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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326   5 FGWIMEKKLAGSGDVAgwqsgntsiVRQNLAWLEEQGLRAIVTLTESSLDGSVLNEFDIVYKHMPITDMSAPQLSSINEF 84
Cdd:cd14504    1 FSWVIPGKLAGMAFPR---------LPEHYAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEF 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  85 VAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLVNTG-MDPLDAITKVRQTRPGSVETLEQEMRIIEYAD 153
Cdd:cd14504   72 LDIVEEANAKNEAVLVHCLAGKGRTGTMLACYLVKTGkISAVDAINEIRRIRPGSIETSEQEKFVIQFAK 141

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326   5 FGWIMEKKLAGSGDVAgwqsgntsiVRQNLAWLEEQGLRAIVTLTESSLDGSVLNEFDIVYKHMPITDMSAPQLSSINEF 84
Cdd:cd14504    1 FSWVIPGKLAGMAFPR---------LPEHYAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEF 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  85 VAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLVNTG-MDPLDAITKVRQTRPGSVETLEQEMRIIEYAD 153
Cdd:cd14504   72 LDIVEEANAKNEAVLVHCLAGKGRTGTMLACYLVKTGkISAVDAINEIRRIRPGSIETSEQEKFVIQFAK 141

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326    22 WQSGNTSIvrQNLAWLEEQGLRAIVTLTESSldgSVLNEFDIVYKHMPITDMSAPQLSS-INEFVAFSGDCIERNKPVLV 100
Cdd:smart00195   9 YLGSYSDA--LNLALLKKLGITHVINVTNEV---PNYNGSDFTYLGVPIDDNTETKISPyFPEAVEFIEDAESKGGKVLV 83

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 297181326   101 HCSAGLGRTGTMLSCFLVNT-GMDPLDAITKVRQTRPGSVETLEQEMRIIEY 151
Cdd:smart00195  84 HCQAGVSRSATLIIAYLMKTrNMSLNDAYDFVKDRRPIISPNFGFLRQLIEY 135

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 297181326  72 DMSAPQLSSINEFVAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLVNTGMDPLDAITKVRQTRPGSV 139
Cdd:PTZ00393 147 DGDAPTVDIVSNWLTIVNNVIKNNRAVAVHCVAGLGRAPVLASIVLIEFGMDPIDAIVFIRDRRKGAI 214

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326   5 FGWIMEKKLAGSGDVAgwqsgntsiVRQNLAWLEEQGLRAIVTLTESSLDGSVLNEFDIVYKHMPITDMSAPQLSSINEF 84
Cdd:cd14504    1 FSWVIPGKLAGMAFPR---------LPEHYAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEF 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  85 VAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLVNTG-MDPLDAITKVRQTRPGSVETLEQEMRIIEYAD 153
Cdd:cd14504   72 LDIVEEANAKNEAVLVHCLAGKGRTGTMLACYLVKTGkISAVDAINEIRRIRPGSIETSEQEKFVIQFAK 141

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  30 VRQNLAWLEEQGLRAIVTL-TESSLD-------GSVLNEFDIVYKHMPITDMSAPqlSSINEFVAFS---GDCIERNKPV 98
Cdd:cd14505   32 LQADLEELKDQGVDDVVTLcTDGELEelgvpdlLEQYQQAGITWHHLPIPDGGVP--SDIAQWQELLeelLSALENGKKV 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 297181326  99 LVHCSAGLGRTGTMLSCFLVNTG--MDPLDAITKVRQTRPGSVETLEQEM 146
Cdd:cd14505  110 LIHCKGGLGRTGLIAACLLLELGdtLDPEQAIAAVRALRPGAIQTPKQEN 159

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  32 QNLAWLEEQGLRAIVTLTESSLDGSVlnEFDIVYKHMPITDMS----APQLSSINEFVAfsgDCIERNKPVLVHCSAGLG 107
Cdd:cd14498   17 QDKELLKKLGITHILNVAGEPPPNKF--PDGIKYLRIPIEDSPdediLSHFEEAIEFIE---EALKKGGKVLVHCQAGVS 91

