cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       20 ERELDEVAR-DFDAVVVLVEDYEL-----PYSLDEWEKRGVEVLHGPIPDFTAPSVEQL-LEILRWIEERVREGKKVLIH 92
Cdd:cd14505  33 QADLEELKDqGVDDVVTLCTDGELeelgvPDLLEQYQQAGITWHHLPIPDGGVPSDIAQwQELLEELLSALENGKKVLIH 112

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
5Z59_A       93 CMGGLGRSGTVGVAWLMY-SRGLSLREALMEVRRKRPGAVETQEQMEVLKE 142
Cdd:cd14505 113 CKGGLGRTGLIAACLLLElGDTLDPEQAIAAVRALRPGAIQTPKQENFLHQ 163

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A         49 WEKRGVEVLHGPIPDFTAPSVEQLLEIL-RWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:pfam00782  31 LYNSGILYLRIPVEDNHETNISKYLEEAvEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERR 110

                          90
                  ....*....|....*..
5Z59_A        128 PGAVETQEQMEVLKELE 144
Cdd:pfam00782 111 PGISPNFGFKRQLLEYE 127

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       20 ERELDEVAR-DFDAVVVLVEDYEL-----PYSLDEWEKRGVEVLHGPIPDFTAPSVEQL-LEILRWIEERVREGKKVLIH 92
Cdd:cd14505  33 QADLEELKDqGVDDVVTLCTDGELeelgvPDLLEQYQQAGITWHHLPIPDGGVPSDIAQwQELLEELLSALENGKKVLIH 112

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
5Z59_A       93 CMGGLGRSGTVGVAWLMY-SRGLSLREALMEVRRKRPGAVETQEQMEVLKE 142
Cdd:cd14505 113 CKGGLGRTGLIAACLLLElGDTLDPEQAIAAVRALRPGAIQTPKQENFLHQ 163

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       32 AVVVLVEDYELPY---SLDEWEKRGVEVLHGPIPDFT-APSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAW 107
Cdd:cd14524  31 GVITMNEEYETRFfcnSKEEWKALGVEQLRLPTVDFTgVPSLEDLEKGVDFILKHREKGKSVYVHCKAGRGRSATIVACY 110

                        90       100       110
                ....*....|....*....|....*....|....*
5Z59_A      108 LMYSRGLSLREALMEVRRKRPGAVETQEQMEVLKE 142
Cdd:cd14524 111 LIQHKGWSPEEAQEFLRSKRPHILLRLSQREVLEE 145

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A          53 GVEVLHGPIPDFTAPSVEQLLEIL-RWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRPGAV 131
Cdd:smart00195  44 DFTYLGVPIDDNTETKISPYFPEAvEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPIIS 123

                           90
                   ....*....|....*
5Z59_A         132 ETQEQMEVLKELEER 146
Cdd:smart00195 124 PNFGFLRQLIEYERK 138

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       48 EWEKRGVEVLHGPIP--DFTAPSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLM-YSRGLSLREALMEVR 124
Cdd:cd14527  36 ELPRPRKRQAYRCVPllDLVAPTPEQLERAVAWIEELRAQGGPVLVHCALGYGRSATVVAAWLLaYGRAKSVAEAEALIR 115

                        90       100
                ....*....|....*....|.
5Z59_A      125 RKRPGAVETQEQMEVLKELEE 145
Cdd:cd14527 116 AARPQVVLNPAQRKALEAWSG 136

