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 1985338694   5 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVMDWPFDDGAPPPSKIVEDW 84
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1985338694  85 LNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLMYLEKYRPKQRL 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 1985338694   5 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVMDWPFDDGAPPPSKIVEDW 84
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1985338694  85 LNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLMYLEKYRPKQRL 158
Cdd:cd18535    81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  31 STFIEDLKKYGATTVVRVC-EVTYDKTPLEKDGITVMDWPFDDGAPPPskiVEDWLNLLKT-KFCEDPGCCVAVHCVAGL 108
Cdd:COG2453    15 GGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDFiDEALREGKKVLVHCRGGI 91

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1985338694 109 GRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSK-QLMYLEKYR 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  37 LKKYGATTVVRVCEVTYDKTP-LEKDGITVMDWPFDDgapppskiVEDWLNLLKTK--FCEDPGCCVAVHCVAGLGRAPV 113
Cdd:pfam00782  14 LSKLGITAVINVTREVDLYNSgILYLRIPVEDNHETN--------ISKYLEEAVEFidDARQKGGKVLVHCQAGISRSAT 85

                          90       100       110
                  ....*....|....*....|....*....|
gi 1985338694 114 LVALALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:pfam00782  86 LIIAYLMKTrNLSLNEAYSFVKE-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 1985338694   5 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVMDWPFDDGAPPPSKIVEDW 84
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1985338694  85 LNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLMYLEKYRPKQRL 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 1985338694   1 MARMNRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVMDWPFDDGAPPPSKI 80
Cdd:cd18537     1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  81 VEDWLNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLMYLEKYRPKQRLRF 160
Cdd:cd18537    81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                  ....*..
gi 1985338694 161 KDPHNHK 167
Cdd:cd18537   161 KDSNGHR 167

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  11 EVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVMDWPFDDGAPPPSKIVEDWLNLLKT 90
Cdd:PTZ00242   10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  91 KFCED--PGCCVAVHCVAGLGRAPVLVALALIESG-MKYEDAIQFIRQKRRGAINSKQLMYLEKYRPKQRLRFkdphnhk 167
Cdd:PTZ00242   90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG------- 162

                  ....*.
gi 1985338694 168 nrCCIM 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 1985338694  22 THNPtnatlSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVMDWPFDDGAPPPSKIVEDWLNLlktkfCEDPGCCVA 101
Cdd:cd14499    44 THTP-----EDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI-----CENEKGAIA 113

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1985338694 102 VHCVAGLGRAPVLVALALI-ESGMKYEDAIQFIRQKRRGAINSKQLMYLEKYRPK 155
Cdd:cd14499   114 VHCKAGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 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 1985338694  17 MRFLITHNPTNaTLSTFIEDLKKYGATTVVRVCEVtydktplekdgitvmdwpfddgapppskIVEDWLNLLKTKfcEDP 96
Cdd:cd14494     7 LRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTLA----------------------------MVDRFLEVLDQA--EKP 55

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1985338694  97 GCCVAVHCVAGLGRAPVLVALALIE-SGMKYEDAIQFIRQKRRGAI--NSKQLMYLEK 151
Cdd:cd14494    56 GEPVLVHCKAGVGRTGTLVACYLVLlGGMSAEEAVRIVRLIRPGGIpqTIEQLDFLIK 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 1985338694  52 TYDKTPLEKDGITVMDWPFDD-GAPPPSKIvedwLNLLKT-KFCEDPGCCVAVHCVAGLGRAPVLVALALI-ESGMKYED 128
Cdd:cd14506    66 SYLPEAFMRAGIYFYNFGWKDyGVPSLTTI----LDIVKVmAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQ 141

                          90
                  ....*....|....*.
gi 1985338694 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 1985338694   65 VMDWPfDDGAPPPSKIVEDWLNLLKT-KFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYE-------DAIQFIRQK 136
Cdd:smart00012   7 YTGWP-DHGVPESPDSILELLRAVKKnLNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQ 85