                         90       100       110
                 ....*....|....*....|....*....|
gi 297181326 108 RTGTMLSCFLVNT-GMDPLDAITKVRQTRP 136
Cdd:cd14498   92 RSATIVIAYLMKKyGWSLEEALELVKSRRP 121

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326    64 VYKHMPITDMSAP-----QLSSINEFVAFSGDCiERNKPVLVHCSAGLGRTGT------MLSCFLVNTG-MDPLDAITKV 131
Cdd:smart00404   4 HYHYTGWPDHGVPespdsILELLRAVKKNLNQS-ESSGPVVVHCSAGVGRTGTfvaidiLLQQLEAEAGeVDIFDTVKEL 82

                           90       100
                   ....*....|....*....|
gi 297181326   132 RQTRPGSVETLEQEMRIIEY 151
Cdd:smart00404  83 RSQRPGMVQTEEQYLFLYRA 102

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 297181326  76 PQLSSINEFVAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLVN-TGMDPLDAITKVRQTRPGS-VETLEQEMRIIE 150
Cdd:cd14494   37 LTLAMVDRFLEVLDQAEKPGEPVLVHCKAGVGRTGTLVACYLVLlGGMSAEEAVRIVRLIRPGGiPQTIEQLDFLIK 113

protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine phosphatase domain-containing protein 1 (PTPDC1) is an uncharacterized non-receptor class protein-tyrosine phosphatase (PTP). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Small interfering RNA (siRNA) knockdown of the ptpdc1 gene is associated with elongated cilia.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  72 DMSAPQLSSINEFVAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLV-NTGMDPLDAITKVRQTRPGSVETLEQEMRIIE 150
Cdd:cd14506   86 DYGVPSLTTILDIVKVMAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQAIRLVRSKRPNSIQTRGQVLCVRE 165

                 ..
gi 297181326 151 YA 152
Cdd:cd14506  166 FA 167

Protein-tyrosine phosphatase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 297181326   94 RNKPVLVHCSAGLGRTGT------MLSCFLVNTGMDPLDAITKVRQTRPGSVETLEQ 144
Cdd:pfam00102 168 RSGPIVVHCSAGIGRTGTfiaidiALQQLEAEGEVDIFQIVKELRSQRPGMVQTLEQ 224

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 297181326  31 RQNLAWLEEQGLRAIVTLT-ESSLDGSVLNefdivYKHMPITDMSAPQLSSINEFVAFSGDCIERNKPVLVHCSAGLGRT 109
Cdd:cd14527   16 RWPSADELPPGVPAVLDLTaELPRPRKRQA-----YRCVPLLDLVAPTPEQLERAVAWIEELRAQGGPVLVHCALGYGRS 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 297181326 110 GTMLSCFLVNTGM--DPLDAITKVRQTRPGSVetLEQEMR 147
Cdd:cd14527   91 ATVVAAWLLAYGRakSVAEAEALIRAARPQVV--LNPAQR 128

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  37 LEEQGLRAIVTLTESSLDGSVLNEFDIVYKHMPITDMSAPQLSSINEFVAFSGDCIERNKP----VLVHCSAGLGRTGTM 112
Cdd:PTZ00242  36 LQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEFAKQSTppetIAVHCVAGLGRAPIL 115

                         90       100
                 ....*....|....*....|....*...
gi 297181326 113 LSCFLVNTG-MDPLDAITKVRQTRPGSV 139
Cdd:PTZ00242 116 VALALVEYGgMEPLDAVGFVREKRKGAI 143

protein tyrosine phosphatase type IVA family; Protein tyrosine phosphatases type IVA (PTP-IVa), also known as protein-tyrosine phosphatases of regenerating liver (PRLs) constitute a family of small, prenylated phosphatases that are the most oncogenic of all PTPs. They stimulate progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. They associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation. Vertebrates contain three members: PRL-1, PRL-2, and PRL-3.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  37 LEEQGLRAIVTLTESSLDGSVLNEFDIVYKHMPITDMSAPQLSSINEFV-----AFSGDCIErNKPVLVHCSAGLGRTGT 111
Cdd:cd14500   33 LKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDWLdllktRFKEEGKP-GACIAVHCVAGLGRAPV 111

