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 9629014     35 VYLGSYNNAMALESSGVPFRYVLNMSMVRYsLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSHTPVLVHCIAG 114
Cdd:pfam00782   1 LYLGSKPTASDAFLSKLGITAVINVTREVD-LYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAG 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 9629014    115 VNRSGAMIMAYLLHTRNRQIPAVIYFLyvyhgiKDIRGAFLENASFKRQLVDHY 168
Cdd:pfam00782  80 ISRSATLIIAYLMKTRNLSLNEAYSFV------KERRPGISPNFGFKRQLLEYE 127

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 9629014   74 VHIPIPDNDQVHIAKyFDGVAAFLERCEKSHTPVLVHCIAGVNRSGAMIMAYLLH 128
Cdd:COG2453  51 LHLPIPDFGAPDDEQ-LQEAVDFIDEALREGKKVLVHCRGGIGRTGTVAAAYLVL 104

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 9629014     35 VYLGSYNNAMALESSGVPFRYVLNMSMVRYsLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSHTPVLVHCIAG 114
Cdd:pfam00782   1 LYLGSKPTASDAFLSKLGITAVINVTREVD-LYNSGILYLRIPVEDNHETNISKYLEEAVEFIDDARQKGGKVLVHCQAG 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 9629014    115 VNRSGAMIMAYLLHTRNRQIPAVIYFLyvyhgiKDIRGAFLENASFKRQLVDHY 168
Cdd:pfam00782  80 ISRSATLIIAYLMKTRNLSLNEAYSFV------KERRPGISPNFGFKRQLLEYE 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   28 ITRITEYVYLG--SYNNAMALESSGVPFryVLNMSMVRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSHT 105
Cdd:cd14514   1 ISQITPHLFLSgaSAATPPLLLSRGITC--IINATTELPDPSYPGIEYLRVPVEDSPHADLSPHFDEVADKIHQVKRRGG 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 9629014  106 PVLVHCIAGVNRSGAMIMAYLLHTRN---RQipaviyflyVYHGIKDIRGAFLENASFKRQLVD 166
Cdd:cd14514  79 RTLVHCVAGVSRSATLCLAYLMKYEGmtlRE---------AYKHVKAARPIIRPNVGFWRQLIE 133

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   29 TRITEYVYLGSYNNAMALES-SGVPFRYVLNMSMvrySLPGSSAT----IVHIPIPDNDQVHIAKYFDGVAAFLERCEKS 103
Cdd:cd14512   2 TRILPNLYLGSQRDSLNLELmQQLGIGYVLNVSN---TCPNPDFIglfhYKRIPVNDSFCQNISPWFDEAIEFIEEAKAS 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 9629014  104 HTPVLVHCIAGVNRSGAMIMAYLL-HTRNRQIPAviyflyvYHGIKDIRGAFLENASFKRQLVD 166
Cdd:cd14512  79 NGGVLVHCLAGISRSATIAIAYLMkRMRMSLDEA-------YDFVKEKRPTISPNFNFMGQLLD 135

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 9629014   76 IPIPDNDQVHIAKYFDGVAAFLERCEKSHTPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAviyflyVYHGIKDIRGAFL 155
Cdd:cd14565  50 IPVEDSHNADISSWFEEAIGFIDKVKASGGRVLVHCQAGISRSATICLAYLMTTRRVRLNE------AFDYVKQRRSVIS 123

                ....*....
gi 9629014  156 ENASFKRQL 164
Cdd:cd14565 124 PNFNFMGQL 132

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 9629014   29 TRITEYVYLGSYNNAMALE---SSGVPfrYVLNMSM-VRYSLPGSSAtIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSH 104
Cdd:cd14570   5 SLIFDHLYLGSEWNASNLEelqGSGVG--YILNVTReIDNFFPGLFA-YHNIRVYDEETTDLLAHWNDAYHFINKAKKNH 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 9629014  105 TPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAviyflyVYHGIKDIRGAFLENASFKRQLVDH 167
Cdd:cd14570  82 SKCLVHCKMGVSRSASTVIAYAMKEFGWSLEK------AYNFVKQKRSITRPNAGFMRQLLEY 138

