N-terminal regulatory rhodanese domain of dual specificity phosphatases (DSP), such as Mapk Phosphatase. This domain is believed to determine substrate specificity by binding the substrate, such as ERK2, and activating the C-terminal catalytic domain by inducing a conformational change. This domain has homology to the Rhodanese Homology Domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687  17 SKTVAWLNEQLELGNERLLLMDCRPQELYESSHIESAINVAIPGIMLRRLQKGNLPVRALFTRGEDRDRFTRRcGTDTVV 96
Cdd:cd01446   1 TIDCAWLAALLREGGERLLLLDCRPFLEYSSSHIRGAVNVCCPTILRRRLQGGKILLQQLLSCPEDRDRLRRG-ESLAVV 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 42764687  97 LYDESSSD---WNENTGGESVlGLLLKKLKDEGCRAFYLED 134
Cdd:cd01446  80 VYDESSSDrerLREDSTAESV-LGKLLRKLQEGCSVYLLKG 119

N-terminal regulatory rhodanese domain of dual specificity phosphatases (DSP), such as Mapk Phosphatase. This domain is believed to determine substrate specificity by binding the substrate, such as ERK2, and activating the C-terminal catalytic domain by inducing a conformational change. This domain has homology to the Rhodanese Homology Domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687  17 SKTVAWLNEQLELGNERLLLMDCRPQELYESSHIESAINVAIPGIMLRRLQKGNLPVRALFTRGEDRDRFTRRcGTDTVV 96
Cdd:cd01446   1 TIDCAWLAALLREGGERLLLLDCRPFLEYSSSHIRGAVNVCCPTILRRRLQGGKILLQQLLSCPEDRDRLRRG-ESLAVV 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 42764687  97 LYDESSSD---WNENTGGESVlGLLLKKLKDEGCRAFYLED 134
Cdd:cd01446  80 VYDESSSDrerLREDSTAESV-LGKLLRKLQEGCSVYLLKG 119

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 42764687   134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 198
Cdd:pfam00782  63 DDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

Rhodanese Homology Domain; An alpha beta fold found duplicated in the Rhodanese protein. The the Cysteine containing enzymatically active version of the domain is also found in the CDC25 class of protein phosphatases and a variety of proteins such as sulfide dehydrogenases and stress proteins such as Senesence specific protein 1 in plants, PspE and GlpE in bacteria and cyanide and arsenate resistance proteins. Inactive versions with a loss of the cysteine are also seen in Dual specificity phosphatases, ubiquitin hydrolases from yeast and in sulfuryltransferases. These are likely to play a role in protein interactions.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 42764687     30 GNERLLLMDCRPQELYESSHIESAINVAIPGIMLRRLQKGNLPVRALFtrgedrdRFTRRCGTDTVVLYDESSSDW 105
Cdd:smart00450   1 NDEKVVLLDVRSPEEYEGGHIPGAVNIPLSELLDRRGELDILEFEELL-------KRLGLDKDKPVVVYCRSGNRS 69

3-mercaptopyruvate sulfurtransferase SseA, contains two rhodanese domains [Inorganic ion transport and metabolism];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687  29 LGNERLLLMDCR-----PQELYESSHIESAINVAI------PGIMLRrlqkGNLPvralftrgeDRDRFTRRCG------ 91
Cdd:COG2897   5 LDDPDVVILDVRwdlpdGRAAYEAGHIPGAVFLDLdtdlsdPRSPGR----HPLP---------SPEAFAALLGalgisn 71

                        90
                ....*....|....
gi 42764687  92 TDTVVLYDESSSDW 105
Cdd:COG2897  72 DTTVVVYDDGGGLF 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 42764687 134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTLGLS 204
Cdd:cd14643  79 DEARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTLGLN 149

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687 134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTLGL 203
Cdd:cd14644  76 DEALSQNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSLGL 145

dual specificity phosphatase domain of mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs, which are involved in gene regulation, cell proliferation, programmed cell death and stress responses, as an important feedback control mechanism that limits MAPK cascades. MKPs, also referred to as typical DUSPs, 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. 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. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687 128 RAFYLEDEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDF 197
Cdd:cd14512  67 EAIEFIEEAKASNGGVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRPTISPNFNFMGQLLDF 136

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 42764687 128 RAFYLEDEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14568  67 KAVEFIEKARASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFEKKL 140

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 42764687 129 AFYLEDEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14567  69 AFEFIEEAHQSGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDL 141

