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 1034671731 162 SFNLDEYEHYEKAENGDLNWIIPDRFIAFCGPHSRARLESGYHQHSPETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGF 241
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 242 DHHDLFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQ 321
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1034671731 322 FLVMKQTNLWLEGD 335
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 1034671731 162 SFNLDEYEHYEKAENGDLNWIIPDRFIAFCGPHSRARLESGYHQHSPETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGF 241
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 242 DHHDLFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQ 321
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1034671731 322 FLVMKQTNLWLEGD 335
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 1034671731  13 EVIKDRLCFAILYSRPKSASNVHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIVHFTGSDQRKQ 92
Cdd:pfam14671   1 EIIPDRLYFATLKSKPKNTPNYHYFSIDDELVYEPFYFDFGPLNLAHLYRFCIKLNKKLKSPELKKKKIVHYTSQDKQKR 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731  93 ANAAFLVGCYMVIYLGRTPEEAYRILIFGETSYIPFRDAAYGSCNFYITLLDCFHAVKKA 152
Cdd:pfam14671  81 ANAAFLIGAYMVLYLNMSPEEALSPLSSISPPFIPFRDASYGPCTYTLTLLDCLKGLEKA 140

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 208 PETYIQYFKNHNVTTIIRLN-KRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLD-ICENAE--GAIAVHCKAGLGR 283
Cdd:COG2453    14 PGGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGR 93

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1034671731 284 TGTLIACYIMKHyRMTAAETIAWVRICRPGSVIGPQQQ 321
Cdd:COG2453    94 TGTVAAAYLVLL-GLSAEEALARVRAARPGAVETPAQR 130

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034671731 258 IVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQTNLW 331
Cdd:pfam00782  57 EAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPG--ISPNFGF--KRQLLEY 126

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 1034671731 162 SFNLDEYEHYEKAENGDLNWIIPDRFIAFCGPHSRARLESGYHQHSPETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGF 241
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 242 DHHDLFFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQ 321
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1034671731 322 FLVMKQTNLWLEGD 335
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 1034671731  13 EVIKDRLCFAILYSRPKSASNVHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIVHFTGSDQRKQ 92
Cdd:pfam14671   1 EIIPDRLYFATLKSKPKNTPNYHYFSIDDELVYEPFYFDFGPLNLAHLYRFCIKLNKKLKSPELKKKKIVHYTSQDKQKR 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731  93 ANAAFLVGCYMVIYLGRTPEEAYRILIFGETSYIPFRDAAYGSCNFYITLLDCFHAVKKA 152
Cdd:pfam14671  81 ANAAFLIGAYMVLYLNMSPEEALSPLSSISPPFIPFRDASYGPCTYTLTLLDCLKGLEKA 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 1034671731 209 ETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENA-------EGAIAVHCKAGL 281
Cdd:cd14500    27 PLYIKELKKYNVTDLVRVCEPTYDKEPLEKAGIKVHDWPFDDGSPPPDDVVDDWLDLLKTRfkeegkpGACIAVHCVAGL 106

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1034671731 282 GRTGTLIACYIMKhYRMTAAETIAWVRICRPGSVIGPQQQFL 323
Cdd:cd14500   107 GRAPVLVAIALIE-LGMKPEDAVEFIRKKRRGAINSKQLQFL 147

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 209 ETYIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDICENA-------EGAIAVHCKAGL 281
Cdd:PTZ00242   30 PLYIKELQRYNVTHLVRVCGPTYDAELLEKNGIEVHDWPFDDGAPPPKAVIDNWLRLLDQEfakqstpPETIAVHCVAGL 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1034671731 282 GRTGTLIACYIMKHYRMTAAETIAWVRICRPGSVIGPQQQFL 323
Cdd:PTZ00242  110 GRAPILVALALVEYGGMEPLDAVGFVREKRKGAINQTQLQFL 151

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 208 PETYIQYFKNHNVTTIIRLN-KRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLD-ICENAE--GAIAVHCKAGLGR 283
Cdd:COG2453    14 PGGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGR 93

