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 56786144   8 FSWVLPGRLAGLALPRLPAHYQFLLDLGVRHLVSLTERGPP-HSDSCPGLTLHRLRIPDFCPPAPDQIDRFVQIVDEANA 86
Cdd:cd14504   1 FSWVIPGKLAGMAFPRLPEHYAYLNENGIRHVVTLTEEPPPeHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEEANA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 56786144  87 RGEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSIETYEQEKAVFQFYQR 148
Cdd:cd14504  81 KNEAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFAKT 142

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 56786144   8 FSWVLPGRLAGLALPRLPAHYQFLLDLGVRHLVSLTERGPP-HSDSCPGLTLHRLRIPDFCPPAPDQIDRFVQIVDEANA 86
Cdd:cd14504   1 FSWVIPGKLAGMAFPRLPEHYAYLNENGIRHVVTLTEEPPPeHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEEANA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 56786144  87 RGEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSIETYEQEKAVFQFYQR 148
Cdd:cd14504  81 KNEAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFAKT 142

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144   24 LPAHYQFLLDLGVRHLVSLTerGPPHSDSC---PGLTLHRLRIPDFCPPAPDQIDRFVQIVDEANAR----GEAVGVHCA 96
Cdd:PTZ00242  29 LPLYIKELQRYNVTHLVRVC--GPTYDAELlekNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEFAKqstpPETIAVHCV 106

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 56786144   97 LGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSI 133
Cdd:PTZ00242 107 AGLGRAPILVALALVEYGGMEPLDAVGFVREKRKGAI 143

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144    29 QFLLDLGVRHLVSLTErgpphSDSCPGLTLHRLRIP--DF--CPPAPDqIDRFVQIVDEANARGEAVGVHCALGFGRTGT 104
Cdd:pfam00782  12 AFLSKLGITAVINVTR-----EVDLYNSGILYLRIPveDNheTNISKY-LEEAVEFIDDARQKGGKVLVHCQAGISRSAT 85

                          90       100
                  ....*....|....*....|....*..
gi 56786144   105 MLACYLVKERGLAAGDAIAEIRRLRPG 131
Cdd:pfam00782  86 LIIAYLMKTRNLSLNEAYSFVKERRPG 112

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 56786144   8 FSWVLPGRLAGLALPRLPAHYQFLLDLGVRHLVSLTERGPP-HSDSCPGLTLHRLRIPDFCPPAPDQIDRFVQIVDEANA 86
Cdd:cd14504   1 FSWVIPGKLAGMAFPRLPEHYAYLNENGIRHVVTLTEEPPPeHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEEANA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 56786144  87 RGEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSIETYEQEKAVFQFYQR 148
Cdd:cd14504  81 KNEAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFAKT 142

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144   8 FSWVLPGRLAGLALP--RLPAHYQFLLDLGVRHLVSLTErgpphsdscpgltlhrlripdfcppapDQIDRFVQIVDEAN 85
Cdd:cd14494   1 FNWIDPLRLIAGALPlsPLEADSRFLKQLGVTTIVDLTL---------------------------AMVDRFLEVLDQAE 53

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  86 ARGEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSI-ETYEQEKAVFQ 144
Cdd:cd14494  54 KPGEPVLVHCKAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGIpQTIEQLDFLIK 113

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 56786144  24 LPAHYQFLLDLGVRHLVSLTERG-------PPHSDSCP--GLTLHRLRIPDFCppAPDQIDRFVQIVDE---ANARGEAV 91
Cdd:cd14505  32 LQADLEELKDQGVDDVVTLCTDGeleelgvPDLLEQYQqaGITWHHLPIPDGG--VPSDIAQWQELLEEllsALENGKKV 109

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 56786144  92 GVHCALGFGRTGTMLACYLV-KERGLAAGDAIAEIRRLRPGSIETYEQE 139
Cdd:cd14505 110 LIHCKGGLGRTGLIAACLLLeLGDTLDPEQAIAAVRALRPGAIQTPKQE 158

