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 50539984   9 FSWVDPGKVAGLAMPRMTAHYQYLLNSGIKHLVTLTERKPPDH-DTCPDLTLHHIKINDFCAPTFEQINRFLTIVEEANA 87
Cdd:cd14504   1 FSWVIPGKLAGMAFPRLPEHYAYLNENGIRHVVTLTEEPPPEHsDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEEANA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50539984  88 SGQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIRRIRRGSIETREQEQMIVQFYQQ 149
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 50539984   9 FSWVDPGKVAGLAMPRMTAHYQYLLNSGIKHLVTLTERKPPDH-DTCPDLTLHHIKINDFCAPTFEQINRFLTIVEEANA 87
Cdd:cd14504   1 FSWVIPGKLAGMAFPRLPEHYAYLNENGIRHVVTLTEEPPPEHsDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEEANA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50539984  88 SGQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIRRIRRGSIETREQEQMIVQFYQQ 149
Cdd:cd14504  81 KNEAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETSEQEKFVIQFAKT 142

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984     34 NSGIKHLVTLTERKPPDHDtcPDLTLHHIKIND-FCAPTFEQINRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLV 112
Cdd:smart00195  24 KLGITHVINVTNEVPNYNG--SDFTYLGVPIDDnTETKISPYFPEAVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLM 101

                           90       100
                   ....*....|....*....|..
gi 50539984    113 KSRKISGIDAINEIRRiRRGSI 134
Cdd:smart00195 102 KTRNMSLNDAYDFVKD-RRPII 122

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 50539984    36 GIKHLVTLTERKPPDHdtcPDLTLHHIKINDF----CAPTFEQINRFltiVEEANASGQAVAVHCLHGFGRTGTMLACYL 111
Cdd:pfam00782  18 GITAVINVTREVDLYN---SGILYLRIPVEDNhetnISKYLEEAVEF---IDDARQKGGKVLVHCQAGISRSATLIIAYL 91

                          90       100
                  ....*....|....*....|...
gi 50539984   112 VKSRKISGIDAInEIRRIRRGSI 134
Cdd:pfam00782  92 MKTRNLSLNEAY-SFVKERRPGI 113

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 50539984   9 FSWVDPGKVAGLAMPRMTAHYQYLLNSGIKHLVTLTERKPPDH-DTCPDLTLHHIKINDFCAPTFEQINRFLTIVEEANA 87
Cdd:cd14504   1 FSWVIPGKLAGMAFPRLPEHYAYLNENGIRHVVTLTEEPPPEHsDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEEANA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50539984  88 SGQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIRRIRRGSIETREQEQMIVQFYQQ 149
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 50539984   9 FSWVDPGKVAGLA--MPRMTAHYQYLLNSGIKHLVTLTErkppdhdtcpdltlhhikindfcaptfEQINRFLTIVEEAN 86
Cdd:cd14494   1 FNWIDPLRLIAGAlpLSPLEADSRFLKQLGVTTIVDLTL---------------------------AMVDRFLEVLDQAE 53

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50539984  87 ASGQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIRRIRRGSIetreqEQMIVQFYQ 148
Cdd:cd14494  54 KPGEPVLVHCKAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGI-----PQTIEQLDF 110

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 50539984  70 PTFEQINRFLTIVEEANasgQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIRRIRRGSI 134
Cdd:cd14499  93 PSDDIVKKFLDICENEK---GAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSV 154

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984     34 NSGIKHLVTLTERKPPDHDtcPDLTLHHIKIND-FCAPTFEQINRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLV 112
Cdd:smart00195  24 KLGITHVINVTNEVPNYNG--SDFTYLGVPIDDnTETKISPYFPEAVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLM 101

                           90       100
                   ....*....|....*....|..
gi 50539984    113 KSRKISGIDAINEIRRiRRGSI 134
Cdd:smart00195 102 KTRNMSLNDAYDFVKD-RRPII 122

