protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962   8 EISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLLKT 87
Cdd:PTZ00242   10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039766962  88 KFREE--PGCCVAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 157
Cdd:PTZ00242   90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEyGGMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG 162

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962   61 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 132
Cdd:smart00404   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|....*
gi 1039766962  133 KRRGAFNSK-QLLYL 146
Cdd:smart00404  85 QRPGMVQTEeQYLFL 99

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962   1 MNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDD 80
Cdd:cd18537     4 MNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQIVDD 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962  81 WLNLLKTKFREEPGCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFRDT 160
Cdd:cd18537    84 WLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFKDS 163

                  ...
gi 1039766962 161 NGH 163
Cdd:cd18537   164 NGH 166

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 1039766962   2 NRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDW 81
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039766962  82 LNLLKTKFREEPGCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRL 155
Cdd:cd18535    81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962   6 PVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLL 85
Cdd:PTZ00393   84 PTKIEHGKIKILILDAPTNDLLPLYIKEMKNYNVTDLVRTCERTYNDGEITSAGINVHELIFPDGDAPTVDIVSNWLTIV 163

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039766962  86 KTKFREEpgCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPK 152
Cdd:PTZ00393  164 NNVIKNN--RAVAVHCVAGLGRAPVLASIVLIEFGMDPIDAIVFIRDRRKGAINKRQLQFLKAYKKK 228

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 1039766962  14 MRFLITHNPTNaTLNKFTEELKKYGVTTLVRVCDAtydkapvekegihvldwpfddgapppnqIVDDWLNLLKTKfrEEP 93
Cdd:cd14494     7 LRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLA----------------------------MVDRFLEVLDQA--EKP 55

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039766962  94 GCCVAVHCVAGLGRAPVLVALALIECG-MKYEDAVQFIRQKRRG--AFNSKQLLYLEK 148
Cdd:cd14494    56 GEPVLVHCKAGVGRTGTLVACYLVLLGgMSAEEAVRIVRLIRPGgiPQTIEQLDFLIK 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 1039766962  32 EELKKYGVTTLVRVCdatydkapvEKEGIHVLDWPFDDGAPPPN-----QIVDDWLNLLKTKFReepgccVAVHCVAGLG 106
Cdd:cd14505    54 GELEELGVPDLLEQY---------QQAGITWHHLPIPDGGVPSDiaqwqELLEELLSALENGKK------VLIHCKGGLG 118

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1039766962 107 RAPVLVALALIECG--MKYEDAVQFIRQKRRGAF-NSKQLLYL 146
Cdd:cd14505   119 RTGLIAACLLLELGdtLDPEQAIAAVRALRPGAIqTPKQENFL 161

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 1039766962   61 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 132
Cdd:smart00012   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|....*
gi 1039766962  133 KRRGAFNSK-QLLYL 146
Cdd:smart00012  85 QRPGMVQTEeQYLFL 99

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 1039766962  32 EELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREepGCCVAVHCVAGLGRAPVL 111
Cdd:cd14498    20 ELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIE-DSPDEDILSHFEEAIEFIEEALKK--GGKVLVHCQAGVSRSATI 96

                          90       100
                  ....*....|....*....|....
gi 1039766962 112 VALALI-ECGMKYEDAVQFIRQKR 134
Cdd:cd14498    97 VIAYLMkKYGWSLEEALELVKSRR 120

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 1039766962  32 EELKKYGVTTLV----RVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQiVDDWLNLLKTKFREEPgccVAVHCVAGLGR 107
Cdd:cd14529    27 ALLKKLGIKTVIdlrgADERAASEEAAAKIDGVKYVNLPLSATRPTESD-VQSFLLIMDLKLAPGP---VLIHCKHGKDR 102

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1039766962 108 APVLVALALIECGMKYEDAV-QFIRQKRRGAFNSKQLLYLEKYRPKMR 154
Cdd:cd14529   103 TGLVSALYRIVYGGSKEEANeDYRLSNRHLEGLRSGIALDSKGGVKGR 150

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 1039766962  32 EELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLLKTkfREEPGCCVAVHCVAGLGRAPVL 111
Cdd:cd14504    22 AYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEE--ANAKNEAVLVHCLAGKGRTGTM 99

