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 2462627036   1 MYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRI 80
Cdd:cd14499    69 LYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRI 148

                          90       100
                  ....*....|....*....|....*.
gi 2462627036  81 CRPGSVIGPQQQFLVMKQTNLWLEGD 106
Cdd:cd14499   149 CRPGSVIGPQQQFLEEKEARLWRAGD 174

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 2462627036   1 MYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRI 80
Cdd:cd14499    69 LYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRI 148

                          90       100
                  ....*....|....*....|....*.
gi 2462627036  81 CRPGSVIGPQQQFLVMKQTNLWLEGD 106
Cdd:cd14499   149 CRPGSVIGPQQQFLEEKEARLWRAGD 174

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036   7 FTDAGFDHHDLFFADGSTPTDAIVKEFLD-ICENAE--GAIAVHCKAGLGRTGTLIACYIMKHyRMTAAETIAWVRICRP 83
Cdd:COG2453    43 LEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGRTGTVAAAYLVLL-GLSAEEALARVRAARP 121

                  ....*....
gi 2462627036  84 GSVIGPQQQ 92
Cdd:COG2453   122 GAVETPAQR 130

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036   30 VKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQTNLW 102
Cdd:smart00195  67 AVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLMKTRNMSLNDAYDFVKDRRPI--ISPNFGF--LRQLIEY 135

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 2462627036   1 MYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRI 80
Cdd:cd14499    69 LYDAKRFTDAGIRHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRI 148

                          90       100
                  ....*....|....*....|....*.
gi 2462627036  81 CRPGSVIGPQQQFLVMKQTNLWLEGD 106
Cdd:cd14499   149 CRPGSVIGPQQQFLEEKEARLWRAGD 174

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462627036  24 TPTDAIVKEFLDICENAE---GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSV--IGPQQQFLVM 96
Cdd:cd14494    36 DLTLAMVDRFLEVLDQAEkpgEPVLVHCKAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGIpqTIEQLDFLIK 113

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036   2 YDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENA-------EGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAET 74
Cdd:PTZ00242   52 YDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEfakqstpPETIAVHCVAGLGRAPILVALALVEYGGMEPLDA 131

                          90       100
                  ....*....|....*....|
gi 2462627036  75 IAWVRICRPGSVIGPQQQFL 94
Cdd:PTZ00242  132 VGFVREKRKGAINQTQLQFL 151

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036   7 FTDAGFDHHDLFFADGSTPTDAIVKEFLD-ICENAE--GAIAVHCKAGLGRTGTLIACYIMKHyRMTAAETIAWVRICRP 83
Cdd:COG2453    43 LEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGRTGTVAAAYLVLL-GLSAEEALARVRAARP 121

                  ....*....
gi 2462627036  84 GSVIGPQQQ 92
Cdd:COG2453   122 GAVETPAQR 130

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 2462627036   5 KRFTDAGFDHHDLFFADGSTPTD-----AIVKEFLdICENAEGAIAVHCKAGLGRTGTLIACY-IMKHYRMTAAETIAWV 78
Cdd:cd14505    66 EQYQQAGITWHHLPIPDGGVPSDiaqwqELLEELL-SALENGKKVLIHCKGGLGRTGLIAACLlLELGDTLDPEQAIAAV 144

                          90
                  ....*....|....*..
gi 2462627036  79 RICRPGSVIGP-QQQFL 94
Cdd:cd14505   145 RALRPGAIQTPkQENFL 161

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036  23 STPTDAIVKE---FLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQ 92
Cdd:cd14524    68 GVPSLEDLEKgvdFILKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQR 140

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFlvMKQ 98
Cdd:cd14498    70 EFIEEALKKGGKVLVHCQAGVSRSATIVIAYLMKKYGWSLEEALELVKSRRP--IISPNPGF--LKQ 132

