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 1869903015   1 MARMNRPAPVEVTYKNMRFLITHNPTNATLNKFIEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQI 80
Cdd:cd18537     1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1869903015  81 VDDWLSLVKIKFREEPGCCIAVHCVAGLGRAPVLVALALIEGGMKYEDAVQFIRH 135
Cdd:cd18537    81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQ 135

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 1869903015   1 MARMNRPAPVEVTYKNMRFLITHNPTNATLNKFIEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQI 80
Cdd:cd18537     1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1869903015  81 VDDWLSLVKIKFREEPGCCIAVHCVAGLGRAPVLVALALIEGGMKYEDAVQFIRH 135
Cdd:cd18537    81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQ 135

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  35 EELKKYGVTTIVRVC-EATYDTTLVEKEGIHVLDWPFDDGAPPSnqiVDDWLSLVK-IKFREEPGCCIAVHCVAGLGRAP 112
Cdd:COG2453    19 ADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGIGRTG 95

                          90       100
                  ....*....|....*....|..
gi 1869903015 113 VLVALALIEGGMKYEDAVQFIR 134
Cdd:COG2453    96 TVAAAYLVLLGLSAEEALARVR 117

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  29 TLNKFIEELKKYgVTTIVRVCEATYDTTLVEKEgIHVLDWPfDDGAPPSNQIVDDWLSLVKiKFREEPGCC-IAVHCVAG 107
Cdd:pfam00102 104 TLKKEKEDEKDY-TVRTLEVSNGGSEETRTVKH-FHYTGWP-DHGVPESPNSLLDLLRKVR-KSSLDGRSGpIVVHCSAG 179

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1869903015 108 LGRAPVLVALALIEGGMKYE------DAVQFIRH 135
Cdd:pfam00102 180 IGRTGTFIAIDIALQQLEAEgevdifQIVKELRS 213

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 1869903015   1 MARMNRPAPVEVTYKNMRFLITHNPTNATLNKFIEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQI 80
Cdd:cd18537     1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1869903015  81 VDDWLSLVKIKFREEPGCCIAVHCVAGLGRAPVLVALALIEGGMKYEDAVQFIRH 135
Cdd:cd18537    81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQ 135

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 1869903015   5 NRPAPVEVTYKNMRFLITHNPTNATLNKFIEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQIVDDW 84
Cdd:cd14500     1 LRPAPTLIEYKGMRFLITDAPTDSNLPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDW 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1869903015  85 LSLVKIKFREE--PGCCIAVHCVAGLGRAPVLVALALIEGGMKYEDAVQFIR 134
Cdd:cd14500    81 LDLLKTRFKEEgkPGACIAVHCVAGLGRAPVLVAIALIELGMKPEDAVEFIR 132

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  11 EVTYKNMRFLITHNPTNATLNKFIEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQIVDDWLSLVKI 90
Cdd:PTZ00242   10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1869903015  91 KFREE--PGCCIAVHCVAGLGRAPVLVALALIE-GGMKYEDAVQFIR 134
Cdd:PTZ00242   90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEyGGMEPLDAVGFVR 136

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  22 THNPtnatlNKFIEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQIVDDWLSLVkikfrEEPGCCIA 101
Cdd:cd14499    44 THTP-----EDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDIC-----ENEKGAIA 113

                          90
                  ....*....|....*....
gi 1869903015 102 VHCVAGLGRAPVLVALALI 120
Cdd:cd14499   114 VHCKAGLGRTGTLIACYLM 132

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  35 EELKKYGVTTIVRVC-EATYDTTLVEKEGIHVLDWPFDDGAPPSnqiVDDWLSLVK-IKFREEPGCCIAVHCVAGLGRAP 112
Cdd:COG2453    19 ADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGIGRTG 95

                          90       100
                  ....*....|....*....|..
gi 1869903015 113 VLVALALIEGGMKYEDAVQFIR 134
Cdd:COG2453    96 TVAAAYLVLLGLSAEEALARVR 117