                          90       100
                  ....*....|....*....|....*.
gi 1039766962 112 VALALIECG-MKYEDAVQFIRQKRRG 136
Cdd:cd14504   100 LACYLVKTGkISAVDAINEIRRIRPG 125

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962  13 NMRFL----ITHnptnaTLNkfTEELKKYGvttLVRVCDATYDKAPVEKEGIHVLDWP-------FDDGApppnQIVDDW 81
Cdd:cd14515    18 NKAKLkklgITH-----VLN--AAEGKKNG---EVNTNAKFYKGSGIIYLGIPASDLPtfdisqyFDEAA----DFIDKA 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039766962  82 LNLLKTKfreepgccVAVHCVAGLGRAPVLV-ALALIECGMKYEDAVQFIRQKRRGAFNS---KQLLYLEK 148
Cdd:cd14515    84 LSDPGGK--------VLVHCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVRKKREIRPNRgflQQLCELND 146

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 1039766962  60 IHVLDWPfDDGAPPPNQIVDDWLNLLKTK--FREEPgccVAVHCVAGLGRAPVLV----ALALIECGMKYE--DAVQFIR 131
Cdd:cd14601   111 IQYIAWP-DHGVPDDSSDFLDFVCLVRNKraGKDEP---VVVHCSAGIGRTGVLItmetAMCLIECNQPVYplDIVRTMR 186

                  ...
gi 1039766962 132 QKR 134
Cdd:cd14601   187 DQR 189

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
                  ....*....|....*....|....*....|....*....|...
gi 1039766962  94 GCCVAVHCVAGLGRAP--VLVALALIeCGMKYEDAVQFIRQKR 134
Cdd:cd14526    94 GGTVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962  32 EELKKYGVTTLVRVCdATYD--KAPVEKEGIHVLDWP-FDDGAPPPNQIVD--DWLNLLKTKFREepgccVAVHCVAGLG 106
Cdd:PRK12361  114 EKLKSNKITAILDVT-AEFDglDWSLTEEDIDYLNIPiLDHSVPTLAQLNQaiNWIHRQVRANKS-----VVVHCALGRG 187

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039766962 107 RApVLVALALIECGMK---YEDAVQFIRQKRRGA-FNSKQLLYLEKYRPK 152
Cdd:PRK12361  188 RS-VLVLAAYLLCKDPdltVEEVLQQIKQIRKTArLNKRQLRALEKMLEQ 236

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1039766962  94 GCCVAVHCVAGLGRAPVL-VALALIECGMKYEDAVQFIRQKR 134
Cdd:cd14568    79 NKRVLVHCLAGISRSATIaIAYIMKHMRMSLDDAYRFVKEKR 120

PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs) include three vertebrate members: LAR (or PTPRF), R-PTP-delta (or PTPRD), and R-PTP-sigma (or PTPRS). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules; they bind to distinct synaptic membrane proteins and are physiologically responsible for mediating presynaptic development by shaping various synaptic adhesion pathways. They play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. LAR-RPTPs contain an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962  44 RVCDATYDKAPVEKEgIHVLDWPfDDGAPPPNQ-IVDDWLNLLKTKfrEEPGCC--VAVHCVAGLGRAPVLVALALIECG 120
Cdd:cd14554   125 KVTDARDGQSRTVRQ-FQFTDWP-EQGVPKSGEgFIDFIGQVHKTK--EQFGQEgpITVHCSAGVGRTGVFITLSIVLER 200

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1039766962 121 MKYEDAVQFirqkrrgaFNSKQLLYLEkyRPKM 153
Cdd:cd14554   201 MRYEGVVDV--------FQTVKLLRTQ--RPAM 223

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 1039766962  65 WPfDDGAPppnQIVDDWLNLLKTKFREEPGCCVAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQKRRGAF 138
Cdd:cd14538   115 WP-DHGTP---QSADPLLRFIRYMRRIHNSGPIVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGMI 190

                  ...
gi 1039766962 139 NSK 141
Cdd:cd14538   191 QTK 193

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 1039766962  60 IHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPgccVAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQK 133
Cdd:cd14596   109 LQFTTWP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQ 184

                  ....*....
gi 1039766962 134 RRGAFNSKQ 142
Cdd:cd14596   185 RYGMIQTKD 193

dual specificity phosphatase domain of class I mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class I MKPs consist of DUSP1/MKP-1, DUSP2 (PAC1), DUSP4/MKP-2 and DUSP5. They are all mitogen- and stress-inducible nuclear MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962  32 EELKKYGVTTLVRV---CDA------TYDKAPVEKEGIHVLDWPFDDGApppnqivdDWLNLLKTKfreepGCCVAVHCV 102
Cdd:cd14565    20 EVLKALGITAVLNVsrnCPNhfedhfQYKSIPVEDSHNADISSWFEEAI--------GFIDKVKAS-----GGRVLVHCQ 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039766962 103 AGLGRAPVlVALA-LIEC-GMKYEDAVQFIRQKR 134
Cdd:cd14565    87 AGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119

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).

