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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801     31 LCLLDVRSKWEYDESHVITALRVKKKNNEY-----------LLPESVDLECVKYCVVYDNNSSTleillkdddddsdsdg 99
Cdd:smart00450   5 VVLLDVRSPEEYEGGHIPGAVNIPLSELLDrrgeldilefeELLKRLGLDKDKPVVVYCRSGNR---------------- 68

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 29840801    100 dgkdlvpqaAIEYGRILTRLTHHPVYILKGGYERFSGTYH 139
Cdd:smart00450  69 ---------SAKAAWLLRELGFKNVYLLDGGYKEWSAAGP 99

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801    164 VPGKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSVIL 243
Cdd:smart00195   4 ILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDF-TYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGKVL 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 29840801    244 IFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKT 299
Cdd:smart00195  83 VHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801     31 LCLLDVRSKWEYDESHVITALRVKKKNNEY-----------LLPESVDLECVKYCVVYDNNSSTleillkdddddsdsdg 99
Cdd:smart00450   5 VVLLDVRSPEEYEGGHIPGAVNIPLSELLDrrgeldilefeELLKRLGLDKDKPVVVYCRSGNR---------------- 68

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 29840801    100 dgkdlvpqaAIEYGRILTRLTHHPVYILKGGYERFSGTYH 139
Cdd:smart00450  69 ---------SAKAAWLLRELGFKNVYLLDGGYKEWSAAGP 99

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 29840801  33 LLDVRSKWEYDESHVITA---------LRVKKKNN---EYLLP-----ESVDLECVKYCVVYDNNSSTLEILLKDdddds 95
Cdd:cd01446  20 LLDCRPFLEYSSSHIRGAvnvccptilRRRLQGGKillQQLLScpedrDRLRRGESLAVVVYDESSSDRERLRED----- 94

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 29840801  96 dsdgdgkdlvpQAAIEYGRILTRLTH--HPVYILKGGYERFSGTY 138
Cdd:cd01446  95 -----------STAESVLGKLLRKLQegCSVYLLKGGFEQFSSEF 128

dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in typical and atypical dual-specificity phosphatases (DUSPs), which function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Atypical DUSPs contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Also included in this family are dual specificity phosphatase-like domains of catalytically inactive members such as serine/threonine/tyrosine-interacting protein (STYX) and serine/threonine/tyrosine interacting like 1 (STYXL1), as well as active phosphatases with substrates that are not phosphoproteins such as PTP localized to the mitochondrion 1 (PTPMT1), which is a lipid phosphatase, and laforin, which is a glycogen phosphatase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 160 PIEIVPGkVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLG 239
Cdd:cd14498   1 PSEILPG-LYLGSLDAAQDKELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIEDSPDEDILSHFEEAIEFIEEALKKG 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 29840801 240 SVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLE 295
Cdd:cd14498  80 GKVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRPIISPNPGFLKQLKE 135

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 29840801 160 PIEIVPGkVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIEIHHHL 238
Cdd:cd14566   1 PVEILPF-LYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEEDGGfKYLQIPIDDHWSQNLSAFFPEAISFIDEARSK 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 29840801 239 GSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLE 295
Cdd:cd14566  80 KCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLD 136

dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins; This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 162 EIVPGkVFVGNFSqACDPKIQKDLKIKAHVNVSMDTGPFFAGDADkLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSV 241
Cdd:cd14514   3 QITPH-LFLSGAS-AATPPLLLSRGITCIINATTELPDPSYPGIE-YLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGR 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 29840801 242 ILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLE 295
Cdd:cd14514  80 TLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 160 PIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDT-GPFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHL 238
Cdd:cd14512   1 PTRILP-NLYLGSQRDSLNLELMQQLGIGYVLNVSNTCpNPDFIGLF-HYKRIPVNDSFCQNISPWFDEAIEFIEEAKAS 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 29840801 239 GSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEW 296
Cdd:cd14512  79 NGGVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRPTISPNFNFMGQLLDF 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 160 PIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTG-PFFAGDaDKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHL 238
Cdd:cd14568   1 PTRILP-HLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPkPDFIPD-SHFLRIPVNDSYCEKLLPWLDKAVEFIEKARAS 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 29840801 239 GSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14568  79 NKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRPTISPNFNFLGQLLEFEKKL 140

