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 966960197   5 NRPAPVEVSYKHMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966960197  85 LSLVKAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

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 966960197   5 NRPAPVEVSYKHMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966960197  85 LSLVKAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  31 STFIEDLKKYGATTVVRVC-EVTYDKTPLEKDGITVVDWPFDDGAPPPgkvVEDWLSLVK-AKFCEAPGSCVAVHCVAGL 108
Cdd:COG2453   15 GGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHCRGGI 91

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 966960197 109 GRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKYR 153
Cdd:COG2453   92 GRTGTVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 137

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966960197   81 VEDWLSLVKAK--FCEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:pfam00782  51 ISKYLEEAVEFidDARQKGGKVLVHCQAGISRSATLIIAYLMKTrNLSLNEAYSFVKE-RRPGIS 114

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 966960197   5 NRPAPVEVSYKHMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 84
Cdd:cd18535    1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966960197  85 LSLVKAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535   81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

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 966960197   1 MARMNRPAPVEVSYKHMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKV 80
Cdd:cd18537    1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  81 VEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRF 160
Cdd:cd18537   81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                 ....*..
gi 966960197 161 KDPHTHK 167
Cdd:cd18537  161 KDSNGHR 167

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  11 EVSYKHMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKA 90
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  91 KFCEA--PGSCVAVHCVAGLGRAPVLVALALIESG-MKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFkdphthk 167
Cdd:PTZ00242  90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG------- 162

                 ....*.
gi 966960197 168 trCCVM 173
Cdd:PTZ00242 163 --CTIM 166

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 966960197   9 PVEVSYKHMRFLiTHNPtnatlSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLv 88
Cdd:cd14499   32 PHDTRKDENGYP-THTP-----EDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI- 104

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966960197  89 kakfCEAPGSCVAVHCVAGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPK 155
Cdd:cd14499  105 ----CENEKGAIAVHCKAGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 168

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 966960197  16 HMRFLITHNPTNaTLSTFIEDLKKYGATTVVRVCEVTydktplekdgitvvdwpfddgapppgkvVEDWLSLVKAKfcEA 95
Cdd:cd14494    6 PLRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLAM----------------------------VDRFLEVLDQA--EK 54

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 966960197  96 PGSCVAVHCVAGLGRAPVLVALALIE-SGMKYEDAIQFIRQKRRGAI--NSKQLTYLEK 151
Cdd:cd14494   55 PGEPVLVHCKAGVGRTGTLVACYLVLlGGMSAEEAVRIVRLIRPGGIpqTIEQLDFLIK 113

protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine phosphatase domain-containing protein 1 (PTPDC1) is an uncharacterized non-receptor class protein-tyrosine phosphatase (PTP). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Small interfering RNA (siRNA) knockdown of the ptpdc1 gene is associated with elongated cilia.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  52 TYDKTPLEKDGITVVDWPFDD-GAPPPGKVvedwLSLVK-AKFCEAPGSCVAVHCVAGLGRAPVLVALALI-ESGMKYED 128
Cdd:cd14506   66 SYLPEAFMRAGIYFYNFGWKDyGVPSLTTI----LDIVKvMAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQ 141

                         90
                 ....*....|....*.
gi 966960197 129 AIQFIRQKRRGAINSK 144
Cdd:cd14506  142 AIRLVRSKRPNSIQTR 157

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 966960197    67 DWPfDDGAPPPGKVVEDWLSLVKAKFCEAPGSC-VAVHCVAGLGRAPVLVALALIESGMKYE-------DAIQFIRQKRR 138
Cdd:smart00012   9 GWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQRP 87

                   ....*..
gi 966960197   139 GAINSKQ 145
Cdd:smart00012  88 GMVQTEE 94

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 966960197  37 LKKYGATTVV------RVCEVT-----YDKTPLEKDGITVVDWPFDDGAP---PPGKVVEDWLSLVKAKfceapgscVAV 102
Cdd:cd14515   22 LKKLGITHVLnaaegkKNGEVNtnakfYKGSGIIYLGIPASDLPTFDISQyfdEAADFIDKALSDPGGK--------VLV 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 966960197 103 HCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYLEK 151
Cdd:cd14515   94 HCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVRKKREIRPNRgflQQLCELND 146

protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; Phosphatase and tensin homolog (PTEN), also phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN or mutated in multiple advanced cancers 1 (MMAC1), is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It is a critical endogenous inhibitor of phosphoinositide signaling. It dephosphorylates phosphoinositide trisphosphate, and therefore, has the function of negatively regulating Akt. The PTEN/PI3K/AKT pathway regulates the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. PTEN contains an N-terminal PIP-binding domain, a protein tyrosine phosphatase (PTP)-like catalytic domain, a regulatory C2 domain responsible for its cellular location, a C-tail containing phosphorylation sites, and a C-terminal PDZ domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  65 VVDWPFDDGAPPPgkvvedwLSLVKAkFCE--------APGSCVAVHCVAGLGRAPVLVALALIESGM--KYEDAIQFIR 134
Cdd:cd14509   62 VAEYPFDDHNPPP-------LELIKP-FCEdvdewlkeDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYG 133

                         90       100
                 ....*....|....*....|...
gi 966960197 135 QKRrgAINSKQLTYlekyrPKQR 157
Cdd:cd14509  134 AKR--TKNKKGVTI-----PSQR 149

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 966960197   81 VEDWLSLVKAK--FCEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:pfam00782  51 ISKYLEEAVEFidDARQKGGKVLVHCQAGISRSATLIIAYLMKTrNLSLNEAYSFVKE-RRPGIS 114

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 966960197  66 VDWPfDDGAPPPGKVVEDWLSLV---KAKF-CEAPgscVAVHCVAGLGRAPVLVALALIESGMKYEDA------IQFIRQ 135
Cdd:cd14554  143 TDWP-EQGVPKSGEGFIDFIGQVhktKEQFgQEGP---ITVHCSAGVGRTGVFITLSIVLERMRYEGVvdvfqtVKLLRT 218

                         90
                 ....*....|....*...
gi 966960197 136 KRRGAINSKQlTYLEKYR 153
Cdd:cd14554  219 QRPAMVQTED-QYQFCYR 235

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  34 IEDLKKYGATTVVRV---CEVTYDKTPLE-------KDGITVVDWPFDDGAP-------PpgKVVEDWLSLVKAkfceap 96
Cdd:cd14526   22 VDRLKKEGVTAVLNLqtdSDMEYWGVDIDsirkackESGIRYVRLPIRDFDTedlrqklP--QAVALLYRLLKN------ 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 966960197  97 GSCVAVHCVAGLGRAP--VLVALALIeSGMKYEDAIQFIRQKR 137
Cdd:cd14526   94 GGTVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197   38 KKYGATTVVRVCEVTYDKTPLEKdgiTV-----VDWPfDDGAPPPGKVVEDWLSLVKaKFCEAPGSC-VAVHCVAGLGRA 111
Cdd:pfam00102 109 KEDEKDYTVRTLEVSNGGSEETR---TVkhfhyTGWP-DHGVPESPNSLLDLLRKVR-KSSLDGRSGpIVVHCSAGIGRT 183

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 966960197  112 PVLVALALIESGMKYE------DAIQFIRQKRRGAINSK-QLTYL 149
Cdd:pfam00102 184 GTFIAIDIALQQLEAEgevdifQIVKELRSQRPGMVQTLeQYIFL 228

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 966960197  68 WPfDDGAPPPGKVVEDWLSLVKAKFCEAPgscVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAI 141
Cdd:cd14538  115 WP-DHGTPQSADPLLRFIRYMRRIHNSGP---IVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGMI 190

                 ...
gi 966960197 142 NSK 144
Cdd:cd14538  191 QTK 193

PTP-like domain of receptor-type tyrosine-protein phosphatase S, repeat 2; Receptor-type tyrosine-protein phosphatase S (PTPRS), also known as receptor-type tyrosine-protein phosphatase sigma (R-PTP-sigma), 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. PTPRS is a receptor for glycosaminoglycans, including heparan sulfate proteoglycan and neural chondroitin sulfate proteoglycans (CSPGs), which present a barrier to axon regeneration. It also plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. PTPRS 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  67 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE------DAIQFIRQKRRG 139
Cdd:cd14627  191 DWP-EQGVPKSGEGFIDFIGQVhKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQRPA 269

                 ....*
gi 966960197 140 AINSK 144
Cdd:cd14627  270 MVQTE 274

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 966960197  37 LKKYGATTVV---RVCEVTYDKTPLEK-DGITVVDWPFDDGAPPPgKVVEDWLSLVKAKFCEAPgscVAVHCVAGLGRAP 112
Cdd:cd14529   29 LKKLGIKTVIdlrGADERAASEEAAAKiDGVKYVNLPLSATRPTE-SDVQSFLLIMDLKLAPGP---VLIHCKHGKDRTG 104