                           90
                   ....*....|....
gi 1985338694  137 RRGAINSK-QLMYL 149
Cdd:smart00012  86 RPGMVQTEeQYLFL 99

dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in typical and atypical dual-specificity phosphatases (DUSPs), which function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Atypical DUSPs contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Also included in this family are dual specificity phosphatase-like domains of catalytically inactive members such as serine/threonine/tyrosine-interacting protein (STYX) and serine/threonine/tyrosine interacting like 1 (STYXL1), as well as active phosphatases with substrates that are not phosphoproteins such as PTP localized to the mitochondrion 1 (PTPMT1), which is a lipid phosphatase, and laforin, which is a glycogen phosphatase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  37 LKKYGATTVVRVCEVTYDktPLEKDGITVMDWPFDDGapPPSKIVEdwlNLLKT-KF---CEDPGCCVAVHCVAGLGRAP 112
Cdd:cd14498    22 LKKLGITHILNVAGEPPP--NKFPDGIKYLRIPIEDS--PDEDILS---HFEEAiEFieeALKKGGKVLVHCQAGVSRSA 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1985338694 113 VLVALALIES-GMKYEDAIQFIRQKRRGA-INS---KQLM 147
Cdd:cd14498    95 TIVIAYLMKKyGWSLEEALELVKSRRPIIsPNPgflKQLK 134

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 1985338694  97 GCCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKRRGAI--NSKQLMYLEKYR 153
Cdd:cd14524    89 GKSVYVHCKAGRGRSATIVACYLIQHkGWSPEEAQEFLRSKRPHILlrLSQREVLEEFYR 148

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694   37 LKKYGATTVVRVCEVtydKTPLEKDGITVMDWPFDDGappPSKIVEDWLNLLKTK--FCEDPGCCVAVHCVAGLGRAPVL 114
Cdd:smart00195  22 LKKLGITHVINVTNE---VPNYNGSDFTYLGVPIDDN---TETKISPYFPEAVEFieDAESKGGKVLVHCQAGVSRSATL 95

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1985338694  115 VALALIES-GMKYEDAIQFIRQkRRGAINS-----KQLMYLEK 151
Cdd:smart00195  96 IIAYLMKTrNMSLNDAYDFVKD-RRPIISPnfgflRQLIEYER 137

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 1985338694  65 VMDWPFDDGAPPPSKI-------VEDWLNllktkfcEDPGCCVAVHCVAGLGRAPVLVALALIESGM--KYEDAIQFIRQ 135
Cdd:cd14509    62 VAEYPFDDHNPPPLELikpfcedVDEWLK-------EDEKNVAAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYGA 134

                  ..
gi 1985338694 136 KR 137
Cdd:cd14509   135 KR 136

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1985338694  93 CEDPGCCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIrQKRRGAIN 142
Cdd:cd14522    85 CLQTGGKVLVHGNAGISRSAALVIAYIMETyGLSYRDAFAYV-QQRRFCIN 134

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 1985338694  66 MDWPfDDGAPppsKIVEDWLNLL----KTKF---CEDPgccVAVHCVAGLGRAPVLVALALIESGMKYEDA------IQF 132
Cdd:cd14554   143 TDWP-EQGVP---KSGEGFIDFIgqvhKTKEqfgQEGP---ITVHCSAGVGRTGVFITLSIVLERMRYEGVvdvfqtVKL 215

                          90       100
                  ....*....|....*....|.
gi 1985338694 133 IRQKRRGAINSKQlMYLEKYR 153
Cdd:cd14554   216 LRTQRPAMVQTED-QYQFCYR 235

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 1985338694  97 GCCVAVHCVAGLGRAPVL-VALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14568    79 NKRVLVHCLAGISRSATIaIAYIMKHMRMSLDDAYRFVKEKR 120

dual specificity phosphatase domain of class II mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  27 NATLSTFIEDLKKYGATTVVRVcevtydkTP------LEKDGITVMDWPFDDgapppskiveDWL-NLLK-----TKFCE 94
Cdd:cd14566    12 NAKDSANIDLLKKYNIKYILNV-------TPnlpntfEEDGGFKYLQIPIDD----------HWSqNLSAffpeaISFID 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1985338694  95 DP---GCCVAVHCVAGLGRA-PVLVALALIESGMKYEDAIQFIRQKRR 138
Cdd:cd14566    75 EArskKCGVLVHCLAGISRSvTVTVAYLMQKLHLSLNDAYDFVKKRKS 122

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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1985338694 100 VAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAINSK 144
Cdd:cd14538   143 IVVHCSAGIGRTGVLitidVALGLIERDLPFDiqDIVKDLREQRQGMIQTK 193

catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  68 WPfDDGAPPPSKIVEDWLNLLKTKFCEDPgccVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAI 141
Cdd:cd14596   114 WP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQRYGMI 189