RNA 5'-triphosphatase domain; This family of RNA-specific cysteine phosphatases includes baculovirus RNA 5'-triphosphatase, dual specificity protein phosphatase 11 (DUSP11), and the RNA triphosphatase domains of metazoan and plant mRNA capping enzymes. RNA/polynucleotide 5'-triphosphatase (EC 3.1.3.33) catalyzes the removal of the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end. mRNA capping enzyme is a bifunctional enzyme that catalyzes the first two steps of cap formation. DUSP11 has RNA 5'-triphosphatase and diphosphatase activity, but only poor protein-tyrosine phosphatase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036   2 YDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICE------NAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETI 75
Cdd:cd14502    66 YDPNDLDDDGYVYYKKVCVRKEPPDAEEVNKFIELVDkflaedNPDKLIAVHCTHGFNRTGFMIVSYLVERLGLTVEQAL 145

                  ....*...
gi 2462627036  76 AWVRICRP 83
Cdd:cd14502   146 EAFAQARP 153

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462627036  21 DGSTPTD-----AIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHyRMTA------AETIAWVRICRPGSV 86
Cdd:cd00047   114 DHGVPSSpedllALVRRVRKEARKPNGPIVVHCSAGVGRTGTFIAIDILLE-RLEAegevdvFEIVKALRKQRPGMV 189

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 94
Cdd:cd14568    70 EFIEKARASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRP--TISPNFNFL 130

dual specificity protein phosphatases 18 and 21; This subfamily contains dual specificity protein phosphatase 18 (DUSP18), dual specificity protein phosphatase 21 (DUSP21), 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. DUSP18, also called low molecular weight dual specificity phosphatase 20 (LMW-DSP20), is a catalytically active phosphatase with a preference for phosphotyrosine over phosphoserine/threonine oligopeptides in vitro. In vivo, it has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP21 is also called low molecular weight dual specificity phosphatase 21 (LMW-DSP21). Its gene has been identified as a potential therapeutic target in human hepatocellular carcinoma. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462627036  42 GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQF 93
Cdd:cd14573    80 GRTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRP--IIRPNNGF 129

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 94
Cdd:cd14512    70 EFIEEAKASNGGVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRP--TISPNFNFM 130

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 94
Cdd:cd14567    71 EFIEEAHQSGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRP--IISPNLNFM 131

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036   2 YDAKRFTDAGFDHHDLFFADGSTPTDA-------IVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIM 64
Cdd:cd17665    67 YDPRDLTNHGVYYKKITCPGHQVPDDKtiqsfkdAVKDFLEKNKDNDKLIGVHCTHGLNRTGYLICRYLI 136

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036   30 VKEFLDICENaEGAIAVHCKAGLGRTGTLIACYIM------KHYRMTAAETIAWVRICRPGSV 86
Cdd:smart00404  29 VKKNLNQSES-SGPVVVHCSAGVGRTGTFVAIDILlqqleaEAGEVDIFDTVKELRSQRPGMV 90

dual specificity protein phosphatases 14, 18, 21, 28 and similar proteins; This family is composed of dual specificity protein phosphatase 14 (DUSP14, also known as MKP-6), 18 (DUSP18), 21 (DUSP21), 28 (DUSP28), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP14 directly interacts and dephosphorylates TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) in T cells, and negatively regulates TCR signaling and immune responses. DUSP18 has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane. DUSP28 has been implicated in hepatocellular carcinoma progression and in migratory activity and drug resistance of pancreatic cancer cells.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2462627036  42 GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRP 83
Cdd:cd14514    78 GRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARP 119

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462627036   9 DAGFDHHDL-FFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACY----------IMKHYRMTA 71
Cdd:cd14529    56 IDGVKYVNLpLSATRPTESDVQSFLLIMDLKLAPGPVLIHCKHGKDRTGLVSALYrivyggskeeANEDYRLSN 129