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
5Z59_A       52 RGVEVLHGPIPDF-TAPSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRP 128
Cdd:cd14514  42 PGIEYLRVPVEDSpHADLSPHFDEVADKIHQVKRRGGRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARP 119

dual specificity phosphatase domain of fungal dual specificity protein phosphatase SDP1, MSG5, and similar proteins; This family is composed of fungal dual specificity protein phosphatases (DUSPs) including Saccharomyces cerevisiae SDP1 and MSG5, and Schizosaccharomyces pombe Pmp1. function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. SDP1 is oxidative stress-induced and dephosphorylates MAPK substrates such as SLT2. MSG5 dephosphorylates the Fus3 and Slt2 MAPKs operating in the mating and cell wall integrity (CWI) pathways, respectively. Pmp1 is responsible for dephosphorylating the CWI MAPK Pmk1. These phosphatases bind to their target MAPKs through a conserved IYT motif located outside of the dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       19 AERELDEvARDFDAVVVL---VEDYELPY-SLDEWEKR--------GVEVLHgpIP-DFTAPSVEQLLEILRWIEERVRE 85
Cdd:cd14521  17 SEPTLEE-ASSFDVVINVakeVKNPFLSDaSLAEKEKTilpgqqvkNPEYIH--VPwDHNSQIQKDLPKLTSIIEDATQS 93

                        90       100       110
                ....*....|....*....|....*....|....
5Z59_A       86 GKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREA 119
Cdd:cd14521  94 GKKVLIHCQCGVSRSASLIIAYIMKKLGLSLNDA 127

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A        2 WPSAkfidGRVAFSRMPAEreldEVARDFDA-------VVVLVEdyELPYSLDEWEKRGVEVlhgPIPDFTAPSVEQLLE 74
Cdd:cd14510  28 FPSS----GKQAFYRNPIE----EVVRFLDTkhpdhykVYNLCS--ERGYDPKYFHNRVERV---PIDDHNVPTLDEMLS 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
5Z59_A       75 ILRWIEERVREGKK--VLIHCMGGLGRSGTVGVAWLMYSRGL-SLREAL--MEVRRKRPGA------VETQEQ 136
Cdd:cd14510  95 FTAEVREWMAADPKnvVAIHCKGGKGRTGTMVCAWLIYSGQFeSAKEALeyFGERRTDKSVsskfqgVETPSQ 167

hypothetical protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
5Z59_A        54 VEVLHGPIPDFTAPSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMY-SRGLSLREALMEVRRKRPGA 130
Cdd:PRK12361 143 IDYLNIPILDHSVPTLAQLNQAINWIHRQVRANKSVVVHCALGRGRSVLVLAAYLLCkDPDLTVEEVLQQIKQIRKTA 220

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       31 DAVVVLVEDYELPYSLDEWE-------KRGVEVLHGPIPDFTA-------PSVEQLLEILrwieerVREGKKVLIHCMGG 96
Cdd:cd14526  31 TAVLNLQTDSDMEYWGVDIDsirkackESGIRYVRLPIRDFDTedlrqklPQAVALLYRL------LKNGGTVYVHCTAG 104

                        90       100       110
                ....*....|....*....|....*....|..
5Z59_A       97 LGRSGTVGVAWLMYSRGLSLREALMEVRRKRP 128
Cdd:cd14526 105 LGRAPATVIAYLYWVLGYSLDEAYYLLTSKRP 136

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
                ....*....|....*....|....*....|....*....|....*....|....*
5Z59_A       74 EILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRP 128
Cdd:cd14566  68 EAISFIDEARSKKCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKS 122

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
                ....*....|....*....|....*....|....*....|...
5Z59_A       85 EGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:cd14515  87 PGGKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRKKR 129

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
5Z59_A       67 PSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:cd14516  97 SLLPQLTDALDFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRR 157

Cyclin-dependent kinase inhibitor 3 (CDKN3); This family consists of cyclin-dependent kinase inhibitor 3 or kinase associated phosphatase proteins from several mammalian species. The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A         40 YELPYSLDEWEKRGVEVLHGPIPDFTAPSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMY-SRGLSLRE 118
Cdd:pfam05706  87 YRVPNLLDLYQQCGIITHHHPIADGGTPDIASCCEIMEELATCLKNNRKTLIHCYGGLGRSCLVAACLLLYlSDSISPEQ 166