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 50539984  30 QYLLNSGIKHLVTLTERKPPDHDTcPDLTLHHIKINDF----CAPTFEQINRFltiVEEANASGQAVAVHCLHGFGRTGT 105
Cdd:cd14498  20 ELLKKLGITHILNVAGEPPPNKFP-DGIKYLRIPIEDSpdedILSHFEEAIEF---IEEALKKGGKVLVHCQAGVSRSAT 95

                        90       100
                ....*....|....*....|....*
gi 50539984 106 MLACYLVKSRKISGIDAINEIRRIR 130
Cdd:cd14498  96 IVIAYLMKKYGWSLEEALELVKSRR 120

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 50539984  62 IKINDFC-----APTFEQINRFLTIVE----EANASGQAVAVHCLHGFGRTGTMLACYLVKsRKISGIDAINEIRRIRRG 132
Cdd:cd14500  59 IKVHDWPfddgsPPPDDVVDDWLDLLKtrfkEEGKPGACIAVHCVAGLGRAPVLVAIALIE-LGMKPEDAVEFIRKKRRG 137

                        90
                ....*....|....*....
gi 50539984 133 SIeTREQEQMIVQFYQQNK 151
Cdd:cd14500 138 AI-NSKQLQFLEKYKPKKK 155

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984     59 LHHIKINDFCAPtfEQINRFLTIVEEANASGQA------VAVHCLHGFGRTGTMLACYLVKSRKISGIDAIN------EI 126
Cdd:smart00404   5 YHYTGWPDHGVP--ESPDSILELLRAVKKNLNQsessgpVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDifdtvkEL 82

                           90
                   ....*....|...
gi 50539984    127 RRIRRGSIETREQ 139
Cdd:smart00404  83 RSQRPGMVQTEEQ 95

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 50539984  66 DFCAPTFEQINRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLVKSRKISGID-AINEIRRIRRGSIETREQEQMIV 144
Cdd:cd14527  53 DLVAPTPEQLERAVAWIEELRAQGGPVLVHCALGYGRSATVVAAWLLAYGRAKSVAeAEALIRAARPQVVLNPAQRKALE 132

                ....
gi 50539984 145 QFYQ 148
Cdd:cd14527 133 AWSG 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 50539984  29 YQYLLNSGIKHLVTLT-ERKPPDHDTCPDLTLHHIKIN--DFCAPTFEQINRFLTIVEEANASGQA---VAVHCLHGFGR 102
Cdd:cd14502  45 EKFRQDRKVGLVIDLTnTDRYYDPNDLDDDGYVYYKKVcvRKEPPDAEEVNKFIELVDKFLAEDNPdklIAVHCTHGFNR 124

                        90       100
                ....*....|....*....|....*....
gi 50539984 103 TGTMLACYLVKSRKISGIDAINEIRRIRR 131
Cdd:cd14502 125 TGFMIVSYLVERLGLTVEQALEAFAQARP 153

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984   34 NSGIKHLVTLTERKPPDHD-TCPDLTLHHIKINDFCAPTFEQINRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLV 112
Cdd:PTZ00393 114 NYNVTDLVRTCERTYNDGEiTSAGINVHELIFPDGDAPTVDIVSNWLTIVNNVIKNNRAVAVHCVAGLGRAPVLASIVLI 193

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 50539984  113 KsRKISGIDAINEIRRIRRGSIETReQEQMIVQFYQQNK 151
Cdd:PTZ00393 194 E-FGMDPIDAIVFIRDRRKGAINKR-QLQFLKAYKKKKK 230

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984    59 LHHIKINDFCAPtfEQINRFLTIVEEANASGQA-----VAVHCLHGFGRTGT----MLACYLVKSRKISGI-DAINEIRR 128
Cdd:pfam00102 136 FHYTGWPDHGVP--ESPNSLLDLLRKVRKSSLDgrsgpIVVHCSAGIGRTGTfiaiDIALQQLEAEGEVDIfQIVKELRS 213