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 56786144  68 PPAPDQIDRFVQIVDEANARGEA---VGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRP 130
Cdd:cd14502  88 PPDAEEVNKFIELVDKFLAEDNPdklIAVHCTHGFNRTGFMIVSYLVERLGLTVEQALEAFAQARP 153

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144   24 LPAHYQFLLDLGVRHLVSLTerGPPHSDSC---PGLTLHRLRIPDFCPPAPDQIDRFVQIVDEANAR----GEAVGVHCA 96
Cdd:PTZ00242  29 LPLYIKELQRYNVTHLVRVC--GPTYDAELlekNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEFAKqstpPETIAVHCV 106

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 56786144   97 LGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSI 133
Cdd:PTZ00242 107 AGLGRAPILVALALVEYGGMEPLDAVGFVREKRKGAI 143

N-terminal triphosphatase domain of mRNA capping enzyme; mRNA capping enzyme, also known as RNA guanylyltransferase and 5'-phosphatase (RNGTT) or mammalian mRNA capping enzyme (Mce1) in mammals, is a bifunctional enzyme that catalyzes the first two steps of cap formation: (1) by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end using the polynucleotide 5'-phosphatase activity (EC 3.1.3.33) of the N-terminal triphosphatase domain; and (2) by transferring the GMP moiety of GTP to the 5'-diphosphate terminus through the C-terminal mRNA guanylyltransferase domain (EC 2.7.7.50). The enzyme is also referred to as CEL-1 in Caenorhabditis elegans.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 56786144  68 PPAPDQIDRFVQIVDEANAR--GEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPGSIetYEQE 139
Cdd:cd17664  89 CPSPEQTETFIRLCENFIEKnpLELIGVHCTHGFNRTGFLICAYLVEKMDWSVEAAVATFAQARPPGI--YKGD 160

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 56786144  29 QFLLDLGVRHLVSLTERGPPHSDScPGLTLHRLRIPDFcPPAP--DQIDRFVQIVDEANARGEAVGVHCALGFGRTGTML 106
Cdd:cd14498  20 ELLKKLGITHILNVAGEPPPNKFP-DGIKYLRIPIEDS-PDEDilSHFEEAIEFIEEALKKGGKVLVHCQAGVSRSATIV 97

                        90       100
                ....*....|....*....|....
gi 56786144 107 ACYLVKERGLAAGDAIAEIRRLRP 130
Cdd:cd14498  98 IAYLMKKYGWSLEEALELVKSRRP 121

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144    29 QFLLDLGVRHLVSLTErgpphSDSCPGLTLHRLRIP--DF--CPPAPDqIDRFVQIVDEANARGEAVGVHCALGFGRTGT 104
Cdd:pfam00782  12 AFLSKLGITAVINVTR-----EVDLYNSGILYLRIPveDNheTNISKY-LEEAVEFIDDARQKGGKVLVHCQAGISRSAT 85

                          90       100
                  ....*....|....*....|....*..
gi 56786144   105 MLACYLVKERGLAAGDAIAEIRRLRPG 131
Cdd:pfam00782  86 LIIAYLMKTRNLSLNEAYSFVKERRPG 112

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144     58 LHRLRIPDFCppAPDQIDRFVQIVDEANARGEA------VGVHCALGFGRTGTMLACYLVKERgLAAG-------DAIAE 124
Cdd:smart00012   5 YHYTGWPDHG--VPESPDSILELLRAVKKNLNQsessgpVVVHCSAGVGRTGTFVAIDILLQQ-LEAEagevdifDTVKE 81

                           90
                   ....*....|....
gi 56786144    125 IRRLRPGSIETYEQ 138
Cdd:smart00012  82 LRSQRPGMVQTEEQ 95