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   27 QITRITEYVYLGSYNNAMALESsgvpFRY-----VLNM-SMVRYSLPGSsATIVHIPIPDNDQVHIAKYFDGVAAFLERC 100
Cdd:cd14523   1 QVGVIKPWLLLSSQDVAHDLET----LKKhkvthILNVaYGVENAFPDD-FTYKTISILDLPETDITSYFPECFEFIDEA 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 9629014  101 EKSHTPVLVHCIAGVNRSGAMIMAYLLHTRNrqipavIYFLYVYHGIKDIRGAFLENASFKRQL 164
Cdd:cd14523  76 KSQDGVVLVHCNAGVSRSASIVIGYLMATEN------LSFEDAFSLVKNARPSIRPNPGFMEQL 133

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 9629014   31 ITEYVYLGS---YNNAMALESSGVPfrYVLNMSMVRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSHTPV 107
Cdd:cd14641   7 ILPFLFLGSahhSSRRETLESLGIT--AVLNVSSSCPNYFEGQFQYKSIPVEDSHMADISAWFQEAIDFIDSVKNSGGRV 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 9629014  108 LVHCIAGVNRSGAMIMAYLLHTRNRQIPAVIYFlyvyhgIKDIRGAFLENASFKRQLV 165
Cdd:cd14641  85 LVHCQAGISRSATICLAYLIQSQRVRLDEAFDF------VKQRRGVISPNFSFMGQLL 136

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014      75 HIPIPDNDqvhIAKYFDGVAAFLERCeKSHTPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAVIYFLYVYHGIKDIRGAF 154
Cdd:smart00012  14 GVPESPDS---ILELLRAVKKNLNQS-ESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDIFDTVKELRSQRPGM 89

                           90
                   ....*....|....*
gi 9629014     155 LENASFKRQLVDHYL 169
Cdd:smart00012  90 VQTEEQYLFLYRALL 104

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 9629014   30 RITEYVYLGSYNNAMALESSG-VPFRYVLNmsmVRYSLP-----GSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKS 103
Cdd:cd14643   8 QILPYLYLGCAKDSTNLDVLGkYGIKYILN---VTPNLPnmfehDGEFKYKQIPISDHWSQNLSQFFPEAISFIDEARSK 84

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 9629014  104 HTPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAviyflyVYHGIKDIRGAFLENASFKRQLVD 166
Cdd:cd14643  85 KCGILVHCLAGISRSVTVTVAYLMQKLNLSLND------AYDFVKRKKSNISPNFNFMGQLLD 141

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 9629014   28 ITRITEYVYLGSYNNAM---ALESSGVPfrYVLNMSmvrYSLPG----SSATIVHIPIPDNDQVHIAKYFDGVAAFLERC 100
Cdd:cd14645  12 PTRILPHLYLGSQKDVLnkdLMAQNGIT--YVLNAS---NSCPKpdfiCESHFMRIPVNDNYCEKLLPWLDKSIEFIDKA 86

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 9629014  101 EKSHTPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAviyflyVYHGIKDIRGAFLENASFKRQLVDH 167
Cdd:cd14645  87 KVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDD------AYRFVKDRRPSISPNFNFLGQLLEY 147

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 9629014   74 VHIPIPDNDQVHIAKyFDGVAAFLERCEKSHTPVLVHCIAGVNRSGAMIMAYLLH 128
Cdd:COG2453  51 LHLPIPDFGAPDDEQ-LQEAVDFIDEALREGKKVLVHCRGGIGRTGTVAAAYLVL 104

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 9629014   29 TRITEYVYLGSYNNAMALES-SGVPFRYVLNMSMVRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSHTPV 107
Cdd:cd14571   5 SRIFPYLYLGSEWNAANLEElQRNRVSHILNVTREIDNFFPERFTYMNIRVYDEEATQLLPHWKETHRFIEAARAQGTRV 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 9629014  108 LVHCIAGVNRSGAMIMAYLLHTRNRQIPAVIYFlyvyhgIKDIRGAFLENASFKRQL 164
Cdd:cd14571  85 LVHCKMGVSRSASTVIAYAMKQYGWTLEQALRH------VRERRPIVQPNPGFLRQL 135

