dual specificity protein phosphatase 28; Dual specificity protein phosphatase 28 (DUSP28), also called VHP, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP that contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells. DUSP28 has an exceptionally low phosphatase activity due to the presence of bulky residues in the active site pocket resulting in low accessibility.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGA 98
Cdd:cd14574     1 LCRVTDSLFISNARAACNEELLAREGVTLCVNVSRQQPFPRAPRVSTLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  99 CLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQ 158
Cdd:cd14574    81 CLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEELQ 140

dual specificity protein phosphatase 28; Dual specificity protein phosphatase 28 (DUSP28), also called VHP, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP that contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells. DUSP28 has an exceptionally low phosphatase activity due to the presence of bulky residues in the active site pocket resulting in low accessibility.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGA 98
Cdd:cd14574     1 LCRVTDSLFISNARAACNEELLAREGVTLCVNVSRQQPFPRAPRVSTLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  99 CLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQ 158
Cdd:cd14574    81 CLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEELQ 140

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 1635381438  26 LFLGSARAAgAEEQLARAGVTLCVNVSRQQPGPRaPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACLVYCKN 105
Cdd:pfam00782   1 LYLGSKPTA-SDAFLSKLGITAVINVTREVDLYN-SGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQA 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1635381438 106 GRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYE 154
Cdd:pfam00782  79 GISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  17 PPLVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPG----PRAPGVAELRVPVFDDPAEDLlAHLEPTCAAMEAA 92
Cdd:PRK12361   93 PAIQKIDENLYLGCRLFPADLEKLKSNKITAILDVTAEFDGldwsLTEEDIDYLNIPILDHSVPTL-AQLNQAINWIHRQ 171

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1635381438  93 VRAGGACLVYCKNGRSRSAAVCTAYLM-RHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQ 158
Cdd:PRK12361  172 VRANKSVVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRKTARLNKRQLRALEKMLEQGK 238

dual specificity protein phosphatase 28; Dual specificity protein phosphatase 28 (DUSP28), also called VHP, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP that contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells. DUSP28 has an exceptionally low phosphatase activity due to the presence of bulky residues in the active site pocket resulting in low accessibility.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGA 98
Cdd:cd14574     1 LCRVTDSLFISNARAACNEELLAREGVTLCVNVSRQQPFPRAPRVSTLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  99 CLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQ 158
Cdd:cd14574    81 CLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEELQ 140

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 1635381438  21 RVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAP-GVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGAC 99
Cdd:cd14498     3 EILPGLYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFPdGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKGGKV 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1635381438 100 LVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQK 152
Cdd:cd14498    83 LVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGA 98
Cdd:cd14573     2 LSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGGR 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1635381438  99 CLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEAL 157
Cdd:cd14573    82 TLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFEL 140

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 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPR-APGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGG 97
Cdd:cd14568     1 PTRILPHLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKPDfIPDSHFLRIPVNDSYCEKLLPWLDKAVEFIEKARASNK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  98 ACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEAL 157
Cdd:cd14568    81 RVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFEKKL 140

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 1635381438  21 RVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACL 100
Cdd:cd14513     3 KIFDHLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGSKVL 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1635381438 101 VYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYE 154
Cdd:cd14513    83 VHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  26 LFLGSARAAgAEEQLARAGVTLCVNVSRQQPGPRaPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACLVYCKN 105
Cdd:pfam00782   1 LYLGSKPTA-SDAFLSKLGITAVINVTREVDLYN-SGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQA 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1635381438 106 GRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYE 154
Cdd:pfam00782  79 GISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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 1635381438  20 VRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGAC 99
Cdd:cd14565     2 VEILPFLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRV 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1635381438 100 LVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEE 155
Cdd:cd14565    82 LVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYES 137

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 1635381438  21 RVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACL 100
Cdd:cd14571     6 RIFPYLYLGSEWNAANLEELQRNRVSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTRVL 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1635381438 101 VYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQA 159
Cdd:cd14571    86 VHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQGILTA 144

