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 1176334766   5 NRPAPVEVCYKNMRFLITHNPTNATLNTFIEDLKKYGATTVVRVCEITYDKTPLEKDGITVMDWPFDDGAPPPTKIVDDW 84
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1176334766  85 LNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 1176334766   5 NRPAPVEVCYKNMRFLITHNPTNATLNTFIEDLKKYGATTVVRVCEITYDKTPLEKDGITVMDWPFDDGAPPPTKIVDDW 84
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1176334766  85 LNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 158
Cdd:cd18535    81 LSLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 154

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766  35 EDLKKYGATTVVRVC-EITYDKTPLEKDGITVMDWPFDDGAPPPtkiVDDWLNLLKT-KFCEDPGCCVAVHCVAGLGRAP 112
Cdd:COG2453    19 ADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPD---DEQLQEAVDFiDEALREGKKVLVHCRGGIGRTG 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1176334766 113 VLVALALIESGMKYEDAIQFIRQKRRGAINSK-QLTYLEKYR 153
Cdd:COG2453    96 TVAAAYLVLLGLSAEEALARVRAARPGAVETPaQRAFLERFA 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 1176334766  37 LKKYGATTVVRVCEITYDKTPlekdGITVMDWPFDDGapPPTKIVDdWLNLLKTK--FCEDPGCCVAVHCVAGLGRAPVL 114
Cdd:pfam00782  14 LSKLGITAVINVTREVDLYNS----GILYLRIPVEDN--HETNISK-YLEEAVEFidDARQKGGKVLVHCQAGISRSATL 86

                          90       100
                  ....*....|....*....|....*....
gi 1176334766 115 VALALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:pfam00782  87 IIAYLMKTrNLSLNEAYSFVKE-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 1176334766   5 NRPAPVEVCYKNMRFLITHNPTNATLNTFIEDLKKYGATTVVRVCEITYDKTPLEKDGITVMDWPFDDGAPPPTKIVDDW 84
Cdd:cd18535     1 NRPAPVEVCYKNMRFLITHNPTNATLSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDW 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1176334766  85 LNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRL 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 1176334766   1 MARMNRPAPVEVCYKNMRFLITHNPTNATLNTFIEDLKKYGATTVVRVCEITYDKTPLEKDGITVMDWPFDDGAPPPTKI 80
Cdd:cd18537     1 MARMNRPAPVEITYKNMRFLITHNPTNATLNKFIEELKKYGVTTVVRVCEATYDTTLVEKEGIQVLDWPFDDGAPPSNQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766  81 VDDWLNLLKTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRF 160
Cdd:cd18537    81 VDDWLNLLKVKFREEPGCCIAVHCVAGLGRAPVLVALALIECGMKYEDAVQFIRQKRRGAFNSKQLLYLEKYRPKMRLRF 160

                  ....*..
gi 1176334766 161 KDPQNHK 167
Cdd:cd18537   161 KDSNGHR 167

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766  11 EVCYKNMRFLITHNPTNATLNTFIEDLKKYGATTVVRVCEITYDKTPLEKDGITVMDWPFDDGAPPPTKIVDDWLNLLKT 90
Cdd:PTZ00242   10 QIEYVLFKFLILDAPSPSNLPLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQ 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766  91 KFCED--PGCCVAVHCVAGLGRAPVLVALALIESG-MKYEDAIQFIRQKRRGAINSKQLTYLEKYRPKQRLRFkdpqnhk 167
Cdd:PTZ00242   90 EFAKQstPPETIAVHCVAGLGRAPILVALALVEYGgMEPLDAVGFVREKRKGAINQTQLQFLKKYKPRKKAAG------- 162

                  ....*.
gi 1176334766 168 nkCCIM 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 1176334766  33 FIEDLKKYGATTVVRVCEITYDKTPLEKDGITVMDWPFDDGAPPPTKIVDDWLNLlktkfCEDPGCCVAVHCVAGLGRAP 112
Cdd:cd14499    50 YIPYFKKLGVTTVVRLNKKLYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDI-----CENEKGAIAVHCKAGLGRTG 124