                         90       100
                 ....*....|....*....|....*.
gi 297181326 112 MLSCFLVNTGMDPLDAITKVRQTRPG 137
Cdd:cd14500  112 LVAIALIELGMKPEDAVEFIRKKRRG 137

fungal protein tyrosine phosphatases; This subfamily contains Saccharomyces cerevisiae protein-tyrosine phosphatases 1 (PTP1) and 2 (PTP2), Schizosaccharomyces pombe PTP1, PTP2, and PTP3, and similar fungal proteins. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. PTP2, together with PTP3, is the major phosphatase that dephosphorylates and inactivates the MAP kinase HOG1 and also modulates its subcellular localization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  72 DMSAP-QLSSINEFVAFSGDCIER---NKPVLVHCSAGLGRTGT------MLSCF-----LVNTGMDPLDAITKV----R 132
Cdd:cd18533  115 DFGVPdSPEDLLTLIKLKRELNDSaslDPPIIVHCSAGVGRTGTfialdsLLDELkrglsDSQDLEDSEDPVYEIvnqlR 194

                         90
                 ....*....|..
gi 297181326 133 QTRPGSVETLEQ 144
Cdd:cd18533  195 KQRMSMVQTLRQ 206

protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; Phosphatase and tensin homolog (PTEN), also phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN or mutated in multiple advanced cancers 1 (MMAC1), is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It is a critical endogenous inhibitor of phosphoinositide signaling. It dephosphorylates phosphoinositide trisphosphate, and therefore, has the function of negatively regulating Akt. The PTEN/PI3K/AKT pathway regulates the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. PTEN contains an N-terminal PIP-binding domain, a protein tyrosine phosphatase (PTP)-like catalytic domain, a regulatory C2 domain responsible for its cellular location, a C-tail containing phosphorylation sites, and a C-terminal PDZ domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 297181326  65 YKHMPITDMSAPQLSSINEFVAFSGDCIERNKP--VLVHCSAGLGRTGTMLSCFLVNTGM--DPLDAITKVRQTR 135
Cdd:cd14509   62 VAEYPFDDHNPPPLELIKPFCEDVDEWLKEDEKnvAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYGAKR 136

RNA 5'-triphosphatase domain; This family of RNA-specific cysteine phosphatases includes baculovirus RNA 5'-triphosphatase, dual specificity protein phosphatase 11 (DUSP11), and the RNA triphosphatase domains of metazoan and plant mRNA capping enzymes. RNA/polynucleotide 5'-triphosphatase (EC 3.1.3.33) catalyzes the removal of the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end. mRNA capping enzyme is a bifunctional enzyme that catalyzes the first two steps of cap formation. DUSP11 has RNA 5'-triphosphatase and diphosphatase activity, but only poor protein-tyrosine phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  24 SGNTSIVRQNLAWLEEQGLraIVTLTESS--LDGSVLNEFDIVYKHMPITDMSAPQLSSINEFVAFSGDCIERNKP---V 98
Cdd:cd14502   37 RFTPSALAEKFRQDRKVGL--VIDLTNTDryYDPNDLDDDGYVYYKKVCVRKEPPDAEEVNKFIELVDKFLAEDNPdklI 114

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 297181326  99 LVHCSAGLGRTGTMLSCFLVNT-GMDPLDAITKVRQTRP 136
Cdd:cd14502  115 AVHCTHGFNRTGFMIVSYLVERlGLTVEQALEAFAQARP 153

atypical dual specificity phosphatases similar to yeast Siw14; This subfamily contains Saccharomyces Siw14 and a novel phosphatase from the Arabidopsis thaliana gene locus At1g05000. Siw14, also known as Oca3, plays a role in actin filament organization and endocytosis. Siw14 has been shown to be an inositol pyrophosphate phosphatase, hydrolyzing the beta-phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5or IP7). The At1g05000 protein, also called AtPFA-DSP1, has been shown to have highest activity toward olyphosphate (poly-P(12-13)) and deoxyribo- and ribonucleoside triphosphates, and less activity toward phosphoenolpyruvate, phosphotyrosine, phosphotyrosine-containing peptides, and phosphatidylinositols. This subfamily belongs to a group of atypical DSPs present in plants, fungi, kinetoplastids, and slime molds called plant and fungi atypical dual-specificity phosphatases (PFA-DSPs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  30 VRQNLAWLEEQGLRAIVTL-TESSLDGSV--LNEFDIVYKHMPITDMSAPQLS----SINEFVAFSGDCieRNKPVLVHC 102
Cdd:cd14528   22 NKKNFPFLRTLGLRSILYLcPEDYPESNLefLKENGIKLFQFGIEGNKEPFVDipeeLIRDALKVLLDP--RNHPVLIHC 99

