dual specificity phosphatase-like domain of serine/threonine/tyrosine interacting like 1; Serine/threonine/tyrosine interacting like 1 (STYXL1), also known as DUSP24 and MK-STYX, is a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). STYXL1 plays a role in regulating pathways by competing with active phosphatases for binding to MAPKs. Similar to MKPs, STYXL1 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, however its C-terminal dual specificity phosphatase-like domain is a pseudophosphatase missing the catalytic cysteine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 152 PQELDAFQPYPIEIVPGEVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMC 231
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1482602550 232 HFIEIHLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILGDS 306
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

dual specificity phosphatase-like domain of serine/threonine/tyrosine interacting like 1; Serine/threonine/tyrosine interacting like 1 (STYXL1), also known as DUSP24 and MK-STYX, is a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). STYXL1 plays a role in regulating pathways by competing with active phosphatases for binding to MAPKs. Similar to MKPs, STYXL1 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, however its C-terminal dual specificity phosphatase-like domain is a pseudophosphatase missing the catalytic cysteine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 152 PQELDAFQPYPIEIVPGEVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMC 231
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1482602550 232 HFIEIHLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILGDS 306
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

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 1482602550 170 VFLGNFSQACDPKIQKdLKIKAHVNVSMDTgpFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSVVLIFST 249
Cdd:pfam00782   1 LYLGSKPTASDAFLSK-LGITAVINVTREV--DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1482602550 250 QGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWE 299
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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 1482602550  33 LFDVRSKWEYDESHVITA---------LRVKKKNN---EYLLP-----ESVDLECVKYCVVYDNNTSTLEVLLEddddds 95
Cdd:cd01446    20 LLDCRPFLEYSSSHIRGAvnvccptilRRRLQGGKillQQLLScpedrDRLRRGESLAVVVYDESSSDRERLRE------ 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1482602550  96 dsdsAGKVSDVVpgAAIEygRILTRLTRhpVYILKGGYERFSGTY 140
Cdd:cd01446    94 ----DSTAESVL--GKLL--RKLQEGCS--VYLLKGGFEQFSSEF 128

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 164 EIVPGEVFLGNFSqACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD---KLLHIRIEDS--PEAQILpflRHMCHFIEIHL 238
Cdd:COG2453     2 WIIPGLLAGGPLP-GGGEADLKREGIDAVVSLTEEEELLLGLLEEaglEYLHLPIPDFgaPDDEQL---QEAVDFIDEAL 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1482602550 239 HLGSVVLIFSTQGISRSCAAVIAYLMHCNeQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 302
Cdd:COG2453    78 REGKKVLVHCRGGIGRTGTVAAAYLVLLG-LSAEEALARVRAARPGAVETPAQRAFLERFAKRL 140

dual specificity phosphatase-like domain of serine/threonine/tyrosine interacting like 1; Serine/threonine/tyrosine interacting like 1 (STYXL1), also known as DUSP24 and MK-STYX, is a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). STYXL1 plays a role in regulating pathways by competing with active phosphatases for binding to MAPKs. Similar to MKPs, STYXL1 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, however its C-terminal dual specificity phosphatase-like domain is a pseudophosphatase missing the catalytic cysteine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 152 PQELDAFQPYPIEIVPGEVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMC 231
Cdd:cd14517     1 PRELDNLKTYPVEILPGFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERAC 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1482602550 232 HFIEIHLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILGDS 306
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKLLGTT 155

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 1482602550 162 PIEIVPGeVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIEIHLHL 240
Cdd:cd14566     1 PVEILPF-LYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEEDGGfKYLQIPIDDHWSQNLSAFFPEAISFIDEARSK 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1482602550 241 GSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLE 297
Cdd:cd14566    80 KCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLD 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 1482602550 170 VFLGNFSQACDPKIQKdLKIKAHVNVSMDTgpFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSVVLIFST 249
Cdd:pfam00782   1 LYLGSKPTASDAFLSK-LGITAVINVTREV--DLYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1482602550 250 QGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWE 299
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

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 1482602550 164 EIVPGeVFLGNFSqACDPKIQKDLKIKAHVNVSMDTGPFFAGDADkLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSV 243
Cdd:cd14514     3 QITPH-LFLSGAS-AATPPLLLSRGITCIINATTELPDPSYPGIE-YLRVPVEDSPHADLSPHFDEVADKIHQVKRRGGR 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1482602550 244 VLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLE 297
Cdd:cd14514    80 TLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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 1482602550 162 PIEIVPgEVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDADkLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLG 241
Cdd:cd14565     1 PVEILP-FLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQ-YKSIPVEDSHNADISSWFEEAIGFIDKVKASG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1482602550 242 SVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWE 299
Cdd:cd14565    79 GRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYE 136