                  ..
5Z59_A        119 AL 120
Cdd:pfam05706 167 AI 168

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
5Z59_A       74 EILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRPgAVETQEqmEVLKELEE 145
Cdd:cd18534  61 EAVDFIEQCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRP-SINLSP--AVAKQLQE 129

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A          62 PDFTAP-SVEQLLEILRWIEERV---REGKKVLIHCMGGLGRSGTVGVAWLMYSRgLSLREALM-------EVRRKRPGA 130
Cdd:smart00404  11 PDHGVPeSPDSILELLRAVKKNLnqsESSGPVVVHCSAGVGRTGTFVAIDILLQQ-LEAEAGEVdifdtvkELRSQRPGM 89

                   ....*.
5Z59_A         131 VETQEQ 136
Cdd:smart00404  90 VQTEEQ 95

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
5Z59_A       74 EILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRPGAVETQEQMEVLKELEE 145
Cdd:cd14567  68 EAFEFIEEAHQSGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRPIISPNLNFMGQLLEFEE 139

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
                ....*....|....*....|....*....|....*....|....*....|.
5Z59_A       80 EERVREGKkVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRPGA 130
Cdd:cd14519  72 EARLNGGN-VLVHCLAGVSRSVTIVAAYLMTVTDLGWRDALKAVRAARPCA 121

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
5Z59_A       60 PIPD-FTAPSVEQLLEILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:cd14639  51 PVEDsHTADISSHFQEAIDFIDCVRRAGGKVLVHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRR 119

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
5Z59_A       60 PIPDFTAPSVEQLL-EILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:cd14644  55 PISDHWSQNLSQFFpEAIEFIDEALSQNCGVLVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDLVKRKK 123

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
5Z59_A       60 PIPDFTAPSVEQLL-EILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:cd14643  58 PISDHWSQNLSQFFpEAISFIDEARSKKCGILVHCLAGISRSVTVTVAYLMQKLNLSLNDAYDFVKRKK 126

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A         62 PDFTAP-SVEQLLEILRWIEERVREGKK--VLIHCMGGLGRSGT---VGVAW--LMYSRGLSLREALMEVRRKRPGAVET 133
Cdd:pfam00102 142 PDHGVPeSPNSLLDLLRKVRKSSLDGRSgpIVVHCSAGIGRTGTfiaIDIALqqLEAEGEVDIFQIVKELRSQRPGMVQT 221

                  ...
5Z59_A        134 QEQ 136
Cdd:pfam00102 222 LEQ 224

dual specificity phosphatase domain of dual specificity protein phosphatase 15; Dual specificity protein phosphatase 15 (DUSP15), also called Vaccinia virus VH1-related dual-specific protein phosphatase Y (VHY) or VH1-related member Y, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). DUSP15 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It is highly expressed in the testis and is located in the plasma membrane in a myristoylation-dependent manner. It may be involved in the regulation of meiotic signal transduction in testis cells. It is also expressed in the brain and has been identified as a regulator of oligodendrocyte differentiation. DUSP15 contains an N-terminal catalytic dual specificity phosphatase domain and a short C-terminal tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       21 RELDEVARDfdAVVVLVEDYELPYSLdeweKRGVEVLHGPIPDF-TAPSVEQLLEILRWIEERVREGKKVLIHCMGGLGR 99
Cdd:cd14582  21 KDLEQLSRN--KITHIISIHESPQPL----LQDITYLRIPLPDTpEAPIKKHFKECISFIHQCRLNGGNCLVHCLAGISR 94

                        90       100       110
                ....*....|....*....|....*....|.
5Z59_A      100 SGTVGVAWLMYSRGLSLREALMEVRRKRPGA 130
Cdd:cd14582  95 STTIVVAYVMAVTELSWQEVLEAIRAVRPIA 125

protein tyrosine phosphatase type IVA 1; Protein tyrosine phosphatase type IVA 1 (PTP-IVa1), also known as protein-tyrosine phosphatase of regenerating liver 1 (PRL-1), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It may play a role in the development and maintenance of differentiating epithelial tissues. PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways. It is a member of the PTP-IVa/PRL family of small, prenylated phosphatases that are the most oncogenic of all PTPs. PRLs associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       32 AVVVLVEDYELPYSLDEWEKRGVEVLHGPIPDFTAPSVEQLLEILRWIEERVRE--GKKVLIHCMGGLGRSgTVGVAWLM 109
Cdd:cd18537  41 GVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQIVDDWLNLLKVKFREepGCCIAVHCVAGLGRA-PVLVALAL 119

