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 2462497808 136 SQPCLPVPSVGLTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRFMRVPINDNYCEKLLPWLDKSI 215
Cdd:cd14645     1 SQPCLPVANVGPTRILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKPDFICESHFMRIPVNDNYCEKLLPWLDKSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462497808 216 EFIDKAKLSSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSL 286
Cdd:cd14645    81 EFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 2462497808 136 SQPCLPVPSVGLTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRFMRVPINDNYCEKLLPWLDKSI 215
Cdd:cd14645     1 SQPCLPVANVGPTRILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKPDFICESHFMRIPVNDNYCEKLLPWLDKSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462497808 216 EFIDKAKLSSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSL 286
Cdd:cd14645    81 EFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 2462497808 154 LYLGSQKDVLNKdLMTQNGISYVLNASNSCPKPDfiCESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSCQVIVHCL 233
Cdd:pfam00782   1 LYLGSKPTASDA-FLSKLGITAVINVTREVDLYN--SGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQ 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462497808 234 AGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:pfam00782  78 AGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEYE 127

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 150 ILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRFM---RVPINDNYCEKLLPWlDKSIEFIDKAKLSSC 226
Cdd:COG2453     3 IIPGLLAGGPLPGGGEADLKREGIDAVVSLTEEEELLLGLLEEAGLeylHLPIPDFGAPDDEQL-QEAVDFIDEALREGK 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 227 QVIVHCLAGISRSATIAIAYIMKTmGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSL 286
Cdd:COG2453    82 KVLVHCRGGIGRTGTVAAAYLVLL-GLSAEEALARVRAARPGAVETPAQRAFLERFAKRL 140

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 2462497808  25 GGPLVIDSRSFVEYNSWHVLSSVNICCSKLVKRRLQQGKVEATEP-----QDVVVYDQSTRDASVLAAdsflsiLLSKLd 99
Cdd:pfam00581   4 GKVVLIDVRPPEEYAKGHIPGAVNVPLSSLSLPPLPLLELLEKLLellkdKPIVVYCNSGNRAAAAAA------LLKAL- 76

                          90
                  ....*....|...
gi 2462497808 100 GCFDsVAILTGGF 112
Cdd:pfam00581  77 GYKN-VYVLDGGF 88

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462497808 216 EFIDKAKLSSCqVIVHCLAGISRSAT-IAIAYImKTMGMSSDDAYRFVKDRR 266
Cdd:PTZ00242   90 EFAKQSTPPET-IAVHCVAGLGRAPIlVALALV-EYGGMEPLDAVGFVREKR 139

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 2462497808 136 SQPCLPVPSVGLTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRFMRVPINDNYCEKLLPWLDKSI 215
Cdd:cd14645     1 SQPCLPVANVGPTRILPHLYLGSQKDVLNKDLMAQNGITYVLNASNSCPKPDFICESHFMRIPVNDNYCEKLLPWLDKSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462497808 216 EFIDKAKLSSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSL 286
Cdd:cd14645    81 EFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEYEKSL 151

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 2462497808 145 VGLTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLS 224
Cdd:cd14646     1 IGPTRILPHLYLGCQRDVLNKELMQQNGIGYVLNASNTCPKPDFIPESHFLRVPVNDSFCEKILPWLDKSVDFIEKAKAS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462497808 225 SCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSLK 287
Cdd:cd14646    81 NGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRPTISPNFNFLGQLLDFEKKIK 143

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808  148 TRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKpDFICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSCQ 227
Cdd:smart00195   2 SEILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPN-YNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGK 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462497808  228 VIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYER 284
Cdd:smart00195  81 VLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYER 137

