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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKLFSRNTVRMIYSPIGLIPN 177
Cdd:cd14573  81 RTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFELFGKNTVHMITSPVGMIPD 158

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 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKLFSRNTVRMIYSPIGLIPN 177
Cdd:cd14573  81 RTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFELFGKNTVHMITSPVGMIPD 158

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 28913648    39 KLTLSNNHITTIINVSAEVvNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRTLLHCAAGVSRSATLCLA 118
Cdd:pfam00782  11 DAFLSKLGITAVINVTREV-DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAGISRSATLIIA 89

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 28913648   119 YLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:pfam00782  90 YLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648   12 ATQQDNIYGLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEV----VNTFFEDIQYVQVPVSD--APNS-YLYDFF 84
Cdd:PRK12361  86 ARKRDSVPAIQKIDENLYLGCRLFPADLEKLKSNKITAILDVTAEFdgldWSLTEEDIDYLNIPILDhsVPTLaQLNQAI 165

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 28913648   85 DPIADHIhgvemRNGRT-LLHCAAGVSRSATLCLAYLM-KYHNMTLLDAHTWTKTCRPIIRPNN 146
Cdd:PRK12361 166 NWIHRQV-----RANKSvVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRKTARLNK 224

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 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKLFSRNTVRMIYSPIGLIPN 177
Cdd:cd14573  81 RTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFELFGKNTVHMITSPVGMIPD 158

dual specificity protein phosphatase 14; dual specificity protein phosphatase 14 (DUSP14), also called mitogen-activated protein kinase (MAPK) phosphatase 6 (MKP-6) or MKP-1-like protein tyrosine phosphatase (MKP-L), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP14 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 dephosphorylates JNK, ERK, and p38 in vitro. It also directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14572   7 GIAQITPSLYLSRGNVASNRHLLLSRGITCIVNATIEIPNFNWPQFEYVKVPLADMPHAPISLYFDSVADKIHSVGRKHG 86

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKLFSRN 163
Cdd:cd14572  87 ATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYERKLFGKS 150

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648     22 SQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRT 101
Cdd:smart00195   2 SEILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKV 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 28913648    102 LLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFK 158
Cdd:smart00195  82 LVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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 28913648    39 KLTLSNNHITTIINVSAEVvNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRTLLHCAAGVSRSATLCLA 118
Cdd:pfam00782  11 DAFLSKLGITAVINVTREV-DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAGISRSATLIIA 89

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 28913648   119 YLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:pfam00782  90 YLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

dual specificity phosphatase domain of dual specificity protein phosphatase 19; Dual specificity protein phosphatase 19 (DUSP19), also called low molecular weight dual specificity phosphatase 3 (LMW-DSP3) or stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1), 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; 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. DUSP19 interacts with the MAPK kinase MKK7, a JNK activator, and inactivates the JNK MAPK pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  21 LSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGR 100
Cdd:cd14523   2 VGVIKPWLLLSSQDVAHDLETLKKHKVTHILNVAYGVENAFPDDFTYKTISILDLPETDITSYFPECFEFIDEAKSQDGV 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 28913648 101 TLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:cd14523  82 VLVHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEYQ 137

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 28913648  21 LSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVN-TFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14568   1 PTRILPHLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKpDFIPDSHFLRIPVNDSYCEKLLPWLDKAVEFIEKARASNK 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKL 159
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 28913648  22 SQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRT 101
Cdd:cd14513   2 SKIFDHLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGSKV 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 28913648 102 LLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:cd14513  82 LVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14641   3 GPVEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNSGG 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:cd14641  83 RVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 139

dual specificity phosphatase domain of class II mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  23 QITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFED--IQYVQVPVSDAPNSYLYDFFdPIADH-IHGVEMRNG 99
Cdd:cd14566   3 EILPFLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEEDggFKYLQIPIDDHWSQNLSAFF-PEAISfIDEARSKKC 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHY 155
Cdd:cd14566  82 GVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLDF 137

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 28913648  23 QITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRTL 102
Cdd:cd14640   3 EILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 28913648 103 LHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKLFS 161
Cdd:cd14640  83 VHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

dual specificity phosphatase domain of dual specificity protein phosphatase 5; Dual specificity protein phosphatase 5 (DUSP5) 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. DUSP5 preferentially dephosphorylates extracellular signal-regulated kinase (ERK), and is involved in ERK signaling and ERK-dependent inflammatory gene expression in adipocytes. It also plays a role in regulating pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain. DUSP5 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 28913648  23 QITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRTL 102
Cdd:cd14639   3 EILPFLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCVRRAGGKVL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 28913648 103 LHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:cd14639  83 VHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYE 136

