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 1907093534 199 SFNLDEYEHYEKAENGDFNWIIPERFLAFCGPHSRSRLESGYHQHSPETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGF 278
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 279 DHHDLFFPDGSTPAESIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQ 358
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1907093534 359 FLVMKQSSLWLEGD 372
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 1907093534 199 SFNLDEYEHYEKAENGDFNWIIPERFLAFCGPHSRSRLESGYHQHSPETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGF 278
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 279 DHHDLFFPDGSTPAESIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQ 358
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1907093534 359 FLVMKQSSLWLEGD 372
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 1907093534  52 ITDRLCFAILYSRPKSATNEHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIIHFTGTDQRKQAN 131
Cdd:pfam14671   3 IPDRLYFATLKSKPKNTPNYHYFSIDDELVYEPFYFDFGPLNLAHLYRFCIKLNKKLKSPELKKKKIVHYTSQDKQKRAN 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907093534 132 AAFLVGCYMVIYLGRTPEDAYRTLIFGDTAYIPFRDAAYGSCSFYITLLDCFHAVKKA 189
Cdd:pfam14671  83 AAFLIGAYMVLYLNMSPEEALSPLSSISPPFIPFRDASYGPCTYTLTLLDCLKGLEKA 140

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 245 PETYIPYFKNHNVTTIIRLN-KRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLD-ICENVK--GAIAVHCKAGLGR 320
Cdd:COG2453    14 PGGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGR 93

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907093534 321 TGTLIGCYLMKHyRMTAAESIAWLRICRPGSVIGPQQQ 358
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 1907093534 294 SIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGsvIGPQQQFlvMKQSSLW 368
Cdd:pfam00782  56 EEAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPG--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 1907093534 199 SFNLDEYEHYEKAENGDFNWIIPERFLAFCGPHSRSRLESGYHQHSPETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGF 278
Cdd:cd14499     1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 279 DHHDLFFPDGSTPAESIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQ 358
Cdd:cd14499    81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                         170
                  ....*....|....
gi 1907093534 359 FLVMKQSSLWLEGD 372
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 1907093534  52 ITDRLCFAILYSRPKSATNEHYFSIDNELEYENFYADFGPLNLAMVYRYCCKINKKLKSITMLRKKIIHFTGTDQRKQAN 131
Cdd:pfam14671   3 IPDRLYFATLKSKPKNTPNYHYFSIDDELVYEPFYFDFGPLNLAHLYRFCIKLNKKLKSPELKKKKIVHYTSQDKQKRAN 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907093534 132 AAFLVGCYMVIYLGRTPEDAYRTLIFGDTAYIPFRDAAYGSCSFYITLLDCFHAVKKA 189
Cdd:pfam14671  83 AAFLIGAYMVLYLNMSPEEALSPLSSISPPFIPFRDASYGPCTYTLTLLDCLKGLEKA 140

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 1907093534 216 FNWIIPERFLAFCGPHSRSRLEsgyhqhspetyipYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESI 295
Cdd:cd14504     1 FSWVIPGKLAGMAFPRLPEHYA-------------YLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQ 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 296 VQEFLDICE--NVKG-AIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIG-PQQQFLV 361
Cdd:cd14504    68 IDEFLDIVEeaNAKNeAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETsEQEKFVI 137

protein tyrosine phosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 248 YIPYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLDICENV---KGAIAVHCKAGLGRTGTL 324
Cdd:PTZ00393  108 YIKEMKNYNVTDLVRTCERTYNDGEITSAGINVHELIFPDGDAPTVDIVSNWLTIVNNViknNRAVAVHCVAGLGRAPVL 187

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1907093534 325 IGCYLMKhYRMTAAESIAWLRICRPGSVIGPQQQFL 360
Cdd:PTZ00393  188 ASIVLIE-FGMDPIDAIVFIRDRRKGAINKRQLQFL 222

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 245 PETYIPYFKNHNVTTIIRLN-KRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLD-ICENVK--GAIAVHCKAGLGR 320
Cdd:COG2453    14 PGGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGR 93

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907093534 321 TGTLIGCYLMKHyRMTAAESIAWLRICRPGSVIGPQQQ 358
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 1907093534 251 YFKNHNVTTIIRLNKR----MYDA----KRFTDAGFDHHDLFFPDGSTPaeSIVQEFLDICENVKGA------IAVHCKA 316
Cdd:cd14505    38 ELKDQGVDDVVTLCTDgeleELGVpdllEQYQQAGITWHHLPIPDGGVP--SDIAQWQELLEELLSAlengkkVLIHCKG 115