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 2462497808 149 RILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPK-----PDFicesRFMRVPINDNYCEKLLPWLDKSIEFIDKAKL 223
Cdd:cd14566     3 EILPFLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNtfeedGGF----KYLQIPIDDHWSQNLSAFFPEAISFIDEARS 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462497808 224 SSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEY 282
Cdd:cd14566    79 KKCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLLDF 137

dual specificity phosphatase domain of dual specificity protein phosphatase 10; Dual specificity protein phosphatase 10 (DUSP10), also called mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP-5), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP10/MKP-5 coordinates skeletal muscle regeneration by negatively regulating mitochondria-mediated apoptosis. It is also an important regulator of intestinal epithelial barrier function and a suppressor of colon tumorigenesis. DUSP10/MKP-5 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 147 LTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDF-ICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSS 225
Cdd:cd14567     1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEgKGGFRYKRLPATDSNKQNLRQYFEEAFEFIEEAHQSG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462497808 226 CQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSL 286
Cdd:cd14567    81 KGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEEDL 141

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 2462497808 136 SQPCLPVpsvgltRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKP-DFICESRFMRVPINDNYCEKLLPWLDKS 214
Cdd:cd14643     1 SQPAFPV------QILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMfEHDGEFKYKQIPISDHWSQNLSQFFPEA 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462497808 215 IEFIDKAKLSSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSLKL 288
Cdd:cd14643    75 ISFIDEARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERTLGL 148

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 2462497808  10 VMDAKKLASLLRGGPGGPLVIDSRSFVEYNSWHVLSSVNICCSKLVKRRLQQGKV---------------EATEPQDVVV 74
Cdd:cd01446     1 TIDCAWLAALLREGGERLLLLDCRPFLEYSSSHIRGAVNVCCPTILRRRLQGGKIllqqllscpedrdrlRRGESLAVVV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462497808  75 YDQSTRDASVLAADSFLSILLSKLD---GCFDSVAILTGGFATFSSCFPGLC 123
Cdd:cd01446    81 YDESSSDRERLREDSTAESVLGKLLrklQEGCSVYLLKGGFEQFSSEFPELC 132

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 150 ILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKpDFICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSCQVI 229
Cdd:cd14640     4 ILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPN-HFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCNGRVL 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462497808 230 VHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:cd14640    83 VHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQLLQFE 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 2462497808 147 LTRILPHLYLGSqKDVLNKDLMTQNGISYVLNASNscPKPDFICES-RFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSS 225
Cdd:cd14514     1 ISQITPHLFLSG-ASAATPPLLLSRGITCIINATT--ELPDPSYPGiEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRG 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462497808 226 CQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLE 281
Cdd:cd14514    78 GRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARPIIRPNVGFWRQLIE 133

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 2462497808 148 TRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPK--PDFIcesRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSS 225
Cdd:cd14513     2 SKIFDHLYLGSEWNASNLEELQNNGVKYILNVTREIDNffPGRF---TYHNIRVWDEESTNLLPYWNETYRFIKEARRKG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462497808 226 CQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:cd14513    79 SKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 136

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 2462497808 150 ILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPdFICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSCQVI 229
Cdd:cd14639     4 ILPFLYLGSAYHASKCEFLANLHITALLNVSRRSSEA-CKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCVRRAGGKVL 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462497808 230 VHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:cd14639    83 VHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYE 136

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 2462497808 147 LTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNScPKPdfICESR-FMRVPINDNYCEKLLPWLDKSIEFIDKAKLSS 225
Cdd:cd14519     1 MNKILPGLYVGNFRDAKDAEQLRENGITHILSIHDS-ARP--LLEDIkYLCIPAADTPEQNISQHFRECINFIHEARLNG 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462497808 226 CQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:cd14519    78 GNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEFE 135

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family 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. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 152 PHLYLGSQKDVLNKDLMTQNGISYVLNASNSC------PKPDFICES--RFMRVPINDNYCEKLLPWLDKSIEFIDKA-K 222
Cdd:cd14515     6 PGIYIGDESTAKNKAKLKKLGITHVLNAAEGKkngevnTNAKFYKGSgiIYLGIPASDLPTFDISQYFDEAADFIDKAlS 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462497808 223 LSSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRpSISPNFNFLGQLLEYERSL 286
Cdd:cd14515    86 DPGGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRKKR-EIRPNRGFLQQLCELNDKL 148