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 160 PIEIVPGkVFVGNFSQACDPKIQKDLKIkAHVnVSMDTGPFFAGDADKLLH---IRIEDSPEAQILPFLRHMCHFIEIHH 236
Cdd:cd14520   1 MKLVRPG-LYIGNADDAADYLSLREAGI-THV-LTVDSEEPIDAPPVGKLVrkfVPALDEESTDLLSRLDECLDFIDEGR 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 29840801 237 HLGSViLIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKT 299
Cdd:cd14520  78 AEGAV-LVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLYEAM 139

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 29840801 160 PIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDadklLH---IRIEDSPEAQILPFLRHMCHFIEIHH 236
Cdd:cd14639   1 PVEILP-FLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQ----YHykwIPVEDSHTADISSHFQEAIDFIDCVR 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 29840801 237 HLGSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWE 297
Cdd:cd14639  76 RAGGKVLVHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYE 136

dual specificity phosphatase domain of dual specificity protein phosphatase 1; Dual specificity protein phosphatase 1 (DUSP1), also called mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. Human MKP-1 dephosphorylates MAPK1/ERK2, regulating its activity during the meiotic cell cycle. Although initially MKP-1 was considered to be ERK-specific, it has been shown that MKP-1 also dephosphorylates both JNK and p38 MAPKs. DUSP1/MKP-1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. It is a central regulator of a variety of functions in the immune, metabolic, cardiovascular, and nervous systems. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 160 PIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLG 239
Cdd:cd14638   1 PVEILP-FLYLGSAYHASRKDMLDTLGITALINVSANCPNHFEGHY-QYKSIPVEDNHKADISSWFNEAIDFIDSVKNAG 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 29840801 240 SVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILG 302
Cdd:cd14638  79 GRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFESQVLA 141

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 29840801 163 IVPGkVFVGNFSQACDPKIQKDLKIkAHVnVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSVI 242
Cdd:cd14519   4 ILPG-LYVGNFRDAKDAEQLRENGI-THI-LSIHDSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIHEARLNGGNV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 29840801 243 LIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEK 298
Cdd:cd14519  81 LVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 136

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 29840801 157 QP-YPIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIEI 234
Cdd:cd14643   2 QPaFPVQILP-YLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGEfKYKQIPISDHWSQNLSQFFPEAISFIDE 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 29840801 235 HHHLGSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14643  81 ARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 168 VFVGNFSQACDPKIQKDLKIKAHVNVSMDTgPFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSVILIFST 247
Cdd:cd14574   8 LFISNARAACNEELLAREGVTLCVNVSRQQ-PFPRAPRVSTLRVPVFDDPAEDLYRHFEQCADAIEAAVRRGGKCLVYCK 86

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 29840801 248 QGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14574  87 NGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEEL 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 29840801 159 YPIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIE--IH 235
Cdd:cd14644   2 FPVQILP-NLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEKNGDfHYKQIPISDHWSQNLSQFFPEAIEFIDeaLS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 29840801 236 HHLGsvILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14644  81 QNCG--VLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQLLDFEKSL 143

dual specificity phosphatase domain of dual specificity protein phosphatase 6; Dual specificity protein phosphatase 6 (DUSP6), also called mitogen-activated protein kinase (MAPK) phosphatase 3 (MKP-3) or dual specificity protein phosphatase PYST1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP6/MKP-3 plays an important role in obesity-related hyperglycemia by promoting hepatic glucose output. MKP-3 deficiency attenuates body weight gain induced by a high-fat diet, protects mice from developing obesity-related hepatosteatosis, and reduces adiposity, possibly by repressing adipocyte differentiation. It also contributes to p53-controlled cellular senescence. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 159 YPIEIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIEIHHH 237
Cdd:cd14642   2 FPVEILP-YLYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFENAGEfKYKQIPISDHWSQNLSQFFPEAISFIDEARG 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 29840801 238 LGSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14642  81 KNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 143

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 29840801 191 VNVSMDTGPFFAGdADKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSVILIFSTQGISRSCAAIIAYLMHSNEQTLQ 270
Cdd:cd14570  34 LNVTREIDNFFPG-LFAYHNIRVYDEETTDLLAHWNDAYHFINKAKKNHSKCLVHCKMGVSRSASTVIAYAMKEFGWSLE 112

                        90       100
                ....*....|....*....|....*..
gi 29840801 271 RSWAYVKKCKNNMCPNRGLVSQLLEWE 297
Cdd:cd14570 113 KAYNFVKQKRSITRPNAGFMRQLLEYE 139

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 29840801 199 PFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKK 278
Cdd:cd14646  42 PDFIPES-HFLRVPVNDSFCEKILPWLDKSVDFIEKAKASNGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKE 120

