protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735  43 DISYILVNLIVCSYPVNTYPKLLYRNSLDDLILFLTVYHgKGNFRIFNFRGEKEDSDykdndligiaAKFESKdfeiqel 122
Cdd:cd14497    1 DLSYITPRIIAMSFPATGYPESLYRNSIDDVANFLNTHH-PDHYMIFNLSEEEYDDD----------SKFEGR------- 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 123 rstlindgkipispidletrtlveeetnnviCERIGWLDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGKGRSGM 202
Cdd:cd14497   63 -------------------------------VLHYGFPDHHPPPLGLLLEIVDDIDSWLSEDPNNVAVVHCKAGKGRTGT 111

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 398364735 203 ITVAYLMKYLQC-PLGEARLIFMQARFKYGMtNGVTIPSQLRYLRYHEFF 251
Cdd:cd14497  112 VICAYLLYYGQYsTADEALEYFAKKRFKEGL-PGVTIPSQLRYLQYFERL 160

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735  43 DISYILVNLIVCSYPVNTYPKLLYRNSLDDLILFLTVYHgKGNFRIFNFRGEKEDSDykdndligiaAKFESKdfeiqel 122
Cdd:cd14497    1 DLSYITPRIIAMSFPATGYPESLYRNSIDDVANFLNTHH-PDHYMIFNLSEEEYDDD----------SKFEGR------- 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 123 rstlindgkipispidletrtlveeetnnviCERIGWLDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGKGRSGM 202
Cdd:cd14497   63 -------------------------------VLHYGFPDHHPPPLGLLLEIVDDIDSWLSEDPNNVAVVHCKAGKGRTGT 111

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 398364735 203 ITVAYLMKYLQC-PLGEARLIFMQARFKYGMtNGVTIPSQLRYLRYHEFF 251
Cdd:cd14497  112 VICAYLLYYGQYsTADEALEYFAKKRFKEGL-PGVTIPSQLRYLQYFERL 160

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735   170 LEEIVDGIENylSVSKNRVAVLHCRMGKGRSGMITVAYLMKYLQCPLGEARLIFMQARFK 229
Cdd:smart00195  64 FPEAVEFIED--AESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPI 121

hypothetical protein; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 398364735 160 LDHFPPPFELLEEIVDGIENYlsVSKNRVAVLHCRMGKGRSGMITVAYLM 209
Cdd:PRK12361 151 LDHSVPTLAQLNQAINWIHRQ--VRANKSVVVHCALGRGRSVLVLAAYLL 198

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735  43 DISYILVNLIVCSYPVNTYPKLLYRNSLDDLILFLTVYHgKGNFRIFNFRGEKEDSDykdndligiaAKFESKdfeiqel 122
Cdd:cd14497    1 DLSYITPRIIAMSFPATGYPESLYRNSIDDVANFLNTHH-PDHYMIFNLSEEEYDDD----------SKFEGR------- 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 123 rstlindgkipispidletrtlveeetnnviCERIGWLDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGKGRSGM 202
Cdd:cd14497   63 -------------------------------VLHYGFPDHHPPPLGLLLEIVDDIDSWLSEDPNNVAVVHCKAGKGRTGT 111

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 398364735 203 ITVAYLMKYLQC-PLGEARLIFMQARFKYGMtNGVTIPSQLRYLRYHEFF 251
Cdd:cd14497  112 VICAYLLYYGQYsTADEALEYFAKKRFKEGL-PGVTIPSQLRYLQYFERL 160

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735  39 GLRLDISYILVNLIVCSYPVNTYPKLlYRNSLDDLILFLTVYHgKGNFRIFNFRGEKE-DSDYKDNDLIGIaakfeskdf 117
Cdd:cd14510   11 GFDLDLTYVTDRVIAMSFPSSGKQAF-YRNPIEEVVRFLDTKH-PDHYKVYNLCSERGyDPKYFHNRVERV--------- 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 118 eiqelrstlindgkipisPIDletrtlveeetnnvicerigwlDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGK 197
Cdd:cd14510   80 ------------------PID----------------------DHNVPTLDEMLSFTAEVREWMAADPKNVVAIHCKGGK 119

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 398364735 198 GRSGMITVAYLMKYLQCP-LGEARLIFMQARFKYGMTN---GVTIPSQLRYLRYHEF 250
Cdd:cd14510  120 GRTGTMVCAWLIYSGQFEsAKEALEYFGERRTDKSVSSkfqGVETPSQSRYVGYFEK 176