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 28913648  28 LFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFEDI-QYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGRTLLHCA 106
Cdd:cd14517  19 LYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNdQVLHIPVEDSVEADLLSFFERACSFIDKHKNNGSRVLVFST 98

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 28913648 107 AGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKLF 160
Cdd:cd14517  99 LGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLL 152

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 28913648  21 LSQITASLFISNSAVANDKLTLSNNHITTIINvSAE---VVNT---FFED--IQYVQVPVSDAPNSYLYDFFDPIADHIH 92
Cdd:cd14575  11 VNEVWPGLYIGDEKTALDRYSLQKLGITHILN-AAHgkwNVDTgaeYYKDmtIHYYGVEADDLPTFNLSQFFYSAAEFIH 89

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 28913648  93 -GVEMRNGRTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIrPNNGFWEQL 152
Cdd:cd14575  90 qALSDPHNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQVAQRRCIL-PNRGFLKQL 149

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 28913648  21 LSQITASLFISNSAVANDKLTLSNNHITTIINV-SAEVVNTFFEDIQYVQVPVSDAPNSYLYDFFDPIADHI-------- 91
Cdd:cd14518   1 LSRILGGLYLGGIEPLNRNRLLKAENITHILSViPGDVPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIdsalfgng 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 28913648  92 ---HGVEMRNGRTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:cd14518  81 kdeDEEKKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYH 148

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 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVN-TFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRN 98
Cdd:cd14646   2 GPTRILPHLYLGCQRDVLNKELMQQNGIGYVLNASNTCPKpDFIPESHFLRVPVNDSFCEKILPWLDKSVDFIEKAKASN 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 28913648  99 GRTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKL 159
Cdd:cd14646  82 GRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKI 142

dual specificity phosphatase-like domain of serine/threonine/tyrosine-interacting protein; Serine/threonine/tyrosine-interacting protein (STYX), also called protein tyrosine phosphatase-like protein, is a catalytically inactive member of the protein tyrosine phosphatase family that plays an integral role in regulating pathways by competing with active phosphatases for binding to MAPKs. It acts as a nuclear anchor for MAPKs, affecting their nucleocytoplasmic shuttling.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  23 QITASLFIS--NSAVANDKLTLSNNHITTII----NVSAEVVN-TFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVE 95
Cdd:cd14522   7 EILPGLYLGpySAAMKSKLEVLLKHGITHIVcvrqNIEANFIKpNFPDHFRYLVLDVADNPTENIIRHFPTVKEFIDDCL 86

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 28913648  96 MRNGRTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:cd14522  87 QTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147

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 28913648  20 GLSQITASLFISNSAVANDKLTLSNNHITTIINVSAEVVN-TFFEDIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRN 98
Cdd:cd14645  11 GPTRILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKpDFICESHFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVSN 90

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 28913648  99 GRTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKL 159
Cdd:cd14645  91 CRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 28913648  23 QITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNtFFE---DIQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNG 99
Cdd:cd14644   5 QILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPN-FFEkngDFHYKQIPISDHWSQNLSQFFPEAIEFIDEALSQNC 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648 100 RTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKL 159
Cdd:cd14644  84 GVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSL 143

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  23 QITASLFISNSAVANDKLTLSNNHITTIINVSAEVVNTFFED--IQYVQVPVSDAPNSYLYDFFDPIADHIHGVEMRNGR 100
Cdd:cd14643   8 QILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDgeFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKKCG 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 28913648 101 TLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYEFKL 159
Cdd:cd14643  88 ILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28913648  42 LSNNHITTIINVSA--EVVNTFFED--IQYVQVPVSD--APNsylYDFFDPIADHIHGVEMRNGRTLLHCAAGVSRSATL 115
Cdd:COG2453  21 LKREGIDAVVSLTEeeELLLGLLEEagLEYLHLPIPDfgAPD---DEQLQEAVDFIDEALREGKKVLVHCRGGIGRTGTV 97

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 28913648 116 CLAYLMkYHNMTLLDAHTWTKTCRPIIRPNNGFWEQLIHYE 156
Cdd:COG2453  98 AAAYLV-LLGLSAEEALARVRAARPGAVETPAQRAFLERFA 137

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 28913648  63 EDIQYVQVPVSDApnsylydFFDPIADHIH-GVEM------RNGRTLLHCAAGVSRSATLCLAYLMKYHNMTLLDAHTWT 135
Cdd:cd14524  54 LGVEQLRLPTVDF-------TGVPSLEDLEkGVDFilkhreKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFL 126