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 528504278   9 PVEVCYNSMRFVITHNPTNQTLDTFIEDLKRYDAKTVVRVCESTYDKTPLEKHGITVMDWPFDDGAPPPTKIVDDWISLL 88
Cdd:cd18535    5 PVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLL 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  89 KKSFSEDPGCCVAVHCVAGLGRAPVLVAVALIEGGMKYEEAIHLIRLKRHGAFNSKQLTYLEKYRSKKRL 158
Cdd:cd18535   85 KTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 528504278   9 PVEVCYNSMRFVITHNPTNQTLDTFIEDLKRYDAKTVVRVCESTYDKTPLEKHGITVMDWPFDDGAPPPTKIVDDWISLL 88
Cdd:cd18535    5 PVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLL 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  89 KKSFSEDPGCCVAVHCVAGLGRAPVLVAVALIEGGMKYEEAIHLIRLKRHGAFNSKQLTYLEKYRSKKRL 158
Cdd:cd18535   85 KTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  31 DTFIEDLKRYDAKTVVRVC-ESTYDKTPLEKHGITVMDWPFDDGAPPPTKIVD---DWI-SLLKKsfsedpGCCVAVHCV 105
Cdd:COG2453   15 GGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQeavDFIdEALRE------GKKVLVHCR 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 528504278 106 AGLGRAPVLVAVALIEGGMKYEEAIHLIRLKRHGAFNSK-QLTYLEKYR 153
Cdd:COG2453   89 GGIGRTGTVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 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
                  ....*....|....*....|....*....|....*....|..
gi 528504278   97 GCCVAVHCVAGLGRAPVLVAVALIE-GGMKYEEAIHLIRLKR 137
Cdd:pfam00782  69 GGKVLVHCQAGISRSATLIIAYLMKtRNLSLNEAYSFVKERR 110

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 528504278   9 PVEVCYNSMRFVITHNPTNQTLDTFIEDLKRYDAKTVVRVCESTYDKTPLEKHGITVMDWPFDDGAPPPTKIVDDWISLL 88
Cdd:cd18535    5 PVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLL 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  89 KKSFSEDPGCCVAVHCVAGLGRAPVLVAVALIEGGMKYEEAIHLIRLKRHGAFNSKQLTYLEKYRSKKRL 158
Cdd:cd18535   85 KTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 528504278   1 MAWLNGLYPVEVCYNSMRFVITHNPTNQTLDTFIEDLKRYDAKTVVRVCESTYDKTPLEKHGITVMDWPFDDGAPPPTKI 80
Cdd:cd18537    1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  81 VDDWISLLKKSFSEDPGCCVAVHCVAGLGRAPVLVAVALIEGGMKYEEAIHLIRLKRHGAFNSKQLTYLEKYRSKKRLRF 160
Cdd:cd18537   81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                 ....*..
gi 528504278 161 KDPFKHR 167
Cdd:cd18537  161 KDSNGHR 167

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  11 EVCYNSMRFVITHNPTNQTLDTFIEDLKRYDAKTVVRVCESTYDKTPLEKHGITVMDWPFDDGAPPPTKIVDDWISLLKK 90
Cdd:PTZ00242  10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528504278  91 SFSED--PGCCVAVHCVAGLGRAPVLVAVALIE-GGMKYEEAIHLIRLKRHGAFNSKQLTYLEKYRSKKRLRF 160
Cdd:PTZ00242  90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEyGGMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG 162

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 528504278  33 FIEDLKRYDAKTVVRVCESTYDKTPLEKHGITVMDWPFDDGAPPPTKIVDDWISLlkksfSEDPGCCVAVHCVAGLGRAP 112
Cdd:cd14499   50 YIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI-----CENEKGAIAVHCKAGLGRTG 124

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 528504278 113 VLVAVALI-EGGMKYEEAIHLIRLKRHGAFNSKQLTYLEKY 152
Cdd:cd14499  125 TLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEK 165

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 528504278   1 MAWLnglyPVEVCYNSMRFVITHNP------TNQTLDTFIEDLKRYDAKTVVRVC---ESTYDKTP-----LEKHGITVM 66
Cdd:cd14505    1 IDWL----PLSMLGNAGSLGLTPCPgckfkdHRRDLQADLEELKDQGVDDVVTLCtdgELEELGVPdlleqYQQAGITWH 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  67 DWPFDDGAPPP-----TKIVDDWISLLKKsfsedpGCCVAVHCVAGLGRAPVLVAVALIE--GGMKYEEAIHLIRLKRHG 139
Cdd:cd14505   77 HLPIPDGGVPSdiaqwQELLEELLSALEN------GKKVLIHCKGGLGRTGLIAACLLLElgDTLDPEQAIAAVRALRPG 150