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 9629014   31 ITEYVYLGSYNNAMALES-SGVPFRYVLNMSMVRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSHTPVLV 109
Cdd:cd14639   4 ILPFLYLGSAYHASKCEFlANLHITALLNVSRRSSEACKGQYHYKWIPVEDSHTADISSHFQEAIDFIDCVRRAGGKVLV 83

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 9629014  110 HCIAGVNRSGAMIMAYLLHTRNRQIPAViyFLYvyhgIKDIRGAFLENASFKRQLVDH 167
Cdd:cd14639  84 HCEAGISRSPTICMAYLMKTKRFRLEEA--FDY----IKQRRSLISPNFGFMGQLLQY 135

dual specificity phosphatase domain of dual specificity protein phosphatase 12 and similar proteins; Dual specificity protein phosphatase 12 (DUSP12), also called YVH1, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP12 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It targets p38 MAPK to regulate macrophage response to bacterial infection. It also ameliorates cardiac hypertrophy in response to pressure overload through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 has been identified as a modulator of cell cycle progression, a function independent of phosphatase activity and mediated by its C-terminal zinc-binding domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   35 VYLGSYNNAM---ALESSGVpfRYVLNMSMVRYSLPGSSATIVH--IPIPDNDQVHIAKYFDGVAAFLERCeKSHTPVLV 109
Cdd:cd14520   8 LYIGNADDAAdylSLREAGI--THVLTVDSEEPIDAPPVGKLVRkfVPALDEESTDLLSRLDECLDFIDEG-RAEGAVLV 84

                        90       100
                ....*....|....*....|
gi 9629014  110 HCIAGVNRSGAMIMAYLLHT 129
Cdd:cd14520  85 HCHAGVSRSAAVVTAYLMKT 104

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 9629014   76 IPIPDNDQVHIAKYFDGVAAFLERCEKSHTPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAVIyflyvyHGIKDIRGAFL 155
Cdd:cd14519  49 IPAADTPEQNISQHFRECINFIHEARLNGGNVLVHCLAGVSRSVTIVAAYLMTVTDLGWRDAL------KAVRAARPCAN 122

                        90
                ....*....|...
gi 9629014  156 ENASFKRQLVDHY 168
Cdd:cd14519 123 PNFGFQRQLQEFE 135

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 9629014   30 RITEYVYLGSYNNAMALES-SGVPFRYVLNmsmVRYSLPG-----SSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKS 103
Cdd:cd14644   5 QILPNLYLGSARDSANLETlAKLGIRYILN---VTPNLPNffeknGDFHYKQIPISDHWSQNLSQFFPEAIEFIDEALSQ 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 9629014  104 HTPVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAviyflyVYHGIKDIRGAFLENASFKRQLVD 166
Cdd:cd14644  82 NCGVLVHCLAGISRSVTVTVAYLMQKLNLSLND------AYDLVKRKKSNISPNFNFMGQLLD 138

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   29 TRITEYVYLGSY----NNAMALESSGVpfRYVLNM---SMVRYsLPGSSATI-----------VHIPIPDNDQVHIAKYF 90
Cdd:cd14526   4 SRILPNLIVGSCpqnpEDVDRLKKEGV--TAVLNLqtdSDMEY-WGVDIDSIrkackesgiryVRLPIRDFDTEDLRQKL 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 9629014   91 DGVAAFLER-CEKSHTpVLVHCIAGVNRSGAMIMAYLLHTRNRQIPAVIYFL 141
Cdd:cd14526  81 PQAVALLYRlLKNGGT-VYVHCTAGLGRAPATVIAYLYWVLGYSLDEAYYLL 131

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 9629014   28 ITRITEYVYLGS---YNNAMALESSGVPFryVLNMSMVRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCEKSH 104
Cdd:cd14573   2 LSRITESLYLSNgvaANNRTLLAANRITC--VINVSLEVANGLPPGIEYLHVPVADSPDTRLRDYFDPIADKIHTVEARG 79

                        90       100
                ....*....|....*....|...
gi 9629014  105 TPVLVHCIAGVNRSGAMIMAYLL 127
Cdd:cd14573  80 GRTLLHCVAGVSRSATLCLAYLM 102

