N-terminal domain conserved in slingshot (SSH) phosphatases; This domain or region conserved in Bilateria is found N-terminal to the DEK_C-like and catalytic domains of slingshot phosphatases. Slingshot is a cofilin-specific phosphatase. Dephosphorylation reactivates cofilin, which in turn depolymerizes actin and is thus required for actin filament reorganization. Slingshot is a member of the dual-specificity protein phosphatase family. This N-terminal SSH region may be involved in P-cofilin binding (the model C-terminus plus the DEK_C-like domain, which are characterized as the "B" domain in some of the literature), and may be required for the F-actin mediated activation of slingshot (the N-terminal region of this model, sometimes referred to as the "A" domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525   3 LVTLQRSPTPSAASSSASNSELEAGSEEDRKLNLSLSESFFMVKGAALFLQQGSSPQGQRSLQHpHKHAGDLPQHLQVMI 82
Cdd:cd11652     1 LVTVQRSPTPSGNSNPDGSDDEEEGDEEQRRKRLQRSESFFAVKGAALILPQGDRTNRPREIAS-HKHAGELQQHLQAMF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525  83 NLLRCEDRIKLAVRLESAWADRVRYMVVVYSSGRQDTEENILLGVDFSSKESkSCTIGMVLRLWSDTKIHLDGDGGFSVS 162
Cdd:cd11652    80 NLLRPEDTIKLAVRLESVRSNRTRYLVVVSTLGRQDTEESILLGVDFPPKES-SCTIGLVLPIWSDTQVHLDGDGGFSVT 158

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462532525 163 TAGRMHIFKPVSVQAMWSALQVLHKACEVARRHNYFPGGVALIWATYYESCISSEQSCINEWNAMQDLESTRPDS 237
Cdd:cd11652   159 SDGKTHIFKPVSVQAMWSALQVLHKACEVAREANYFPGGLALTWVSYYQSRISSDQSCLNEWEAMDDLESHRPDS 233

DEK C terminal domain; DEK is a chromatin associated protein that is linked with cancers and autoimmune disease. This domain is found at the C terminal of DEK and is of clinical importance since it can reverse the characteriztic abnormal DNA-mutagen sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients. The structure of this domain shows it to be homologous to the E2F/DP transcription factor family. This domain is also found in chitin synthase proteins like Swiss:Q8TF96, and in protein phosphatases such as Swiss:Q6NN85.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462532525 251 TERLIKAKLRSIMMSQDLENVTSKEIRNELEKQMNCNLKELKEFIDNEMLLIL 303
Cdd:pfam08766   2 TDEEIREAIREILRTADLETVTKKQVRKQLEERLGVDLSERKAFINALIDEIL 54

N-terminal domain conserved in slingshot (SSH) phosphatases; This domain or region conserved in Bilateria is found N-terminal to the DEK_C-like and catalytic domains of slingshot phosphatases. Slingshot is a cofilin-specific phosphatase. Dephosphorylation reactivates cofilin, which in turn depolymerizes actin and is thus required for actin filament reorganization. Slingshot is a member of the dual-specificity protein phosphatase family. This N-terminal SSH region may be involved in P-cofilin binding (the model C-terminus plus the DEK_C-like domain, which are characterized as the "B" domain in some of the literature), and may be required for the F-actin mediated activation of slingshot (the N-terminal region of this model, sometimes referred to as the "A" domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525   3 LVTLQRSPTPSAASSSASNSELEAGSEEDRKLNLSLSESFFMVKGAALFLQQGSSPQGQRSLQHpHKHAGDLPQHLQVMI 82
Cdd:cd11652     1 LVTVQRSPTPSGNSNPDGSDDEEEGDEEQRRKRLQRSESFFAVKGAALILPQGDRTNRPREIAS-HKHAGELQQHLQAMF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525  83 NLLRCEDRIKLAVRLESAWADRVRYMVVVYSSGRQDTEENILLGVDFSSKESkSCTIGMVLRLWSDTKIHLDGDGGFSVS 162
Cdd:cd11652    80 NLLRPEDTIKLAVRLESVRSNRTRYLVVVSTLGRQDTEESILLGVDFPPKES-SCTIGLVLPIWSDTQVHLDGDGGFSVT 158