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 2462497808 147 LTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRfMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSC 226
Cdd:cd14574     1 LCRVTDSLFISNARAACNEELLAREGVTLCVNVSRQQPFPRAPRVST-LRVPVFDDPAEDLYRHFEQCADAIEAAVRRGG 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462497808 227 QVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSLK 287
Cdd:cd14574    80 KCLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVAEPNPGFWSQLQRYEEELQ 140

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 2462497808 148 TRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPkpDFICES-RFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSC 226
Cdd:cd14571     5 SRIFPYLYLGSEWNAANLEELQRNRVSHILNVTREID--NFFPERfTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGT 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462497808 227 QVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:cd14571    83 RVLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQ 139

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 2462497808 148 TRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPK--PDFICesrFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSS 225
Cdd:cd14570     5 SLIFDHLYLGSEWNASNLEELQGSGVGYILNVTREIDNffPGLFA---YHNIRVYDEETTDLLAHWNDAYHFINKAKKNH 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462497808 226 CQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYE 283
Cdd:cd14570    82 SKCLVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEYE 139

dual specificity phosphatase domain of dual specificity protein phosphatase 15; Dual specificity protein phosphatase 15 (DUSP15), also called Vaccinia virus VH1-related dual-specific protein phosphatase Y (VHY) or VH1-related member Y, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). DUSP15 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 highly expressed in the testis and is located in the plasma membrane in a myristoylation-dependent manner. It may be involved in the regulation of meiotic signal transduction in testis cells. It is also expressed in the brain and has been identified as a regulator of oligodendrocyte differentiation. DUSP15 contains an N-terminal catalytic dual specificity phosphatase domain and a short C-terminal tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 146 GLTRILPHLYLGSQKDVLNKDLMTQNGISYVLNASNScPKPdFICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSS 225
Cdd:cd14582     4 GMTKVLPGLYLGNFIDAKDLEQLSRNKITHIISIHES-PQP-LLQDITYLRIPLPDTPEAPIKKHFKECISFIHQCRLNG 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462497808 226 CQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEY 282
Cdd:cd14582    82 GNCLVHCLAGISRSTTIVVAYVMAVTELSWQEVLEAIRAVRPIANPNPGFKQQLEEF 138

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 2462497808 148 TRILPH-LYLGSQKDVLNKDLMTQNGISYVLNASNSCP---KPDFI--CESRFMRVPINDnycekllpwldkSIEFIDKA 221
Cdd:cd18534     2 TEILPGfLYLGSYDNASRAELLKAQGITRILNTVPDCQnlyKNSFTyhVLSEEKTVPFAE------------AVDFIEQC 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462497808 222 KLSSCQVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEY 282
Cdd:cd18534    70 RKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSPAVAKQLQEF 130

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 2462497808 150 ILP-HLYLGSQKDVLNKDLMTQNGISYVLNASNSCPKPDFICESRFMRVPINDNYCEKLLPWLDKSIEFIDKAKLSSCQV 228
Cdd:cd14517    14 ILPgFLYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDQVLHIPVEDSVEADLLSFFERACSFIDKHKNNGSRV 93

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462497808 229 IVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRPSISPNFNFLGQLLEYERSL 286
Cdd:cd14517    94 LVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQLSEWEEKL 151

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 152 PHLYLGSQKDVLNKDLMTQNGISYVLNASNSCPK--PDFI--CESRFMRVPINDNYCEKLLPWLDKSIEFIDKA-KLSSC 226
Cdd:cd14578     6 PGLYLGDQDIAANRRELRRLGITHILNASHSKWRggAEYYegLNIRYLGIEAHDSPAFDMSIHFYPAADFIHRAlSQPGG 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462497808 227 QVIVHCLAGISRSATIAIAYIMKTMGMSSDDAYRFVKDRRpSISPNFNFLGQLLEYERSL 286
Cdd:cd14578    86 KILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTVKDHR-GIIPNRGFLRQLLALDRRL 144