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 1907150416 178 TFDAEEYEHYERVENGDFNWIVPGKFLAFSGPHPKSKIENGYPLHAPEAYFPYFKKNNVTTIVRLNKKIYEAKRFTDAGF 257
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 258 EHYDLFFIDGSTPSDNIVRRFLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGPQQH 337
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1907150416 338 FLKEKQASLWVQGD 351
Cdd:cd14499   161 FLEEKEARLWRAGD 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 1907150416 178 TFDAEEYEHYERVENGDFNWIVPGKFLAFSGPHPKSKIENGYPLHAPEAYFPYFKKNNVTTIVRLNKKIYEAKRFTDAGF 257
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 258 EHYDLFFIDGSTPSDNIVRRFLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGPQQH 337
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1907150416 338 FLKEKQASLWVQGD 351
Cdd:cd14499   161 FLEEKEARLWRAGD 174

Dual specificity protein phosphatase, N-terminal half; The active core of the dual specificity protein phosphatase is made up of two globular domains both with the DSP-like fold. This family represents the N-terminal half of the core. These domains are arranged in tandem, and are associated via an extensive interface to form a single globular whole. The conserved PTP signature motif (Cys-[X]5-Arg) that defines the catalytic centre of all PTP-family members is located within the C-terminal domain, family DSPc, pfam00782. Although the centre of the catalytic site is formed from DSPc, two loops from the N-terminal domain, DSPn, also contribute to the catalytic site, facilitating peptide substrate specificity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416  13 EFMKDRLYFATLRNRPKSTINIHYFSIDEELVYENFYADFGPLNLAMVYRYCCKLNkklkpkkmfknvpflRKLESYSLS 92
Cdd:pfam14671   1 EIIPDRLYFATLKSKPKNTPNYHYFSIDDELVYEPFYFDFGPLNLAHLYRFCIKLN---------------KKLKSPELK 65

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907150416  93 RKKIVHYTSFDQRKRANAAFLIGAYAVIYLKKTPEEAYRALLSGsNPPYLPFRDASFGNCTYNLTVLDCLQGIRKG 168
Cdd:pfam14671  66 KKKIVHYTSQDKQKRANAAFLIGAYMVLYLNMSPEEALSPLSSI-SPPFIPFRDASYGPCTYTLTLLDCLKGLEKA 140

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 197 WIVPGKFlaFSGPHPKSKIEngyplhapeayfpYFKKNNVTTIVRLN-KKIYEAKRFTDAGFEHYDLFFIDGSTPSDNIV 275
Cdd:COG2453     2 WIIPGLL--AGGPLPGGGEA-------------DLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQL 66

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 276 RRFLN-ICENTE--GAIAVHCKAGLGRTGTLIACYVMKHyRFTHAEIIAWIRICRPGSIIGPQQH-FLKE 341
Cdd:COG2453    67 QEAVDfIDEALRegKKVLVHCRGGIGRTGTVAAAYLVLL-GLSAEEALARVRAARPGAVETPAQRaFLER 135

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907150416 273 NIVRRFLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGsiIGPQQHFLKE 341
Cdd:pfam00782  56 EEAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPG--ISPNFGFKRQ 122

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 1907150416 178 TFDAEEYEHYERVENGDFNWIVPGKFLAFSGPHPKSKIENGYPLHAPEAYFPYFKKNNVTTIVRLNKKIYEAKRFTDAGF 257
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 258 EHYDLFFIDGSTPSDNIVRRFLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGPQQH 337
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1907150416 338 FLKEKQASLWVQGD 351
Cdd:cd14499   161 FLEEKEARLWRAGD 174

