Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196     44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNnqkFIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRS 123
Cdd:smart00195   1 PSEILPHLYLGSYSDALNLALLKKLGITHVINVT-NEVPNYNG---SDFTYLGVPIDDNTETKISPYFPEAVEFIEDAES 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17552196    124 KEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYSTT 185
Cdd:smart00195  77 KGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196     44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNnqkFIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRS 123
Cdd:smart00195   1 PSEILPHLYLGSYSDALNLALLKKLGITHVINVT-NEVPNYNG---SDFTYLGVPIDDNTETKISPYFPEAVEFIEDAES 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17552196    124 KEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYSTT 185
Cdd:smart00195  77 KGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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 17552196    51 LYLSGRTVSQNSeLLKEKNITTVINVSdREVVNYKNNQKFIKnyrfYAMSDTASAKFDGIIEEAVRIIHDSRSKEEGVLV 130
Cdd:pfam00782   1 LYLGSKPTASDA-FLSKLGITAVINVT-REVDLYNSGILYLR----IPVEDNHETNISKYLEEAVEFIDDARQKGGKVLV 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 17552196   131 HCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVY 182
Cdd:pfam00782  75 HCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPGISPNFGFKRQLLEY 126

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196   33 STKLHNLSSRK------ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdrevvnyknnqkfiknyrfyamsdtasAK 106
Cdd:PRK12361  78 GTRLYNAWARKrdsvpaIQKIDENLYLGCRLFPADLEKLKSNKITAILDVT---------------------------AE 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  107 FDGI--------------------------IEEAVRIIHDSRSKEEGVLVHCFLGVSRSATLVAFYLISA-LSINWRDAV 159
Cdd:PRK12361 131 FDGLdwslteedidylnipildhsvptlaqLNQAINWIHRQVRANKSVVVHCALGRGRSVLVLAAYLLCKdPDLTVEEVL 210

                        170       180
                 ....*....|....*....|.
gi 17552196  160 DFIHHRRFSANPNFgflHQLK 180
Cdd:PRK12361 211 QQIKQIRKTARLNK---RQLR 228

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196     44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNnqkFIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRS 123
Cdd:smart00195   1 PSEILPHLYLGSYSDALNLALLKKLGITHVINVT-NEVPNYNG---SDFTYLGVPIDDNTETKISPYFPEAVEFIEDAES 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17552196    124 KEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYSTT 185
Cdd:smart00195  77 KGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIISPNFGFLRQLIEYERK 138

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 17552196  44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSDrevvnykNNQKFI--KNYRFYAMSDTASAKFDGIIEEAVRIIHDS 121
Cdd:cd14519   1 MNKILPGLYVGNFRDAKDAEQLRENGITHILSIHD-------SARPLLedIKYLCIPAADTPEQNISQHFRECINFIHEA 73

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17552196 122 RSKEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVY 182
Cdd:cd14519  74 RLNGGNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCANPNFGFQRQLQEF 134

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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQKFikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14566   3 EILPFLYLGNAKDSANIDLLKKYNIKYILNVTPNLPNTFEEDGGF--KYLQIPIDDHWSQNLSAFFPEAISFIDEARSKK 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLK 180
Cdd:cd14566  81 CGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSNISPNFNFMGQLL 135

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNqkfIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14512   3 RILPNLYLGSQRDSLNLELMQQLGIGYVLNVSNTCPNPDFIG---LFHYKRIPVNDSFCQNISPWFDEAIEFIEEAKASN 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQL 179
Cdd:cd14512  80 GGVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRPTISPNFNFMGQL 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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNNQKfikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14565   3 EILPFLYLGSAYHASRREVLKALGITAVLNVS-RNCPNHFEDHF---QYKSIPVEDSHNADISSWFEEAIGFIDKVKASG 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYST 184
Cdd:cd14565  79 GRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRSVISPNFNFMGQLLQYES 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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQKFikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14643   8 QILPYLYLGCAKDSTNLDVLGKYGIKYILNVTPNLPNMFEHDGEF--KYKQIPISDHWSQNLSQFFPEAISFIDEARSKK 85

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYSTT 185
Cdd:cd14643  86 CGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKKSNISPNFNFMGQLLDFERT 145

dual specificity phosphatase domain of dual specificity protein phosphatase 9; Dual specificity protein phosphatase 9 (DUSP9), also called mitogen-activated protein kinase (MAPK) phosphatase 4 (MKP-4), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP9 is a mediator of bone morphogenetic protein (BMP) signaling to control the appropriate ERK activity critical for the determination of embryonic stem cell fate. Down-regulation of DUSP9 expression has been linked to severe pre-eclamptic placenta as well as cancers such as hepatocellular carcinoma. DUSP9 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQKFikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14644   5 QILPNLYLGSARDSANLETLAKLGIRYILNVTPNLPNFFEKNGDF--HYKQIPISDHWSQNLSQFFPEAIEFIDEALSQN 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQL 179
Cdd:cd14644  83 CGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKKSNISPNFNFMGQL 136

