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 2462617522  10 VEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 89
Cdd:cd18535    30 IEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKTKFCEDPGCCVAVHCVAGLGRAPV 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462617522  90 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 134
Cdd:cd18535   110 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 2462617522  10 VEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 89
Cdd:cd18535    30 IEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKTKFCEDPGCCVAVHCVAGLGRAPV 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462617522  90 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 134
Cdd:cd18535   110 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522   4 MNRPAPVE-DLKKYGATTVVRVC-EVTYDKTPLEKDGITVVDWPFDDGAPPPgkvVEDWLSLVK-AKFCEAPGSCVAVHC 80
Cdd:COG2453    11 GPLPGGGEaDLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDfIDEALREGKKVLVHC 87

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462617522  81 VAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKYR 129
Cdd:COG2453    88 RGGIGRTGTVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 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 2462617522  57 VEDWLSLVKAK--FCEAPGSCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQkRRGAIN 118
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 2462617522  10 VEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPV 89
Cdd:cd18535    30 IEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLLKTKFCEDPGCCVAVHCVAGLGRAPV 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462617522  90 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 134
Cdd:cd18535   110 LVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 2462617522   1 MARMNRPAPVE------------------------DLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKV 56
Cdd:cd18537     1 MARMNRPAPVEityknmrflithnptnatlnkfieELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522  57 VEDWLSLVKAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRF 136
Cdd:cd18537    81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                  ....*..
gi 2462617522 137 KDPHTHK 143
Cdd:cd18537   161 KDSNGHR 167

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522   5 NRPAPVEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLVKAKFCEA--PGSCVAVHCVA 82
Cdd:PTZ00242   28 NLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEFAKQstPPETIAVHCVA 107

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462617522  83 GLGRAPVLVALALIESG-MKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFkdphthktrCCVM 149
Cdd:PTZ00242  108 GLGRAPILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG---------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 2462617522   6 RPAPVEDL----KKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLvkakfCEAPGSCVAVHCV 81
Cdd:cd14499    43 PTHTPEDYipyfKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI-----CENEKGAIAVHCK 117

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462617522  82 AGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPK 131
Cdd:cd14499   118 AGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 168

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522  10 VEDLKKYGATTVVRVC---EVTYDKTP-----LEKDGITVVDWPFDDGAPPP-----GKVVEDWLSLVKAkfceapGSCV 76
Cdd:cd14505    36 LEELKDQGVDDVVTLCtdgELEELGVPdlleqYQQAGITWHHLPIPDGGVPSdiaqwQELLEELLSALEN------GKKV 109

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462617522  77 AVHCVAGLGRAPVLVALALIESG--MKYEDAIQFIRQKRRGAI-NSKQLTYL 125
Cdd:cd14505   110 LIHCKGGLGRTGLIAACLLLELGdtLDPEQAIAAVRALRPGAIqTPKQENFL 161

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462617522  57 VEDWLSLVKAKfcEAPGSCVAVHCVAGLGRAPVLVALALIE-SGMKYEDAIQFIRQKRRGAI--NSKQLTYLEK 127
Cdd:cd14494    42 VDRFLEVLDQA--EKPGEPVLVHCKAGVGRTGTLVACYLVLlGGMSAEEAVRIVRLIRPGGIpqTIEQLDFLIK 113

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522   43 DWPfDDGAPPPGKVVEDWLSLVKAKFCEAPGSC-VAVHCVAGLGRAPVLVALALIESGMKYE-------DAIQFIRQKRR 114
Cdd:smart00404   9 GWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQRP 87

                   ....*..
gi 2462617522  115 GAINSKQ 121
Cdd:smart00404  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 2462617522   4 MNRPApvedLKKYGATTVV------RVCEVT-----YDKTPLEKDGITVVDWPFDDGAP---PPGKVVEDWLSLVKAKfc 69
Cdd:cd14515    17 KNKAK----LKKLGITHVLnaaegkKNGEVNtnakfYKGSGIIYLGIPASDLPTFDISQyfdEAADFIDKALSDPGGK-- 90

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462617522  70 eapgscVAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYLEK 127
Cdd:cd14515    91 ------VLVHCVEGVSRSATLVlAYLMIYQNMTLEEAIRTVRKKREIRPNRgflQQLCELND 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 2462617522  41 VVDWPFDDGAPPPgkvvedwLSLVKAkFCE--------APGSCVAVHCVAGLGRAPVLVALALIESGM--KYEDAIQFIR 110
Cdd:cd14509    62 VAEYPFDDHNPPP-------LELIKP-FCEdvdewlkeDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYG 133

                          90       100
                  ....*....|....*....|...
gi 2462617522 111 QKRrgAINSKQLTYlekyrPKQR 133
Cdd:cd14509   134 AKR--TKNKKGVTI-----PSQR 149