Dual specificity protein phosphatase, N-terminal half; The active core of the dual specificity protein phosphatase is made up of two globular domains both with the DSP-like fold. This family represents the N-terminal half of the core. These domains are arranged in tandem, and are associated via an extensive interface to form a single globular whole. The conserved PTP signature motif (Cys-[X]5-Arg) that defines the catalytic centre of all PTP-family members is located within the C-terminal domain, family DSPc, pfam00782. Although the centre of the catalytic site is formed from DSPc, two loops from the N-terminal domain, DSPn, also contribute to the catalytic site, facilitating peptide substrate specificity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416  13 EFMKDRLYFATLRNRPKSTINIHYFSIDEELVYENFYADFGPLNLAMVYRYCCKLNkklkpkkmfknvpflRKLESYSLS 92
Cdd:pfam14671   1 EIIPDRLYFATLKSKPKNTPNYHYFSIDDELVYEPFYFDFGPLNLAHLYRFCIKLN---------------KKLKSPELK 65

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907150416  93 RKKIVHYTSFDQRKRANAAFLIGAYAVIYLKKTPEEAYRALLSGsNPPYLPFRDASFGNCTYNLTVLDCLQGIRKG 168
Cdd:pfam14671  66 KKKIVHYTSQDKQKRANAAFLIGAYMVLYLNMSPEEALSPLSSI-SPPFIPFRDASYGPCTYTLTLLDCLKGLEKA 140

protein tyrosine phosphatase type IVA family; Protein tyrosine phosphatases type IVA (PTP-IVa), also known as protein-tyrosine phosphatases of regenerating liver (PRLs) constitute a family of small, prenylated phosphatases that are the most oncogenic of all PTPs. They stimulate progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. They associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation. Vertebrates contain three members: PRL-1, PRL-2, and PRL-3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 221 LHAP-----EAYFPYFKKNNVTTIVRLNKKIYEAKRFTDAGFEHYDLFFIDGSTPSDNIVRRFLNICENT-------EGA 288
Cdd:cd14500    18 TDAPtdsnlPLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDWLDLLKTRfkeegkpGAC 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907150416 289 IAVHCKAGLGRTGTLIACYVMKhYRFTHAEIIAWIRICRPGSIIGPQQHFLKE 341
Cdd:cd14500    98 IAVHCVAGLGRAPVLVAIALIE-LGMKPEDAVEFIRKKRRGAINSKQLQFLEK 149

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 202 KFLAFSGPHPKSkiengypLHApeaYFPYFKKNNVTTIVRLNKKIYEAKRFTDAGFEHYDLFFIDGSTPSDNIVRRFLNI 281
Cdd:PTZ00242   17 KFLILDAPSPSN-------LPL---YIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRL 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907150416 282 CENT-------EGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGPQQHFLKE 341
Cdd:PTZ00242   87 LDQEfakqstpPETIAVHCVAGLGRAPILVALALVEYGGMEPLDAVGFVREKRKGAINQTQLQFLKK 153

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 197 WIVPGKFlaFSGPHPKSKIEngyplhapeayfpYFKKNNVTTIVRLN-KKIYEAKRFTDAGFEHYDLFFIDGSTPSDNIV 275
Cdd:COG2453     2 WIIPGLL--AGGPLPGGGEA-------------DLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQL 66

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 276 RRFLN-ICENTE--GAIAVHCKAGLGRTGTLIACYVMKHyRFTHAEIIAWIRICRPGSIIGPQQH-FLKE 341
Cdd:COG2453    67 QEAVDfIDEALRegKKVLVHCRGGIGRTGTVAAAYLVLL-GLSAEEALARVRAARPGAVETPAQRaFLER 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 232 KKNNVTTIVRLNKKiYEAKRF-------TDAGFEHYDLFFID-GSTPSDNIVRR---FLNICENTEGAIAVHCKAGLGRT 300
Cdd:cd14524    25 AKENVRGVITMNEE-YETRFFcnskeewKALGVEQLRLPTVDfTGVPSLEDLEKgvdFILKHREKGKSVYVHCKAGRGRS 103

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1907150416 301 GTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGP-QQHFLKE 341
Cdd:cd14524   104 ATIVACYLIQHKGWSPEEAQEFLRSKRPHILLRLsQREVLEE 145