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  64 PDFC-PPAPDQIDRFVQIVDEANARGEA-VGVHCALGFGRTGTMLACYLVKERGLAAG-----DAIAEIRRLRPGSIETY 136
Cdd:cd00047 113 PDHGvPSSPEDLLALVRRVRKEARKPNGpIVVHCSAGVGRTGTFIAIDILLERLEAEGevdvfEIVKALRKQRPGMVQTL 192

                ..
gi 56786144 137 EQ 138
Cdd:cd00047 193 EQ 194

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144    64 PDFC-PPAPDQIDRFVQIVDEANARGEA--VGVHCALGFGRTGT-----MLACYLVKERGLAAGDAIAEIRRLRPGSIET 135
Cdd:pfam00102 142 PDHGvPESPNSLLDLLRKVRKSSLDGRSgpIVVHCSAGIGRTGTfiaidIALQQLEAEGEVDIFQIVKELRSQRPGMVQT 221

                  ...
gi 56786144   136 YEQ 138
Cdd:pfam00102 222 LEQ 224

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144     64 PDF-CPPAPDQIDRFVQIVDEANARGEA-VGVHCALGFGRTGTMLACY-----LVKERGLAAGDAIAEIRRLRPGSIETY 136
Cdd:smart00194 168 PDHgVPESPESILDLIRAVRKSQSTSTGpIVVHCSAGVGRTGTFIAIDillqqLEAGKEVDIFEIVKELRSQRPGMVQTE 247

                   ..
gi 56786144    137 EQ 138
Cdd:smart00194 248 EQ 249

hypothetical protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 56786144   58 LHRLRIP--DFCPPAPDQIDRFVQIVDEANARGEAVGVHCALGFGRTGTMLACYLV-KERGLAAGDAIAEIRRLR 129
Cdd:PRK12361 143 IDYLNIPilDHSVPTLAQLNQAINWIHRQVRANKSVVVHCALGRGRSVLVLAAYLLcKDPDLTVEEVLQQIKQIR 217

catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) belongs 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 56786144  68 PPAPDQIDRFVQIVDEANARGEAVgVHCALGFGRTGTMLA-----CYLVKERGLAAGDAIAEIRRLRPGSIETYEQ 138
Cdd:cd14596 120 PQSSDQLVKFICYMRKVHNTGPIV-VHCSAGIGRAGVLICvdvllSLIEKDLSFNIKDIVREMRQQRYGMIQTKDQ 194

catalytic domain of tyrosine-protein phosphatase non-receptor type 1 and type 2; Tyrosine-protein phosphatase non-receptor type 1 (PTPN1) type 2 (PTPN2) belong to the family of classical tyrosine-specific protein tyrosine phosphatases, (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN1 (or 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 dephosphorylates and regulates the activity of a number of receptor tyrosine kinases, including the insulin receptor, the EGF receptor, and the PDGF receptor. PTPN2 (or TCPTP), a tumor suppressor, dephosphorylates and inactivates EGFRs, Src family kinases, Janus-activated kinases (JAKs)-1 and -3, and signal transducer and activators of transcription (STATs)-1, -3 and -5, in a cell type and context-dependent manner.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  59 HRLRIPDF-CPPAPDQIDRFVQIVDEANARGEAVG---VHCALGFGRTGT--MLACYLV-----KERGLAAGDAIAEIRR 127
Cdd:cd14545 135 HYTTWPDFgVPESPAAFLNFLQKVRESGSLSSDVGppvVHCSAGIGRSGTfcLVDTCLVliekgNPSSVDVKKVLLEMRK 214

                        90
                ....*....|.
gi 56786144 128 LRPGSIETYEQ 138
Cdd:cd14545 215 YRMGLIQTPDQ 225

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  68 PPAPDQIDRFVQIVDEANARG-EAVGVHCALGFGRTGTMLAC-----YLVKER---GLAAGDAIAEIRRLRPGSIETYEQ 138
Cdd:cd14603 175 PDSPDCMLAMIELARRLQGSGpEPLCVHCSAGCGRTGVICTVdyvrqLLLTQRippDFSIFDVVLEMRKQRPAAVQTEEQ 254