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1176334766 113 VLVALALI-ESGMKYEDAIQFIRQKRRGAINSKQLTYLEKYRPK 155
Cdd:cd14499   125 TLIACYLMkHYGFTAREAIAWLRICRPGSVIGPQQQFLEEKEAR 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 1176334766  17 MRFLITHNPTNaTLNTFIEDLKKYGATTVVRVCEitydktplekdgitvmdwpfddgappptKIVDDWLNLLKTKfcEDP 96
Cdd:cd14494     7 LRLIAGALPLS-PLEADSRFLKQLGVTTIVDLTL----------------------------AMVDRFLEVLDQA--EKP 55

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1176334766  97 GCCVAVHCVAGLGRAPVLVALALIE-SGMKYEDAIQFIRQKRRGAI--NSKQLTYLEK 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 1176334766  52 TYDKTPLEKDGITVMDWPFDD-GAPPPTKIVDdwlnLLKT-KFCEDPGCCVAVHCVAGLGRAPVLVALALI-ESGMKYED 128
Cdd:cd14506    66 SYLPEAFMRAGIYFYNFGWKDyGVPSLTTILD----IVKVmAFALQEGGKVAVHCHAGLGRTGVLIACYLVyALRMSADQ 141

                          90
                  ....*....|....*.
gi 1176334766 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 1176334766   65 VMDWPfDDGAPPPTKIVDDWLNLL-KTKFCEDPGCCVAVHCVAGLGRAPVLVALALIESGMKYE-------DAIQFIRQK 136
Cdd:smart00012   7 YTGWP-DHGVPESPDSILELLRAVkKNLNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEagevdifDTVKELRSQ 85

                   ....*....
gi 1176334766  137 RRGAINSKQ 145
Cdd:smart00012  86 RPGMVQTEE 94

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 1176334766  37 LKKYGATTVVRVCEITYDktPLEKDGITVMDWPFDDGapPPTKIVDdwlNLLKT-KF---CEDPGCCVAVHCVAGLGRAP 112
Cdd:cd14498    22 LKKLGITHILNVAGEPPP--NKFPDGIKYLRIPIEDS--PDEDILS---HFEEAiEFieeALKKGGKVLVHCQAGVSRSA 94

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1176334766 113 VLVALALIES-GMKYEDAIQFIRQKRRGA-INS---KQL 146
Cdd:cd14498    95 TIVIAYLMKKyGWSLEEALELVKSRRPIIsPNPgflKQL 133

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 1176334766  97 GCCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKRRGAI--NSKQLTYLEKYR 153
Cdd:cd14524    89 GKSVYVHCKAGRGRSATIVACYLIQHkGWSPEEAQEFLRSKRPHILlrLSQREVLEEFYR 148

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766   37 LKKYGATTVVRVceiTYDKTPLEKDGITVMDWPFDDGapPPTKIVDDWLNLlkTKF---CEDPGCCVAVHCVAGLGRAPV 113
Cdd:smart00195  22 LKKLGITHVINV---TNEVPNYNGSDFTYLGVPIDDN--TETKISPYFPEA--VEFiedAESKGGKVLVHCQAGVSRSAT 94

                           90       100       110
                   ....*....|....*....|....*....|
gi 1176334766  114 LVALALIES-GMKYEDAIQFIRQkRRGAIN 142
Cdd:smart00195  95 LIIAYLMKTrNMSLNDAYDFVKD-RRPIIS 123

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 1176334766  68 WPfDDGAPPPTKIVDDWLNLLKtKFCEDPGCCVAVHCVAGLGRAPVLVAL-ALIESgMKYE------DAIQFIRQKRRGA 140
Cdd:cd00047   112 WP-DHGVPSSPEDLLALVRRVR-KEARKPNGPIVVHCSAGVGRTGTFIAIdILLER-LEAEgevdvfEIVKALRKQRPGM 188

                          90
                  ....*....|
gi 1176334766 141 I-NSKQLTYL 149
Cdd:cd00047   189 VqTLEQYEFI 198