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 1907150416 229 PYFKKNNVTTIVRLNKKIYEAKRftDAGFEHYDLFFIDgsTPSDNIVR------RFLNICENTEGAIAVHCKAGLGRTGT 302
Cdd:cd14498    20 ELLKKLGITHILNVAGEPPPNKF--PDGIKYLRIPIED--SPDEDILShfeeaiEFIEEALKKGGKVLVHCQAGVSRSAT 95

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907150416 303 LIACYVMKHYRFTHAEIIAWIRICRPgsIIGPQQHFLK 340
Cdd:cd14498    96 IVIAYLMKKYGWSLEEALELVKSRRP--IISPNPGFLK 131

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907150416 273 NIVRRFLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGsiIGPQQHFLKE 341
Cdd:pfam00782  56 EEAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPG--ISPNFGFKRQ 122

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 1907150416 198 IVPGKFLAFSGP--HPKSKIENGYPLHAPEAYFPYFKK-NNVTTIVRLNK--KIYEAKRFTDAGFEHYDLFFIDGSTPSD 272
Cdd:cd14502    12 VGPTRFIPMKTPlsDDYEHLFAPEIRFTPSALAEKFRQdRKVGLVIDLTNtdRYYDPNDLDDDGYVYYKKVCVRKEPPDA 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907150416 273 NIVRRFLNICE------NTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGPqqHFLKE 341
Cdd:cd14502    92 EEVNKFIELVDkflaedNPDKLIAVHCTHGFNRTGFMIVSYLVERLGLTVEQALEAFAQARPPGIYKP--HYIDE 164

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 1907150416 266 DGSTPSD-----NIVRRFLNICENTEGAIAVHCKAGLGRTGTLIA-CYVMKHYRFTH----AEIIAWIRICRPGSIIGPQ 335
Cdd:cd00047   114 DHGVPSSpedllALVRRVRKEARKPNGPIVVHCSAGVGRTGTFIAiDILLERLEAEGevdvFEIVKALRKQRPGMVQTLE 193

                  ..
gi 1907150416 336 QH 337
Cdd:cd00047   194 QY 195

dual specificity phosphatase domain of fungal YVH1-like dual specificity protein phosphatase; This family is composed of Saccharomyces cerevisiae dual specificity protein phosphatase Yvh1 and similar fungal proteins. Yvh1 could function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It regulates cell growth, sporulation, and glycogen accumulation. It plays an important role in ribosome assembly. Yvh1 associates transiently with late pre-60S particles and is required for the release of the nucleolar/nuclear pre-60S factor Mrt4, which is necessary to construct a translation-competent 60S subunit and mature ribosome stalk. Yvh1 contains an N-terminal catalytic dual specificity phosphatase domain and a C-terminal tail.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 231 FKKNNVTTIVRLNKkiYEAKRFTDAGFEHYDLFFIDgsTPSDNIVR------RFLNIC-----------ENTEGAIAVHC 293
Cdd:cd14518    22 LKAENITHILSVIP--GDVPEEYFKGYEHKQIEIDD--VEDENILQhfpetnRFIDSAlfgngkdedeeKKHGGAVLVHC 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907150416 294 KAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPgsIIGPQQHFLkeKQASLW 347
Cdd:cd14518    98 AMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRP--IAEPNDGFM--EQLELY 147

Protein tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 266 DGSTPSDNI-------VRRFLNICENTEGAIAVHCKAGLGRTGTLIACYVM-------KHYRFTHAEIIAWIRICRPGSI 331
Cdd:COG5599   179 DHGAISAEAlknladlIDKKEKIKDPDKLLPVVHCRAGVGRTGTLIACLALsksinalVQITLSVEEIVIDMRTSRNGGM 258

                  .
gi 1907150416 332 I 332
Cdd:COG5599   259 V 259

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 1907150416  273 NIVRRFLNICENTeGAIAVHCKAGLGRTGTLIACYVM------KHYRFTHAEIIAWIRICRPGSI 331
Cdd:smart00012  27 RAVKKNLNQSESS-GPVVVHCSAGVGRTGTFVAIDILlqqleaEAGEVDIFDTVKELRSQRPGMV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 238 TIVRLNKKIYEAKRFTDAGFEHYDlfFIDGSTPSDNIVrrfLNICENTEG--------AIAVHCKAGLGRTGTLIACYVM 309
Cdd:cd14497    44 MIFNLSEEEYDDDSKFEGRVLHYG--FPDHHPPPLGLL---LEIVDDIDSwlsedpnnVAVVHCKAGKGRTGTVICAYLL 118