                  ....
gi 1985338694 142 NSKQ 145
Cdd:cd14596   190 QTKD 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 1985338694  67 DWPfDDGAPPPSKIVEDWLNLL---KTKFCEDPGccVAVHCVAGLGRAPVLVALALIESGMKYE------DAIQFIRQKR 137
Cdd:cd14627   191 DWP-EQGVPKSGEGFIDFIGQVhktKEQFGQDGP--ISVHCSAGVGRTGVFITLSIVLERMRYEgvvdifQTVKMLRTQR 267

                  ....*..
gi 1985338694 138 RGAINSK 144
Cdd:cd14627   268 PAMVQTE 274

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
                  ....*....|....*....|....*....|....*....|..
gi 1985338694  97 GCCVAVHCVAGLGR-APVLVALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14512    79 NGGVLVHCLAGISRsATIAIAYLMKRMRMSLDEAYDFVKEKR 120

protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called tensin-like SH2 domain-containing protein 1 (TENS1) or tumor endothelial marker (TEM6). It is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Tensin-3 contributes to cell migration, anchorage-independent growth, tumorigenesis, and metastasis of cancer cells. It cooperates with Dock5, an exchange factor for the small GTPase Rac, for osteoclast activity to ensure the correct organization of podosomes. Tensin-3 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  11 EVCYKNMRFLITHNPTNATLSTFIEDLK--------KYGAT-TVVRVCEVTYDKTPLEKDgitVMD--WPfDDGAPPPSK 79
Cdd:cd14561     1 DLTYITERIIAVSFPADCSEETYLHNLQdvtrmlksKHGDNyLVLNLSEKRYELTKLNPK---IMDvgWP-DLHAPPLDK 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1985338694  80 I------VEDWLNllktkfcEDPGCCVAVHCVAGLGRAPVLVA 116
Cdd:cd14561    77 MctickaMESWLN-------SDPLHVVVIHCRGGKGRIGVVIS 112

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694   4 MNRPAP-VEVCYKN-----MRFLIThnptnatlstfiedlkKYG-ATTVVRVC-EVTYDKTPLEKDGITVMdwpFDDGAP 75
Cdd:cd14510    26 MSFPSSgKQAFYRNpieevVRFLDT----------------KHPdHYKVYNLCsERGYDPKYFHNRVERVP---IDDHNV 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1985338694  76 PP-------SKIVEDWLNllktkfcEDPGCCVAVHCVAGLGRAPVLVALALIESGM 124
Cdd:cd14510    87 PTldemlsfTAEVREWMA-------ADPKNVVAIHCKGGKGRTGTMVCAWLIYSGQ 135

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 1985338694  63 ITVMDWPfDDGAPPPSKIVEDWLNLLKTKFC--EDPgccVAVHCVAGLGRAPVLV----ALALIESG 123
Cdd:cd14601   111 IQYIAWP-DHGVPDDSSDFLDFVCLVRNKRAgkDEP---VVVHCSAGIGRTGVLItmetAMCLIECN 173

dual specificity phosphatase domain of dual specificity protein phosphatase 15; Dual specificity protein phosphatase 15 (DUSP15), also called Vaccinia virus VH1-related dual-specific protein phosphatase Y (VHY) or VH1-related member Y, functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). DUSP15 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It is highly expressed in the testis and is located in the plasma membrane in a myristoylation-dependent manner. It may be involved in the regulation of meiotic signal transduction in testis cells. It is also expressed in the brain and has been identified as a regulator of oligodendrocyte differentiation. DUSP15 contains an N-terminal catalytic dual specificity phosphatase domain and a short C-terminal tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985338694  30 LSTFIE--DLKKYGATTVVRVCEVTYDKTPLEKDgITVMDWPFDDGAPPP-SKIVEDWLNLLKtkFCEDPGCCVAVHCVA 106
Cdd:cd14582    14 LGNFIDakDLEQLSRNKITHIISIHESPQPLLQD-ITYLRIPLPDTPEAPiKKHFKECISFIH--QCRLNGGNCLVHCLA 90

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1985338694 107 GLGRA-PVLVALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14582    91 GISRStTIVVAYVMAVTELSWQEVLEAIRAVR 122

endonuclease NucS;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1985338694  17 MRFLITHNPTNATLSTFIEDLKKYGAT-TVVRVCEVTYD 54
Cdd:PRK04247    1 MMVEVLENPSIEEAADLLEEAIEKRALvTIFGRCEVEYE 39

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 1985338694 100 VAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQL 146
Cdd:cd14579   111 VLVHCREGYSRSPTLViAYLMLRQKMDVKSALSTVRQKREIGPNDgflKQL 161