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522   7 PAPVEDLKKYGATTV------------VRVCEVTYDKTPLEKDgITV---VDWPfDDGAPPPGKVVEDWLSLVKaKFCEA 71
Cdd:cd00047    61 PEEGGKPLEYGDITVtlvseeelsdytIRTLELSPKGCSESRE-VTHlhyTGWP-DHGVPSSPEDLLALVRRVR-KEARK 137

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462617522  72 PGSCVAVHCVAGLGRAPVLVAL-ALIESgMKYE------DAIQFIRQKRRGAI-NSKQLTYL 125
Cdd:cd00047   138 PNGPIVVHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRKQRPGMVqTLEQYEFI 198

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522   13 LKKYGATTVVRVCEVtydKTPLEKDGITVVDWPFDDGappPGKVVEDWLSLVKAK--FCEAPGSCVAVHCVAGLGRAPVL 90
Cdd:smart00195  22 LKKLGITHVINVTNE---VPNYNGSDFTYLGVPIDDN---TETKISPYFPEAVEFieDAESKGGKVLVHCQAGVSRSATL 95

                           90       100
                   ....*....|....*....|....*....
gi 2462617522   91 VALALIES-GMKYEDAIQFIRQkRRGAIN 118
Cdd:smart00195  96 IIAYLMKTrNMSLNDAYDFVKD-RRPIIS 123

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 2462617522  42 VDWPfDDGAPPPGKVVEDWLSLV---KAKF-CEAPgscVAVHCVAGLGRAPVLVALALIESGMKYEDA------IQFIRQ 111
Cdd:cd14554   143 TDWP-EQGVPKSGEGFIDFIGQVhktKEQFgQEGP---ITVHCSAGVGRTGVFITLSIVLERMRYEGVvdvfqtVKLLRT 218

                          90
                  ....*....|....*...
gi 2462617522 112 KRRGAINSKQlTYLEKYR 129
Cdd:cd14554   219 QRPAMVQTED-QYQFCYR 235

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522  14 KKYGATTVVRVCEVTYDKTPLEKdgiTV-----VDWPfDDGAPPPGKVVEDWLSLVKaKFCEAPGSC-VAVHCVAGLGRA 87
Cdd:pfam00102 109 KEDEKDYTVRTLEVSNGGSEETR---TVkhfhyTGWP-DHGVPESPNSLLDLLRKVR-KSSLDGRSGpIVVHCSAGIGRT 183

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462617522  88 PVLVALALIESGMKYE------DAIQFIRQKRRGAINSK-QLTYL 125
Cdd:pfam00102 184 GTFIAIDIALQQLEAEgevdifQIVKELRSQRPGMVQTLeQYIFL 228

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522   2 ARMnRPAPVEDLKKYGATTVVRVC------EVTYDKTPLEKDGITVvdwpFDDGAPPPGKVVE--DWL-SLVKAkfceap 72
Cdd:PRK12361  106 CRL-FPADLEKLKSNKITAILDVTaefdglDWSLTEEDIDYLNIPI----LDHSVPTLAQLNQaiNWIhRQVRA------ 174

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462617522  73 GSCVAVHCVAGLGRApVLVALALIESGMK---YEDAIQFIRQKRRGA-INSKQLTYLEKYRPKQRLRFKDP 139
Cdd:PRK12361  175 NKSVVVHCALGRGRS-VLVLAAYLLCKDPdltVEEVLQQIKQIRKTArLNKRQLRALEKMLEQGKLNIHKR 244

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522  43 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--RGA 116
Cdd:cd14628   190 DWP-EQGVPKSGEGFIDFIGQVhKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvDIFQTVKMLRtqRPA 268

                          90
                  ....*....|...
gi 2462617522 117 INSKQLTYLEKYR 129
Cdd:cd14628   269 MVQTEDQYQFCYR 281

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 2462617522  43 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE------DAIQFIRQKRRG 115
Cdd:cd14627   191 DWP-EQGVPKSGEGFIDFIGQVhKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQRPA 269

                  ....*
gi 2462617522 116 AINSK 120
Cdd:cd14627   270 MVQTE 274

PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR 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. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF 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 2462617522  43 DWPfDDGAPPPGKVVEDWLSLV-KAKFCEAPGSCVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--RGA 116
Cdd:cd14629   191 DWP-EQGVPKTGEGFIDFIGQVhKTKEQFGQDGPITVHCSAGVGRTGVFITLSIVLERMRYEgvvDMFQTVKTLRtqRPA 269