                  ....*....
gi 1907150416 310 KHYRFTHAE 318
Cdd:cd14497   119 YYGQYSTAD 127

protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; Phosphatase and tensin homolog (PTEN), also phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN or mutated in multiple advanced cancers 1 (MMAC1), is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It is a critical endogenous inhibitor of phosphoinositide signaling. It dephosphorylates phosphoinositide trisphosphate, and therefore, has the function of negatively regulating Akt. The PTEN/PI3K/AKT pathway regulates the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. PTEN contains an N-terminal PIP-binding domain, a protein tyrosine phosphatase (PTP)-like catalytic domain, a regulatory C2 domain responsible for its cellular location, a C-tail containing phosphorylation sites, and a C-terminal PDZ domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907150416 243 NKKIYEAKRFtDAGFEHYDlfFIDGSTPSDNIVRRFLN-----ICENTEGAIAVHCKAGLGRTGTLIACYVM 309
Cdd:cd14509    49 SERSYDPSKF-NGRVAEYP--FDDHNPPPLELIKPFCEdvdewLKEDEKNVAAVHCKAGKGRTGVMICCYLL 117

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 1907150416 287 GAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPgsIIGPQQHFLKE 341
Cdd:cd14572    86 GATLVHCAAGVSRSATLCIAYLMKYHRVSLLEAYNWVKARRP--VIRPNVGFWRQ 138

dual specificity phosphatase domain of slingshot homolog 3; Dual specificity protein phosphatase slingshot homolog 3 (SSH3), also called SSH-like protein 3, is part of the slingshot (SSH) family, whose members specifically dephosphorylate and reactivate Ser-3-phosphorylated cofilin (P-cofilin), an actin-binding protein that plays an essential role in actin filament dynamics. The Xenopus homolog (xSSH) is involved in the gastrulation movement. Mouse SSH3 dephosphorylates actin-depolymerizing factor (ADF) and cofilin but is dispensable for development. There are at least two human SSH3 isoforms reported: hSSH-3L (long) and hSSH-3. As SSH family phosphatases, they 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, hSSH-3L contains a C-terminal tail while hSSH-3 does not.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 226 AYFPYFKKNNVTTIVRLNKKI--YEAKRFTDAGFEHYDLFFIDgSTPSDNIVRRFLNICENTEGAIAVHCKAGLGRTGTL 303
Cdd:cd14571    20 ANLEELQRNRVSHILNVTREIdnFFPERFTYMNIRVYDEEATQ-LLPHWKETHRFIEAARAQGTRVLVHCKMGVSRSAST 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907150416 304 IACYVMKHYRFTHAEIIAWIRICRPgsIIGPQQHFLKEKQ 343
Cdd:cd14571    99 VIAYAMKQYGWTLEQALRHVRERRP--IVQPNPGFLRQLQ 136

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 1907150416 277 RFLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRpgSIIGPQQHFLKE 341
Cdd:cd14513    69 RFIKEARRKGSKVLVHCKMGVSRSASTVIAYAMKEYGWSLEQALEHVKERR--SCIKPNPGFLRQ 131

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 1907150416 223 APEAYFPYFKKNNVTTIVRLNKKIYEAKRF----TDAGFEHYDL-FFIDGSTPSDNIVRRFLNICENTEGAIAVHCKAGL 297
Cdd:cd14529    21 SPDEDRALLKKLGIKTVIDLRGADERAASEeaaaKIDGVKYVNLpLSATRPTESDVQSFLLIMDLKLAPGPVLIHCKHGK 100