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), 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 I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRpgSVIGPQQQFL 94
Cdd:cd14640    69 EYIDSVKDCNGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRR--SIISPNFSFM 129

dual specificity phosphatase domain of class I mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class I MKPs consist of DUSP1/MKP-1, DUSP2 (PAC1), DUSP4/MKP-2 and DUSP5. They are all mitogen- and stress-inducible nuclear MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462627036  27 DAIvkEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 94
Cdd:cd14565    66 EAI--GFIDKVKASGGRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRS--VISPNFNFM 129

protein tyrosine phosphatase type IVA 2; Protein tyrosine phosphatase type IVA 2 (PTP-IVa2), also known as protein-tyrosine phosphatase of regenerating liver 2 (PRL-2), stimulates progression from G1 into S phase during mitosis and promotes tumors. It regulates tumor cell migration and invasion through an ERK-dependent signaling pathway. Its overexpression correlates with breast tumor formation and progression. PRL-2 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 2462627036   2 YDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDIC-----ENAEGAIAVHCKAGLGRTGTLIACYIMKhYRMTAAETIA 76
Cdd:cd18536    50 YDKAPVEKEGIQVLDWPFDDGAPPPNQIVDDWLNLLktkfrEEPGCCVAVHCVAGLGRAPVLVALALIE-CGMKYEDAVQ 128

                          90
                  ....*....|....*...
gi 2462627036  77 WVRICRPGSVIGPQQQFL 94
Cdd:cd18536   129 FIRQKRRGAFNSKQLLYL 146

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036   6 RFTDAGFDHHDL---FFADGSTPTdaiVKEFLDICENA--------EGAIAVHCKAGLGRTGTLIACYIM 64
Cdd:cd14510    65 RGYDPKYFHNRVervPIDDHNVPT---LDEMLSFTAEVrewmaadpKNVVAIHCKGGKGRTGTMVCAWLI 131

dual specificity phosphatase domain of fungal dual specificity protein phosphatase PPS1-like; This subfamily contains fungal proteins with similarity to dual specificity protein phosphatase PPS1 from Saccharomyces cerevisiae, which has a role in the DNA synthesis phase of the cell cycle. As a dual specificity protein phosphatase, PPS1 functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It contains a C-terminal catalytic dual specificity phosphatase domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462627036  21 DGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQFL 94
Cdd:cd14516    96 DSLLPQLTDALDFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRRLNIIIQPNLRFF 169

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 2462627036   2 YDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDIC-----ENAEGAIAVHCKAGLGRTGTLIACYIMKHyRMTAAETIA 76
Cdd:cd18537    53 YDTTLVEKEGIQVLDWPFDDGAPPSNQIVDDWLNLLkvkfrEEPGCCIAVHCVAGLGRAPVLVALALIEC-GMKYEDAVQ 131

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462627036  77 WVRICRPGSVIGPQQqflvmkqtnLWLEGDYFRQKLKGQENGQHR 121
Cdd:cd18537   132 FIRQKRRGAFNSKQL---------LYLEKYRPKMRLRFKDSNGHR 167

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462627036  21 DGSTPTDAivKEFLDICE--------NAEGAIAVHCKAGLGRTGTLIACYIMkHYRMTA------AETIAWVRICRPGSV 86
Cdd:pfam00102 143 DHGVPESP--NSLLDLLRkvrkssldGRSGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAegevdiFQIVKELRSQRPGMV 219

                          90
                  ....*....|.
gi 2462627036  87 IGPQQ-QFLVM 96
Cdd:pfam00102 220 QTLEQyIFLYD 230

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462627036  33 FLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRpgSVIGPQQQFL 94
Cdd:cd14513    70 FIKEARRKGSKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERR--SCIKPNPGFL 129

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462627036  41 EGAIAVHCKAGLGRTGTLIACYIMKHyRMTAA------ETIAWVRICRPGSVIGPQQ-QFL 94
Cdd:cd14554   174 EGPITVHCSAGVGRTGVFITLSIVLE-RMRYEgvvdvfQTVKLLRTQRPAMVQTEDQyQFC 233

dual specificity phosphatase domain of dual specificity protein phosphatase 8; Dual specificity protein phosphatase 8 (DUSP8), also called DUSP hVH-5 or M3/6, 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. DUSP8 controls basal and acute stress-induced ERK1/2 signaling in adult cardiac myocytes, which impacts contractility, ventricular remodeling, and disease susceptibility. It also plays a role in decreasing ureteric branching morphogenesis by inhibiting p38MAPK. DUSP8 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFL 94
Cdd:cd14645    81 EFIDKAKVSNCRVIVHCLAGISRSATIAIAYIMKTMGLSSDDAYRFVKDRRPS--ISPNFNFL 141

catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) and type 6 (PTPN6) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 and PTPN6, are also called SH2 domain-containing tyrosine phosphatase 2 (SHP2) and 1 (SHP1), respectively. They contain two tandem SH2 domains: a catalytic PTP domain, and a C-terminal tail with regulatory properties. Although structurally similar, they have different localization and different roles in signal transduction. PTPN11/SHP2 is expressed ubiquitously and plays a positive role in cell signaling, leading to cell activation, while PTPN6/SHP1 expression is restricted mainly to hematopoietic and epithelial cells and functions as a negative regulator of signaling events.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462627036  39 NAEGAIAVHCKAGLGRTGTLIAC-YIMKHYR-------MTAAETIAWVRICRPGSVIGPQQ-QFLVM 96
Cdd:cd14544   177 PHAGPIVVHCSAGIGRTGTFIVIdMLLDQIKrkgldcdIDIQKTIQMVRSQRSGMVQTEAQyKFIYV 243

Inositol hexakisphosphate; Inositol hexakisphosphate, often called phytate, is found in abundance in seeds and acting as an inorganic phosphate reservoir. Phytases are phosphatases that hydrolyze phytate to less-phosphorylated myo-inositol derivatives and inorganic phosphate. The active-site sequence (HCXXGXGR) of the phytase identified from the gut micro-organizm Selenomonas ruminantium forms a loop (P loop) at the base of a substrate binding pocket that is characteriztic of protein tyrosine phosphatases (PTPs). The depth of this pocket is an important determinant of the substrate specificity of PTPs. In humans this enzyme is thought to aid bone mineralization and salvage the inositol moiety prior to apoptosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462627036   1 MYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENA--EGAIAVHCKAGLGRT--GTLIACYIM 64
Cdd:pfam14566  90 VYERLKAEGPGVDYRRIPITDEKAPLEEDFDALISIVKDApeDTALVFNCQMGRGRTttAMVIADLVR 157

YopH and related bacterial protein tyrosine phosphatases; Yersinia outer protein H (YopH) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. YopH is an essential virulence determinant of the pathogenic bacterium by dephosphorylating several focal adhesion proteins including p130Cas in human epithelial cells, resulting in the disruption of focal adhesions and cell detachment from the extracellular matrix. It contains an N-terminal domain that contains signals required for TTSS-mediated delivery of YopH into host cells and a C-terminal catalytic PTP domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462627036  46 VHCKAGLGRTGTLIACYIMKHYR--MTAAETIAWVRICRPGSVIGPQQQFLVMKQ 98
Cdd:cd14559   173 IHCRAGVGRTGQLAAAMELNKSPnnLSVEDIVSDMRTSRNGKMVQKDEQLDTLKE 227

catalytic domain of the kinase interaction motif (KIM) family of protein-tyrosine phosphatases; The kinase interaction motif (KIM) family of protein-tyrosine phosphatases (PTPs) includes tyrosine-protein phosphatases non-receptor type 7 (PTPN7) and non-receptor type 5 (PTPN5), and protein-tyrosine phosphatase receptor type R (PTPRR). PTPN7 is also called hematopoietic protein-tyrosine phosphatase (HePTP) while PTPN5 is also called striatal-enriched protein-tyrosine phosphatase (STEP). They belong to the family of classical tyrosine-specific PTPs (EC 3.1.3.48) that catalyze the dephosphorylation of phosphotyrosine peptides. KIM-PTPs are characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. They are highly specific to the MAPKs ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38, over JNK (c-Jun N-terminal kinase); they dephosphorylate these kinases and thereby critically modulate cell proliferation and differentiation.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYI 63
Cdd:cd14547   154 EEARQTEPHRGPIVVHCSAGIGRTGCFIATSI 185

