protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A        18 GSHMNRPAPvEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQI 97
Cdd:PTZ00242   1 STLIECKDR-QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A        98 VDDWLNLLKTKFREE--PGCCVAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMR 174
Cdd:PTZ00242  80 IDNWLRLLDQEFAKQstPPETIAVHCVAGLGRAPILVALALVEyGGMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKK 159

                 ...
5K24_A       175 LRF 177
Cdd:PTZ00242 160 AAG 162

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A          81 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 152
Cdd:smart00404   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|....*
5K24_A         153 KRRGAFNSK-QLLYL 166
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       19 SHMNRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIV 98
Cdd:cd18537   2 ARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQIV 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       99 DDWLNLLKTKFREEPGCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFR 178
Cdd:cd18537  82 DDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRFK 161

                ....*
5K24_A      179 DTNGH 183
Cdd:cd18537 162 DSNGH 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       22 NRPAPVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDW 101
Cdd:cd18535   1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
5K24_A      102 LNLLKTKFREEPGCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRL 175
Cdd:cd18535  81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A        26 PVEISYENMRFLITHNPTNATLNKFTEELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLL 105
Cdd:PTZ00393  84 PTKIEHGKIKILILDAPTNDLLPLYIKEMKNYNVTDLVRTCERTYNDGEITSAGINVHELIFPDGDAPTVDIVSNWLTIV 163

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
5K24_A       106 KTKFREEpgCCVAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPK 172
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       34 MRFLITHNPTNaTLNKFTEELKKYGVTTLVRVCDAtydkapvekegihvldwpfddgapppnqIVDDWLNLLKTKfrEEP 113
Cdd:cd14494   7 LRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLA----------------------------MVDRFLEVLDQA--EKP 55

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
5K24_A      114 GCCVAVHCVAGLGRAPVLVALALIECG-MKYEDAVQFIRQKRRG--AFNSKQLLYLEK 168
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       52 EELKKYGVTTLVRVCdatydkapvEKEGIHVLDWPFDDGAPPPN-----QIVDDWLNLLKTKFReepgccVAVHCVAGLG 126
Cdd:cd14505  54 GELEELGVPDLLEQY---------QQAGITWHHLPIPDGGVPSDiaqwqELLEELLSALENGKK------VLIHCKGGLG 118

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
5K24_A      127 RAPVLVALALIECG--MKYEDAVQFIRQKRRGAF-NSKQLLYL 166
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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A          81 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGRAPVLVALALIECGMKYE-------DAVQFIRQ 152
Cdd:smart00012   6 HYTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRS 84

                           90
                   ....*....|....*
5K24_A         153 KRRGAFNSK-QLLYL 166
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       52 EELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREepGCCVAVHCVAGLGRAPVL 131
Cdd:cd14498  20 ELLKKLGITHILNVAGEPPPNKFPDGIKYLRIPIE-DSPDEDILSHFEEAIEFIEEALKK--GGKVLVHCQAGVSRSATI 96

                        90       100       110
                ....*....|....*....|....*....|....*...
5K24_A      132 VALALI-ECGMKYEDAVQFIRQKRRGA-FNS---KQLL 164
Cdd:cd14498  97 VIAYLMkKYGWSLEEALELVKSRRPIIsPNPgflKQLK 134

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       80 IHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCCVaVHCVAGLGRAPVLVAL-ALIECgMKYE------DAVQFIRQ 152
Cdd:cd00047 107 LHYTGWP-DHGVPSSPEDLLALVRRVRKEARKPNGPIV-VHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRK 183

                        90
                ....*....|....*
5K24_A      153 KRRGAF-NSKQLLYL 166
Cdd:cd00047 184 QRPGMVqTLEQYEFI 198

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       52 EELKKYGVTTLVRVCDATYDKAPVEKEGIHVLDWPFDDGAPPPNQIVDDWLNLLKTkfREEPGCCVAVHCVAGLGRAPVL 131
Cdd:cd14504  22 AYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQIDEFLDIVEE--ANAKNEAVLVHCLAGKGRTGTM 99

                        90       100
                ....*....|....*....|....*.
5K24_A      132 VALALIECG-MKYEDAVQFIRQKRRG 156
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       33 NMRFL----ITHnptnaTLNkfTEELKKYGvttLVRVCDATYDKAPVEKEGIHVLDWP-------FDDGApppnQIVDDW 101
Cdd:cd14515  18 NKAKLkklgITH-----VLN--AAEGKKNG---EVNTNAKFYKGSGIIYLGIPASDLPtfdisqyFDEAA----DFIDKA 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
5K24_A      102 LNLLKTKfreepgccVAVHCVAGLGRAPVLV-ALALIECGMKYEDAVQFIRQKRRGAFNS---KQLLYLEK 168
Cdd:cd14515  84 LSDPGGK--------VLVHCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVRKKREIRPNRgflQQLCELND 146

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A          80 IHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCCVaVHCVAGLGRAPVLVALALIECGMKYE------DAVQFIRQK 153
Cdd:smart00194 162 YHYTNWP-DHGVPESPESILDLIRAVRKSQSTSTGPIV-VHCSAGVGRTGTFIAIDILLQQLEAGkevdifEIVKELRSQ 239

                           90
                   ....*....|....
5K24_A         154 RRGAFNSK-QLLYL 166
Cdd:smart00194 240 RPGMVQTEeQYIFL 253

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
                ....*....|....*....|....*....|....*....|...
5K24_A      114 GCCVAVHCVAGLGRAP--VLVALALIeCGMKYEDAVQFIRQKR 154
Cdd:cd14526  94 GGTVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A        52 EELKKYGVTTLVRVCdATYD--KAPVEKEGIHVLDWP-FDDGAPPPNQIVD--DWLNLLKTKFREepgccVAVHCVAGLG 126
Cdd:PRK12361 114 EKLKSNKITAILDVT-AEFDglDWSLTEEDIDYLNIPiLDHSVPTLAQLNQaiNWIHRQVRANKS-----VVVHCALGRG 187

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
5K24_A       127 RApVLVALALIECGMK---YEDAVQFIRQKRRGA-FNSKQLLYLEKYRPK 172
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
                ....*....|....*....|....*....|....*....|..
5K24_A      114 GCCVAVHCVAGLGRAPVL-VALALIECGMKYEDAVQFIRQKR 154
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       64 RVCDATYDKAPVEKEgIHVLDWPfDDGAPPPNQ-IVDDWLNLLKTKfrEEPGCC--VAVHCVAGLGRAPVLVALALIECG 140
Cdd:cd14554 125 KVTDARDGQSRTVRQ-FQFTDWP-EQGVPKSGEgFIDFIGQVHKTK--EQFGQEgpITVHCSAGVGRTGVFITLSIVLER 200

                        90       100       110
                ....*....|....*....|....*....|...
5K24_A      141 MKYEDAVQFirqkrrgaFNSKQLLYLEkyRPKM 173
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       85 WPfDDGAPppnQIVDDWLNLLKTKFREEPGCCVAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQKRRGAF 158
Cdd:cd14538 115 WP-DHGTP---QSADPLLRFIRYMRRIHNSGPIVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGMI 190

                ...
5K24_A      159 NSK 161
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       80 IHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPgccVAVHCVAGLGRAPVL----VALALIECGMKYE--DAVQFIRQK 153
Cdd:cd14596 109 LQFTTWP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQ 184

                ....*....
5K24_A      154 RRGAFNSKQ 162
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5K24_A       52 EELKKYGVTTLVRV---CDA------TYDKAPVEKEGIHVLDWPFDDGApppnqivdDWLNLLKTKfreepGCCVAVHCV 122
Cdd:cd14565  20 EVLKALGITAVLNVsrnCPNhfedhfQYKSIPVEDSHNADISSWFEEAI--------GFIDKVKAS-----GGRVLVHCQ 86

                        90       100       110
                ....*....|....*....|....*....|....
5K24_A      123 AGLGRAPVlVALA-LIEC-GMKYEDAVQFIRQKR 154
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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5K24_A      114 GCCVAVHCVAGLGR-APVLVALALIECGMKYEDAVQFIRQKR 154
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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5K24_A      117 VAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKR 154
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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5K24_A       81 HVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEP-GCCVAVHCVAGLGRAPVLVALALIECGMKYEDAV 147
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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5K24_A       85 WPfDDGAPppnqivDDWLNLLKTKFR--------EEPgccVAVHCVAGLGRAPVLV----ALALIEC 139
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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5K24_A       55 KKYGVTTLvRVCDATYDKAPVEKEGIHVLDWPfDDGAPPPNQIVDDWLNLLKTKFREEPGCC-VAVHCVAGLGRAPVLVA 133
Cdd:cd14606 136 TEYKLRTL-QVSPLDNGELIREIWHYQYLSWP-DHGVPSEPGGVLSFLDQINQRQESLPHAGpIIVHCSAGIGRTGTIIV 213

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5K24_A      134 LALI---------ECGMKYEDAVQFIRQKRRG 156
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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5K24_A       93 PPNQIVDDWLNLLKtKFREE---PGCCVAVHCVAGLGRAPVLVALALIEC-GMKYEDAVQFIRQKR 154
Cdd:cd17665  90 PDDKTIQSFKDAVK-DFLEKnkdNDKLIGVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQAR 154