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 1482602550 162 PIEIVPGeVFLGNFSQACDPKIQKDLKIkAHVnVSMDTGPFFAGDADKLLH---IRIEDSPEAQILPFLRHMCHFIEIHL 238
Cdd:cd14520     1 MKLVRPG-LYIGNADDAADYLSLREAGI-THV-LTVDSEEPIDAPPVGKLVrkfVPALDEESTDLLSRLDECLDFIDEGR 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1482602550 239 HLGSVvLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKT 301
Cdd:cd14520    78 AEGAV-LVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPDVKPNDGFLKQLKLYEAM 139

dual specificity phosphatase domain of dual specificity protein phosphatase 2; Dual specificity protein phosphatase 2 (DUSP2), also called dual specificity protein phosphatase PAC-1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other mitogen-activated protein kinase (MAPK) phosphatases (MKPs), it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP2 can preferentially dephosphorylate ERK1/2 and p38, but not JNK in vitro. It is predominantly expressed in hematopoietic tissues with high T-cell content, such as thymus, spleen, lymph nodes, peripheral blood and other organs such as the brain and liver. It has a critical and positive role in inflammatory responses. DUSP2 mRNA and protein are significantly reduced in most solid cancers including breast, colon, lung, ovary, kidney and prostate, and the suppression of DUSP2 is associated with tumorigenesis and malignancy. DUSP2 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 159 QPYPIEIVPgEVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHL 238
Cdd:cd14641     1 QGGPVEILP-FLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQF-QYKSIPVEDSHMADISAWFQEAIDFIDSVK 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1482602550 239 HLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTIL 303
Cdd:cd14641    79 NSGGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFETQVL 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 1482602550 213 IRIEDSPEAQILPFLRHMCHFIEIHLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLV 292
Cdd:cd14521    66 IHVPWDHNSQIQKDLPKLTSIIEDATQSGKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDAYDLLKSRSPWIGPNMSLI 145

                          90
                  ....*....|
gi 1482602550 293 SQLLEWEKTI 302
Cdd:cd14521   146 FQLMEFEKVL 155

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 1482602550 165 IVPGeVFLGNFSQACDPKIQKDLKIkAHVnVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSVV 244
Cdd:cd14519     4 ILPG-LYVGNFRDAKDAEQLRENGI-THI-LSIHDSARPLLEDIKYLCIPAADTPEQNISQHFRECINFIHEARLNGGNV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1482602550 245 LIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEK 300
Cdd:cd14519    81 LVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFEK 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 1482602550 162 PIEIVPGeVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLG 241
Cdd:cd14638     1 PVEILPF-LYLGSAYHASRKDMLDTLGITALINVSANCPNHFEGHY-QYKSIPVEDNHKADISSWFNEAIDFIDSVKNAG 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1482602550 242 SVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILGDSVT 308
Cdd:cd14638    79 GRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQLLQFESQVLAPSCS 145

dual specificity phosphatase domain of dual specificity protein phosphatase 19; Dual specificity protein phosphatase 19 (DUSP19), also called low molecular weight dual specificity phosphatase 3 (LMW-DSP3) or stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP19 interacts with the MAPK kinase MKK7, a JNK activator, and inactivates the JNK MAPK pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 164 EIVPGeVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAgDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSV 243
Cdd:cd14523     4 VIKPW-LLLSSQDVAHDLETLKKHKVTHILNVAYGVENAFP-DDFTYKTISILDLPETDITSYFPECFEFIDEAKSQDGV 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1482602550 244 VLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWE 299
Cdd:cd14523    82 VLVHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPSIRPNPGFMEQLKEYQ 137

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 1482602550 159 QP-YPIEIVPgEVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIEI 236
Cdd:cd14643     2 QPaFPVQILP-YLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGEfKYKQIPISDHWSQNLSQFFPEAISFIDE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1482602550 237 HLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 302
Cdd:cd14643    81 ARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTL 146

dual specificity phosphatase domain of slingshot homolog 3; Dual specificity protein phosphatase slingshot homolog 3 (SSH3), also called SSH-like protein 3, 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. The Xenopus homolog (xSSH) is involved in the gastrulation movement. Mouse SSH3 dephosphorylates actin-depolymerizing factor (ADF) and cofilin but is dispensable for development. There are at least two human SSH3 isoforms reported: hSSH-3L (long) and hSSH-3. 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-3L contains a C-terminal tail while hSSH-3 does not.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 162 PIEIVPgEVFLGNFSQACD-PKIQKDlKIKAHVNVSMDTGPFFAgDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHL 240
Cdd:cd14571     4 PSRIFP-YLYLGSEWNAANlEELQRN-RVSHILNVTREIDNFFP-ERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1482602550 241 GSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQL 295
Cdd:cd14571    81 GTRVLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQL 135