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 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQP--GPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAG 96
Cdd:cd14567     1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPlyHEGKGGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1635381438  97 GACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQAQ 160
Cdd:cd14567    81 KGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDLNNG 144

dual specificity phosphatase domain of slingshot homolog 2; Dual specificity protein phosphatase slingshot homolog 2 (SSH2), also called SSH-like protein 2, is part of the slingshot (SSH) family, whose members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. SSH2 has been identified as a target of protein kinase D1 that regulates cofilin phosphorylation and remodeling of the actin cytoskeleton during neutrophil chemotaxis. There are at least two human SSH2 isoforms reported: hSSH-2L (long) and hSSH-2. As SSH family phosphatases, they contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. In addition, hSSH-2L contains a long C-terminal tail while hSSH-2 does not.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  26 LFLGSARAAGAEEQLARAGVTLCVNVSRQQPGpRAPGVAELR-VPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACLVYCK 104
Cdd:cd14569    11 VFLGSEWNASNLEDLQNRGVRYILNVTREIDN-FFPGLFEYHnIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCK 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1635381438 105 NGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQA 159
Cdd:cd14569    90 MGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 144

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 1635381438  19 LVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVsRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGA 98
Cdd:cd14582     5 MTKVLPGLYLGNFIDAKDLEQLSRNKITHIISI-HESPQPLLQDITYLRIPLPDTPEAPIKKHFKECISFIHQCRLNGGN 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1635381438  99 CLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKY 153
Cdd:cd14582    84 CLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

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 1635381438  49 VNVSrQQPGPRAPGVAE--LRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACLVYCKNGRSRSAAVCTAYLMRHRGLSL 126
Cdd:cd14517    42 INVS-MDADELFKSGNDqvLHIPVEDSVEADLLSFFERACSFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSL 120

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1635381438 127 AKAFQMVKSARPVAEPNPGFWSQLQKYEEAL 157
Cdd:cd14517   121 KDAWKYLLKCKNNMRPNRGFVKQLSEWEEKL 151

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 1635381438  21 RVAPSLFLGSARAAGAEEQLARAGVTLCVNVSrQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACL 100
Cdd:cd14581     6 KVLPGLYLGNFKDARDREQLSKNNITHILSVH-DSARPMLEGMTYLCIPAADSPSQNLTQHFKESIKFIHECRLRGEGCL 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1635381438 101 VYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYE 154
Cdd:cd14581    85 VHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFE 138

dual specificity phosphatase domain of dual specificity protein phosphatase 2; Dual specificity protein phosphatase 2 (DUSP2), also called dual specificity protein phosphatase PAC-1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other mitogen-activated protein kinase (MAPK) phosphatases (MKPs), it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP2 can preferentially dephosphorylate ERK1/2 and p38, but not JNK in vitro. It is predominantly expressed in hematopoietic tissues with high T-cell content, such as thymus, spleen, lymph nodes, peripheral blood and other organs such as the brain and liver. It has a critical and positive role in inflammatory responses. DUSP2 mRNA and protein are significantly reduced in most solid cancers including breast, colon, lung, ovary, kidney and prostate, and the suppression of DUSP2 is associated with tumorigenesis and malignancy. DUSP2 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  20 VRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGAC 99
Cdd:cd14641     5 VEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNSGGRV 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1635381438 100 LVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYE 154
Cdd:cd14641    85 LVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 139

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 1635381438  20 VRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGAC 99
Cdd:cd14640     2 VEILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRV 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438 100 LVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQA 159
Cdd:cd14640    82 LVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