                ....*.
gi 56786144 139 EKAVFQ 144
Cdd:cd14603 255 YEFLYH 260

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  35 GVRHLVSLTERGPPHSDSCPGLtlHRLRIPDFCPPAPDQIDRF---VQIVDEANARGeAVGVHCALGFGRTGTMLACYLV 111
Cdd:cd14520  26 GITHVLTVDSEEPIDAPPVGKL--VRKFVPALDEESTDLLSRLdecLDFIDEGRAEG-AVLVHCHAGVSRSAAVVTAYLM 102

                        90
                ....*....|....*....
gi 56786144 112 KERGLAAGDAIAEIRRLRP 130
Cdd:cd14520 103 KTEQLSFEEALASLRECKP 121

dual specificity phosphatase domain of dual specificity protein phosphatase 16; Dual specificity protein phosphatase 16 (DUSP16), also called mitogen-activated protein kinase (MAPK) phosphatase 7 (MKP-7), 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. DUSP16/MKP-7 plays an essential role in perinatal survival and selectively controls the differentiation and cytokine production of myeloid cells. It is acetylated by Mycobacterium tuberculosis Eis protein, which leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation, and thus, initiating suppression of host immune responses. DUSP16/MKP-7 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  50 SDSCPGLTL----HRLRIP---DFCPPAPDQIDRFVQIVDEANARGEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAI 122
Cdd:cd14646  36 SNTCPKPDFipesHFLRVPvndSFCEKILPWLDKSVDFIEKAKASNGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAY 115

                ....*...
gi 56786144 123 AEIRRLRP 130
Cdd:cd14646 116 RFVKEKRP 123

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 56786144  23 RLPAHYqflldlgvrHLVSLTERGPPHSDSCPGlTLHRLRIPDFCPPAPDQIDRFVQIVDE---ANARGEAVgVHCALGF 99
Cdd:cd14497  38 HHPDHY---------MIFNLSEEEYDDDSKFEG-RVLHYGFPDHHPPPLGLLLEIVDDIDSwlsEDPNNVAV-VHCKAGK 106

                        90       100       110
                ....*....|....*....|....*....|....*
gi 56786144 100 GRTGTMLACYLVKERGLA-AGDAIAEI--RRLRPG 131
Cdd:cd14497 107 GRTGTVICAYLLYYGQYStADEALEYFakKRFKEG 141

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  29 QFLLDLGVRHLVSLTERGPPHSDScpGLtLHRLRIP---DFCPPAPDQIDRFVQIVDEANARGEAVGVHCALGFGRTGTM 105
Cdd:cd14512  20 ELMQQLGIGYVLNVSNTCPNPDFI--GL-FHYKRIPvndSFCQNISPWFDEAIEFIEEAKASNGGVLVHCLAGISRSATI 96

                        90       100
                ....*....|....*....|....*
gi 56786144 106 LACYLVKERGLAAGDAIAEIRRLRP 130
Cdd:cd14512  97 AIAYLMKRMRMSLDEAYDFVKEKRP 121

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  60 RLRIPDFCPPAPDQIDRFVQIVD---EANARGEAVGVHCALGFGRTGTMLACYLVKERGLAAGDAIAEIRRLRPG----- 131
Cdd:cd14574  47 TLRVPVFDDPAEDLYRHFEQCADaieAAVRRGGKCLVYCKNGRSRSAAVCIAYLMKHRGLSLQDAFQVVKAARPVaepnp 126

                        90
                ....*....|..
gi 56786144 132 ----SIETYEQE 139
Cdd:cd14574 127 gfwsQLQRYEEE 138

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the first PTP domain (repeat 1).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  47 PPHSDSC--PGLT--LHRLRIPDF-CPPAPDQIDRFVQIVDEAN-ARGEAVGVHCALGFGRTGTMLAC-----YLVKERG 115
Cdd:cd14620 117 PQLPDGCkaPRLVtqLHFTSWPDFgVPFTPIGMLKFLKKVKSVNpVHAGPIVVHCSAGVGRTGTFIVIdamidMMHAEQK 196