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 966960197 113 VLVALALIESGMKYEDAI-QFIRQKRRGAINSKQLTYLEKYRPKQR 157
Cdd:cd14529  105 LVSALYRIVYGGSKEEANeDYRLSNRHLEGLRSGIALDSKGGVKGR 150

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  34 IEDLKKYGATTVVRVC------EVTYDKTPLEKDGITVvdwpFDDGAPPPGKVVE--DWL-SLVKAkfceapGSCVAVHC 104
Cdd:PRK12361 113 LEKLKSNKITAILDVTaefdglDWSLTEEDIDYLNIPI----LDHSVPTLAQLNQaiNWIhRQVRA------NKSVVVHC 182

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966960197 105 VAGLGRApVLVALALIESGMK---YEDAIQFIRQKRRGA-INSKQLTYLEKYRPKQRLRFKDP 163
Cdd:PRK12361 183 ALGRGRS-VLVLAAYLLCKDPdltVEEVLQQIKQIRKTArLNKRQLRALEKMLEQGKLNIHKR 244

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 966960197  68 WPfDDGAPPPGKVVEDWLSLVKAKFCEAPgscVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAI 141
Cdd:cd14596  114 WP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQRYGMI 189

                 ....
gi 966960197 142 NSKQ 145
Cdd:cd14596  190 QTKD 193

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966960197  76 PPGKVVEDWLSLVKaKF---CEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKR 137
Cdd:cd17665   90 PDDKTIQSFKDAVK-DFlekNKDNDKLIGVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQAR 154

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
                 ....*....|....*....|....*....|....*....|....*..
gi 966960197  93 CEAPGSCVAVHCVAGLGRAPVlVALA-LIES-GMKYEDAIQFIRQKR 137
Cdd:cd14565   74 VKASGGRVLVHCQAGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119

dual specificity phosphatase and pro isomerase domain containing 1; Dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1) was initially named as such because computational prediction appeared to encode a protein of 446 amino acids in length that included two catalytic domains: a proline isomerase and a dual specificity phosphatase (DUSP). However, it was subsequently shown that the true open reading frame only encompassed the DUSP domain and the gene product was therefore renamed DUSP27. This is distinct from inactive DUSP27. DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). DUPD1/DUSP27 has been shown to have catalytic activity with preference for phosphotyrosine over phosphothreonine and phosphoserine residues. It associates with the short form of the prolactin (PRL) receptor and plays a role in PRL-mediated MAPK inhibition in ovarian cells.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966960197  96 PGSCVAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKR-----RGAInsKQLTYLEKYRPKQR 157
Cdd:cd14575   95 PHNKLLVHCVMGRSRSATLVlAYLMIYKNMTVVDAIEQVAQRRcilpnRGFL--KQLRELDIQLAEER 160

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 966960197  97 GSCVaVHCVAGLGRApVLVALALIES--GMKYEDAIQFIRQKR 137
Cdd:cd14519   78 GNVL-VHCLAGVSRS-VTIVAAYLMTvtDLGWRDALKAVRAAR 118

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 966960197  89 KAKFCeapGSCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14512   74 EAKAS---NGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966960197  45 VVRVCEVTYDKTPLEKDGITVVDWPfDDGAPP-PGKVVEdWLSLVKAKFCEAPGSC-VAVHCVAGLGRAPVLVALALI-- 120
Cdd:cd14606  142 TLQVSPLDNGELIREIWHYQYLSWP-DHGVPSePGGVLS-FLDQINQRQESLPHAGpIIVHCSAGIGRTGTIIVIDMLme 219

                         90       100       110
                 ....*....|....*....|....*....|.
gi 966960197 121 -------ESGMKYEDAIQFIRQKRRGAINSK 144
Cdd:cd14606  220 nistkglDCDIDIQKTIQMVRAQRSGMVQTE 250

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), 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. DUSP3 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 favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 966960197 100 VAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYL 149
Cdd:cd14579  111 VLVHCREGYSRSPTLViAYLMLRQKMDVKSALSTVRQKREIGPNDgflKQLCQL 164

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 966960197  97 GSCVAVHCVAGLGRAP-VLVALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14567   80 GKGVLVHCQAGVSRSAtIVIAYLMKHTRMTMTDAYKFVKNKR 121