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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078   56 YPKGPLLVLPEKIYLYSEPTVKELLPFDVVINVAEEANDLRM----------------QVPAVEYHHYRWEHDSQIALDL 119
Cdd:cd14521   1 YPDGPVCVLPPNIYLYSEPTLEEASSFDVVINVAKEVKNPFLsdaslaekektilpgqQVKNPEYIHVPWDHNSQIQKDL 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6322078  120 PSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:cd14521  81 PKLTSIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLIFQLMEFEKVL 155

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078   56 YPKGPLLVLPEKIYLYSEPTVKELLPFDVVINVAEEANDLRM----------------QVPAVEYHHYRWEHDSQIALDL 119
Cdd:cd14521   1 YPDGPVCVLPPNIYLYSEPTLEEASSFDVVINVAKEVKNPFLsdaslaekektilpgqQVKNPEYIHVPWDHNSQIQKDL 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6322078  120 PSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:cd14521  81 PKLTSIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLIFQLMEFEKVL 155

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078      60 PLLVLPeKIYLYSEPTVKEL-----LPFDVVINVAEEA------NDLRMQVPAVeyhhyrWEHDSQIALDLPSLTSIIHA 128
Cdd:smart00195   1 PSEILP-HLYLGSYSDALNLallkkLGITHVINVTNEVpnyngsDFTYLGVPID------DNTETKISPYFPEAVEFIED 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6322078     129 ATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:smart00195  74 AESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYE 136

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078   56 YPKGPLLVLPEKIYLYSEPTVKELLPFDVVINVAEEANDLRM----------------QVPAVEYHHYRWEHDSQIALDL 119
Cdd:cd14521   1 YPDGPVCVLPPNIYLYSEPTLEEASSFDVVINVAKEVKNPFLsdaslaekektilpgqQVKNPEYIHVPWDHNSQIQKDL 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6322078  120 PSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:cd14521  81 PKLTSIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLIFQLMEFEKVL 155

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078      60 PLLVLPeKIYLYSEPTVKEL-----LPFDVVINVAEEA------NDLRMQVPAVeyhhyrWEHDSQIALDLPSLTSIIHA 128
Cdd:smart00195   1 PSEILP-HLYLGSYSDALNLallkkLGITHVINVTNEVpnyngsDFTYLGVPID------DNTETKISPYFPEAVEFIED 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6322078     129 ATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:smart00195  74 AESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYE 136

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 6322078   85 VINVAEEANDlrMQVPAVEYHHYRWEHD--SQIALDLPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLS 162
Cdd:cd14514  29 IINATTELPD--PSYPGIEYLRVPVEDSphADLSPHFDEVADKIHQVKRRGGRTLVHCVAGVSRSATLCLAYLMKYEGMT 106

                        90       100
                ....*....|....*....|....*..
gi 6322078  163 LRHSYDLLKSRADKINPSIGLIFQLME 189
Cdd:cd14514 107 LREAYKHVKAARPIIRPNVGFWRQLIE 133

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078  136 ILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVALN 195
Cdd:cd14567  83 VLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDLN 142

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6322078  119 LPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:cd14568  65 LDKAVEFIEKARASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFE 137

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 6322078   50 LDVRRIYPkgpLLVLPEKIYLYSE-----PTVKELLPFDVVINVAEEANDLrMQVPAVEYHHYRWEHD--SQIALDLPSL 122
Cdd:cd14517   4 LDNLKTYP---VEILPGFLYMGNYkqacdKKIQKDLKIKAHINVSMDADEL-FKSGNDQVLHIPVEDSveADLLSFFERA 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6322078  123 TSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:cd14517  80 CSFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWE 148

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 6322078  110 EHDSQ-IALDLPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLM 188
Cdd:cd14643  61 DHWSQnLSQFFPEAISFIDEARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLL 140