                        90       100
                ....*....|....*....|..
gi 29840801 279 CKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14646 121 KRPTISPNFNFLGQLLDFEKKI 142

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 29840801 168 VFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGdADKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSVILIFST 247
Cdd:cd14569  11 VFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPG-LFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCK 89

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 29840801 248 QGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILG 302
Cdd:cd14569  90 MGVSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLA 144

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 29840801 162 EIVPGkVFVGNFSQACDPKIQKDLKI-----KAHVNVSMDTGPFFAGDADKLLH-IRIEDSPEAQILPFLRHMCHFIeiH 235
Cdd:cd14575  13 EVWPG-LYIGDEKTALDRYSLQKLGIthilnAAHGKWNVDTGAEYYKDMTIHYYgVEADDLPTFNLSQFFYSAAEFI--H 89

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 29840801 236 HHLG---SVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKcKNNMCPNRGLVSQLLEWEKTI 300
Cdd:cd14575  90 QALSdphNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQVAQ-RRCILPNRGFLKQLRELDIQL 156

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801     31 LCLLDVRSKWEYDESHVITALRVKKKNNEY-----------LLPESVDLECVKYCVVYDNNSSTleillkdddddsdsdg 99
Cdd:smart00450   5 VVLLDVRSPEEYEGGHIPGAVNIPLSELLDrrgeldilefeELLKRLGLDKDKPVVVYCRSGNR---------------- 68

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 29840801    100 dgkdlvpqaAIEYGRILTRLTHHPVYILKGGYERFSGTYH 139
Cdd:smart00450  69 ---------SAKAAWLLRELGFKNVYLLDGGYKEWSAAGP 99

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 29840801 189 AHVNVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIeiHHHL---GSVILIFSTQGISRSCAAIIAYLMHSN 265
Cdd:cd14580  34 AHGKLFCQGGDDFYGTSVDYYGVPANDLPDFDISPYFYSAAEFI--HRALntpGAKVLVHCAVGVSRSATLVLAYLMIYH 111

                        90       100
                ....*....|....*....|....*....
gi 29840801 266 EQTLQRSWAYVKKcKNNMCPNRGLVSQLL 294
Cdd:cd14580 112 QLSLVQAIKTVKE-RRWIFPNRGFLKQLR 139

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 29840801 162 EIVPGkVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDadKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGSV 241
Cdd:cd14581   6 KVLPG-LYLGNFKDARDREQLSKNNITHILSVHDSARPMLEGM--TYLCIPAADSPSQNLTQHFKESIKFIHECRLRGEG 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 29840801 242 ILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKT 299
Cdd:cd14581  83 CLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFEKH 140

dual specificity phosphatase domain of plant IBR5-like protein phosphatases; This subfamily is composed of Arabidopsis thaliana INDOLE-3-BUTYRIC ACID (IBA) RESPONSE 5 (IBR5) and similar plant proteins. IBR5 protein is also called SKP1-interacting partner 33. The IBR5 gene encodes a dual-specificity phosphatase (DUSP) which acts as a positive regulator of plant responses to auxin and abscisic acid. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. IBR5 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs. It has been shown to target MPK12, which is a negative regulator of auxin signaling.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29840801 160 PIEIVPGKVFVGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDadkllhIRIEDSPEAQILPFlRHMCHFIEIHHHLG 239
Cdd:cd18534   1 PTEILPGFLYLGSYDNASRAELLKAQGITRILNTVPDCQNLYKNS------FTYHVLSEEKTVPF-AEAVDFIEQCRKDK 73

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 29840801 240 SVILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVK 277
Cdd:cd18534  74 ARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVK 111

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 29840801  33 LLDVRSKWEYDESHVITA---------LRVKKKNN---EYLLP-----ESVDLECVKYCVVYDNNSSTLEILLKDdddds 95
Cdd:cd01446  20 LLDCRPFLEYSSSHIRGAvnvccptilRRRLQGGKillQQLLScpedrDRLRRGESLAVVVYDESSSDRERLRED----- 94

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 29840801  96 dsdgdgkdlvpQAAIEYGRILTRLTH--HPVYILKGGYERFSGTY 138
Cdd:cd01446  95 -----------STAESVLGKLLRKLQegCSVYLLKGGFEQFSSEF 128

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 29840801 162 EIVPgKVFVGNFSQACDPKIQKDLKIKAHVNVS-------MDTGP-FFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIE 233
Cdd:cd14579  23 EVYP-RIYVGNASVAQNIMRLQRLGITHVLNAAegksfmhVNTNAeFYEDTGITYHGIKANDTQHFNLSAYFEEAADFID 101