                        90       100
                ....*....|....*....|....*....
gi 56786144 116 LAAGDAIAEIRRLRPGSIETYEQEKAVFQ 144
Cdd:cd14620 197 VDVFEFVSRIRNQRPQMVQTDMQYSFIYQ 225

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  31 LLDLGVRHLVSLTerGPPHSDSCPGLTLHRLRIPDFcPPAP--DQIDRFVQIVDEANARGEAVGVHCALGFGRTGTMLAC 108
Cdd:cd14514  21 LLSRGITCIINAT--TELPDPSYPGIEYLRVPVEDS-PHADlsPHFDEVADKIHQVKRRGGRTLVHCVAGVSRSATLCLA 97

                        90       100
                ....*....|....*....|..
gi 56786144 109 YLVKERGLAAGDAIAEIRRLRP 130
Cdd:cd14514  98 YLMKYEGMTLREAYKHVKAARP 119

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 56786144  55 GLTLHRLRIPDFCPPAPDQIDRFVQIVDE--ANARGEAVGVHCALGFGRTGTMLACYLVkERGLAAGDAIAEIRRLRPGS 132
Cdd:cd18535  58 GITVVDWPFDDGAPPPGKVVEDWLSLLKTkfCEDPGCCVAVHCVAGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGA 136

                ...
gi 56786144 133 IET 135
Cdd:cd18535 137 INS 139

protein tyrosine phosphatase-like domain of paladin, repeat 2; Paladin is a putative phosphatase, which in mouse is expressed in endothelial cells during embryonic development and in arterial smooth muscle cells in adults. It has been suggested to be an antiphosphatase that regulates the activity of specific neural crest regulatory factors and thus, modulates neural crest cell formation and migration. Paladin contains two tyrosine-protein phosphatase domains. This model represents repeat 2.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 56786144  38 HLVSLTERGPPHSDSCPGLTLHRLRIPDFCPPAPDQIDRFVQIVDEANAR--GEAVGVHCALGFGRTGTMLA 107
Cdd:cd17660  85 QTFSPREPGNLEQLIPVGLTYRRIPIPDFCAPREEDFDRLLEAMKSALAEdsGTAFVFNCLDGKGRTTTAMV 156

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 56786144  68 PPAPDQIDRFVQIVDEANARGEAVgVHCALGFGRTGTMLA-----CYLVKERGLAAGDAIAEIRRLRPGSIETYEQ 138
Cdd:cd14538 121 PQSADPLLRFIRYMRRIHNSGPIV-VHCSAGIGRTGVLITidvalGLIERDLPFDIQDIVKDLREQRQGMIQTKDQ 195

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 56786144   7 NFSWVLPGRLAGlALPRLPAHYQFLLDLGVRHLVSLTER-------GPPHS--DSCP--GLTLHRLRIPDFCPPapDQID 75
Cdd:cd14526   2 NYSRILPNLIVG-SCPQNPEDVDRLKKEGVTAVLNLQTDsdmeywgVDIDSirKACKesGIRYVRLPIRDFDTE--DLRQ 78

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 56786144  76 RF---VQIVDEANARGEAVGVHCALGFGR-TGTMLAcYLVKERGLAAGDAIAEIRRLRP 130
Cdd:cd14526  79 KLpqaVALLYRLLKNGGTVYVHCTAGLGRaPATVIA-YLYWVLGYSLDEAYYLLTSKRP 136

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56786144  56 LTLHRLRIPDF-CPPAPDQIDRFVQIVDEANARGEAVG---VHCALGFGRTGTML---ACYLVKER-----GLAAGDAIA 123
Cdd:cd14608 157 LHFHYTTWPDFgVPESPASFLNFLFKVRESGSLSPEHGpvvVHCSAGIGRSGTFCladTCLLLMDKrkdpsSVDIKKVLL 236