                         90
                 ....*....|...
gi 297181326 103 SAGLGRTGTMLSC 115
Cdd:cd14528  100 NKGKHRTGCLVGC 112

protein tyrosine phosphatase type IVA 3; Protein tyrosine phosphatase type IVA 3 (PTP-IVa3), also known as protein-tyrosine phosphatase of regenerating liver 3 (PRL-3), stimulates progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. It exerts its oncogenic functions through activation of PI3K/Akt, which is a key regulator of the rapamycin-sensitive mTOR complex 1. PRL-3 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  37 LEEQGLRAIVTLTESSLDGSVLNEFDIVYKHMPITDMSAPQLSSINEFVAF--SGDCIERNKPVLVHCSAGLGRTGTMLS 114
Cdd:cd18535   33 LKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLlkTKFCEDPGCCVAVHCVAGLGRAPVLVA 112

                         90       100
                 ....*....|....*....|....*..
gi 297181326 115 CFLVNTGMDPLDAITKVRQTRPGSVET 141
Cdd:cd18535  113 LALIESGMKYEDAIQFIRQKRRGAINS 139

catalytic domain of R3 subfamily receptor-type tyrosine-protein phosphatases and similar proteins; R3 subfamily receptor-type phosphotyrosine phosphatases (RPTP) are characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. Vertebrate members include receptor-type tyrosine-protein phosphatase-like O (PTPRO), J (PTPRJ), Q (PTPRQ), B (PTPRB), V (PTPRV) and H (PTPRH). They belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Most members are PTPs, except for PTPRQ, which dephosphorylates phosphatidylinositide substrates. PTPRV is characterized only in rodents; its function has been lost in humans. Both vertebrate and invertebrate R3 subfamily RPTPs are involved in the control of a variety of cellular processes, including cell growth, differentiation, mitotic cycle and oncogenic transformation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  44 AIVTLTESSLDGSVLNEFDIVY--KHMPIT--------DMSAPQLS-SINEFVAFSGDCIERN-KPVLVHCSAGLGRTGT 111
Cdd:cd14548   98 TVTMLSESVLPDWTIREFKLERgdEVRSVRqfhftawpDHGVPEAPdSLLRFVRLVRDYIKQEkGPTIVHCSAGVGRTGT 177

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 297181326 112 MLSC-FLVNT-----GMDPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14548  178 FIALdRLLQQiesedYVDIFGIVYDLRKHRPLMVQTEAQ 216

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 297181326  77 QLSSINEFVAFSGDCIERNKPVLVHCSAGLGRTGT------MLSCFLVNTGMDPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14598  134 EIQSVRRHTNSTIDPKSPNPPVLVHCSAGVGRTGVvilseiMIACLEHNEMLDIPRVLDMLRQQRMMMVQTLSQ 207

catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), type 18 (PTPN18) and type 12 (PTPN12) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signaling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signaling molecules. TPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 297181326  97 PVLVHCSAGLGRTGTMlsCF------LVNTGMDP-----LDAITKVRQTRPGSVETLEQ 144
Cdd:cd14542  140 PICVHCSAGCGRTGTI--CAidyvwnLLKTGKIPeefslFDLVREMRKQRPAMVQTKEQ 196

catalytic domain of tyrosine-protein phosphatase non-receptor type 20 and type 13; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) and type 13 (PTPN13, also known as PTPL1) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization. Human PTPN13 is an important regulator of tumor aggressiveness.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  92 IERNKPVLVHCSAGLGRTGTMLsCFLVNTGM-------DPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14538  137 IHNSGPIVVHCSAGIGRTGVLI-TIDVALGLierdlpfDIQDIVKDLREQRQGMIQTKDQ 195