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1034671731 284 TGTLIACYIMKHyRMTAAETIAWVRICRPGSVIGPQQQ 321
Cdd:COG2453    94 TGTVAAAYLVLL-GLSAEEALARVRAARPGAVETPAQR 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 1034671731 212 IQYFKNHNVTTIIRLNKR----MYDA----KRFTDAGFDHHDLFFADGSTPTD-----AIVKEFLdICENAEGAIAVHCK 278
Cdd:cd14505    36 LEELKDQGVDDVVTLCTDgeleELGVpdllEQYQQAGITWHHLPIPDGGVPSDiaqwqELLEELL-SALENGKKVLIHCK 114

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1034671731 279 AGLGRTGTLIACY-IMKHYRMTAAETIAWVRICRPGSVIGP-QQQFL 323
Cdd:cd14505   115 GGLGRTGLIAACLlLELGDTLDPEQAIAAVRALRPGAIQTPkQENFL 161

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034671731 258 IVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQTNLW 331
Cdd:pfam00782  57 EAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPG--ISPNFGF--KRQLLEY 126

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 1034671731 182 IIPDRFIAfcgphSRARLESGYHQH-------SPETYIQYFKNH-NVTTIIRLNK--RMYDAKRFTDAGFDHHDLFFADG 251
Cdd:cd14502    12 VGPTRFIP-----MKTPLSDDYEHLfapeirfTPSALAEKFRQDrKVGLVIDLTNtdRYYDPNDLDDDGYVYYKKVCVRK 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034671731 252 STPTDAIVKEFLDIC------ENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRP 312
Cdd:cd14502    87 EPPDAEEVNKFIELVdkflaeDNPDKLIAVHCTHGFNRTGFMIVSYLVERLGLTVEQALEAFAQARP 153

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 1034671731 215 FKNHNVTTIIRLNKrmYDAKRFTDAGFDHHDLFFADgsTPTDAIVKEF-----------------LDICENAEGAIAVHC 277
Cdd:cd14518    22 LKAENITHILSVIP--GDVPEEYFKGYEHKQIEIDD--VEDENILQHFpetnrfidsalfgngkdEDEEKKHGGAVLVHC 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034671731 278 KAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFlvMKQTNLWLE 333
Cdd:cd14518    98 AMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRP--IAEPNDGF--MEQLELYHE 149

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 1034671731  55 LNLAMVYRYCCKINKKLKsitmLRKKIVHFTgsdQRKQANAAFLVGCYMVIYLGRTPEEAYRILIFGETSYIPfrdaayg 134
Cdd:cd14494    37 LTLAMVDRFLEVLDQAEK----PGEPVLVHC---KAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGIP------- 102

                          90
                  ....*....|...
gi 1034671731 135 scnFYITLLDCFH 147
Cdd:cd14494   103 ---QTIEQLDFLI 112

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 1034671731 179 LNWIIPD-RFIAFCGPhsrarLESGYHQHSPETyiQYF-----------KNHNVTTIIRLN--KRMYDAKRFTDAGFDHH 244
Cdd:cd17665     8 VGQRIPGtRFIAFKVP-----LRKSFFANLPPE--QRFtpkdlveqvekRGEKLGLVIDLTntTRYYDPRDLTNHGVYYK 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034671731 245 DLFFADGSTPTDA-------IVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIM 293
Cdd:cd17665    81 KITCPGHQVPDDKtiqsfkdAVKDFLEKNKDNDKLIGVHCTHGLNRTGYLICRYLI 136

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 1034671731 206 HSPET-----YIQYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFADGSTPTDAIVKEFLDIC-----ENAEGAIAV 275
Cdd:cd18536    20 HNPTNatlnkFTEELKKYGVTTLVRVCDATYDKAPVEKEGIQVLDWPFDDGAPPPNQIVDDWLNLLktkfrEEPGCCVAV 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1034671731 276 HCKAGLGRTGTLIACYIMKhYRMTAAETIAWVRICRPGSVIGPQQQFL 323
Cdd:cd18536   100 HCVAGLGRAPVLVALALIE-CGMKYEDAVQFIRQKRRGAFNSKQLLYL 146

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 1034671731 250 DGSTPTD-----AIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHyRMTA------AETIAWVRICRPGSV 315
Cdd:cd00047   114 DHGVPSSpedllALVRRVRKEARKPNGPIVVHCSAGVGRTGTFIAIDILLE-RLEAegevdvFEIVKALRKQRPGMV 189