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 140 ETRTLVEEETNNVICERIGWLDHFPPPFELLEEIVDGIENYLSvSKNRVAVlHCRMGKGRSGMITVAYLMkYLQCPLGEA 219
Cdd:COG2453   36 EELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDFIDEALR-EGKKVLV-HCRGGIGRTGTVAAAYLV-LLGLSAEEA 112

                         90       100       110
                 ....*....|....*....|....*....|
gi 398364735 220 RLIFMQARFKYgmtngVTIPSQLRYLRYHE 249
Cdd:COG2453  113 LARVRAARPGA-----VETPAQRAFLERFA 137

dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in typical and atypical dual-specificity phosphatases (DUSPs), which 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. 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. Atypical DUSPs contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Also included in this family are dual specificity phosphatase-like domains of catalytically inactive members such as serine/threonine/tyrosine-interacting protein (STYX) and serine/threonine/tyrosine interacting like 1 (STYXL1), as well as active phosphatases with substrates that are not phosphoproteins such as PTP localized to the mitochondrion 1 (PTPMT1), which is a lipid phosphatase, and laforin, which is a glycogen phosphatase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 398364735 170 LEEIVDGIENYLSvSKNRVAVlHCRMGKGRSGMITVAYLMKYLQCPLGEArLIFMQAR 227
Cdd:cd14498   65 FEEAIEFIEEALK-KGGKVLV-HCQAGVSRSATIVIAYLMKKYGWSLEEA-LELVKSR 119

protein tyrosine phosphatase-like domain of tensin-2; Tensin-2 (TNS2) is also called tensin-like C1 domain-containing phosphatase (TENC1) or C1 domain-containing phosphatase and tensin homolog (C1-TEN). It is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Tensin-2 is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It also modulates cell contractility and remodeling of collagen fibers through the DLC1, a RhoGAP that binds to tensins in focal adhesions. Tensin-2 may have phosphatase activity; it reduces AKT1 phosphorylation. It contains an N-terminal region with a zinc finger, a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 158 GWLDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGKGRSGMITVAYlMKYLQCPLG--EARLIFMQARFKYGMTNG 235
Cdd:cd14562   65 GWPDLHAPPLDKICSICKAMETWLNADPQHVVVLHCKGNKGKTGVIVAAY-MHYSKISAGadQALSTLAMRKFCEDKVAT 143

                         90
                 ....*....|..
gi 398364735 236 VTIPSQLRYLRY 247
Cdd:cd14562  144 SLQPSQRRYISY 155

protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. It plays an essential role in TGF-beta-induced myofibroblast differentiation and myofibroblast-mediated formation of extracellular fibronectin and collagen matrix. It also positively regulates RhoA activity through its interaction with DLC1, a RhoGAP-containing tumor suppressor; the tensin-1-DLC1-RhoA signaling axis is critical in regulating cellular functions that lead to angiogenesis. Tensin-1 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735  43 DISYILVNLIVCSYPVNTYPKLlYRNSLDDLILFLTVYHGkGNFRIFNFRGEKEDsdykdndligiaakfeskdfeIQEL 122
Cdd:cd14560    1 DLVYITERIISVSFPSTAEEPS-FRSNLKEVAQMLKSKHG-DNYLLFNLSERRHD---------------------ISKL 57

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 123 RSTLINdgkipispidletrtlveeetnnvicerIGWLDHFPPPFELLEEIVDGIENYLSVSKNRVAVLHCRMGKGRSGM 202
Cdd:cd14560   58 HPKVLD----------------------------FGWPDLHAPALEKICSICKAMDTWLNADPHNVVVIHNKGNRGRTGV 109

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 398364735 203 ITVAYlMKY--LQCPLGEARLIFMQARFKYGMTNGVTIPSQLRYLRY 247
Cdd:cd14560  110 VIAAY-MHYsnISASADQALDRFAMKRFYEDKVVPVGQPSQKRYVHY 155

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398364735 168 ELLEEIVDGIENYLSvsKNRVAVLHCRMGKGRSGMITVAYLMKYLQCPLGEArLIFMQARFKYGMtngVTIPSQLRYL 245
Cdd:cd14494   40 AMVDRFLEVLDQAEK--PGEPVLVHCKAGVGRTGTLVACYLVLLGGMSAEEA-VRIVRLIRPGGI---PQTIEQLDFL 111

dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as VH1-like phosphatase Z (VHZ) or low molecular mass dual specificity phosphatase 3 (LDP-3), 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. DUSP23 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 able to enhance activation of JNK and p38 MAPK, and has been shown to dephosphorylate p44-ERK1 (MAPK3) in vitro. It has been associated with cell growth and human primary cancers. It has also been identified as a cell-cell adhesion regulatory protein; it promotes the dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 398364735 140 ETRTLVEEETNNVICERIGWLDHFPPPFELLEEIVDGIENylSVSKNRVAVLHCRMGKGRSGMITVAYLMKY 211
Cdd:cd14504   38 EPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEE--ANAKNEAVLVHCLAGKGRTGTMLACYLVKT 107