                ....*....
gi 6322078  189 EWEVALNAK 197
Cdd:cd14643 141 DFERTLGLN 149

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6322078  126 IHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:cd14565  71 IDKVKASGGRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYE 136

dual specificity phosphatase domain of slingshot homolog 1; Dual specificity protein phosphatase slingshot homolog 1 (SSH1), also called SSH-like protein 1, is part of the slingshot (SSH) family, whose members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. SSH1 links NOD1 signaling to actin remodeling, facilitating the changes that leads to NF-kappaB activation and innate immune responses. There are at least two human SSH1 isoforms reported: hSSH-1L (long) and hSSH-1S (short). As SSH family phosphatases, they contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. They also contain C-terminal tails, differing in the lengths of the tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078   66 EKIYLYSEPTVKELLPF-----DVVINVAEEANDLrmqVPAV-EYHHYRWEHDSqiALDLPS----LTSIIHAATTKREK 135
Cdd:cd14570   9 DHLYLGSEWNASNLEELqgsgvGYILNVTREIDNF---FPGLfAYHNIRVYDEE--TTDLLAhwndAYHFINKAKKNHSK 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6322078  136 ILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVALNA 196
Cdd:cd14570  84 CLVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYEGILDA 144

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 6322078  106 HYRW----EHDSQ-IALDLPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPS 180
Cdd:cd14644  50 HYKQipisDHWSQnLSQFFPEAIEFIDEALSQNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPN 129

                        90
                ....*....|....
gi 6322078  181 IGLIFQLMEWEVAL 194
Cdd:cd14644 130 FNFMGQLLDFEKSL 143

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078   63 VLPEKIYLYSEPTVKELLP----FDVVINVAEEANDLRMQVPA--VEYHHYRWEhDsqiaLDLPSLTSI------IHAAT 130
Cdd:COG2453   3 IIPGLLAGGPLPGGGEADLkregIDAVVSLTEEEELLLGLLEEagLEYLHLPIP-D----FGAPDDEQLqeavdfIDEAL 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6322078  131 TKREKILIHCQCGLSRSATLIIAYIMkYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:COG2453  78 REGKKVLVHCRGGIGRTGTVAAAYLV-LLGLSAEEALARVRAARPGAVETPAQRAFLERFAKRL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6322078  126 IHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:cd14513  71 IKEARRKGSKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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 6322078   87 NVAEEANDLRM-QVPAVEYhhyrWEHDsqIALDLPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRH 165
Cdd:cd14642  41 NLFENAGEFKYkQIPISDH----WSQN--LSQFFPEAISFIDEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMND 114

                        90       100
                ....*....|....*....|....*....
gi 6322078  166 SYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:cd14642 115 AYDIVKMKKSNISPNFNFMGQLLDFERTL 143

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078   59 GPLLVLPEkIYLYSEPTV--KELLPFDVVINVAEEANDLRMQVPAVEYHHYRWE-HDSQIALDLPSL---TSIIHAATTK 132
Cdd:cd14646   2 GPTRILPH-LYLGCQRDVlnKELMQQNGIGYVLNASNTCPKPDFIPESHFLRVPvNDSFCEKILPWLdksVDFIEKAKAS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 6322078  133 REKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVALNAK 197
Cdd:cd14646  81 NGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKIKNQ 145

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 6322078   81 PFDVVINVAEeandLRMQV---PAVEYHHYrwehdsqialdLPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMK 157
Cdd:cd14574  38 PFPRAPRVST----LRVPVfddPAEDLYRH-----------FEQCADAIEAAVRRGGKCLVYCKNGRSRSAAVCIAYLMK 102

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 6322078  158 YHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:cd14574 103 HRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEEL 139

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 6322078   59 GPLLVLPEkIYLYSEPTV--KELLPFDVVINVAEEANDLRMQVPAVEYHHYRWE-HDSQIALDLPSL---TSIIHAATTK 132
Cdd:cd14645  11 GPTRILPH-LYLGSQKDVlnKDLMAQNGITYVLNASNSCPKPDFICESHFMRIPvNDNYCEKLLPWLdksIEFIDKAKVS 89

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6322078  133 REKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVAL 194
Cdd:cd14645  90 NCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 6322078  106 HYRWE-------HDSQIALDLPSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKIN 178
Cdd:cd14638  44 HYQYKsipvednHKADISSWFNEAIDFIDSVKNAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIIS 123

