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 30424589  19 GLSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKG 98
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30424589  99 RTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQLFGKNTMQMMDSPMGRIPD 176
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 30424589  19 GLSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKG 98
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30424589  99 RTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQLFGKNTMQMMDSPMGRIPD 176
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 30424589    38 KLLLSSNQITTVINVSVEVaNTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRTLLHCAAGVSRSAALCLA 117
Cdd:pfam00782  11 DAFLSKLGITAVINVTREV-DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAGISRSATLIIA 89

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 30424589   118 YLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:pfam00782  90 YLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30424589   15 PSIRglsQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVA----NTFYEDIQYVQVPVVDAPVARLSNFFDSVAdRI 90
Cdd:PRK12361  93 PAIQ---KIDENLYLGCRLFPADLEKLKSNKITAILDVTAEFDgldwSLTEEDIDYLNIPILDHSVPTLAQLNQAIN-WI 168

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 30424589   91 HSvEMQKGRT-LLHCAAGVSRSAALCLAYLM-KYHAMSLVDAHTWTKSCRPIIRPNS 145
Cdd:PRK12361 169 HR-QVRANKSvVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIRKTARLNK 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 30424589  19 GLSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKG 98
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARGG 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30424589  99 RTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQLFGKNTMQMMDSPMGRIPD 176
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 30424589  16 SIRGLSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEM 95
Cdd:cd14572   4 DLGGIAQITPSLYLSRGNVASNRHLLLSRGITCIVNATIEIPNFNWPQFEYVKVPLADMPHAPISLYFDSVADKIHSVGR 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30424589  96 QKGRTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQLFGKN 162
Cdd:cd14572  84 KHGATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYERKLFGKS 150

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30424589     21 SQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRT 100
Cdd:smart00195   2 SEILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKV 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 30424589    101 LLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:smart00195  82 LVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYE 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 30424589    38 KLLLSSNQITTVINVSVEVaNTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRTLLHCAAGVSRSAALCLA 117
Cdd:pfam00782  11 DAFLSKLGITAVINVTREV-DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAGISRSATLIIA 89

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 30424589   118 YLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:pfam00782  90 YLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 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 30424589  22 QITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRTL 101
Cdd:cd14565   3 EILPFLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKVKASGGRVL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 30424589 102 LHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQ 157
Cdd:cd14565  83 VHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYESQ 138

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 30424589  20 LSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVAN-TFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKG 98
Cdd:cd14568   1 PTRILPHLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKpDFIPDSHFLRIPVNDSYCEKLLPWLDKAVEFIEKARASNK 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 30424589  99 RTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14568  81 RVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFE 137

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 30424589  21 SQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRT 100
Cdd:cd14513   2 SKIFDHLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRKGSKV 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 30424589 101 LLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14513  82 LVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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 30424589  22 QITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRTL 101
Cdd:cd14640   3 EILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 30424589 102 LHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQLF 159
Cdd:cd14640  83 VHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVL 140

dual specificity phosphatase domain of dual specificity protein phosphatase 22, 15, and similar proteins; Dual specificity protein phosphatase 22 (DUSP22, also known as VHX) and 15 (DUSP15, also known as VHY) function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). They are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. The both contain N-terminal myristoylation recognition sequences and myristoylation regulates their subcellular location. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. DUSP15 has been identified as a regulator of oligodendrocyte differentiation. DUSP22 is a single domain protein containing only the catalytic dual specificity phosphatase domain while DUSP15 contains a short C-terminal tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30424589  20 LSQITKSLFISNGVAANNKLLLSSNQITTVINVSvEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGR 99
Cdd:cd14519   1 MNKILPGLYVGNFRDAKDAEQLRENGITHILSIH-DSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIHEARLNGGN 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 30424589 100 TLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14519  80 VLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFE 135

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 30424589  22 QITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRTL 101
Cdd:cd14639   3 EILPFLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCVRRAGGKVL 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 30424589 102 LHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14639  83 VHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYE 136

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 30424589  20 LSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYED--IQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQK 97
Cdd:cd14567   1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKggFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSG 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30424589  98 GRTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQL 158
Cdd:cd14567  81 KGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDL 141

