N-terminal domain pseudophosphatase 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. The N-terminal pseudophosphatase domain lacks the catalytic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064  52 ITDRLCFAILYSRPKSASNVHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIVHFTGSDQRKQAN 131
Cdd:cd17657    6 IPDRLYFASLRGPPKSTDNTHYFSIDDELVYEPFFADFGPLNLAQIYRFCCKLNKKLKSPSLASKKIVHYTSLDPKKRAN 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119613064 132 AAFLVGCYMVIYLGRTPEEAYRILIFGETSYIPFRDAAYGSCNFYITLLDCFHAVKKAM 190
Cdd:cd17657   86 AAFLIGAYAVIYLGKTPEEAYRPLESGEPPFLPFRDASYGPCTYELTVLDCLKGLEKAL 144

N-terminal domain pseudophosphatase 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. The N-terminal pseudophosphatase domain lacks the catalytic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064  52 ITDRLCFAILYSRPKSASNVHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIVHFTGSDQRKQAN 131
Cdd:cd17657    6 IPDRLYFASLRGPPKSTDNTHYFSIDDELVYEPFFADFGPLNLAQIYRFCCKLNKKLKSPSLASKKIVHYTSLDPKKRAN 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119613064 132 AAFLVGCYMVIYLGRTPEEAYRILIFGETSYIPFRDAAYGSCNFYITLLDCFHAVKKAM 190
Cdd:cd17657   86 AAFLIGAYAVIYLGKTPEEAYRPLESGEPPFLPFRDASYGPCTYELTVLDCLKGLEKAL 144

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 246 ETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENA-------EGAIAVHCKAGL 318
Cdd:PTZ00242  30 PLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEfakqstpPETIAVHCVAGL 109

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 119613064 319 GRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQFL 360
Cdd:PTZ00242 110 GRAPILVALALVEYGGMEPLDAVGFVREKRKGAINQTQLQFL 151

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064   253 KNHNVTTIIRL--NKRMYDAKRFTDAGFDHHDlFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIM 330
Cdd:smart00195  23 KKLGITHVINVtnEVPNYNGSDFTYLGVPIDD-NTETKISPYFPEAVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLM 101

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 119613064   331 KHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQTNLW 368
Cdd:smart00195 102 KTRNMSLNDAYDFVKDRRPI--ISPNFGF--LRQLIEY 135

N-terminal domain pseudophosphatase 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. The N-terminal pseudophosphatase domain lacks the catalytic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064  52 ITDRLCFAILYSRPKSASNVHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIVHFTGSDQRKQAN 131
Cdd:cd17657    6 IPDRLYFASLRGPPKSTDNTHYFSIDDELVYEPFFADFGPLNLAQIYRFCCKLNKKLKSPSLASKKIVHYTSLDPKKRAN 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119613064 132 AAFLVGCYMVIYLGRTPEEAYRILIFGETSYIPFRDAAYGSCNFYITLLDCFHAVKKAM 190
Cdd:cd17657   86 AAFLIGAYAVIYLGKTPEEAYRPLESGEPPFLPFRDASYGPCTYELTVLDCLKGLEKAL 144

dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as VH1-like phosphatase Z (VHZ) or low molecular mass dual specificity phosphatase 3 (LDP-3), 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. DUSP23 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 able to enhance activation of JNK and p38 MAPK, and has been shown to dephosphorylate p44-ERK1 (MAPK3) in vitro. It has been associated with cell growth and human primary cancers. It has also been identified as a cell-cell adhesion regulatory protein; it promotes the dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 218 WIIPDRFIAFCGPHSRArlesgyhqhspetYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVK 297
Cdd:cd14504    3 WVIPGKLAGMAFPRLPE-------------HYAYLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQID 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119613064 298 EFLDICENAE---GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIG-PQQQFLV 361
Cdd:cd14504   70 EFLDIVEEANaknEAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETsEQEKFVI 137