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                  ....*....|....*....|....*....|....*....|..
gi 1039766962  94 GCCVAVHCVAGLGR-APVLVALALIECGMKYEDAVQFIRQKR 134
Cdd:cd14512    79 NGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

dual specificity phosphatase domain of dual specificity protein phosphatase 22, 15, and similar proteins; Dual specificity protein phosphatase 22 (DUSP22, also known as VHX) and 15 (DUSP15, also known as VHY) function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). They are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. The both contain N-terminal myristoylation recognition sequences and myristoylation regulates their subcellular location. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. DUSP15 has been identified as a regulator of oligodendrocyte differentiation. DUSP22 is a single domain protein containing only the catalytic dual specificity phosphatase domain while DUSP15 contains a short C-terminal tail.

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                  ....*....|....*....|....*....|....*....
gi 1039766962  97 VAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKR 134
Cdd:cd14519    80 VLVHCLAGVSRSVTIVAAYLMTvTDLGWRDALKAVRAAR 118

catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type tyrosine-protein phosphatase J (PTPRJ or R-PTP-J), also known as receptor-type tyrosine-protein phosphatase eta (R-PTP-eta) or density-enhanced phosphatase 1 (DEP-1) OR CD148, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRJ is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats (eight in PTPRJ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed in various cell types including epithelial, hematopoietic, and endothelial cells. It plays a role in cell adhesion, migration, proliferation and differentiation. It dephosphorylates or contributes to the dephosphorylation of various substrates including protein kinases such as FLT3, PDGFRB, MET, RET (variant MEN2A), VEGFR-2, LYN, SRC, MAPK1, MAPK3, and EGFR, as well as PIK3R1 and PIK3R2.

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gi 1039766962  61 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEP-GCCVAVHCVAGLGRAPVLVALALIECGMKYEDAV 127
Cdd:cd14615   131 HFTSWP-DHGVPETTDLLINFRHLVREYMKQNPpNSPILVHCSAGVGRTGTFIAIDRLIYQIENENVV 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039766962  65 WPfDDGAPppnqivDDWLNLLKTKFR--------EEPgccVAVHCVAGLGRAPVLV----ALALIEC 119
Cdd:cd14541   116 WP-DHGVP------DDSSDFLDFVKRvrqnrvgmVEP---TVVHCSAGIGRTGVLItmetAMCLIEA 172

catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein phosphatase non-receptor type 6 (PTPN6), also called SH2 domain-containing protein-tyrosine phosphatase 1 (SHP1 or SHP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN6 expression is restricted mainly to hematopoietic and epithelial cells. It is an important regulator of hematopoietic cells, downregulating pathways that promote cell growth, survival, adhesion, and activation. It regulates glucose homeostasis by modulating insulin signalling in the liver and muscle, and it also negatively regulates bone resorption, affecting both the formation and the function of osteoclasts. PTPN6 contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039766962  35 KKYGVTTLvRVCDATYDKAPVEKEGIHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGRAPVLVA 113
Cdd:cd14606   136 TEYKLRTL-QVSPLDNGELIREIWHYQYLSWP-DHGVPSEPGGVLSFLDQINQRQESLPHAGpIIVHCSAGIGRTGTIIV 213

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1039766962 114 LALI---------ECGMKYEDAVQFIRQKRRG 136
Cdd:cd14606   214 IDMLmenistkglDCDIDIQKTIQMVRAQRSG 245

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1039766962  73 PPNQIVDDWLNLLKtKFREE---PGCCVAVHCVAGLGRAPVLVALALIEC-GMKYEDAVQFIRQKR 134
Cdd:cd17665    90 PDDKTIQSFKDAVK-DFLEKnkdNDKLIGVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQAR 154