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP13A is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30424589  27 LFISNGVAANNKLLLSSNQITTVINVS-----VEVANTFY-EDIQYVQVPVVDAPVARLSNFFDSVADRIH-SVEMQKGR 99
Cdd:cd14580   8 LFLGDLATAHNRFGLWKLGITHVLNAAhgklfCQGGDDFYgTSVDYYGVPANDLPDFDISPYFYSAAEFIHrALNTPGAK 87

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 30424589 100 TLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIrPNSGFWEQLIHYELQL 158
Cdd:cd14580  88 VLVHCAVGVSRSATLVLAYLMIYHQLSLVQAIKTVKERRWIF-PNRGFLKQLRKLDQQL 145

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 30424589  20 LSQITKSLFISNGVAANNKLLLSSNQITTVINV-SVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHS------ 92
Cdd:cd14518   1 LSRILGGLYLGGIEPLNRNRLLKAENITHILSViPGDVPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIDSalfgng 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30424589  93 -----VEMQKGRTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14518  81 kdedeEKKHGGAVLVHCAMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRPIAEPNDGFMEQLELYH 148

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), 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. DUSP3 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 favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30424589  22 QITKSLFISNGVAANNKLLLSSNQITTVINVS-------VEVANTFYED--IQYVQVPVVDAPVARLSNFFDSVADRIH- 91
Cdd:cd14579  23 EVYPRIYVGNASVAQNIMRLQRLGITHVLNAAegksfmhVNTNAEFYEDtgITYHGIKANDTQHFNLSAYFEEAADFIDk 102

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30424589  92 SVEMQKGRTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPiIRPNSGFWEQLIHYELQL 158
Cdd:cd14579 103 ALAQKNGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKRE-IGPNDGFLKQLCQLNDKL 168

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 30424589  19 GLSQITKSLFISNGVAANNKLLLSSNQITTVINVSvEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKG 98
Cdd:cd14581   3 GMNKVLPGLYLGNFKDARDREQLSKNNITHILSVH-DSARPMLEGMTYLCIPAADSPSQNLTQHFKESIKFIHECRLRGE 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 30424589  99 RTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14581  82 GCLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFE 138

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 30424589  12 IPQPSIrGLSQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVAN-TFYEDIQYVQVPVVDAPVARLSNFFDSVADRI 90
Cdd:cd14645   5 LPVANV-GPTRILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKpDFICESHFMRIPVNDNYCEKLLPWLDKSIEFI 83

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30424589  91 HSVEMQKGRTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQL 158
Cdd:cd14645  84 DKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 30424589  18 RGLSQITKSLFI---SNGVAANNKLLLSsNQITTVINV-SVEVANT----FYEDIQYVQVPVVDAPVARLSNFFDSVADR 89
Cdd:cd14522   3 REMQEILPGLYLgpySAAMKSKLEVLLK-HGITHIVCVrQNIEANFikpnFPDHFRYLVLDVADNPTENIIRHFPTVKEF 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30424589  90 IHSVEMQKGRTLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14522  82 IDDCLQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147

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 30424589  21 SQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRT 100
Cdd:cd14570   5 SLIFDHLYLGSEWNASNLEELQGSGVGYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNDAYHFINKAKKNHSKC 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 30424589 101 LLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYE 155
Cdd:cd14570  85 LVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYE 139

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 30424589  22 QITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYE--DIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGR 99
Cdd:cd14644   5 QILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEKngDFHYKQIPISDHWSQNLSQFFPEAIEFIDEALSQNCG 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 30424589 100 TLLHCAAGVSRSAALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGFWEQLIHYELQL 158
Cdd:cd14644  85 VLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSL 143

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 30424589  49 VINVSVEVANTFYEDIQYVQVPVVDAPV----------------ARLSNFFDSVADRIHSVEMQKGRTLLHCAAGVSRSA 112
Cdd:cd14521  30 VINVAKEVKNPFLSDASLAEKEKTILPGqqvknpeyihvpwdhnSQIQKDLPKLTSIIEDATQSGKKVLIHCQCGVSRSA 109

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 30424589 113 ALCLAYLMKYHAMSLVDAHTWTKSCRPIIRPNSGfweqLIhYELQLFGKNT 163
Cdd:cd14521 110 SLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMS----LI-FQLMEFEKVL 155

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 30424589  21 SQITKSLFISNGVAANNKLLLSSNQITTVINVSVEVANTFYEDIQYVQVPVVDAPVARLSNFFDSVADRIHSVEMQKGRT 100
Cdd:cd14569   5 TQIFEHVFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPGLFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKC 84