                          90
                  ....*....|...
gi 2462617522 117 INSKQLTYLEKYR 129
Cdd:cd14629   270 MVQTEDQYQLCYR 282

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2462617522  69 CEAPGSCVAVHCVAGLGRAPVL-VALALIESGMKYEDAIQFIRQKR 113
Cdd:cd14568    75 ARASNKRVLVHCLAGISRSATIaIAYIMKHMRMSLDDAYRFVKEKR 120

dual specificity protein phosphatase 13 isoform B; Dual specificity protein phosphatase 13 isoform B (DUSP13B), also called testis- and skeletal-muscle-specific DSP (TMDP) or dual specificity phosphatase SKRP4, 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. DUSP13B 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. DUSP13B inactivates MAPK activation in the order of selectivity, JNK = p38 > ERK in cells. It may play a role in protection from external stress during spermatogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522  66 AKFCEA----PGSCVAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYLEK 127
Cdd:cd14577    92 ARFIRAalssPNGRVLVHCAMGISRSATLVlAFLMICEDLTLVDAIQTVRAHRDICPNSgflRQLRELDN 161

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 2462617522  69 CEAPGSCVAVHCVAGLGRAPVlVALA-LIES-GMKYEDAIQFIRQKR 113
Cdd:cd14565    74 VKASGGRVLVHCQAGISRSAT-ICLAyLMTTrRVRLNEAFDYVKQRR 119

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 2462617522  73 GSCVaVHCVAGLGRApVLVALALIES--GMKYEDAIQFIRQKR 113
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 2462617522  65 KAKFCeapGSCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIRQKR 113
Cdd:cd14512    74 EAKAS---NGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein phosphatase non-receptor type 12 (PTPN12), also called PTP-PEST or protein-tyrosine phosphatase G1 (PTPG1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling. It regulates various physiological processes, including cell migration, immune response, and neuronal activity, by dephosphorylating multiple substrates including HER2, FAK, PYK2, PSTPIP, WASP, p130Cas, paxillin, Shc, catenin, c-Abl, ArgBP2, p190RhoGAP, RhoGDI, cell adhesion kinase beta, and Rho GTPase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462617522  42 VDWPfDDGAPPPGKVVEDWLSLVKaKFCEAPGSCVAVHCVAGLGRAPVLVAL----ALIESGMKYED-----AIQFIRQK 112
Cdd:cd14604   194 VNWP-DHDVPSSFDSILDMISLMR-KYQEHEDVPICIHCSAGCGRTGAICAIdytwNLLKAGKIPEEfnvfnLIQEMRTQ 271

                  ....*....
gi 2462617522 113 RRGAINSKQ 121
Cdd:cd14604   272 RHSAVQTKE 280

dual specificity phosphatase domain of slingshot family phosphatases; The slingshot (SSH) family of dual specificity protein phosphatases is composed of Drosophila slingshot phosphatase and its vertebrate homologs: SSH1, SSH2 and SSH3. Its members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. In Drosophila, loss of ssh gene function causes prominent elevation in the levels of P-cofilin and filamentous actin and disorganized epidermal cell morphogenesis, including bifurcation phenotypes of bristles and wing hairs. SSH family phosphatases contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. In addition, many members contain a C-terminal tail. The SSH-N domain plays critical roles in P-cofilin recognition, F-actin-mediated activation, and subcellular localization of SSHs.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462617522  73 GSCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIrQKRRGAINSKQ--LTYLEKY 128
Cdd:cd14513    78 GSKVLVHCKMGVSRsASTVIAYAMKEYGWSLEQALEHV-KERRSCIKPNPgfLRQLITY 135

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 2462617522  21 VVRVCEVTYDKTPLEKDGITVVDWPfDDGAPP-PGKVVEdWLSLVKAKFCEAPGSC-VAVHCVAGLGRAPVLVALALI-- 96
Cdd:cd14606   142 TLQVSPLDNGELIREIWHYQYLSWP-DHGVPSePGGVLS-FLDQINQRQESLPHAGpIIVHCSAGIGRTGTIIVIDMLme 219

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462617522  97 -------ESGMKYEDAIQFIRQKRRGAINSK 120
Cdd:cd14606   220 nistkglDCDIDIQKTIQMVRAQRSGMVQTE 250

dual specificity phosphatase domain of dual specificity protein phosphatase 16; Dual specificity protein phosphatase 16 (DUSP16), also called mitogen-activated protein kinase (MAPK) phosphatase 7 (MKP-7), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class III subfamily and is a JNK/p38-selective cytoplasmic MKP. DUSP16/MKP-7 plays an essential role in perinatal survival and selectively controls the differentiation and cytokine production of myeloid cells. It is acetylated by Mycobacterium tuberculosis Eis protein, which leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation, and thus, initiating suppression of host immune responses. DUSP16/MKP-7 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2462617522  70 EAPGSCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIRQKR 113
Cdd:cd14646    78 KASNGRVLVHCLAGISRsATIAIAYIMKRMDMSLDEAYRFVKEKR 122

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
                  ....*....|....*....|....*....|....*....|....*.
gi 2462617522  73 GSCVAVHCVAGLGRAPVLVALALiesgMKYE-----DAIQFIRQKR 113
Cdd:cd14514    77 GGRTLVHCVAGVSRSATLCLAYL----MKYEgmtlrEAYKHVKAAR 118