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462532525 163 TAGRMHIFKPVSVQAMWSALQVLHKACEVARRHNYFPGGVALIWATYYESCISSEQSCINEWNAMQDLESTRPDS 237
Cdd:cd11652   159 SDGKTHIFKPVSVQAMWSALQVLHKACEVAREANYFPGGLALTWVSYYQSRISSDQSCLNEWEAMDDLESHRPDS 233

DEK C terminal domain; DEK is a chromatin associated protein that is linked with cancers and autoimmune disease. This domain is found at the C terminal of DEK and is of clinical importance since it can reverse the characteriztic abnormal DNA-mutagen sensitivity in fibroblasts from ataxia-telangiectasia (A-T) patients. The structure of this domain shows it to be homologous to the E2F/DP transcription factor family. This domain is also found in chitin synthase proteins like Swiss:Q8TF96, and in protein phosphatases such as Swiss:Q6NN85.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462532525 251 TERLIKAKLRSIMMSQDLENVTSKEIRNELEKQMNCNLKELKEFIDNEMLLIL 303
Cdd:pfam08766   2 TDEEIREAIREILRTADLETVTKKQVRKQLEERLGVDLSERKAFINALIDEIL 54

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525 312 IFDHLYLGSEWNASNLEELQGSGVDYILNVTREidnfFPGL--------FAYHNIRVYDeETTDLLAHWNEAyhfINKAN 383
Cdd:PRK12361   98 IDENLYLGCRLFPADLEKLKSNKITAILDVTAE----FDGLdwslteedIDYLNIPILD-HSVPTLAQLNQA---INWIH 169

                  ...
gi 2462532525 384 KQR 386
Cdd:PRK12361  170 RQV 172

N-terminal domain conserved in slingshot (SSH) phosphatases; This domain or region conserved in Bilateria is found N-terminal to the DEK_C-like and catalytic domains of slingshot phosphatases. Slingshot is a cofilin-specific phosphatase. Dephosphorylation reactivates cofilin, which in turn depolymerizes actin and is thus required for actin filament reorganization. Slingshot is a member of the dual-specificity protein phosphatase family. This N-terminal SSH region may be involved in P-cofilin binding (the model C-terminus plus the DEK_C-like domain, which are characterized as the "B" domain in some of the literature), and may be required for the F-actin mediated activation of slingshot (the N-terminal region of this model, sometimes referred to as the "A" domain).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525   3 LVTLQRSPTPSAASSSASNSELEAGSEEDRKLNLSLSESFFMVKGAALFLQQGSSPQGQRSLQHpHKHAGDLPQHLQVMI 82
Cdd:cd11652     1 LVTVQRSPTPSGNSNPDGSDDEEEGDEEQRRKRLQRSESFFAVKGAALILPQGDRTNRPREIAS-HKHAGELQQHLQAMF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525  83 NLLRCEDRIKLAVRLESAWADRVRYMVVVYSSGRQDTEENILLGVDFSSKESkSCTIGMVLRLWSDTKIHLDGDGGFSVS 162
Cdd:cd11652    80 NLLRPEDTIKLAVRLESVRSNRTRYLVVVSTLGRQDTEESILLGVDFPPKES-SCTIGLVLPIWSDTQVHLDGDGGFSVT 158

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462532525 163 TAGRMHIFKPVSVQAMWSALQVLHKACEVARRHNYFPGGVALIWATYYESCISSEQSCINEWNAMQDLESTRPDS 237
Cdd:cd11652   159 SDGKTHIFKPVSVQAMWSALQVLHKACEVAREANYFPGGLALTWVSYYQSRISSDQSCLNEWEAMDDLESHRPDS 233

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKANKQ 385
Cdd:cd14513     1 ASKIFDHLYLGSEWNASNLEELQNNGVKYILNVTREIDNFFPGRFTYHNIRVWDEESTNLLPYWNETYRFIKEARRK 77

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 2462532525 306 MDKPSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKANKQ 385
Cdd:cd14571     1 MDRPSRIFPYLYLGSEWNAANLEELQRNRVSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQ 80