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 1869903015  34 IEELKKYGVTTIVRVCEATYDTTlvEKEGIHVLDWPFDDGapPSNQIVDDWLSLVK-IKFREEPGCCIAVHCVAGLGRAP 112
Cdd:cd14498    19 KELLKKLGITHILNVAGEPPPNK--FPDGIKYLRIPIEDS--PDEDILSHFEEAIEfIEEALKKGGKVLVHCQAGVSRSA 94

                          90       100
                  ....*....|....*....|...
gi 1869903015 113 VLVALALI-EGGMKYEDAVQFIR 134
Cdd:cd14498    95 TIVIAYLMkKYGWSLEEALELVK 117

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 1869903015  34 IEELKKYGVTTIVRVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQIVDDWLSLV-KIKFREEPgccIAVHCVAGLGRAP 112
Cdd:cd14504    21 YAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVeEANAKNEA---VLVHCLAGKGRTG 97

                          90       100
                  ....*....|....*....|....
gi 1869903015 113 VLVALALI-EGGMKYEDAVQFIRH 135
Cdd:cd14504    98 TMLACYLVkTGKISAVDAINEIRR 121

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 1869903015   64 HVLDWPfDDGAPPSNQIVDDWLSLVKIKFREEPGCC-IAVHCVAGLGRAPVLVALALIEGGMKYE-------DAVQFIRH 135
Cdd:smart00012   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

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 1869903015  35 EELKKYGVTTIV----RVCEATYDTTLVEKEGIHVLDWPFDDGAPPSNQiVDDWLSLVKIKFREEPgccIAVHCVAGLGR 110
Cdd:cd14529    27 ALLKKLGIKTVIdlrgADERAASEEAAAKIDGVKYVNLPLSATRPTESD-VQSFLLIMDLKLAPGP---VLIHCKHGKDR 102

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1869903015 111 APVLVALALIEGGMKYEDAVQFIRHGVELLTASNFCI 147
Cdd:cd14529   103 TGLVSALYRIVYGGSKEEANEDYRLSNRHLEGLRSGI 139

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  29 TLNKFIEELKKYgVTTIVRVCEATYDTTLVEKEgIHVLDWPfDDGAPPSNQIVDDWLSLVKiKFREEPGCC-IAVHCVAG 107
Cdd:pfam00102 104 TLKKEKEDEKDY-TVRTLEVSNGGSEETRTVKH-FHYTGWP-DHGVPESPNSLLDLLRKVR-KSSLDGRSGpIVVHCSAG 179

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1869903015 108 LGRAPVLVALALIEGGMKYE------DAVQFIRH 135
Cdd:pfam00102 180 IGRTGTFIAIDIALQQLEAEgevdifQIVKELRS 213

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1869903015  63 IHVLDWPfDDGAPPSNQIVDDWLSLVKIK--FREEPgccIAVHCVAGLGRAPVLV----ALALIEGG 123
Cdd:cd14601   111 IQYIAWP-DHGVPDDSSDFLDFVCLVRNKraGKDEP---VVVHCSAGIGRTGVLItmetAMCLIECN 173

PTP-like domain of receptor-type tyrosine-protein phosphatase D, repeat 2; Receptor-type tyrosine-protein phosphatase-like D (PTPRD), also known as receptor-type tyrosine-protein phosphatase delta (R-PTP-delta), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which 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 that play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. PTPRD is involved in pre-synaptic differentiation through interaction with SLITRK2. It contains 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). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  67 DWPfDDGAPPSNQIVDDWLSLVKiKFREEPG--CCIAVHCVAGLGRAPVLVALALIEGGMKYEDAVQFIR 134
Cdd:cd14628   190 DWP-EQGVPKSGEGFIDFIGQVH-KTKEQFGqdGPISVHCSAGVGRTGVFITLSIVLERMRYEGVVDIFQ 257

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1869903015  63 IHVLDWPfDDGAPPSNQIVDDWLSLVKiKFREEPGCCIAVHCVAGLGRAPVLVAL 117
Cdd:cd00047   107 LHYTGWP-DHGVPSSPEDLLALVRRVR-KEARKPNGPIVVHCSAGVGRTGTFIAI 159