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 17552196  45 SEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNNQKFIKNYRFYamsDTASAKFDGIIEEAVRIIHDSRSK 124
Cdd:cd14513   2 SKIFDHLYLGSEWNASNLEELQNNGVKYILNVT-REIDNFFPGRFTYHNIRVW---DEESTNLLPYWNETYRFIKEARRK 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17552196 125 EEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYS 183
Cdd:cd14513  78 GSKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERRSCIKPNPGFLRQLITYE 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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQkfikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14639   3 EILPFLYLGSAYHASKCEFLANLHITALLNVSRRSSEACKGQY----HYKWIPVEDSHTADISSHFQEAIDFIDCVRRAG 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYST 184
Cdd:cd14639  79 GKVLVHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRRSLISPNFGFMGQLLQYES 137

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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDrEVVNYKNNQKfikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14641   6 EILPFLFLGSAHHSSRRETLESLGITAVLNVSS-SCPNYFEGQF---QYKSIPVEDSHMADISAWFQEAIDFIDSVKNSG 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYST 184
Cdd:cd14641  82 GRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRRGVISPNFSFMGQLLQFET 140

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQKFikNYRFYAMSDTASAKFDGIIEEAVRIIHDSRS 123
Cdd:cd14567   1 LTPILPFLYLGNERDAQDIDTLQRLNIGYVLNVTTHLPLYHEGKGGF--RYKRLPATDSNKQNLRQYFEEAFEFIEEAHQ 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17552196 124 KEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQL 179
Cdd:cd14567  79 SGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQL 134

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 17552196  43 KISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNNQKFIKNYRFYamsDTASAKFDGIIEEAVRIIHDSR 122
Cdd:cd14571   3 RPSRIFPYLYLGSEWNAANLEELQRNRVSHILNVT-REIDNFFPERFTYMNIRVY---DEEATQLLPHWKETHRFIEAAR 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17552196 123 SKEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVYS 183
Cdd:cd14571  79 AQGTRVLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRPIVQPNPGFLRQLQTYQ 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 17552196  44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdrevvNYKNNQKFIKNYRFY--AMSDTASAKFDGIIEEAVRIIHDS 121
Cdd:cd14645  12 PTRILPHLYLGSQKDVLNKDLMAQNGITYVLNAS-----NSCPKPDFICESHFMriPVNDNYCEKLLPWLDKSIEFIDKA 86

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17552196 122 RSKEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVY 182
Cdd:cd14645  87 KVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPSISPNFNFLGQLLEY 147

dual specificity protein phosphatases 18 and 21; This subfamily contains dual specificity protein phosphatase 18 (DUSP18), dual specificity protein phosphatase 21 (DUSP21), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP18, also called low molecular weight dual specificity phosphatase 20 (LMW-DSP20), is a catalytically active phosphatase with a preference for phosphotyrosine over phosphoserine/threonine oligopeptides in vitro. In vivo, it has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP21 is also called low molecular weight dual specificity phosphatase 21 (LMW-DSP21). Its gene has been identified as a potential therapeutic target in human hepatocellular carcinoma. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  43 KISEILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQKFIKnyrfYAMSDTASAKFDGIIEEAVRIIHDSR 122
Cdd:cd14573   1 RLSRITESLYLSNGVAANNRTLLAANRITCVINVSLEVANGLPPGIEYLH----VPVADSPDTRLRDYFDPIADKIHTVE 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196 123 SKEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVY 182
Cdd:cd14573  77 ARGGRTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRPIIRPNNGFWEQLIHY 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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSdrevVNYKNNQKFIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14638   3 EILPFLYLGSAYHASRKDMLDTLGITALINVS----ANCPNHFEGHYQYKSIPVEDNHKADISSWFNEAIDFIDSVKNAG 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLkvysttkaKEFRNQLISERC 199
Cdd:cd14638  79 GRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFSFMGQL--------LQFESQVLAPSC 144

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 17552196  46 EILPNLYLSGRTVSQNSELLKEKNITTVINVSDrevvNYKNNQKFIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKE 125
Cdd:cd14640   3 EILPFLYLGSAYHAARRDMLDALGITALLNVSS----DCPNHFEGHYQYKCIPVEDNHKADISSWFMEAIEYIDSVKDCN 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 17552196 126 EGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQL 179
Cdd:cd14640  79 GRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRRSIISPNFSFMGQL 132

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP13A is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  44 ISEILPNLYLSGRTVSQNSELLKEKNITTVINVSDREVVNYKNNQKFIKNYRFYAMSDTASAKFD--GIIEEAVRIIHDS 121
Cdd:cd14580   1 VDEVWPNLFLGDLATAHNRFGLWKLGITHVLNAAHGKLFCQGGDDFYGTSVDYYGVPANDLPDFDisPYFYSAAEFIHRA 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17552196 122 RSKEEG-VLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFsANPNFGFLHQL 179
Cdd:cd14580  81 LNTPGAkVLVHCAVGVSRSATLVLAYLMIYHQLSLVQAIKTVKERRW-IFPNRGFLKQL 138