                          90
                  ....*....|.
gi 50539984   129 IRRGSIETREQ 139
Cdd:pfam00102 214 QRPGMVQTLEQ 224

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 50539984  66 DFCAPTFEQINRFLTIVEE--ANASGQAVAVHCLHGFGRTGTMLACYLVKSRKI-SGIDAIN 124
Cdd:cd14509  69 DHNPPPLELIKPFCEDVDEwlKEDEKNVAAVHCKAGKGRTGVMICCYLLYLGKFpSAKEALD 130

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 50539984  59 LHHIKINDFCAPT-FEQINRFLTIV-EEANASGQAVAVHCLHGFGRTGTMLACY-----LVKSRKISGIDAINEIRRIRR 131
Cdd:cd00047 107 LHYTGWPDHGVPSsPEDLLALVRRVrKEARKPNGPIVVHCSAGVGRTGTFIAIDillerLEAEGEVDVFEIVKALRKQRP 186

                ....*...
gi 50539984 132 GSIETREQ 139
Cdd:cd00047 187 GMVQTLEQ 194

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 50539984  49 PDHDTCPDLTLHHIKIND-FCAPTFEQINRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIR 127
Cdd:cd14646  40 PKPDFIPESHFLRVPVNDsFCEKILPWLDKSVDFIEKAKASNGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVK 119

                ...
gi 50539984 128 RIR 130
Cdd:cd14646 120 EKR 122

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  35 SGIKHLVT-LTERKPPDHDTcPDLTlhhikindfcaptfEQINRFLTIVEEANASGQAVaVHCLHGFGRTGTMLA----- 108
Cdd:cd14596 100 TGENRLIKhLQFTTWPDHGT-PQSS--------------DQLVKFICYMRKVHNTGPIV-VHCSAGIGRAGVLICvdvll 163

                        90       100       110
                ....*....|....*....|....*....|.
gi 50539984 109 CYLVKSRKISGIDAINEIRRIRRGSIETREQ 139
Cdd:cd14596 164 SLIEKDLSFNIKDIVREMRQQRYGMIQTKDQ 194

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 50539984  20 LAMPRMTAHYQYLLNSGIKHLVTLTERKPPDH--------DTCPDLTLHH-----IKINDFCAPTFEQINRFLTIVEEAN 86
Cdd:cd14510  24 IAMSFPSSGKQAFYRNPIEEVVRFLDTKHPDHykvynlcsERGYDPKYFHnrverVPIDDHNVPTLDEMLSFTAEVREWM 103

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 50539984  87 ASG--QAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAINEIRRIRR 131
Cdd:cd14510 104 AADpkNVVAIHCKGGKGRTGTMVCAWLIYSGQFESAKEALEYFGERR 150

Tyrosine phosphatase family; This family is closely related to the pfam00102 and pfam00782 families.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984     6 PPNFSWVDPGKVAGlAMPRmTAHYQYLLNSGIKHLVTLTERKPPDHDTC----PDLTLHHIKIND----FCAPTFEQINR 77
Cdd:pfam03162   4 PLNFSPVEPGLYRS-SYPR-ANNFSFLRSLRLKTIISLSPEPYPQDNLQflesEHIKLYHIHMEGnkdpFVNIPSHLLRR 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 50539984    78 FL-TIVEEANasgQAVAVHCLHGFGRTGTMLACYlvksRKISGIDA---INEIRRIRRGSIETREQE 140
Cdd:pfam03162  82 ALkLLLNKDN---YPVLIHCNRGKHRTGLVIGCL----RKLQKWSLasiLNEYRRFSGSKARIVDEE 141