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 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKAnKQRHN 388
Cdd:cd14565     1 PVEILPFLYLGSAYHASRREVLKALGITAVLNVSRNCPNHFEDHFQYKSIPVEDSHNADISSWFEEAIGFIDKV-KASGG 79

                  .
gi 2462532525 389 K 389
Cdd:cd14565    80 R 80

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462532525  309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKANKQRHN 388
Cdd:smart00195   1 PSEILPHLYLGSYSDALNLALLKKLGITHVINVTNEVPNYNGSDFTYLGVPIDDNTETKISPYFPEAVEFIEDAESKGGK 80

                   ..
gi 2462532525  389 KL 390
Cdd:smart00195  81 VL 82

dual specificity phosphatase domain of mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs, which are involved in gene regulation, cell proliferation, programmed cell death and stress responses, as an important feedback control mechanism that limits MAPK cascades. MKPs, also referred to as typical DUSPs, function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNF-FPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKANKQ 385
Cdd:cd14512     1 PTRILPNLYLGSQRDSLNLELMQQLGIGYVLNVSNTCPNPdFIGLFHYKRIPVNDSFCQNISPWFDEAIEFIEEAKAS 78

dual specificity phosphatase domain of class III mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class III MKPs consist of DUSP8, DUSP10/MKP-5 and DUSP16/MKP-7, and are JNK/p38-selective phosphatases, which are found in both the cell nucleus and cytoplasm. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNF-FPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKA 382
Cdd:cd14568     1 PTRILPHLYLGSQRDVLDKDLMQRNGISYVLNVSNTCPKPdFIPDSHFLRIPVNDSYCEKLLPWLDKAVEFIEKA 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFIN 380
Cdd:cd14641     4 PVEILPFLFLGSAHHSSRRETLESLGITAVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFID 75

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 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFP--GLFAYHNIRVYDEETTDLLAHWNEAYHFINKANKQR 386
Cdd:cd14643     6 PVQILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEhdGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSKK 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFIN 380
Cdd:cd14639     1 PVEILPFLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFID 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKANKQR 386
Cdd:cd14640     1 PVEILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCN 78

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 2462532525 312 IFDHLYLGSEWNASNLEELQGSGVDYILNVTREID--------NFFPGL-FAYHNIRVYDEETTDLLAHWNEAYHFINKA 382
Cdd:cd14579    24 VYPRIYVGNASVAQNIMRLQRLGITHVLNAAEGKSfmhvntnaEFYEDTgITYHGIKANDTQHFNLSAYFEEAADFIDKA 103

                  ....*...
gi 2462532525 383 NKQRHNKL 390
Cdd:cd14579   104 LAQKNGRV 111

dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462532525 309 PSLIFDHLYLGSEWNASNLEELQGSGVDYILNVTR-EIDNFFPGLFAYHNIRVYDEETTDLLAHWNEAYHFINKA 382
Cdd:cd14518     1 LSRILGGLYLGGIEPLNRNRLLKAENITHILSVIPgDVPEEYFKGYEHKQIEIDDVEDENILQHFPETNRFIDSA 75

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 2462532525 312 IFDHLYLGSEWNASNLEELQGSGVDYILNVTREIDNFF----PGLFA-----YHNIRVYDEETTDLLAHWNEAYHFINKA 382
Cdd:cd14515     4 VWPGIYIGDESTAKNKAKLKKLGITHVLNAAEGKKNGEvntnAKFYKgsgiiYLGIPASDLPTFDISQYFDEAADFIDKA 83

                  ....*...
gi 2462532525 383 NKQRHNKL 390
Cdd:cd14515    84 LSDPGGKV 91

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462532525 316 LYLGSEWNASNLEELQGSGVDYILNVTREIDNFFPGLFA-YHNIRVYDEETTDLLAHWNEAYHFINKANKQRH 387
Cdd:cd14517    19 LYMGNYKQACDKKIQKDLKIKAHINVSMDADELFKSGNDqVLHIPVEDSVEADLLSFFERACSFIDKHKNNGS 91