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1907093534 317 GLGRTGTLIGCYLM-KHYRMTAAESIAWLRICRPGSVIGP-QQQFL 360
Cdd:cd14505   116 GLGRTGLIAACLLLeLGDTLDPEQAIAAVRALRPGAIQTPkQENFL 161

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 1907093534 252 FKNHNVTTIIRLNKrmYDAKRFTDAGFDHHDLFFPDGSTpaESIVQEF-----------------LDICENVKGAIAVHC 314
Cdd:cd14518    22 LKAENITHILSVIP--GDVPEEYFKGYEHKQIEIDDVED--ENILQHFpetnrfidsalfgngkdEDEEKKHGGAVLVHC 97

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907093534 315 KAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPgsVIGPQQQFlvMKQSSLWLE 370
Cdd:cd14518    98 AMGKSRSVTVVIAYLMYKYNLSVSQALHAVRRKRP--IAEPNDGF--MEQLELYHE 149

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 1907093534 294 SIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGsvIGPQQQFlvMKQSSLW 368
Cdd:pfam00782  56 EEAVEFIDDARQKGGKVLVHCQAGISRSATLIIAYLMKTRNLSLNEAYSFVKERRPG--ISPNFGF--KRQLLEY 126

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 1907093534 243 HSP-----ETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLDI-----CENVKGAIAV 312
Cdd:cd18535    19 HNPtnatlSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLlktkfCEDPGCCVAV 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907093534 313 HCKAGLGRTGTLIGCYLMKHyRMTAAESIAWLRICRPGSVIGPQQQFL 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 1907093534 217 NWIIPE-RFLAFCGPhsrsrLESGYHQHSPETYIpyF-----------KNHNVTTIIRLN--KRMYDAKRFTDAGFDHHD 282
Cdd:cd17665     9 GQRIPGtRFIAFKVP-----LRKSFFANLPPEQR--FtpkdlveqvekRGEKLGLVIDLTntTRYYDPRDLTNHGVYYKK 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907093534 283 LFFPDGSTPAESIVQEFLDI-------CENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESI 341
Cdd:cd17665    82 ITCPGHQVPDDKTIQSFKDAvkdflekNKDNDKLIGVHCTHGLNRTGYLICRYLIDVDGMSPDDAI 147

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 1907093534 286 PDGSTPAEsiVQEFLDICENVK-------GAIAVHCKAGLGRTGTLIG-CYLMKHYRMTAAESIAW----LRICRPGSV 352
Cdd:cd00047   113 PDHGVPSS--PEDLLALVRRVRkearkpnGPIVVHCSAGVGRTGTFIAiDILLERLEAEGEVDVFEivkaLRKQRPGMV 189

Protein tyrosine phosphatase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 286 PDGSTPAESIVQEFLD-------ICENVKGAIAVHCKAGLGRTGTLIGCY-LMKH------YRMTAAESIAWLRICRPGS 351
Cdd:COG5599   178 PDHGAISAEALKNLADlidkkekIKDPDKLLPVVHCRAGVGRTGTLIACLaLSKSinalvqITLSVEEIVIDMRTSRNGG 257

                          90
                  ....*....|..
gi 1907093534 352 VIGPQQQFLVMK 363
Cdd:COG5599   258 MVQTSEQLDVLV 269

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 1907093534  92 LNLAMVYRYCCKINKKLKsitmLRKKIIHFTgtdQRKQANAAFLVGCYMVIYLGRTPEDAYRTLIFGDTAYIPfrdaayg 171
Cdd:cd14494    37 LTLAMVDRFLEVLDQAEK----PGEPVLVHC---KAGVGRTGTLVACYLVLLGGMSAEEAVRIVRLIRPGGIP------- 102

                          90
                  ....*....|...
gi 1907093534 172 scsFYITLLDCFH 184
Cdd:cd14494   103 ---QTIEQLDFLI 112

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 1907093534 259 TIIRLNKRMYDAKRFTDAGFDHHDlfFPDGSTPAESIVQEFLDICE--------NVkgaIAVHCKAGLGRTGTLIGCYLM 330
Cdd:cd14497    44 MIFNLSEEEYDDDSKFEGRVLHYG--FPDHHPPPLGLLLEIVDDIDswlsedpnNV---AVVHCKAGKGRTGTVICAYLL 118