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 17552196  43 KISEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNNQKFIKNYRFYamsDTASAKFDGIIEEAVRIIHDSR 122
Cdd:cd14570   3 KASLIFDHLYLGSEWNASNLEELQGSGVGYILNVT-REIDNFFPGLFAYHNIRVY---DEETTDLLAHWNDAYHFINKAK 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196 123 SKEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQLKVY 182
Cdd:cd14570  79 KNHSKCLVHCKMGVSRSASTVIAYAMKEFGWSLEKAYNFVKQKRSITRPNAGFMRQLLEY 138

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 17552196  46 EILPN-LYLSGRTVSQNSELLKEKNITTVINVSDrevvnyKNNQKFIK---NYRFYAMSDTASAKFDGIIEEAVRIIHDS 121
Cdd:cd14517  13 EILPGfLYMGNYKQACDKKIQKDLKIKAHINVSM------DADELFKSgndQVLHIPVEDSVEADLLSFFERACSFIDKH 86

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 17552196 122 RSKEEGVLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRFSANPNFGFLHQL 179
Cdd:cd14517  87 KNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNNMRPNRGFVKQL 144

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 17552196  45 SEILPN-LYLSGRTVSQNSELLKEKNITTVINVsdrevvnYKNNQKFIKN-YRFYAMSDTASAKFDgiieEAVRIIHDSR 122
Cdd:cd18534   2 TEILPGfLYLGSYDNASRAELLKAQGITRILNT-------VPDCQNLYKNsFTYHVLSEEKTVPFA----EAVDFIEQCR 70

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17552196 123 SKEEGVLVHCFLGVSRSATLVAFYLISALsiNWR--DAVDFIHHRRFSANPNFGFLHQLKVY 182
Cdd:cd18534  71 KDKARVLVHCMSGQSRSPAVVIAYLMKHK--GWRlaESYQWVKERRPSINLSPAVAKQLQEF 130

dual specificity protein phosphatase 13 isoform B; Dual specificity protein phosphatase 13 isoform B (DUSP13B), also called testis- and skeletal-muscle-specific DSP (TMDP) or dual specificity phosphatase SKRP4, 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. DUSP13B 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. DUSP13B inactivates MAPK activation in the order of selectivity, JNK = p38 > ERK in cells. It may play a role in protection from external stress during spermatogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  37 HNLSSRKISEILPNLYLSGRTVSQNSELLKEKNITTVINV-SDREVVNykNNQKFIK--NYRFYAMSDTASAKFD--GII 111
Cdd:cd14577  11 RRAPTGHVNEVWPNLYLGDAYAARDKSVLIQLGITHIVNAaSGKFHVN--TGPKFYRdmNIDYYGVEADDNPFFDlsVYF 88

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17552196 112 EEAVRIIHDSRSKEEG-VLVHCFLGVSRSATLVAFYLISALSINWRDAVDFIHHRRfSANPNFGFLHQLKV 181
Cdd:cd14577  89 YPVARFIRAALSSPNGrVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHR-DICPNSGFLRQLRE 158

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17552196     90 FIKNYRFYAMSDTASAKFDGIIEEAVRIIHDSRSKEEG---VLVHCFLGVSRSATLVAFYLISALSINWRDAVDF 161
Cdd:smart00404   1 TVKHYHYTGWPDHGVPESPDSILELLRAVKKNLNQSESsgpVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDI 75

protein-tyrosine phosphatase mitochondrial 1; Protein-tyrosine phosphatase mitochondrial 1 or PTP localized to the mitochondrion 1 (PTPMT1), also called phosphoinositide lipid phosphatase (PLIP), phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1, or PTEN-like phosphatase, is a lipid phosphatase or phosphatidylglycerophosphatase (EC 3.1.3.27) which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. It is essential for the biosynthesis of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. PTPMT1 also plays a crucial role in hematopoietic stem cell (HSC) function, and has been shown to display activity toward phosphoprotein substrates.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17552196  58 VSQNSELLKEKNITTVINVSDREVVNY-KNNQKFIKNY----RFYAMSD-TASAKFDgIIEEAVRIIHDSRSKEEGVLVH 131
Cdd:cd14524  17 RSMTVALVAKENVRGVITMNEEYETRFfCNSKEEWKALgveqLRLPTVDfTGVPSLE-DLEKGVDFILKHREKGKSVYVH 95

                        90       100       110
                ....*....|....*....|....*....|....*
gi 17552196 132 CFLGVSRSATLVAFYLISALSINWRDAVDFIHHRR 166
Cdd:cd14524  96 CKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKR 130

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 17552196  45 SEILPNLYLSGRTVSQNSELLKEKNITTVINVSdREVVNYKNNQKFIKNYRFYamsDTASAKFDGIIEEAVRIIHDSRSK 124
Cdd:cd14569   5 TQIFEHVFLGSEWNASNLEDLQNRGVRYILNVT-REIDNFFPGLFEYHNIRVY---DEEATDLLAYWNDTYKFISKAKKH 80