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 1034671731 214 YFKNHNVTTIIRL-NKRMYDAKRF---TDAGFDHHDL-FFADGSTPTDAIVKEFLDICENAEGAIAVHCKAGLGRTGTLI 288
Cdd:cd14529    28 LLKKLGIKTVIDLrGADERAASEEaaaKIDGVKYVNLpLSATRPTESDVQSFLLIMDLKLAPGPVLIHCKHGKDRTGLVS 107

                          90       100
                  ....*....|....*....|..
gi 1034671731 289 ACY----------IMKHYRMTA 300
Cdd:cd14529   108 ALYrivyggskeeANEDYRLSN 129

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 227 NKRMYDAKRFTD--AGFDhhdlfFADGSTPTDAIVKEFldiCENA--------EGAIAVHCKAGLGRTGTLIACYIM--K 294
Cdd:cd14509    49 SERSYDPSKFNGrvAEYP-----FDDHNPPPLELIKPF---CEDVdewlkedeKNVAAVHCKAGKGRTGVMICCYLLylG 120

                          90
                  ....*....|..
gi 1034671731 295 HYRmTAAETIAW 306
Cdd:cd14509   121 KFP-SAKEALDF 131

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 1034671731 261 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 323
Cdd:cd14512    70 EFIEEAKASNGGVLVHCLAGISRSATIAIAYLMKRMRMSLDEAYDFVKEKRP--TISPNFNFM 130

Protein tyrosine phosphatase, catalytic domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034671731  250 DGSTPTD-----AIVKEFLDICENAEGAIAVHCKAGLGRTGTLIACYIM-----KHYRMTAAETIAWVRICRPGSV 315
Cdd:smart00194 169 DHGVPESpesilDLIRAVRKSQSTSTGPIVVHCSAGVGRTGTFIAIDILlqqleAGKEVDIFEIVKELRSQRPGMV 244

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 1034671731 213 QYFKNHnvTTIIRLNKRMYDAK-----RFTDAGF-DHH----DLFFAdgstptdaIVK---EFLDicENAEGAIAVHCKA 279
Cdd:cd14497    37 THHPDH--YMIFNLSEEEYDDDskfegRVLHYGFpDHHppplGLLLE--------IVDdidSWLS--EDPNNVAVVHCKA 104

                          90
                  ....*....|....*
gi 1034671731 280 GLGRTGTLIACYIMK 294
Cdd:cd14497   105 GKGRTGTVICAYLLY 119

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034671731  259 VKEFLDICENaEGAIAVHCKAGLGRTGTLIACYIM------KHYRMTAAETIAWVRICRPGSV 315
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 1034671731 271 GAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRP 312
Cdd:cd14514    78 GRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARP 119

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 1034671731 261 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRpgSVIGPQQQFL 323
Cdd:cd14640    69 EYIDSVKDCNGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRR--SIISPNFSFM 129

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671731 215 FKNHnvTTIIRL-NKRMYDAKRFtdagfdHHDL---FFADGSTPTdaiVKEFLDICENA--------EGAIAVHCKAGLG 282
Cdd:cd14510    52 HPDH--YKVYNLcSERGYDPKYF------HNRVervPIDDHNVPT---LDEMLSFTAEVrewmaadpKNVVAIHCKGGKG 120

                          90
                  ....*....|.
gi 1034671731 283 RTGTLIACYIM 293
Cdd:cd14510   121 RTGTMVCAWLI 131

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 1034671731 256 DAIvkEFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 323
Cdd:cd14565    66 EAI--GFIDKVKASGGRVLVHCQAGISRSATICLAYLMTTRRVRLNEAFDYVKQRRS--VISPNFNFM 129

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 1034671731 261 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQ 327
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 1034671731 269 AEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPGsvIGPQQQFlvMKQ 327
Cdd:cd14520    78 AEGAVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPD--VKPNDGF--LKQ 132

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 1034671731 261 EFLDICENAEGAIAVHCKAGLGRTGTLIACYIMKHYRMTAAETIAWVRICRPgsVIGPQQQFL 323
Cdd:cd14646    72 DFIEKAKASNGRVLVHCLAGISRSATIAIAYIMKRMDMSLDEAYRFVKEKRP--TISPNFNFL 132