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1176334766  93 CEDPGCCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIrQKRRGAINSKQ--LTYLEKYRP 154
Cdd:cd14522    85 CLQTGGKVLVHGNAGISRSAALVIAYIMETyGLSYRDAFAYV-QQRRFCINPNEgfVHQLKEYEA 148

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 1176334766  66 MDWPfDDGAPpptKIVDDWLNLL----KTKF---CEDPgccVAVHCVAGLGRAPVLVALALIESGMKYEDA------IQF 132
Cdd:cd14554   143 TDWP-EQGVP---KSGEGFIDFIgqvhKTKEqfgQEGP---ITVHCSAGVGRTGVFITLSIVLERMRYEGVvdvfqtVKL 215

                          90       100
                  ....*....|....*....|.
gi 1176334766 133 IRQKRRGAINSKQlTYLEKYR 153
Cdd:cd14554   216 LRTQRPAMVQTED-QYQFCYR 235

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1176334766  97 GCCVAVHCVAGLGRAP--VLVALALIeSGMKYEDAIQFIRQKR 137
Cdd:cd14526    94 GGTVYVHCTAGLGRAPatVIAYLYWV-LGYSLDEAYYLLTSKR 135

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766  34 IEDLKKYGATTVVRV-CEITYDKTPLEKDGITVMDWP-FDDGAPPPTKIVD--DWLNLLKTKfcedpGCCVAVHCVAGLG 109
Cdd:PRK12361  113 LEKLKSNKITAILDVtAEFDGLDWSLTEEDIDYLNIPiLDHSVPTLAQLNQaiNWIHRQVRA-----NKSVVVHCALGRG 187

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1176334766 110 RApVLVALALIESGMK---YEDAIQFIRQKRRGA-INSKQLTYLEKYRPKQRLRFKDP 163
Cdd:PRK12361  188 RS-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 1176334766  67 DWPfDDGAPPPTKIVDDWLNLL---KTKFCEDPGccVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--R 138
Cdd:cd14628   190 DWP-EQGVPKSGEGFIDFIGQVhktKEQFGQDGP--ISVHCSAGVGRTGVFITLSIVLERMRYEgvvDIFQTVKMLRtqR 266

                          90
                  ....*....|....*
gi 1176334766 139 GAINSKQLTYLEKYR 153
Cdd:cd14628   267 PAMVQTEDQYQFCYR 281

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 1176334766   4 MNRPAP-VEVCYKN-----MRFLIThnptnatlntfiedlkKYG-ATTVVRVC-EITYDKTPLEKDGITVMdwpFDDGAP 75
Cdd:cd14510    26 MSFPSSgKQAFYRNpieevVRFLDT----------------KHPdHYKVYNLCsERGYDPKYFHNRVERVP---IDDHNV 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1176334766  76 PP-------TKIVDDWLNllktkfcEDPGCCVAVHCVAGLGRAPVLVALALIESGM 124
Cdd:cd14510    87 PTldemlsfTAEVREWMA-------ADPKNVVAIHCKGGKGRTGTMVCAWLIYSGQ 135

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 1176334766  68 WPfDDGAPPPTKIVDDWLNLLKTKFCEDPgccVAVHCVAGLGRAPVL----VALALIESGMKYE--DAIQFIRQKRRGAI 141
Cdd:cd14596   114 WP-DHGTPQSSDQLVKFICYMRKVHNTGP---IVVHCSAGIGRAGVLicvdVLLSLIEKDLSFNikDIVREMRQQRYGMI 189

                  ....
gi 1176334766 142 NSKQ 145
Cdd:cd14596   190 QTKD 193

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 1176334766  67 DWPfDDGAPPPTKIVDDWLNLL---KTKFCEDPGccVAVHCVAGLGRAPVLVALALIESGMKYE---DAIQFIRQKR--R 138
Cdd:cd14629   191 DWP-EQGVPKTGEGFIDFIGQVhktKEQFGQDGP--ITVHCSAGVGRTGVFITLSIVLERMRYEgvvDMFQTVKTLRtqR 267