Protein tyrosine phosphatase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  59 LHHIKINDFCAPTFEQINRFL-TIVEEAN---ASGQAVAVHCLHGFGRTGTMLACY-LVKSRK------ISGIDAINEIR 127
Cdd:COG5599 172 LHVKNWPDHGAISAEALKNLAdLIDKKEKikdPDKLLPVVHCRAGVGRTGTLIACLaLSKSINalvqitLSVEEIVIDMR 251

                        90       100
                ....*....|....*....|...
gi 50539984 128 RIR-RGSIETREQEQMIVQFYQQ 149
Cdd:COG5599 252 TSRnGGMVQTSEQLDVLVKLAEQ 274

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 50539984  65 NDFCAPTFEQINRFLTIVEE--ANASGQAVAVHCLHGFGRTGTMLACYLVKSrKISGIDAINEIRRIRRGSIETRE 138
Cdd:cd18535  67 DDGAPPPGKVVEDWLSLLKTkfCEDPGCCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKRRGAINSKQ 141

dual specificity phosphatase domain of dual specificity protein phosphatase 7; Dual specificity protein phosphatase 7 (DUSP7), also called mitogen-activated protein kinase (MAPK) phosphatase X (MKP-X) or dual specificity protein phosphatase PYST2, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class II subfamily and is an ERK-selective cytoplasmic MKP. DUSP7 has been shown as an essential regulator of multiple steps in oocyte meiosis. Due to alternative promoter usage, the PYST2 gene gives rise to two isoforms, PYST2-S and PYST2-L. PYST2-L is over-expressed in leukocytes derived from AML and ALL patients as well as in some solid tumors and lymphoblastoid cell lines; it plays a role in cell-crowding. It contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  36 GIKHLVTLTERKPPDHDTCPDLTLHHIKINDFCAPTFEQI-NRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLVKS 114
Cdd:cd14643  31 GIKYILNVTPNLPNMFEHDGEFKYKQIPISDHWSQNLSQFfPEAISFIDEARSKKCGILVHCLAGISRSVTVTVAYLMQK 110

                        90
                ....*....|....
gi 50539984 115 RKISGIDAINEIRR 128
Cdd:cd14643 111 LNLSLNDAYDFVKR 124

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  73 EQINRFLTIVEEANA----SGQAVA---------VHCLHGFGRTGTMLACYLVksrkISGIDAiNEIRRIRRGSIETREQ 139
Cdd:cd14540 123 EDVSGFLDFLEEINSvrrhTNQDVAghnrnpptlVHCSAGVGRTGVVILADLM----LYCLDH-NEELDIPRVLALLRHQ 197

                        90
                ....*....|..
gi 50539984 140 EQMIVQFYQQNK 151
Cdd:cd14540 198 RMLLVQTLAQYK 209

dual specificity phosphatase domain of dual specificity protein phosphatase 8; Dual specificity protein phosphatase 8 (DUSP8), also called DUSP hVH-5 or M3/6, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP8 controls basal and acute stress-induced ERK1/2 signaling in adult cardiac myocytes, which impacts contractility, ventricular remodeling, and disease susceptibility. It also plays a role in decreasing ureteric branching morphogenesis by inhibiting p38MAPK. DUSP8 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  52 DTCP------DLTLHHIKIND-FCAPTFEQINRFLTIVEEANASGQAVAVHCLHGFGRTGTMLACYLVKSRKISGIDAIN 124
Cdd:cd14645  46 NSCPkpdficESHFMRIPVNDnYCEKLLPWLDKSIEFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYR 125

                        90
                ....*....|
gi 50539984 125 EIRRiRRGSI 134
Cdd:cd14645 126 FVKD-RRPSI 134

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 50539984  29 YQYLLNSGIKHLVTLTERKPPDHDTCPDLTLHHIKINDfcAPT---FEQINRFLTIVEEANASGqAVAVHCLHGFGRTGT 105
Cdd:cd14520  19 YLSLREAGITHVLTVDSEEPIDAPPVGKLVRKFVPALD--EEStdlLSRLDECLDFIDEGRAEG-AVLVHCHAGVSRSAA 95