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 42764687 139 KNCG--VLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 198
Cdd:cd14565  75 KASGgrVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYE 136

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 42764687 134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14646  75 EKAKASNGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKI 142

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 42764687 143 VLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14521  97 VLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLIFQLMEFEKVL 155

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 42764687 139 KNCG--VLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 198
Cdd:cd14641  78 KNSGgrVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFE 139

dual specificity phosphatase domain of dual specificity protein phosphatase 12 and similar proteins; Dual specificity protein phosphatase 12 (DUSP12), also called YVH1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP12 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It targets p38 MAPK to regulate macrophage response to bacterial infection. It also ameliorates cardiac hypertrophy in response to pressure overload through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 has been identified as a modulator of cell cycle progression, a function independent of phosphatase activity and mediated by its C-terminal zinc-binding domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 42764687 134 DEARGKNcGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERT 200
Cdd:cd14520  74 DEGRAEG-AVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLYEAM 139

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 42764687 135 EARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 198
Cdd:cd14519  72 EARLNGGNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFE 135

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 42764687 127 CRAFYLEDEARGKNCgvLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERT 200
Cdd:cd14581  69 SIKFIHECRLRGEGC--LVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFEKH 140

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 42764687 139 KNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14572  84 KHGATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYERKL 146

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 42764687  97 LYDESSSD----WNEntggesvlglllkklkdegcrAFYLEDEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMND 172
Cdd:cd14513  52 VWDEESTNllpyWNE---------------------TYRFIKEARRKGSKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQ 110

                        90       100
                ....*....|....*....|....*.
gi 42764687 173 AYDIVKMKKSNISPNFNFMGQLLDFE 198
Cdd:cd14513 111 ALEHVKERRSCIKPNPGFLRQLITYE 136

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 42764687 134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFE 198
Cdd:cd14522  83 DDCLQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVQQRRFCINPNEGFVHQLKEYE 147

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 42764687 135 EARGKNcgVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14573  76 EARGGR--TLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFEL 140

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 42764687 125 EGCRAFYLEDEARGKNCgvLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 201
Cdd:cd14574  65 EQCADAIEAAVRRGGKC--LVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEEL 139

dual specificity protein phosphatase 26; Dual specificity protein phosphatase 26 (DUSP26), also called mitogen-activated protein kinase (MAPK) phosphatase 8 (MKP-8) or low-molecular-mass dual-specificity phosphatase 4 (LDP-4), 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. DUSP26 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 a brain phosphatase highly overexpressed in neuroblastoma and has also been identified as a p53 phosphatase, dephosphorylating phospho-Ser20 and phospho-Ser37 in the p53 transactivation domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 42764687 135 EARGKncgVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSnISPNFNFMGQLLDFERTL 201
Cdd:cd14578  82 QPGGK---ILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDHRG-IIPNRGFLRQLLALDRRL 144

Rhodanese Homology Domain; An alpha beta fold found duplicated in the Rhodanese protein. The the Cysteine containing enzymatically active version of the domain is also found in the CDC25 class of protein phosphatases and a variety of proteins such as sulfide dehydrogenases and stress proteins such as Senesence specific protein 1 in plants, PspE and GlpE in bacteria and cyanide and arsenate resistance proteins. Inactive versions with a loss of the cysteine are also seen in Dual specificity phosphatases, ubiquitin hydrolases from yeast and in sulfuryltransferases. These are likely to play a role in protein interactions.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 42764687     30 GNERLLLMDCRPQELYESSHIESAINVAIPGIMLRRLQKGNLPVRALFtrgedrdRFTRRCGTDTVVLYDESSSDW 105
Cdd:smart00450   1 NDEKVVLLDVRSPEEYEGGHIPGAVNIPLSELLDRRGELDILEFEELL-------KRLGLDKDKPVVVYCRSGNRS 69

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 42764687  37 MDcRPQELYESSHIESAINVAipgiMLRRLQkgNLPVRALFTRGEDRDRFTRRC-GTDTVVLYDESSSD----WNENTgg 111
Cdd:cd14569   1 MD-SPTQIFEHVFLGSEWNAS----NLEDLQ--NRGVRYILNVTREIDNFFPGLfEYHNIRVYDEEATDllayWNDTY-- 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687 112 esvlglllkklkdegcrAFYLEDEARGKNCgvLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFM 191
Cdd:cd14569  72 -----------------KFISKAKKHGSKC--LVHCKMGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFM 132