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 119613064 216 LNWIIPDRFIAFCGPHSRarlesgyhqhsPETYIQYFKNHNVTTIIRLnkrmydakrftdagfdhhdlffadgstpTDAI 295
Cdd:cd14494    1 FNWIDPLRLIAGALPLSP-----------LEADSRFLKQLGVTTIVDL----------------------------TLAM 41

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119613064 296 VKEFLDICENAE---GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSV--IGPQQQFLVM 362
Cdd:cd14494   42 VDRFLEVLDQAEkpgEPVLVHCKAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGIpqTIEQLDFLIK 113

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 248 YIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENA---EGAIAVHCKAGLGRTGTL 324
Cdd:PTZ00393 108 YIKEMKNYNVTDLVRTCERTYNDGEITSAGINVHELIFPDGDAPTVDIVSNWLTIVNNViknNRAVAVHCVAGLGRAPVL 187

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 119613064 325 IACYIMKhYRMTAAETIAWVRICRPGSVIGPQQQFL 360
Cdd:PTZ00393 188 ASIVLIE-FGMDPIDAIVFIRDRRKGAINKRQLQFL 222

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 119613064 246 ETY--IQYFKNHNVTTIIRLNKR----------------MYDAKRFTDAGFDHHDLFFADGSTPTDAIVkefLDICENA- 306
Cdd:cd14506   27 DKYgiIEQFKEKGIKTVINLQEPgehascgpglepesgfSYLPEAFMRAGIYFYNFGWKDYGVPSLTTI---LDIVKVMa 103

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119613064 307 -----EGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSV--------IGPQQQFL 360
Cdd:cd14506  104 falqeGGKVAVHCHAGLGRTGVLIACYLVYALRMSADQAIRLVRSKRPNSIqtrgqvlcVREFAQFL 170

Dual specificity phosphatase, catalytic domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064   253 KNHNVTTIIRL--NKRMYDAKRFTDAGFDHHDlFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIM 330
Cdd:smart00195  23 KKLGITHVINVtnEVPNYNGSDFTYLGVPIDD-NTETKISPYFPEAVEFIEDAESKGGKVLVHCQAGVSRSATLIIAYLM 101

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 119613064   331 KHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQTNLW 368
Cdd:smart00195 102 KTRNMSLNDAYDFVKDRRPI--ISPNFGF--LRQLIEY 135

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 119613064 289 STPTDAIVKE---FLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQ 358
Cdd:cd14524   68 GVPSLEDLEKgvdFILKHREKGKSVYVHCKAGRGRSATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLSQR 140

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 119613064 219 IIPDRFIAfcgphSRARLESGYHQH-------SPETYIQYFKNH-NVTTIIRLNK--RMYDAKRFTDAGFDHHDLFFADG 288
Cdd:cd14502   12 VGPTRFIP-----MKTPLSDDYEHLfapeirfTPSALAEKFRQDrKVGLVIDLTNtdRYYDPNDLDDDGYVYYKKVCVRK 86

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119613064 289 STPTDAIVKEFLDIC------ENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRP 349
Cdd:cd14502   87 EPPDAEEVNKFIELVdkflaeDNPDKLIAVHCTHGFNRTGFMIVSYLVERLGLTVEQALEAFAQARP 153

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 119613064 243 HSP-----ETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDI-----CENAEGAIAV 312
Cdd:cd18535   19 HNPtnatlSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLlktkfCEDPGCCVAV 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 119613064 313 HCKAGLGRTGTLIACYIMKHyRMTAAETIAWVRICRPGSVIGPQQQFL 360
Cdd:cd18535   99 HCVAGLGRAPVLVALALIES-GMKYEDAIQFIRQKRRGAINSKQLTYL 145