                        90       100
                ....*....|....*....|
gi 6322078  179 PSIGLIFQLMEWEVALNAKT 198
Cdd:cd14638 124 PNFSFMGQLLQFESQVLAPS 143

dual specificity phosphatase and pro isomerase domain containing 1; Dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1) was initially named as such because computational prediction appeared to encode a protein of 446 amino acids in length that included two catalytic domains: a proline isomerase and a dual specificity phosphatase (DUSP). However, it was subsequently shown that the true open reading frame only encompassed the DUSP domain and the gene product was therefore renamed DUSP27. This is distinct from inactive DUSP27. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). DUPD1/DUSP27 has been shown to have catalytic activity with preference for phosphotyrosine over phosphothreonine and phosphoserine residues. It associates with the short form of the prolactin (PRL) receptor and plays a role in PRL-mediated MAPK inhibition in ovarian cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078  116 ALDLPSL---------TSIIHAA-TTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYD-LLKSRAdkINPSIGLI 184
Cdd:cd14575  69 ADDLPTFnlsqffysaAEFIHQAlSDPHNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEqVAQRRC--ILPNRGFL 146

                        90
                ....*....|
gi 6322078  185 FQLMEWEVAL 194
Cdd:cd14575 147 KQLRELDIQL 156

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 6322078   66 EKIYLYSE---PTVKELLPFDV--VINVAEEANDLrmqVPAV-EYHHYRwEHDSQiALDLPSLTS----IIHAATTKREK 135
Cdd:cd14569   9 EHVFLGSEwnaSNLEDLQNRGVryILNVTREIDNF---FPGLfEYHNIR-VYDEE-ATDLLAYWNdtykFISKAKKHGSK 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6322078  136 ILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWEVALNA 196
Cdd:cd14569  84 CLVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 144

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078  126 IHAA-TTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADkINPSIGLIFQLMEWEVAL 194
Cdd:cd14577  95 IRAAlSSPNGRVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHRD-ICPNSGFLRQLRELDNRL 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6322078  126 IHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEWE 191
Cdd:cd14581  73 IHECRLRGEGCLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFE 138

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6322078  120 PSLTSI------IHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPS 180
Cdd:cd14524  70 PSLEDLekgvdfILKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLR 136

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6322078  124 SIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLSLRHSYDLLKSRADKINPSIGLIFQLMEW 190
Cdd:cd14582  72 SFIHQCRLNGGNCLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 6322078  124 SIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLS 162
Cdd:cd14494  47 EVLDQAEKPGEPVLVHCKAGVGRTGTLVACYLVLLGGMS 85

dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as VH1-like phosphatase Z (VHZ) or low molecular mass dual specificity phosphatase 3 (LDP-3), 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. DUSP23 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 able to enhance activation of JNK and p38 MAPK, and has been shown to dephosphorylate p44-ERK1 (MAPK3) in vitro. It has been associated with cell growth and human primary cancers. It has also been identified as a cell-cell adhesion regulatory protein; it promotes the dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6322078   90 EEANDLRMQVPAVEYHHYRWE-----HDSQIAldlpSLTSIIHAATTKREKILIHCQCGLSRSATLIIAYIMKYHNLS 162
Cdd:cd14504  38 EPPPEHSDTCPGLRYHHIPIEdytppTLEQID----EFLDIVEEANAKNEAVLVHCLAGKGRTGTMLACYLVKTGKIS 111

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6322078     104 YHHYRWEhDSQIALDLPSLTSIIHAATTKREK------ILIHCQCGLSRSATLIIAYIMkyhnlslrhsYDLLKSRADKI 177
Cdd:smart00012   5 YHYTGWP-DHGVPESPDSILELLRAVKKNLNQsessgpVVVHCSAGVGRTGTFVAIDIL----------LQQLEAEAGEV 73

                           90
                   ....*....|..
gi 6322078     178 NpsiglIFQLME 189
Cdd:smart00012  74 D-----IFDTVK 80

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                        10        20
                ....*....|....*....|....*..
gi 6322078  136 ILIHCQCGLSRSATLIIAYIMKYHNLS 162
Cdd:cd14497  98 AVVHCKAGKGRTGTVICAYLLYYGQYS 124