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 9629014   28 ITRITEYVYLGsynnAMALESSGVPFRYVLNMSMV-----RYSLPGSSATIV----------HIPIPDNDQV-HIAKYFD 91
Cdd:cd14524   2 YDRIDDTVILG----ALPFRSMTVALVAKENVRGVitmneEYETRFFCNSKEewkalgveqlRLPTVDFTGVpSLEDLEK 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 9629014   92 GVAaFLERCEKSHTPVLVHCIAGVNRSGAMIMAYLLHTRN 131
Cdd:cd14524  78 GVD-FILKHREKGKSVYVHCKAGRGRSATIVACYLIQHKG 116

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 9629014   68 GSSATIVHIPIPDNDQVHIAKYFDGVAAFLERC-EKSHTPVLVHCIAGVNRSGAMIMAYLL 127
Cdd:cd14580  48 GTSVDYYGVPANDLPDFDISPYFYSAAEFIHRAlNTPGAKVLVHCAVGVSRSATLVLAYLM 108

dual specificity protein phosphatase 22; Dual specificity protein phosphatase 22 (DUSP22), also called JNK-stimulatory phosphatase-1 (JSP-1), low molecular weight dual specificity phosphatase 2 (LMW-DSP2), mitogen-activated protein kinase phosphatase x (MKP-x) or VHR-related MKPx (VHX), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP22 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. It also regulates cell death by acting as a scaffold protein for the ASK1-MKK7-JNK signal transduction pathway independently of its phosphatase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   76 IPIPDNDQVHIAKYFDGVAAFLERCEKSHTPVLVHCIAGVNRSGAMIMAYLLhtrnrqipAVIYFLY--VYHGIKDIRGA 153
Cdd:cd14581  52 IPAADSPSQNLTQHFKESIKFIHECRLRGEGCLVHCLAGVSRSVTLVVAYIM--------TVTDFGWedALSAVKAARSC 123

                        90       100
                ....*....|....*....|..
gi 9629014  154 FLENASFKRQL-------VDHY 168
Cdd:cd14581 124 ANPNMGFQRQLqefekheVHQY 145

Predicted phosphohydrolase, protein tyrosine phosphatase (PTP) superfamily, DUF442 family [General function prediction only];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 9629014   74 VHIPI----PDNDQVhiakyfdgvAAFLERCEKSHTPVLVHCIAGvNRSGAMIMAYLLHTRNRQIPAVI 138
Cdd:COG3453  60 VHIPVtggaITDEDV---------EAFAAALAAAPGPVLAHCRSG-TRSSALWALYQAGKGGMSPEEAL 118

catalytic domain of tyrosine-protein phosphatase non-receptor type 14; Tyrosine-protein phosphatase non-receptor type 14 (PTPN14), also called protein-tyrosine phosphatase pez, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN14 is a potential tumor suppressor and plays a regulatory role in the Hippo and Wnt/beta-catenin signaling pathways. It contains an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   62 VRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCE--KSHT------------PVLVHCIAGVNRSGAMIMAYLL 127
Cdd:cd14599 163 VKHLLSGQERTVWHLQYTDWPDHGCPEEVQGFLSYLEEIQsvRRHTnsmldstkncnpPIVVHCSAGVGRTGVVILTELM 242

                        90
                ....*....|....*....
gi 9629014  128 -----HTRNRQIPAVIYFL 141
Cdd:cd14599 243 igcleHNEKVEVPVMLRHL 261

catalytic domain of tyrosine-protein phosphatase non-receptor type 21; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21), also called protein-tyrosine phosphatase D1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN21 is a component of a multivalent scaffold complex nucleated by focal adhesion kinase (FAK) at specific intracellular sites. It promotes cytoskeleton events that induce cell adhesion and migration by modulating Src-FAK signaling. It can also selectively associate with and stimulate Tec family kinases and modulate Stat3 activation. Human PTPN21 may also play a pathologic role in gastrointestinal tract tumorigenesis. PTPN21 contains an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   62 VRYSLPGSSATIVHIPIPDNDQVHIAKYFDGVAAFLERCE--KSHT-----------PVLVHCIAGVNRSGAMIMAYLL- 127
Cdd:cd14598  97 IKHLLTGQERTVWHLQYTDWPEHGCPEDLKGFLSYLEEIQsvRRHTnstidpkspnpPVLVHCSAGVGRTGVVILSEIMi 176