                        170
                 ....*....|.
gi 528504278 140 AF-NSKQLTYL 149
Cdd:cd14505  151 AIqTPKQENFL 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  17 MRFVITHNPTNqTLDTFIEDLKRYDAKTVVRVCEStydktplekhgitvmdwpfddgappptkIVDDWISLLKKSFSedP 96
Cdd:cd14494    7 LRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLA----------------------------MVDRFLEVLDQAEK--P 55

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528504278  97 GCCVAVHCVAGLGRAPVLVAVALIE-GGMKYEEAIHLIRLKRHG--AFNSKQLTYLEK 151
Cdd:cd14494   56 GEPVLVHCKAGVGRTGTLVACYLVLlGGMSAEEAVRIVRLIRPGgiPQTIEQLDFLIK 113

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 528504278    65 VMDWPfDDGAPPPTKIVDDWISLLKKSFSEDPGCC-VAVHCVAGLGRAPVLVAVALIEGGMKYE-------EAIHLIRLK 136
Cdd:smart00012   7 YTGWP-DHGVPESPDSILELLRAVKKNLNQSESSGpVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQ 85

                   ....*....
gi 528504278   137 RHGAFNSKQ 145
Cdd:smart00012  86 RPGMVQTEE 94

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 528504278  65 VMDWPFDDGAPPPTKIVDDWISLLKKSFSEDPGCCVAVHCVAGLGRAPVLVAVALIEGGM--KYEEAIHLIRLKRhgAFN 142
Cdd:cd14509   62 VAEYPFDDHNPPPLELIKPFCEDVDEWLKEDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYGAKR--TKN 139

                 ....*
gi 528504278 143 SKQLT 147
Cdd:cd14509  140 KKGVT 144

protein-tyrosine phosphatase mitochondrial 1; Protein-tyrosine phosphatase mitochondrial 1 or PTP localized to the mitochondrion 1 (PTPMT1), also called phosphoinositide lipid phosphatase (PLIP), phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1, or PTEN-like phosphatase, is a lipid phosphatase or phosphatidylglycerophosphatase (EC 3.1.3.27) which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). It is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. It is essential for the biosynthesis of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. PTPMT1 also plays a crucial role in hematopoietic stem cell (HSC) function, and has been shown to display activity toward phosphoprotein substrates.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528504278  97 GCCVAVHCVAGLGRAPVLVAVALIE-GGMKYEEAIHLIRLKR-HGAFNSKQLTYLEKYRSK 155
Cdd:cd14524   89 GKSVYVHCKAGRGRSATIVACYLIQhKGWSPEEAQEFLRSKRpHILLRLSQREVLEEFYRK 149

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278    55 KTPLEKHGITVMDWPFDDGapPPTKIVDDWISLLKK-SFSEDPGCCVAVHCVAGLGRAPVLVAVALIE-GGMKYEEAIHL 132
Cdd:smart00195  37 VPNYNGSDFTYLGVPIDDN--TETKISPYFPEAVEFiEDAESKGGKVLVHCQAGVSRSATLIIAYLMKtRNMSLNDAYDF 114

                   ....*
gi 528504278   133 IRLKR 137
Cdd:smart00195 115 VKDRR 119

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 528504278  68 WPfDDGAPPPTKIVDDWISLLKKSFSEDPGCCVaVHCVAGLGRAPVLVAV-ALIEgGMKYE------EAIHLIRLKRHGA 140
Cdd:cd00047  112 WP-DHGVPSSPEDLLALVRRVRKEARKPNGPIV-VHCSAGVGRTGTFIAIdILLE-RLEAEgevdvfEIVKALRKQRPGM 188

                         90
                 ....*....|
gi 528504278 141 F-NSKQLTYL 149
Cdd:cd00047  189 VqTLEQYEFI 198

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  50 ESTYDKTPLEKHgitVMDWPFDDGAPPPT----KIVDDWISLLkksfSEDPGCCVAVHCVAGLGRAPVLVAVALIEGGM- 124
Cdd:cd14497   51 EEYDDDSKFEGR---VLHYGFPDHHPPPLglllEIVDDIDSWL----SEDPNNVAVVHCKAGKGRTGTVICAYLLYYGQy 123

                         90       100       110
                 ....*....|....*....|....*....|..
gi 528504278 125 -KYEEAIHLIRLKR-----HGAFNSKQLTYLE 150
Cdd:cd14497  124 sTADEALEYFAKKRfkeglPGVTIPSQLRYLQ 155