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 1482602550 161 YPIEIVPGeVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDAD-KLLHIRIEDSPEAQILPFLRHMCHFIEIHLH 239
Cdd:cd14642     2 FPVEILPY-LYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFENAGEfKYKQIPISDHWSQNLSQFFPEAISFIDEARG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1482602550 240 LGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 302
Cdd:cd14642    81 KNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTL 143

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 1482602550 170 VFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDADkLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSVVLIFST 249
Cdd:cd14573     9 LYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIE-YLHVPVADSPDTRLRDYFDPIADKIHTVEARGGRTLLHCV 87

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1482602550 250 QGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILGDSVTNIMD 312
Cdd:cd14573    88 AGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHYEFELFGKNTVHMIT 150

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 1482602550 162 PIEIVPgEVFLGNFSQACDPKIQKDLKIKAHVNVSMDT-GPFFAGDAdKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHL 240
Cdd:cd14646     3 PTRILP-HLYLGCQRDVLNKELMQQNGIGYVLNASNTCpKPDFIPES-HFLRVPVNDSFCEKILPWLDKSVDFIEKAKAS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1482602550 241 GSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI 302
Cdd:cd14646    81 NGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKI 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 1482602550 170 VFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGdADKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSVVLIFST 249
Cdd:cd14569    11 VFLGSEWNASNLEDLQNRGVRYILNVTREIDNFFPG-LFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCK 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1482602550 250 QGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILG 304
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 1482602550 164 EIVPGeVFLGNFSQACDPKIQKDLKI-----KAHVNVSMDTGPFFAGDADKLLH-IRIEDSPEAQILPFLRHMCHFIEIH 237
Cdd:cd14575    13 EVWPG-LYIGDEKTALDRYSLQKLGIthilnAAHGKWNVDTGAEYYKDMTIHYYgVEADDLPTFNLSQFFYSAAEFIHQA 91

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1482602550 238 LHL-GSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKcKNNMCPNRGLVSQLLEWEKTI 302
Cdd:cd14575    92 LSDpHNKLLVHCVMGRSRSATLVLAYLMIYKNMTVVDAIEQVAQ-RRCILPNRGFLKQLRELDIQL 156

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 1482602550 164 EIVPGeVFLGNFSQACDPKIQKDLKIKAHVNVSMDTGPFFAGDadKLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSV 243
Cdd:cd14581     6 KVLPG-LYLGNFKDARDREQLSKNNITHILSVHDSARPMLEGM--TYLCIPAADSPSQNLTQHFKESIKFIHECRLRGEG 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1482602550 244 VLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKT 301
Cdd:cd14581    83 CLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARSCANPNMGFQRQLQEFEKH 140

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 1482602550 209 KLLHIRIEDSPEAQILPFLRHMCHFIEIHLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPN 288
Cdd:cd14645    58 HFMRIPVNDNYCEKLLPWLDKSIEFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPN 137

                          90
                  ....*....|....
gi 1482602550 289 RGLVSQLLEWEKTI 302
Cdd:cd14645   138 FNFLGQLLEYEKSL 151

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 1482602550 244 VLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTILGDS 306
Cdd:cd14572    88 TLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRPVIRPNVGFWRQLIDYERKLFGKS 150

dual specificity phosphatase domain of fungal dual specificity protein phosphatase PPS1-like; This subfamily contains fungal proteins with similarity to dual specificity protein phosphatase PPS1 from Saccharomyces cerevisiae, which has a role in the DNA synthesis phase of the cell cycle. As a dual specificity protein phosphatase, PPS1 functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It contains a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1482602550 223 ILPFLRHMCHFIEIHLHLGSVVLIFSTQGISRSCAAVIAYLMHCNEQTLQRSWAYVKKCKNNMC--PNRGLVSQLLEWEK 300
Cdd:cd14516    98 LLPQLTDALDFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRRLNIIiqPNLRFFYELFKWEE 177