNRNRLLKAENITHILSVIPGDVPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIDSALfgngkde 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039772821 258 ----RLHSVVLVFSTRGISRSVAAVVALLMH-YN 286
Cdd:cd14518    84 deekKHGGAVLVHCAMGKSRSVTVVIAYLMYkYN 117

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 1039772821 181 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 260
Cdd:cd14640     1 PVEILP-FLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHY-QYKCIPVEDNHKADISSWFMEAIEYIDSVKDCN 78

                          90       100
                  ....*....|....*....|...
gi 1039772821 261 SVVLVFSTRGISRSVAAVVALLM 283
Cdd:cd14640    79 GRVLVHCQAGISRSATICLAYLM 101

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 1039772821 180 YPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISmETTPYFIGNAD--KLLHIKLEDSPDTLLFDYFRHICHFIELHL 257
Cdd:cd14642     2 FPVEILP-YLYLGCAKDSTNLDVLEEFGIKYILNVT-PNLPNLFENAGefKYKQIPISDHWSQNLSQFFPEAISFIDEAR 79

                          90       100
                  ....*....|....*....|....*..
gi 1039772821 258 RLHSVVLVFSTRGISRSVAAVVALLMH 284
Cdd:cd14642    80 GKNCGVLVHCLAGISRSVTVTVAYLMQ 106

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 1039772821 178 QP-YPVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAD-KLLHIKLEDSPDTLLFDYFRHICHFIEL 255
Cdd:cd14643     2 QPaFPVQILP-YLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGEfKYKQIPISDHWSQNLSQFFPEAISFIDE 80

                          90       100
                  ....*....|....*....|....*....
gi 1039772821 256 HLRLHSVVLVFSTRGISRSVAAVVALLMH 284
Cdd:cd14643    81 ARSKKCGILVHCLAGISRSVTVTVAYLMQ 109

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 1039772821 181 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGNAdKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 260
Cdd:cd14638     1 PVEILP-FLYLGSAYHASRKDMLDTLGITALINVSANCPNHFEGHY-QYKSIPVEDNHKADISSWFNEAIDFIDSVKNAG 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772821 261 SVVLVFSTRGISRSVAAVVALLMHYNEETLK 291
Cdd:cd14638    79 GRVFVHCQAGISRSATICLAYLMRTNRVKLD 109

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 1039772821 183 EILPGrVYLGKISQACNAKMHKDLKIkAHVnISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIElHLRLHS- 261
Cdd:cd14582     7 KVLPG-LYLGNFIDAKDLEQLSRNKI-THI-ISIHESPQPLLQDITYLRIPLPDTPEAPIKKHFKECISFIH-QCRLNGg 82

                          90       100
                  ....*....|....*....|..
gi 1039772821 262 VVLVFSTRGISRSVAAVVALLM 283
Cdd:cd14582    83 NCLVHCLAGISRSTTIVVAYVM 104

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 1039772821 181 PVEILPGRVYLGKISQACNAKMHKDLKIKAHVNiSMETTPYFIGNADKLLHIKLEDSPDtllfdyFRHICHFIELHLRLH 260
Cdd:cd18534     1 PTEILPGFLYLGSYDNASRAELLKAQGITRILN-TVPDCQNLYKNSFTYHVLSEEKTVP------FAEAVDFIEQCRKDK 73

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1039772821 261 SVVLVFSTRGISRSVAAVVALLMHyneetlksrvpARGW 299
Cdd:cd18534    74 ARVLVHCMSGQSRSPAVVIAYLMK-----------HKGW 101

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 1039772821 181 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFiGNADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRLH 260
Cdd:cd14571     4 PSRIFP-YLYLGSEWNAANLEELQRNRVSHILNVTREIDNFF-PERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQG 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772821 261 SVVLVFSTRGISRSVAAVVALLMHYNEETLK 291
Cdd:cd14571    82 TRVLVHCKMGVSRSASTVIAYAMKQYGWTLE 112

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 1039772821 181 PVEILPgRVYLGKISQACNAKMHKDLKIKAHVNISMETTPYFIGN-ADKLLHIKLEDSPDTLLFDYFRHICHFIELHLRL 259
Cdd:cd14567     1 LTPILP-FLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKgGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQS 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039772821 260 HSVVLVFSTRGISRSVAAVVALLMHYNEETL 290
Cdd:cd14567    80 GKGVLVHCQAGVSRSATIVIAYLMKHTRMTM 110

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), 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. DUSP13A 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. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039772821 210 AHVNISMETTPYFIGNADKLLHIKLEDSPDTLLFDYFRHICHFIelHLRLHSV---VLVFSTRGISRSVAAVVALLMHYN 286
Cdd:cd14580    34 AHGKLFCQGGDDFYGTSVDYYGVPANDLPDFDISPYFYSAAEFI--HRALNTPgakVLVHCAVGVSRSATLVLAYLMIYH 111

                          90
                  ....*....|....*....
gi 1039772821 287 EETLKS---RVPARGWSCP 302
Cdd:cd14580   112 QLSLVQaikTVKERRWIFP 130