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 1635381438  24 PSLFLGSARAAGAE--EQLARAGVT--LCV--NVSRQQPGPRAP-GVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAG 96
Cdd:cd14522    10 PGLYLGPYSAAMKSklEVLLKHGIThiVCVrqNIEANFIKPNFPdHFRYLVLDVADNPTENIIRHFPTVKEFIDDCLQTG 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1635381438  97 GACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYE 154
Cdd:cd14522    90 GKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147

dual specificity protein phosphatase 13 isoform B; Dual specificity protein phosphatase 13 isoform B (DUSP13B), also called testis- and skeletal-muscle-specific DSP (TMDP) or dual specificity phosphatase SKRP4, 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. DUSP13B 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. DUSP13B inactivates MAPK activation in the order of selectivity, JNK = p38 > ERK in cells. It may play a role in protection from external stress during spermatogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  22 VAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQP----GP---RAPGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVR 94
Cdd:cd14577    21 VWPNLYLGDAYAARDKSVLIQLGITHIVNAASGKFhvntGPkfyRDMNIDYYGVEADDNPFFDLSVYFYPVARFIRAALS 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1635381438  95 A-GGACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAePNPGFWSQLQKYEEAL 157
Cdd:cd14577   101 SpNGRVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHRDIC-PNSGFLRQLRELDNRL 163

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 1635381438  20 VRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSrqqpgPRAPGVAEL-------RVPVFDDPAEDLLAHLEPTCAAMEAA 92
Cdd:cd14644     4 VQILPNLYLGSARDSANLETLAKLGIRYILNVT-----PNLPNFFEKngdfhykQIPISDHWSQNLSQFFPEAIEFIDEA 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1635381438  93 VRAGGACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEAL 157
Cdd:cd14644    79 LSQNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSL 143

protein-tyrosine phosphatase mitochondrial 1; Protein-tyrosine phosphatase mitochondrial 1 or PTP localized to the mitochondrion 1 (PTPMT1), also called phosphoinositide lipid phosphatase (PLIP), phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1, or PTEN-like phosphatase, is a lipid phosphatase or phosphatidylglycerophosphatase (EC 3.1.3.27) which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. It is essential for the biosynthesis of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. PTPMT1 also plays a crucial role in hematopoietic stem cell (HSC) function, and has been shown to display activity toward phosphoprotein substrates.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  21 RVAPSLFLGSARAAG-AEEQLARAGVTLCVNVSRQQPGPR---------APGVAELRVPVFDDPAEDLLAHLEPTCAAME 90
Cdd:cd14524     4 RIDDTVILGALPFRSmTVALVAKENVRGVITMNEEYETRFfcnskeewkALGVEQLRLPTVDFTGVPSLEDLEKGVDFIL 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1635381438  91 AAVRAGGACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKY 153
Cdd:cd14524    84 KHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQREVLEEF 146

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1635381438  89 MEAAVRAGGACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKY 153
Cdd:cd18534    66 IEQCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSPAVAKQLQEF 130

dual specificity phosphatase domain of dual specificity protein phosphatase 7; Dual specificity protein phosphatase 7 (DUSP7), also called mitogen-activated protein kinase (MAPK) phosphatase X (MKP-X) or dual specificity protein phosphatase PYST2, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP7 has been shown as an essential regulator of multiple steps in oocyte meiosis. Due to alternative promoter usage, the PYST2 gene gives rise to two isoforms, PYST2-S and PYST2-L. PYST2-L is over-expressed in leukocytes derived from AML and ALL patients as well as in some solid tumors and lymphoblastoid cell lines; it plays a role in cell-crowding. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635381438  20 VRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSrqqpgPRAPGVAE-------LRVPVFDDPAEDLLAHLEPTCAAMEAA 92
Cdd:cd14643     7 VQILPYLYLGCAKDSTNLDVLGKYGIKYILNVT-----PNLPNMFEhdgefkyKQIPISDHWSQNLSQFFPEAISFIDEA 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1635381438  93 VRAGGACLVYCKNGRSRSAAVCTAYLMRHRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEAL 157
Cdd:cd14643    82 RSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146