dual specificity phosphatase-like domain of serine/threonine/tyrosine interacting like 1; Serine/threonine/tyrosine interacting like 1 (STYXL1), also known as DUSP24 and MK-STYX, is a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). STYXL1 plays a role in regulating pathways by competing with active phosphatases for binding to MAPKs. Similar to MKPs, STYXL1 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, however its C-terminal dual specificity phosphatase-like domain is a pseudophosphatase missing the catalytic cysteine.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462627036  32 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQTNLW 102
Cdd:cd14517    81 SFIDKHKNNGSRVLVFSTLGISRSVAVAIAYLMYHYKWSLKDAWKYLLKCKNN--MRPNRGF--VKQLSEW 147

dual specificity protein phosphatase 22; Dual specificity protein phosphatase 22 (DUSP22), also called JNK-stimulatory phosphatase-1 (JSP-1), low molecular weight dual specificity phosphatase 2 (LMW-DSP2), mitogen-activated protein kinase phosphatase x (MKP-x) or VHR-related MKPx (VHX), 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. DUSP22 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. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. It also regulates cell death by acting as a scaffold protein for the ASK1-MKK7-JNK signal transduction pathway independently of its phosphatase activity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462627036  33 FLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRP--GSVIGPQQQ 92
Cdd:cd14581    72 FIHECRLRGEGCLVHCLAGVSRSVTLVVAYIMTVTDFGWEDALSAVKAARScaNPNMGFQRQ 133

catalytic domain of receptor-type tyrosine-protein phosphatase O; Receptor-type tyrosine-protein phosphatase O (PTPRO or R-PTP-O), also known as glomerular epithelial protein 1 or protein tyrosine phosphatase U2 (PTP-U2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRO is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is essential for sustaining the structure and function of foot processes by regulating tyrosine phosphorylation of podocyte proteins. It has been identified as a synaptic cell adhesion molecule (CAM) that serves as a potent initiator of synapse formation. It is also a tumor suppressor in several types of cancer, such as hepatocellular carcinoma, lung cancer, and breast cancer.

                          10        20
                  ....*....|....*....|....*....
gi 2462627036  41 EGAIAVHCKAGLGRTGTLIAC-YIMKHYR 68
Cdd:cd14614   179 KGPMIIHCSAGVGRTGTFIALdRLLQHIR 207

catalytic domain of R3 subfamily receptor-type tyrosine-protein phosphatases and similar proteins; R3 subfamily receptor-type phosphotyrosine phosphatases (RPTP) are characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. Vertebrate members include receptor-type tyrosine-protein phosphatase-like O (PTPRO), J (PTPRJ), Q (PTPRQ), B (PTPRB), V (PTPRV) and H (PTPRH). They belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Most members are PTPs, except for PTPRQ, which dephosphorylates phosphatidylinositide substrates. PTPRV is characterized only in rodents; its function has been lost in humans. Both vertebrate and invertebrate R3 subfamily RPTPs are involved in the control of a variety of cellular processes, including cell growth, differentiation, mitotic cycle and oncogenic transformation.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 2462627036  28 AIVKEFLDICENAEGAIAVHCKAGLGRTGTLIA 60
Cdd:cd14548   148 RFVRLVRDYIKQEKGPTIVHCSAGVGRTGTFIA 180

protein tyrosine phosphatase 1 from Arabidopsis thaliana and similar plant PTPs; Arabidopsis thaliana protein tyrosine phosphatase 1 (AtPTP1) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. AtPTP1 dephosphorylates and inhibits MAP kinase 6 (MPK6) in non-oxidative stress conditions. Together with MAP kinase phosphatase 1 (MKP1) it expresses salicylic acid (SA) and camalexin biosynthesis, and therefore, modulating defense response.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462627036  41 EGAIAVHCKAGLGRTGTLIACY-----IMKHyRMTA---AETIAWVRICRPGSV 86
Cdd:cd17658   143 AGPIVVHCSAGIGRTGAYCTIHntirrILEG-DMSAvdlSKTVRKFRSQRIGMV 195