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 216 LNWIIPD-RFIAFCGPhsrarLESGYHQHSPETyiQYF-----------KNHNVTTIIRLN--KRMYDAKRFTDAGFDHH 281
Cdd:cd17665    8 VGQRIPGtRFIAFKVP-----LRKSFFANLPPE--QRFtpkdlveqvekRGEKLGLVIDLTntTRYYDPRDLTNHGVYYK 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 119613064 282 DLFFADGSTPTDA-------IVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIM 330
Cdd:cd17665   81 KITCPGHQVPDDKtiqsfkdAVKDFLEKNKDNDKLIGVHCTHGLNRTGYLICRYLI 136

Protein tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 287 DGSTPTDAIVKEFLD-ICENA------EGAIAVHCKAGLGRTGTLIACYIM-------KHYRMTAAETIAWVRICRPGSV 352
Cdd:COG5599  179 DHGAISAEALKNLADlIDKKEkikdpdKLLPVVHCRAGVGRTGTLIACLALsksinalVQITLSVEEIVIDMRTSRNGGM 258

                         90
                 ....*....|.
gi 119613064 353 IGPQQQFLVMK 363
Cdd:COG5599  259 VQTSEQLDVLV 269

N-terminal triphosphatase domain of mRNA capping enzyme; mRNA capping enzyme, also known as RNA guanylyltransferase and 5'-phosphatase (RNGTT) or mammalian mRNA capping enzyme (Mce1) in mammals, is a bifunctional enzyme that catalyzes the first two steps of cap formation: (1) by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end using the polynucleotide 5'-phosphatase activity (EC 3.1.3.33) of the N-terminal triphosphatase domain; and (2) by transferring the GMP moiety of GTP to the 5'-diphosphate terminus through the C-terminal mRNA guanylyltransferase domain (EC 2.7.7.50). The enzyme is also referred to as CEL-1 in Caenorhabditis elegans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 220 IPDRFIAFCGPhsrarLESGYHQHSPETYI-------QYFKNHNVTT--IIRLNK--RMYDAKRFTDAGFDHHDLFFA-D 287
Cdd:cd17664   12 VAGKFLPFKTP-----LGPRYDDQVPEENRfhpsmlfNYLKSLKVKLglWIDLTNtnRFYDRNEVEKEGCKYIKLQCKgH 86

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119613064 288 GSTPTDAIVKEFLDICE-----NAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRP 349
Cdd:cd17664   87 GECPSPEQTETFIRLCEnfiekNPLELIGVHCTHGFNRTGFLICAYLVEKMDWSVEAAVATFAQARP 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 119613064 287 DGSTPTD-----AIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHyRMTA------AETIAWVRICRPGSV 352
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 119613064 298 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 360
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 119613064 308 GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQF 359
Cdd:cd14573   80 GRTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRP--IIRPNNGF 129

dual specificity protein phosphatase 14; dual specificity protein phosphatase 14 (DUSP14), also called mitogen-activated protein kinase (MAPK) phosphatase 6 (MKP-6) or MKP-1-like protein tyrosine phosphatase (MKP-L), 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. DUSP14 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. DUSP14 dephosphorylates JNK, ERK, and p38 in vitro. It also 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 119613064 308 GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQF 359
Cdd:cd14572   86 GATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRP--VIRPNVGF 135

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 119613064 298 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 360
Cdd:cd14567   71 EFIEEAHQSGKGVLVHCQAGVSRSATIVIAYLMKHTRMTMTDAYKFVKNKRP--IISPNLNFM 131

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 119613064 308 GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsvIGPQQQFL 360
Cdd:cd14515   89 GKVLVHCVEGVSRSATLVLAYLMIYQNMTLEEAIRTVRKKRE---IRPNRGFL 138

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119613064   296 VKEFLDICENaEGAIAVHCKAGLGRTGTLIACYIM------KHYRMTAAETIAWVRICRPGSV 352
Cdd:smart00012  29 VKKNLNQSES-SGPVVVHCSAGVGRTGTFVAIDILlqqleaEAGEVDIFDTVKELRSQRPGMV 90