                       170
                ....*....|
gi 42764687 192 GQLLDFERTL 201
Cdd:cd14569 133 RQLEEYQGIL 142

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
                ....*....|....*....|....*....|....*....|....*....|...
gi 42764687 134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISP 186
Cdd:cd14524  83 LKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILL 135

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 42764687 139 KNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSnISPNFNFMGQLLDFERTL 201
Cdd:cd14579 107 KNGRVLVHCREGYSRSPTLVIAYLMLRQKMDVKSALSTVRQKRE-IGPNDGFLKQLCQLNDKL 168

Rhodanese-like domain; Rhodanese has an internal duplication. This Pfam represents a single copy of this duplicated domain. The domain is found as a single copy in other proteins, including phosphatases and ubiquitin C-terminal hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687    29 LGNERLLLMDCRPQELYESSHIESAINVAIPGIMLRrlqkgNLPVRALFTRGEDRDRFtrrcgtDTVVLYDESSSDWNEN 108
Cdd:pfam00581   1 LEDGKVVLIDVRPPEEYAKGHIPGAVNVPLSSLSLP-----PLPLLELLEKLLELLKD------KPIVVYCNSGNRAAAA 69

                  .
gi 42764687   109 T 109
Cdd:pfam00581  70 A 70

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 42764687 143 VLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVkMKKSNISPNFNFMGQLLDFERTLGL 203
Cdd:cd14575  99 LLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQV-AQRRCILPNRGFLKQLRELDIQLAE 158

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 42764687 132 LEDEARGKNCgVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKS 182
Cdd:cd14526  87 LYRLLKNGGT-VYVHCTAGLGRAPATVIAYLYWVLGYSLDEAYYLLTSKRP 136

Thiosulfate sulfurtransferase (TST), N-terminal, inactive domain. TST contains 2 copies of the Rhodanese Homology Domain; this is the 1st repeat, which does not contain the catalytically active Cys residue. The role of the 1st repeat is uncertain, but it is believed to be involved in protein interaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42764687  19 TVAWLNEQLElgNERLLLMDCR-------PQELYESSHIESAINVAIPGIMLRRL-QKGNLPvralftrgeDRDRFTRRC 90
Cdd:cd01448   3 SPDWLAEHLD--DPDVRILDARwylpdrdGRKEYLEGHIPGAVFFDLDEDLDDKSpGPHMLP---------SPEEFAELL 71

                        90       100
                ....*....|....*....|.
gi 42764687  91 GT------DTVVLYDESSSDW 105
Cdd:cd01448  72 GSlgisndDTVVVYDDGGGFF 92

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
                ....*....|....*....|....*....|....*....|
gi 42764687 134 DEARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDA 173
Cdd:cd14504  76 EEANAKNEAVLVHCLAGKGRTGTMLACYLVKTGKISAVDA 115

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
                   ....*....|....*....|....*....|....*....|
gi 42764687    143 VLVHCLAGISRSVT-VTVAYLMQKLNLSMN--DAYDIVKM 179
Cdd:smart00012  42 VVVHCSAGVGRTGTfVAIDILLQQLEAEAGevDIFDTVKE 81

Rhodanese Homology Domain (RHOD); an alpha beta fold domain found duplicated in the rhodanese protein. The cysteine containing enzymatically active version of the domain is also found in the Cdc25 class of protein phosphatases and a variety of proteins such as sulfide dehydrogenases and certain stress proteins such as senesence specific protein 1 in plants, PspE and GlpE in bacteria and cyanide and arsenate resistance proteins. Inactive versions (no active site cysteine) are also seen in dual specificity phosphatases, ubiquitin hydrolases from yeast and in sulfuryltransferases, where they are believed to play a regulatory role in multidomain proteins.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 42764687  29 LGNERLLLMDCRPQELYESSHIESAINVAIPGIMLRRLQKGNlpvralftrgeDRDRftrrcgtdTVVLYDES 101
Cdd:cd00158   6 LDDEDAVLLDVREPEEYAAGHIPGAINIPLSELEERAALLEL-----------DKDK--------PIVVYCRS 59

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 42764687 132 LEDEARGKNCGVLVHCLAGISRS-VTVTVAYLMQKLNLSMN-DAYDIVKM 179
Cdd:cd00047 131 VRKEARKPNGPIVVHCSAGVGRTgTFIAIDILLERLEAEGEvDVFEIVKA 180