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  34 IEDLKRYDAKTVVRV-CE-STYDKTPLEKHgITVMDWP-FDDGAPPPTKIV------DDWISLLKKsfsedpgccVAVHC 104
Cdd:PRK12361 113 LEKLKSNKITAILDVtAEfDGLDWSLTEED-IDYLNIPiLDHSVPTLAQLNqainwiHRQVRANKS---------VVVHC 182

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528504278 105 VAGLGRAPVLVAVALI--EGGMKYEEAIHLIRLKRHGA-FNSKQLTYLEKYRSKKRLRFKDP 163
Cdd:PRK12361 183 ALGRGRSVLVLAAYLLckDPDLTVEEVLQQIKQIRKTArLNKRQLRALEKMLEQGKLNIHKR 244

catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein phosphatase non-receptor type 4 (PTPN4), also called protein-tyrosine phosphatase MEG1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses. It specifically inhibits the TRIF-dependent TLR4 pathway by suppressing tyrosine phosphorylation of TRAM. It is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain; the PDZ domain regulates the catalytic activity of PTPN4.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 528504278  63 ITVMDWPfDDGAPPPTKIVDDWISLL--KKSFSEDPgccVAVHCVAGLGRAPVLV----AVALIEGG 123
Cdd:cd14601  111 IQYIAWP-DHGVPDDSSDFLDFVCLVrnKRAGKDEP---VVVHCSAGIGRTGVLItmetAMCLIECN 173

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 528504278  67 DWPfDDGAPPPTKIVDDWISLL---KKSFSEDPGccVAVHCVAGLGRAPVLVAVALIEGGMKYE------EAIHLIRLKR 137
Cdd:cd14627  191 DWP-EQGVPKSGEGFIDFIGQVhktKEQFGQDGP--ISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQR 267

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528504278  67 DWPfDDGAPPPTKIVDDWISLL---KKSFSEDPGccVAVHCVAGLGRAPVLVAVALIEGGMKYEEAIHLIR 134
Cdd:cd14629  191 DWP-EQGVPKTGEGFIDFIGQVhktKEQFGQDGP--ITVHCSAGVGRTGVFITLSIVLERMRYEGVVDMFQ 258

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278   29 TLDTFIEDLKRYdAKTVVRVCESTYDKTPLEKHgITVMDWPfDDGAPPPTKIVDDWISLLKKSFSEDPGCCVAVHCVAGL 108
Cdd:pfam00102 104 TLKKEKEDEKDY-TVRTLEVSNGGSEETRTVKH-FHYTGWP-DHGVPESPNSLLDLLRKVRKSSLDGRSGPIVVHCSAGI 180

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 528504278  109 GRAPVLVAVALIEGGMKYEEAIHL------IRLKRHGAFNSK-QLTYL 149
Cdd:pfam00102 181 GRTGTFIAIDIALQQLEAEGEVDIfqivkeLRSQRPGMVQTLeQYIFL 228

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528504278  66 MDWPfDDGAPPPTKIVDDWISLLKKsFSEDPGCCVAVHCVAGLGRAPVLVAV----ALIEGGMKYEE-----AIHLIRLK 136
Cdd:cd14604  194 VNWP-DHDVPSSFDSILDMISLMRK-YQEHEDVPICIHCSAGCGRTGAICAIdytwNLLKAGKIPEEfnvfnLIQEMRTQ 271

                 ....*....
gi 528504278 137 RHGAFNSKQ 145
Cdd:cd14604  272 RHSAVQTKE 280

unknown subfamily of bacterial and plant dual specificity protein phosphatases; This subfamily is composed of uncharacterized bacterial and plant dual-specificity protein phosphatases. DUSPs function as a protein-serine/threonine phosphatases (EC 3.1.3.16) and a protein-tyrosine-phosphatases (EC 3.1.3.48).

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                 ....*....|....*....|....*....|....*....|
gi 528504278 100 VAVHCVAGLGR-APVLVAVALIEGGMK-YEEAIHLIRLKR 137
Cdd:cd14527   79 VLVHCALGYGRsATVVAAWLLAYGRAKsVAEAEALIRAAR 118

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.

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                 ....*....|....*....|....*....|....*....|....*.
gi 528504278  97 GCCVAVHCVAGLGRAPVLvAVALIeggMKY-----EEAIHLIRLKR 137
Cdd:cd14568   79 NKRVLVHCLAGISRSATI-AIAYI---MKHmrmslDDAYRFVKEKR 120

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.

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                 ....*....|....*....|....*....|....*....|....*.
gi 528504278  97 GCCVAVHCVAGLGRAPVLVAVALieggMKYE-----EAIHLIRLKR 137
Cdd:cd14514   77 GGRTLVHCVAGVSRSATLCLAYL----MKYEgmtlrEAYKHVKAAR 118