                  .
gi 1907093534 331 K 331
Cdd:cd14497   119 Y 119

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 242 QHSPETYIPYFKNHNVTTIIRL-NKRMYDAKRF---TDAGFDHHDLFFPDGStPAESIVQEFLDICE--NVKGAIAVHCK 315
Cdd:cd14529    19 QLSPDEDRALLKKLGIKTVIDLrGADERAASEEaaaKIDGVKYVNLPLSATR-PTESDVQSFLLIMDlkLAPGPVLIHCK 97

                          90
                  ....*....|....*
gi 1907093534 316 AGLGRTGTLIGCYLM 330
Cdd:cd14529    98 HGKDRTGLVSALYRI 112

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534  280 HHDLFFPDGSTPAESI-VQEFLDICENV------KGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRIC----- 347
Cdd:smart00012   5 YHYTGWPDHGVPESPDsILELLRAVKKNlnqsesSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDIFDTVkelrs 84

                   ....*.
gi 1907093534  348 -RPGSV 352
Cdd:smart00012  85 qRPGMV 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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907093534 277 GFDHHDLFFPDgsTPAESIVQEF---LDICENVK---GAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRP 349
Cdd:cd14514    43 GIEYLRVPVED--SPHADLSPHFdevADKIHQVKrrgGRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARP 119

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 1907093534 252 FKNHnvTTIIRL-NKRMYDAKRFtdagfdHHDL---FFPDGSTPAesiVQEFLDICENVKG--------AIAVHCKAGLG 319
Cdd:cd14510    52 HPDH--YKVYNLcSERGYDPKYF------HNRVervPIDDHNVPT---LDEMLSFTAEVREwmaadpknVVAIHCKGGKG 120

                          90
                  ....*....|.
gi 1907093534 320 RTGTLIGCYLM 330
Cdd:cd14510   121 RTGTMVCAWLI 131

catalytic domain of receptor-type tyrosine-protein phosphatase R; Receptor-type tyrosine-protein phosphatase-like R (PTPRR or R-PTP-R), also called protein-tyrosine phosphatase PCPTP1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRR is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. The human and mouse PTPRR gene produces multiple neuronal protein isoforms of varying sizes (in human, PTPPBS-alpha, beta, gamma and delta). All isoforms contain the KIM motif and the catalytic PTP domain. PTPRR-deficient mice show significant defects in fine motor coordination and balance skills that are reminiscent of a mild ataxia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907093534 285 FPDGSTP--AESIVQEFLDICEN-----VKGAIAVHCKAGLGRTG----TLIGCYLMKHYRMTAAESIA-WLRICRPGSV 352
Cdd:cd14611   136 WPDHKTPdsAQPLLQLMLDVEEDrlaspGRGPVVVHCSAGIGRTGcfiaTTIGCQQLKEEGVVDVLSIVcQLRVDRGGMV 215

                  ....*
gi 1907093534 353 IGPQQ 357
Cdd:cd14611   216 QTSEQ 220

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 1907093534 298 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPgsVIGPQQQFL 360
Cdd:cd14568    70 EFIEKARASNKRVLVHCLAGISRSATIAIAYIMKHMRMSLDDAYRFVKEKRP--TISPNFNFL 130

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 1907093534 298 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGP 355
Cdd:cd18534    64 DFIEQCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSP 121

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 1907093534 298 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRpgSVIGPQQQFL 360
Cdd:cd14640    69 EYIDSVKDCNGRVLVHCQAGISRSATICLAYLMMKKRVRLEEAFEFVKQRR--SIISPNFSFM 129

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907093534 302 ICENVK-GAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGsvIGPQQQFlvMKQ 364
Cdd:cd14520    73 IDEGRAeGAVLVHCHAGVSRSAAVVTAYLMKTEQLSFEEALASLRECKPD--VKPNDGF--LKQ 132

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 1907093534 298 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRpgSVIGPQQQFL 360
Cdd:cd14638    69 DFIDSVKNAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRR--SIISPNFSFM 129

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907093534 285 FPDGSTP----AESIVQeFLDICEN----VKGAIAVHCKAGLGRTGTLIGC-YLMKHYR 334
Cdd:cd14614   150 WPDHGVPtanaAESILQ-FVQMVRQqavkSKGPMIIHCSAGVGRTGTFIALdRLLQHIR 207

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907093534 261 IRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLDICENV--KGAIAVHCKAGLGRT--GTLIGCyLMK 331
Cdd:pfam14566  84 VQTPEEVYERLKAEGPGVDYRRIPITDEKAPLEEDFDALISIVKDApeDTALVFNCQMGRGRTttAMVIAD-LVR 157