catalytic domain of tyrosine-protein phosphatase non-receptor type 5; Tyrosine-protein phosphatase non-receptor type 5 (PTPN5), also called striatum-enriched protein-tyrosine phosphatase (STEP) or neural-specific PTP, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN5/STEP is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. It is a CNS-enriched protein that regulates key signaling proteins required for synaptic strengthening, as well as NMDA and AMPA receptor trafficking. PTPN5 is implicated in multiple neurologic and neuropsychiatric disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, and fragile X syndrome.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 297181326  72 DMSAPQLSSINEFVAFSGDCIERNKPVLVHCSAGLGRTG----TMLSCF-LVNTG-MDPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14613  169 DNAPPLLQLVQEVEEARQQAEPNCGPVIVHCSAGIGRTGcfiaTSICCKqLRNEGvVDILRTTCQLRLDRGGMIQTCEQ 247

catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein phosphatase non-receptor type 4 (PTPN4), also called protein-tyrosine phosphatase MEG1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses. It specifically inhibits the TRIF-dependent TLR4 pathway by suppressing tyrosine phosphorylation of TRAM. It is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain; the PDZ domain regulates the catalytic activity of PTPN4.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  72 DMSAPQLSSinEFVAFSgdCIERNK------PVLVHCSAGLGRTGTMLS-----CFL-VNTGMDPLDAITKVRQTRPGSV 139
Cdd:cd14601  118 DHGVPDDSS--DFLDFV--CLVRNKragkdePVVVHCSAGIGRTGVLITmetamCLIeCNQPVYPLDIVRTMRDQRAMMI 193

                 ....*
gi 297181326 140 ETLEQ 144
Cdd:cd14601  194 QTPSQ 198

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 297181326  56 SVLNEF--DIVYKHMPITDMSAPQLSS-INEFVAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLVNT-GMDPLDAITKV 131
Cdd:cd14523   37 GVENAFpdDFTYKTISILDLPETDITSyFPECFEFIDEAKSQDGVVLVHCNAGVSRSASIVIGYLMATeNLSFEDAFSLV 116

                 ....*..
gi 297181326 132 RQTRPGS 138
Cdd:cd14523  117 KNARPSI 123

catalytic domain of tyrosine-protein phosphatase non-receptor type 18; Tyrosine-protein phosphatase non-receptor type 18 (PTPN18), also called brain-derived phosphatase, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. The N-terminal catalytic PTP domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation, and its C-terminal PEST domain promotes K48-linked HER2 ubiquitination and its destruction via the proteasome pathway.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 297181326  97 PVLVHCSAGLGRTGTMLSCFLVN----TGMDP-----LDAITKVRQTRPGSVETLEQ 144
Cdd:cd14603  198 PLCVHCSAGCGRTGVICTVDYVRqlllTQRIPpdfsiFDVVLEMRKQRPAAVQTEEQ 254

dual-specificity phosphatase domain of dual specificity protein phosphatase 11 and similar proteins; dual specificity protein phosphatase 11 (DUSP11), also known as RNA/RNP complex-1-interacting phosphatase or phosphatase that interacts with RNA/RNP complex 1 (PIR1), has RNA 5'-triphosphatase and diphosphatase activity, but only poor protein-tyrosine phosphatase activity. It has activity for short RNAs but is less active toward mononucleotide triphosphates, suggesting that its primary function in vivo is to dephosphorylate RNA 5'-ends. It may play a role in nuclear mRNA metabolism. Also included in this subfamily is baculovirus RNA 5'-triphosphatase for Autographa californica nuclear polyhedrosis virus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  27 TSIVRQnlawLEEQG--LRAIVTLTESS--LDGSVLNEFDIVYKHMPITDMSAPQLSSINEFVAFSGDCIERN----KPV 98
Cdd:cd17665   41 KDLVEQ----VEKRGekLGLVIDLTNTTryYDPRDLTNHGVYYKKITCPGHQVPDDKTIQSFKDAVKDFLEKNkdndKLI 116

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 297181326  99 LVHCSAGLGRTGTMLSCFLVNT-GMDPLDAITKVRQTRPGSVE 140
Cdd:cd17665  117 GVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQARGHPIE 159