                        90       100
                ....*....|....*....|....*
gi 50539984 106 MLACYLVKSRKISGIDAINEIRRIR 130
Cdd:cd14520  96 VVTAYLMKTEQLSFEEALASLRECK 120

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  37 IKHLVTLTERKPPDHDTcpdltlhhikindfcaPTFEQ-INRFLTIVEEANASGQAVaVHCLHGFGRTGTMLA-----CY 110
Cdd:cd14538 104 VHHITHLNFTTWPDHGT----------------PQSADpLLRFIRYMRRIHNSGPIV-VHCSAGIGRTGVLITidvalGL 166

                        90       100
                ....*....|....*....|....*....
gi 50539984 111 LVKSRKISGIDAINEIRRIRRGSIETREQ 139
Cdd:cd14538 167 IERDLPFDIQDIVKDLREQRQGMIQTKDQ 195

dual specificity phosphatase domain of dual specificity protein phosphatase 10; Dual specificity protein phosphatase 10 (DUSP10), also called mitogen-activated protein kinase (MAPK) phosphatase 5 (MKP-5), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP10/MKP-5 coordinates skeletal muscle regeneration by negatively regulating mitochondria-mediated apoptosis. It is also an important regulator of intestinal epithelial barrier function and a suppressor of colon tumorigenesis. DUSP10/MKP-5 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  32 LLNSGIKHLVTLTERKPPDHDTCPDLTLHHIKINDFCAPT----FEQINRFLtivEEANASGQAVAVHCLHGFGRTGTML 107
Cdd:cd14567  22 LQRLNIGYVLNVTTHLPLYHEGKGGFRYKRLPATDSNKQNlrqyFEEAFEFI---EEAHQSGKGVLVHCQAGVSRSATIV 98

                        90
                ....*....|....*
gi 50539984 108 ACYLVKSRKISGIDA 122
Cdd:cd14567  99 IAYLMKHTRMTMTDA 113

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 50539984  57 LTLHHIKINDFCAPtfEQINRFLTIVEEANASGQ------AVAVHCLHGFGRTGTML---ACYLV--KSRKISGID---A 122
Cdd:cd14608 157 LHFHYTTWPDFGVP--ESPASFLNFLFKVRESGSlspehgPVVVHCSAGIGRSGTFCladTCLLLmdKRKDPSSVDikkV 234

                        90
                ....*....|....*..
gi 50539984 123 INEIRRIRRGSIETREQ 139
Cdd:cd14608 235 LLEMRKFRMGLIQTADQ 251

Protein tyrosine phosphatase-like domains of phytases and similar domains; This subfamily contains the tandem protein tyrosine phosphatase (PTP)-like domains of protein tyrosine phosphatase-like phytases (PTPLPs) and similar domains including the PTP domain of Pseudomonas syringae tyrosine-protein phosphatase hopPtoD2. PTPLPs, also known as cysteine phytases, are one of four known classes of phytases, enzymes that degrade phytate (inositol hexakisphosphate [InsP(6)]) to less-phosphorylated myo-inositol derivatives. Phytate is the most abundant cellular inositol phosphate and plays important roles in a broad scope of cellular processes, including DNA repair, RNA processing and export, development, apoptosis, and pathogenicity. PTPLPs adopt a PTP fold, including the active-site signature sequence (CX5R(S/T)) and utilize a classical PTP reaction mechanism. However, these enzymes display no catalytic activity against classical PTP substrates due to several unique structural features that confer specificity for myo-inositol polyphosphates.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 50539984  62 IKINDFCAPTFEQINRFLTIVEE--ANASgqaVAVHCLHGFGRTGTMLACY--------------LVKSRKISGIDAINE 125
Cdd:cd14495 160 IAATDHVWPDDEEIDAFVAFYRSlpADAW---LHFHCRAGKGRTTTFMVMYdmlknpkdvsfddiIARQYLIGGNYLAYE 236