                          90
                  ....*....|....*
gi 1176334766 139 GAINSKQLTYLEKYR 153
Cdd:cd14629   268 PAMVQTEDQYQLCYR 282

bacterial protein tyrosine and dual-specificity phosphatases related to Pseudomonas aeruginosa TpbA; This subfamily contains bacterial protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DUSPs) related to Pseudomonas aeruginosa TpbA, a DUSP that negatively regulates biofilm formation by converting extracellular quorum sensing signals and to Mycobacterium tuberculosis PtpB, a PTP virulence factor that attenuates host immune defenses by interfering with signal transduction pathways in macrophages. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides, while DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and PTPs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1176334766  37 LKKYGATTVV----RVCEITYDKTPLEKDGITVMDWPFDDGAPPPT------KIVDDWLNllktkfcEDPgccVAVHCVA 106
Cdd:cd14529    29 LKKLGIKTVIdlrgADERAASEEAAAKIDGVKYVNLPLSATRPTESdvqsflLIMDLKLA-------PGP---VLIHCKH 98

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1176334766 107 GLGRAPVLVALALIESGMKYEDAI-QFIRQKRRGAINSKQLTYLEKYRPKQR 157
Cdd:cd14529    99 GKDRTGLVSALYRIVYGGSKEEANeDYRLSNRHLEGLRSGIALDSKGGVKGR 150

dual-specificity phosphatase domain of dual specificity protein phosphatase 11 and similar proteins; dual specificity protein phosphatase 11 (DUSP11), also known as RNA/RNP complex-1-interacting phosphatase or phosphatase that interacts with RNA/RNP complex 1 (PIR1), has RNA 5'-triphosphatase and diphosphatase activity, but only poor protein-tyrosine phosphatase activity. It has activity for short RNAs but is less active toward mononucleotide triphosphates, suggesting that its primary function in vivo is to dephosphorylate RNA 5'-ends. It may play a role in nuclear mRNA metabolism. Also included in this subfamily is baculovirus RNA 5'-triphosphatase for Autographa californica nuclear polyhedrosis virus.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1176334766  76 PPTKIVDDWLNLLK--TKFCEDPGCCVAVHCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKR 137
Cdd:cd17665    90 PDDKTIQSFKDAVKdfLEKNKDNDKLIGVHCTHGLNRTGYLICRYLIDVdGMSPDDAIEAFEQAR 154

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 1176334766  11 EVCYKNMRFLITHNPTNATLNTFIEDLK--------KYGAT-TVVRVCEITYDKTPLEKDgitVMD--WPfDDGAPPPTK 79
Cdd:cd14561     1 DLTYITERIIAVSFPADCSEETYLHNLQdvtrmlksKHGDNyLVLNLSEKRYELTKLNPK---IMDvgWP-DLHAPPLDK 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1176334766  80 I------VDDWLNllktkfcEDPGCCVAVHCVAGLGRAPVLVA 116
Cdd:cd14561    77 MctickaMESWLN-------SDPLHVVVIHCRGGKGRIGVVIS 112

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 1176334766 100 VAVHCVAGLGRApVLVALALIES--GMKYEDAIQFIRQKR 137
Cdd:cd14519    80 VLVHCLAGVSRS-VTIVAAYLMTvtDLGWRDALKAVRAAR 118

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), 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. DUSP13A 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. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1176334766  96 PGCCVAVHCVAGLGRAPVLV-ALALIESGMKYEDAIQFIRQKRRGAINS---KQLTYLE 150
Cdd:cd14580    84 PGAKVLVHCAVGVSRSATLVlAYLMIYHQLSLVQAIKTVKERRWIFPNRgflKQLRKLD 142

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1176334766  92 FCEDPGCC---VAVHCVAGLGRAP-VLVALALIESGMKYEDAIQFIRQKR 137
Cdd:cd14567    72 FIEEAHQSgkgVLVHCQAGVSRSAtIVIAYLMKHTRMTMTDAYKFVKNKR 121