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
                 ....*....|....*....|....*....|....*....|...
gi 398364735 177 IENYLSVSKNRVAVlHCRMGKGRSGMITVAYLMKYLQCPLGEA 219
Cdd:cd14515   80 IDKALSDPGGKVLV-HCVEGVSRSATLVLAYLMIYQNMTLEEA 121

hypothetical protein; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 398364735 160 LDHFPPPFELLEEIVDGIENYlsVSKNRVAVLHCRMGKGRSGMITVAYLM 209
Cdd:PRK12361 151 LDHSVPTLAQLNQAINWIHRQ--VRANKSVVVHCALGRGRSVLVLAAYLL 198

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364735 150 NNVICERIgwLDHFPPPFELLEEIVdgienylsvSKNRVAVLHCRMGKGRSGMITVAYLMKYLQCPLGEA 219
Cdd:cd14568   54 NDSYCEKL--LPWLDKAVEFIEKAR---------ASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDA 112

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
                 ....*....|....*....|....*....|....*....|...
gi 398364735 170 LEEIVDGIENylsVSKNRVAVL-HCRMGKGRSGMITVAYLMKY 211
Cdd:cd14514   63 FDEVADKIHQ---VKRRGGRTLvHCVAGVSRSATLCLAYLMKY 102

dual specificity protein phosphatase 28; Dual specificity protein phosphatase 28 (DUSP28), also called VHP, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It is an atypical DUSP that contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells. DUSP28 has an exceptionally low phosphatase activity due to the presence of bulky residues in the active site pocket resulting in low accessibility.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 398364735 170 LEEIVDGIENylSVSKNRVAVLHCRMGKGRSGMITVAYLMKYLQCPLGEARLIFMQAR 227
Cdd:cd14574   64 FEQCADAIEA--AVRRGGKCLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAAR 119

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
                 ....*....|....*....|....*....|.
gi 398364735 192 HCRMGKGRSGMITVAYLMKYLQCPLGEARLI 222
Cdd:cd14516  122 HCRVGVSRSATVVIAEVMKHLRMSLVDAYLF 152

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 398364735 167 FELLEEIVDGIENYLSVSknrvAVL-HCRMGKGRSGMITVAYLMKYLQCPLGEA 219
Cdd:cd14520   63 LSRLDECLDFIDEGRAEG----AVLvHCHAGVSRSAAVVTAYLMKTEQLSFEEA 112

dual specificity protein phosphatase 14; dual specificity protein phosphatase 14 (DUSP14), also called mitogen-activated protein kinase (MAPK) phosphatase 6 (MKP-6) or MKP-1-like protein tyrosine phosphatase (MKP-L), 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. DUSP14 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. DUSP14 dephosphorylates JNK, ERK, and p38 in vitro. It also 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.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 398364735 182 SVSKNRVAVL-HCRMGKGRSGMITVAYLMKYLQCPLGEA 219
Cdd:cd14572   80 SVGRKHGATLvHCAAGVSRSATLCIAYLMKYHRVSLLEA 118

N-terminal protein tyrosine phosphatase-like domain of auxilin; Auxilin, also called auxilin-1 or DnaJ homolog subfamily C member 6 (DNAJC6), is a J-domain containing protein that recruits the ATP-dependent chaperone Hsc70 to newly budded clathrin-coated vesicles and promotes uncoating of clathrin-coated vesicles, driving the clathrin assembly#disassembly cycle. Mutations in the DNAJC6 gene, encoding auxilin, are associated with early-onset Parkinson's disease. Auxilin contains an N-terminal protein tyrosine phosphatase (PTP)-like domain similar to the PTP-like domain of PTEN, a phosphoinositide 3-phosphatase, and a C-terminal region with clathrin-binding and J domains.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 398364735  42 LDISYILVNLIVCSYPVNTYpKLLYRNSLDDLILFLTVYHGKgNFRIFNF 91
Cdd:cd14563    9 LDISYITSRIIVMSYPAEGV-ELGFRNHIEDVRSFLDSRHLD-HYTVFNL 56

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 398364735   157 IGWLDH-FPPPFELLEEIVDGIENYLSVSKNRVAVL-HCRMGKGRSGMITVAYLM 209
Cdd:smart00404   8 TGWPDHgVPESPDSILELLRAVKKNLNQSESSGPVVvHCSAGVGRTGTFVAIDIL 62