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 119613064 298 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRpgSVIGPQQQFL 360
Cdd:cd14640   69 EYIDSVKDCNGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRR--SIISPNFSFM 129

dual specificity phosphatase domain of dual specificity protein phosphatase 1; Dual specificity protein phosphatase 1 (DUSP1), also called mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1), 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. Human MKP-1 dephosphorylates MAPK1/ERK2, regulating its activity during the meiotic cell cycle. Although initially MKP-1 was considered to be ERK-specific, it has been shown that MKP-1 also dephosphorylates both JNK and p38 MAPKs. DUSP1/MKP-1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. It is a central regulator of a variety of functions in the immune, metabolic, cardiovascular, and nervous systems. It 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 119613064 298 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRpgSVIGPQQQFL 360
Cdd:cd14638   69 DFIDSVKNAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRR--SIISPNFSFM 129

Protein tyrosine phosphatase-like domains of phytases and similar domains; This subfamily contains the tandem protein tyrosine phosphatase (PTP)-like domains of protein tyrosine phosphatase-like phytases (PTPLPs) and similar domains including the PTP domain of Pseudomonas syringae tyrosine-protein phosphatase hopPtoD2. PTPLPs, also known as cysteine phytases, are one of four known classes of phytases, enzymes that degrade phytate (inositol hexakisphosphate [InsP(6)]) to less-phosphorylated myo-inositol derivatives. Phytate is the most abundant cellular inositol phosphate and plays important roles in a broad scope of cellular processes, including DNA repair, RNA processing and export, development, apoptosis, and pathogenicity. PTPLPs adopt a PTP fold, including the active-site signature sequence (CX5R(S/T)) and utilize a classical PTP reaction mechanism. However, these enzymes display no catalytic activity against classical PTP substrates due to several unique structural features that confer specificity for myo-inositol polyphosphates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119613064 276 AGFDHHDLFFADGSTPTDAIVKEFLDICEN--AEGAIAVHCKAGLGRTGTLIACY-IMKHYRMTAAETIawvrICRPGSv 352
Cdd:cd14495  153 KGAHYVRIAATDHVWPDDEEIDAFVAFYRSlpADAWLHFHCRAGKGRTTTFMVMYdMLKNPKDVSFDDI----IARQYL- 227

                         90       100
                 ....*....|....*....|....*..
gi 119613064 353 IGPQQQFLVMKQTNLWLeGDYFRQKLK 379
Cdd:cd14495  228 IGGNYLAYEVDKDKNWK-RPYYEERAQ 253

dual specificity phosphatase domain of dual specificity protein phosphatase 19; Dual specificity protein phosphatase 19 (DUSP19), also called low molecular weight dual specificity phosphatase 3 (LMW-DSP3) or stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It 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. DUSP19 interacts with the MAPK kinase MKK7, a JNK activator, and inactivates the JNK MAPK pathway.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119613064 298 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQ 364
Cdd:cd14523   70 EFIDEAKSQDGVVLVHCNAGVSRSASIVIGYLMATENLSFEDAFSLVKNARPS--IRPNPGF--MEQ 132

dual specificity phosphatase domain of dual specificity protein phosphatase 12 and similar proteins; Dual specificity protein phosphatase 12 (DUSP12), also called YVH1, 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. DUSP12 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 targets p38 MAPK to regulate macrophage response to bacterial infection. It also ameliorates cardiac hypertrophy in response to pressure overload through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 has been identified as a modulator of cell cycle progression, a function independent of phosphatase activity and mediated by its C-terminal zinc-binding domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 119613064 306 AEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQ 364
Cdd:cd14520   78 AEGAVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPD--VKPNDGF--LKQ 132

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119613064 293 DAIvkEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFL 360
Cdd:cd14566   68 EAI--SFIDEARSKKCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSN--ISPNFNFM 131

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119613064 298 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 360
Cdd:cd14646   72 DFIEKAKASNGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRP--TISPNFNFL 132