PTP-like domain of receptor-type tyrosine-protein phosphatase C, repeat 2; Receptor-type tyrosine-protein phosphatase C (PTPRC), also known as CD45, leukocyte common antigen (LCA) or GP180, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRC/CD45 is found in all nucleated hematopoietic cells and is an essential regulator of T- and B-cell antigen receptor signaling. It controls immune response, both positively and negatively, by dephosphorylating a number of signaling molecules such as the Src family kinases, the CD3zeta chain of TCY, and ZAP-70 kinase. Mutations in the human PTPRC/CD45 gene are associated with severe combined immunodeficiency (SCID) and multiple sclerosis. PTPRC/CD45 contains an extracellular receptor-like region with fibronectin type III (FN3) repeats, a short transmembrane segment, and a cytoplasmic region comprising of a membrane proximal catalytically active PTP domain (repeat 1 or D1) and a membrane distal catalytically impaired PTP-like domain (repeat 2, or D2). This model represents repeat 2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  93 ERNKPVLVHCSAGLGRTGTMlsCFLVNT-------GM-DPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14558  140 GRSVPIVVHCSDGSSRTGIF--CALWNLlesaeteKVvDVFQVVKALRKQRPGMVSTLEQ 197

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and type 4 (PTPN4) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 and PTPN4 are large modular proteins containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 297181326  97 PVLVHCSAGLGRTGTMLscfLVNTGM---------DPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14541  145 PTVVHCSAGIGRTGVLI---TMETAMclieanepvYPLDIVRTMRDQRAMLIQTPSQ 198

bacterial protein tyrosine and dual-specificity phosphatases related to Pseudomonas aeruginosa TpbA; This subfamily contains bacterial protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DUSPs) related to Pseudomonas aeruginosa TpbA, a DUSP that negatively regulates biofilm formation by converting extracellular quorum sensing signals and to Mycobacterium tuberculosis PtpB, a PTP virulence factor that attenuates host immune defenses by interfering with signal transduction pathways in macrophages. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides, while DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and PTPs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297181326  31 RQNLAWLEEQGLRAIVTL----TESSLDGSVLNEFDIVYKHMPItDMSAPQLSSINEFVAFSGDcIERNKPVLVHCSAGL 106
Cdd:cd14529   23 DEDRALLKKLGIKTVIDLrgadERAASEEAAAKIDGVKYVNLPL-SATRPTESDVQSFLLIMDL-KLAPGPVLIHCKHGK 100

                         90
                 ....*....|.
gi 297181326 107 GRTGTMLSCFL 117
Cdd:cd14529  101 DRTGLVSALYR 111

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 297181326   60 EFDIVYKHMPITDMSAPQLSSINEFVAFSGDCIERNKPVLVHCSAGLGRTGTMLSCFLV 118
Cdd:pfam05706  98 QCGIITHHHPIADGGTPDIASCCEIMEELATCLKNNRKTLIHCYGGLGRSCLVAACLLL 156

catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 1; Receptor-type tyrosine-protein phosphatase A (PTPRA) and E (PTPRE) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA and PTPRE share several functions including regulation of Src family kinases and voltage-gated potassium (Kv) channels. They both contain a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the first catalytic PTP domain (repeat 1).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 297181326  94 RNKPVLVHCSAGLGRTGT------MLSCFLVNTGMDPLDAITKVRQTRPGSVETLEQ 144
Cdd:cd14551  140 RAGPIVVHCSAGVGRTGTfividaMLDMMHAEGKVDVFGFVSRIRQQRSQMVQTDMQ 196

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 297181326  37 LEEQGLRAIVTL-TESSL-----DGSVLN----EFDIVYKHMPITDMSAPQLSS-INEFVAFSGDCIERNKPVLVHCSAG 105
Cdd:cd14526   25 LKKEGVTAVLNLqTDSDMeywgvDIDSIRkackESGIRYVRLPIRDFDTEDLRQkLPQAVALLYRLLKNGGTVYVHCTAG 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 297181326 106 LGRTGTMLSCFLV-NTGMDPLDAITKVRQTRP 136
Cdd:cd14526  105 LGRAPATVIAYLYwVLGYSLDEAYYLLTSKRP 136