                          90
                  ....*....|..
gi 1907150416 298 GRTGTLIACYVM 309
Cdd:cd14529   101 DRTGLVSALYRI 112

dual specificity protein phosphatase 26; Dual specificity protein phosphatase 26 (DUSP26), also called mitogen-activated protein kinase (MAPK) phosphatase 8 (MKP-8) or low-molecular-mass dual-specificity phosphatase 4 (LDP-4), 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. DUSP26 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 a brain phosphatase highly overexpressed in neuroblastoma and has also been identified as a p53 phosphatase, dephosphorylating phospho-Ser20 and phospho-Ser37 in the p53 transactivation domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 247 YEAKRFTDAGFEHYDLFFIDGST---PSDNIVRRFLNiceNTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWI 323
Cdd:cd14578    45 YEGLNIRYLGIEAHDSPAFDMSIhfyPAADFIHRALS---QPGGKILVHCAVGVSRSATLVLAYLMIHHHMTLVEAIKTV 121

                          90
                  ....*....|....*...
gi 1907150416 324 RICRPgsiIGPQQHFLKE 341
Cdd:cd14578   122 KDHRG---IIPNRGFLRQ 136

unknown subfamily of atypical dual-specificity phosphatases from fungi; This uncharacterized subfamily belongs to the plant and fungi atypical dual-specificity phosphatases (PFA-DSPs) group of atypical DSPs that present in plants, fungi, kinetoplastids, and slime molds. They share structural similarity with atypical- and lipid phosphatase DSPs from mammals. The PFA-DSP group is composed of active as well as inactive phosphatases. This unknown subgroup contains the conserved the CxxxxxR catalytic motif present in active cysteine phosphatases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907150416 218 GYPLhaPEAyFPYFKKNNVTTIVRLNKKIY---EAKRFTDAGFEHYDLFfIDG------STPsDNIVRRFLNICENTEG- 287
Cdd:cd18538    17 SFPK--PEN-FGFLKSLGLRTILTLVQEEYspeFLNFLRENGIQHFHIA-MLGnkdpkvSIP-DHTMNRILRIILDKENh 91

                          90       100
                  ....*....|....*....|
gi 1907150416 288 AIAVHCKAGLGRTGTLIACY 307
Cdd:cd18538    92 PILVHCNKGKHRTGCVIACF 111

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 1907150416 278 FLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPgsIIGPQQHFL 339
Cdd:cd14568    71 FIEKARASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRP--TISPNFNFL 130

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 1907150416 286 EGAIAVHCKAGLGRTGTLIACY-VMKHYRFTHA----EIIAWIRICRPGSIIGPQQ-HFL 339
Cdd:cd14554   174 EGPITVHCSAGVGRTGVFITLSiVLERMRYEGVvdvfQTVKLLRTQRPAMVQTEDQyQFC 233

dual specificity phosphatase domain of plant IBR5-like protein phosphatases; This subfamily is composed of Arabidopsis thaliana INDOLE-3-BUTYRIC ACID (IBA) RESPONSE 5 (IBR5) and similar plant proteins. IBR5 protein is also called SKP1-interacting partner 33. The IBR5 gene encodes a dual-specificity phosphatase (DUSP) which acts as a positive regulator of plant responses to auxin and abscisic acid. DUSPs 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. IBR5 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. It has been shown to target MPK12, which is a negative regulator of auxin signaling.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907150416 278 FLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPGSIIGP 334
Cdd:cd18534    65 FIEQCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSP 121

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
                  ....*....|....*....|....*....|....*....|....
gi 1907150416 291 VHCKAGLGRTGTLIACYVMKHYRFTHA--EIIAWIRICRPGSII 332
Cdd:cd14559   173 IHCRAGVGRTGQLAAAMELNKSPNNLSveDIVSDMRTSRNGKMV 216

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 1907150416 278 FLNICENTEGAIAVHCKAGLGRTGTLIACYVMKHYRFTHAEIIAWIRICRPgsIIGPQQHFL 339
Cdd:cd14512    71 FIEEAKASNGGVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRP--TISPNFNFM 130