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 1869903015  35 EELKKYGVTTIVrvcEATYDTTLVEKEGIHVLDWPFDDGapPSNQIvDDWLSLV--KIKFREEPGCCIAVHCVAGLGRAP 112
Cdd:cd14514    19 PLLLSRGITCII---NATTELPDPSYPGIEYLRVPVEDS--PHADL-SPHFDEVadKIHQVKRRGGRTLVHCVAGVSRSA 92

                          90       100
                  ....*....|....*....|....*...
gi 1869903015 113 VLVALALieggMKYE-----DAVQFIRH 135
Cdd:cd14514    93 TLCLAYL----MKYEgmtlrEAYKHVKA 116

dual specificity phosphatase domain of class II 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 II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic 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 1869903015   9 PVEVTykNMRFLithnpTNATLNKFIEELKKYGVTTIVRVceaTYD--TTLVEKEGIHVLDWPfddgappsnqIVDDW-- 84
Cdd:cd14566     1 PVEIL--PFLYL-----GNAKDSANIDLLKKYNIKYILNV---TPNlpNTFEEDGGFKYLQIP----------IDDHWsq 60

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1869903015  85 -LSLV---KIKFREEP---GCCIAVHCVAGLGRA-PVLVALALIEGGMKYEDAVQFIR 134
Cdd:cd14566    61 nLSAFfpeAISFIDEArskKCGVLVHCLAGISRSvTVTVAYLMQKLHLSLNDAYDFVK 118

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 1869903015  11 EVTYKNMRFL----ITHnptnaTLNKfiEELKKYGvttIVRVCEATYDTTLVEKEGIHVLDWPFDDGAP---PSNQIVDD 83
Cdd:cd14515    13 ESTAKNKAKLkklgITH-----VLNA--AEGKKNG---EVNTNAKFYKGSGIIYLGIPASDLPTFDISQyfdEAADFIDK 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1869903015  84 WLSlvkikfreEPGCCIAVHCVAGLGRAPVLV-ALALIEGGMKYEDAVQFIR 134
Cdd:cd14515    83 ALS--------DPGGKVLVHCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVR 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869903015  32 KFIEELKKYGVTTIVRVCEATYDTTlVEKE--GIHVLDWPfDDGAPPSnqiVDDWLSLVKIK----FREEPGCCIAVHCV 105
Cdd:cd18533    76 ELVSEEENDDGGFIVREFELSKEDG-KVKKvyHIQYKSWP-DFGVPDS---PEDLLTLIKLKrelnDSASLDPPIIVHCS 150

                          90
                  ....*....|..
gi 1869903015 106 AGLGRAPVLVAL 117
Cdd:cd18533   151 AGVGRTGTFIAL 162

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 1869903015  64 HVLDWPfDDGAPPSNQIVDDWLSLVKIKFREEP-GCCIAVHCVAGLGRAPVLVALALIEGGMKYEDAV 130
Cdd:cd14615   131 HFTSWP-DHGVPETTDLLINFRHLVREYMKQNPpNSPILVHCSAGVGRTGTFIAIDRLIYQIENENVV 197

dual specificity phosphatase-like domain of serine/threonine/tyrosine-interacting protein; Serine/threonine/tyrosine-interacting protein (STYX), also called protein tyrosine phosphatase-like protein, is a catalytically inactive member of the protein tyrosine phosphatase family that plays an integral role in regulating pathways by competing with active phosphatases for binding to MAPKs. It acts as a nuclear anchor for MAPKs, affecting their nucleocytoplasmic shuttling.

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gi 1869903015  75 PPSNQIVDDWLSlvkikfreePGCCIAVHCVAGLGRAPVLVALALIEG-GMKYEDAVQFIRHgvelltaSNFCI 147
Cdd:cd14522    76 PTVKEFIDDCLQ---------TGGKVLVHGNAGISRSAALVIAYIMETyGLSYRDAFAYVQQ-------RRFCI 133

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.

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gi 1869903015  97 GCCIAVHCVAGLGRAP--VLVALALIEgGMKYEDAVQFI 133
Cdd:cd14526    94 GGTVYVHCTAGLGRAPatVIAYLYWVL-GYSLDEAYYLL 131