                        90       100       110
                ....*....|....*....|....*....|..
5Z59_A      110 YSRGLSLREALMEVRRKRPGAVETQEQMEVLK 141
Cdd:cd18537 120 IECGMKYEDAVQFIRQKRRGAFNSKQLLYLEK 151

YopH and related bacterial protein tyrosine phosphatases; Yersinia outer protein H (YopH) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. YopH is an essential virulence determinant of the pathogenic bacterium by dephosphorylating several focal adhesion proteins including p130Cas in human epithelial cells, resulting in the disruption of focal adhesions and cell detachment from the extracellular matrix. It contains an N-terminal domain that contains signals required for TTSS-mediated delivery of YopH into host cells and a C-terminal catalytic PTP domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       54 VEVLH-GPIPDFTAPSVEQLLEILRWIEERVREGKKVL-----------------IHCMGGLGRSGTVGVAWLM--YSRG 113
Cdd:cd14559 118 IPVVHvTNWPDHTAISSEGLKELADLVNKSAEEKRNFYkskgssaindknkllpvIHCRAGVGRTGQLAAAMELnkSPNN 197

                        90       100       110
                ....*....|....*....|....*....|
5Z59_A      114 LSLREALMEVRRKRPG-AVETQEQMEVLKE 142
Cdd:cd14559 198 LSVEDIVSDMRTSRNGkMVQKDEQLDTLKE 227

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
                ....*....|....*....|....*....|....*....|....*....|....*
5Z59_A       74 EILRWIEERVREGKKVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKRP 128
Cdd:cd14571  69 ETHRFIEAARAQGTRVLVHCKMGVSRSASTVIAYAMKQYGWTLEQALRHVRERRP 123

catalytic domain of tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein phosphatase non-receptor type 1 (PTPN1), also called protein-tyrosine phosphatase 1B (PTP-1B), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN1/PTP-1B is the first PTP to be purified and characterized and is the prototypical intracellular PTP found in a wide variety of human tissues. It contains an N-terminal catalytic PTP domain, followed by two tandem proline-rich motifs that mediate interaction with SH3-domain-containing proteins, and a small hydrophobic stretch that localizes the enzyme to the endoplasmic reticulum (ER). It dephosphorylates and regulates the activity of a number of receptor tyrosine kinases, including the insulin receptor, the EGF receptor, and the PDGF receptor.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5Z59_A       18 PAERELDEVARDFDAVVVLV-EDYELPYSLDEWEKRGV------EVLH---GPIPDFTAP-SVEQLLEILRWIEER---V 83
Cdd:cd14608 111 PQKEEKEMIFEDTNLKLTLIsEDIKSYYTVRQLELENLttqetrEILHfhyTTWPDFGVPeSPASFLNFLFKVRESgslS 190

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
5Z59_A       84 REGKKVLIHCMGGLGRSGTVGVA----WLMYSR----GLSLREALMEVRRKRPGAVETQEQM 137
Cdd:cd14608 191 PEHGPVVVHCSAGIGRSGTFCLAdtclLLMDKRkdpsSVDIKKVLLEMRKFRMGLIQTADQL 252

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
                ....*....|....*....|....*....|....*....|
5Z59_A       88 KVLIHCMGGLGRSGTVGVAWLMYSRGLSLREALMEVRRKR 127
Cdd:cd14577 105 RVLVHCAMGISRSATLVLAFLMICEDLTLVDAIQTVRAHR 144