                        90
                ....*....|....*...
gi 9629014  128 ----HTRNRQIPAVIYFL 141
Cdd:cd14598 177 acleHNEMLDIPRVLDML 194

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
                ....*....|....*....|....*....|....*....|....*....|...
gi 9629014   76 IPIPDNDQVHIAKYFDGVAAFLERC-EKSHTPVLVHCIAGVNRSGAMIMAYLL 127
Cdd:cd14579  79 IKANDTQHFNLSAYFEEAADFIDKAlAQKNGRVLVHCREGYSRSPTLVIAYLM 131

unknown subfamily of bacterial and plant dual specificity protein phosphatases; This subfamily is composed of uncharacterized bacterial and plant dual-specificity protein phosphatases. DUSPs function as a protein-serine/threonine phosphatases (EC 3.1.3.16) and a protein-tyrosine-phosphatases (EC 3.1.3.48).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9629014   27 QITRITEYVYLGSYNNAMALESSgvpFRYVLNMSMvrySLPGSSATIVH--IPI-----PDNDQVHIAkyfdgvAAFLER 99
Cdd:cd14527   4 AYDEVLPGLYLGRWPSADELPPG---VPAVLDLTA---ELPRPRKRQAYrcVPLldlvaPTPEQLERA------VAWIEE 71

                        90       100
                ....*....|....*....|....*....
gi 9629014  100 CEKSHTPVLVHCIAGVNRSGAMIMAYLLH 128
Cdd:cd14527  72 LRAQGGPVLVHCALGYGRSATVVAAWLLA 100

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and type 14 (PTPN14) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Both PTPN21 and PTPN14 contain an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 9629014  104 HTPVLVHCIAGVNRSGAMIMA-----YLLHTRNRQIPAVI 138
Cdd:cd14540 152 NPPTLVHCSAGVGRTGVVILAdlmlyCLDHNEELDIPRVL 191

dual specificity phosphatase and pro isomerase domain containing 1; Dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1) was initially named as such because computational prediction appeared to encode a protein of 446 amino acids in length that included two catalytic domains: a proline isomerase and a dual specificity phosphatase (DUSP). However, it was subsequently shown that the true open reading frame only encompassed the DUSP domain and the gene product was therefore renamed DUSP27. This is distinct from inactive DUSP27. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). DUPD1/DUSP27 has been shown to have catalytic activity with preference for phosphotyrosine over phosphothreonine and phosphoserine residues. It associates with the short form of the prolactin (PRL) receptor and plays a role in PRL-mediated MAPK inhibition in ovarian cells.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 9629014   80 DNDQVHIAKYFDGVAAFLERC-EKSHTPVLVHCIAGVNRSGAMIMAYLLHTRN 131
Cdd:cd14575  71 DLPTFNLSQFFYSAAEFIHQAlSDPHNKLLVHCVMGRSRSATLVLAYLMIYKN 123

C-terminal dual-specificity phosphatase domain of CDC14 family proteins; The cell division control protein 14 (CDC14) family is highly conserved in all eukaryotes, although the roles of its members seem to have diverged during evolution. Yeast Cdc14, the best characterized member of this family, is a dual-specificity phosphatase that plays key roles in cell cycle control. It preferentially dephosphorylates cyclin-dependent kinase (CDK) targets, which makes it the main antagonist of CDK in the cell. Cdc14 functions at the end of mitosis and it triggers the events that completely eliminates the activity of CDK and other mitotic kinases. It is also involved in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint, and in chromosome segregation. Cdc14 phosphatases also function in DNA replication, DNA damage checkpoint, and DNA repair. Vertebrates may contain more than one Cdc14 homolog; humans have three (CDC14A, CDC14B, and CDC14C). CDC14 family proteins contain a highly conserved N-terminal pseudophosphatase domain that contributes to substrate specificity and a C-terminal catalytic dual-specificity phosphatase domain with the PTP signature motif.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 9629014   85 HIAKYF-DG-------VAAFLERCEKSHTPVLVHCIAGVNRSGAMIMAYL 126
Cdd:cd14499  82 HYDLYFpDGstpsddiVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYL 131