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 568983315  10 SFNLDEYEHYEKAENGDFNWIIPERFLAFCGPHSRSRLESGYHQHSPETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGF 89
Cdd:cd14499    1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  90 DHHDLFFPDGSTPAESIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQ 169
Cdd:cd14499   81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                        170
                 ....*....|....
gi 568983315 170 FLVMKQSSLWLEGD 183
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 568983315  10 SFNLDEYEHYEKAENGDFNWIIPERFLAFCGPHSRSRLESGYHQHSPETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGF 89
Cdd:cd14499    1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  90 DHHDLFFPDGSTPAESIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQ 169
Cdd:cd14499   81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                        170
                 ....*....|....
gi 568983315 170 FLVMKQSSLWLEGD 183
Cdd:cd14499  161 FLEEKEARLWRAGD 174

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  56 PETYIPYFKNHNVTTIIRLN-KRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLD-ICENVK--GAIAVHCKAGLGR 131
Cdd:COG2453   14 PGGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGR 93

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568983315 132 TGTLIGCYLMKHyRMTAAESIAWLRICRPGSVIGPQQQ 169
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 568983315  105 SIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGsvIGPQQQFlvMKQSSLW 179
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 568983315  10 SFNLDEYEHYEKAENGDFNWIIPERFLAFCGPHSRSRLESGYHQHSPETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGF 89
Cdd:cd14499    1 TFDLEEYEHYERVENGDLNWIVPGKFLAFSGPHDTRKDENGYPTHTPEDYIPYFKKLGVTTVVRLNKKLYDAKRFTDAGI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  90 DHHDLFFPDGSTPAESIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQ 169
Cdd:cd14499   81 RHYDLYFPDGSTPSDDIVKKFLDICENEKGAIAVHCKAGLGRTGTLIACYLMKHYGFTAREAIAWLRICRPGSVIGPQQQ 160

                        170
                 ....*....|....
gi 568983315 170 FLVMKQSSLWLEGD 183
Cdd:cd14499  161 FLEEKEARLWRAGD 174

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 568983315  27 FNWIIPERFLAFCGPHSRSRLEsgyhqhspetyipYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESI 106
Cdd:cd14504    1 FSWVIPGKLAGMAFPRLPEHYA-------------YLNENGIRHVVTLTEEPPPEHSDTCPGLRYHHIPIEDYTPPTLEQ 67

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315 107 VQEFLDICE--NVKG-AIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIG-PQQQFLV 172
Cdd:cd14504   68 IDEFLDIVEeaNAKNeAVLVHCLAGKGRTGTMLACYLVKTGKISAVDAINEIRRIRPGSIETsEQEKFVI 137

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  59 YIPYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLDICENV---KGAIAVHCKAGLGRTGTL 135
Cdd:PTZ00393 108 YIKEMKNYNVTDLVRTCERTYNDGEITSAGINVHELIFPDGDAPTVDIVSNWLTIVNNViknNRAVAVHCVAGLGRAPVL 187

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568983315 136 IGCYLMKhYRMTAAESIAWLRICRPGSVIGPQQQFL 171
Cdd:PTZ00393 188 ASIVLIE-FGMDPIDAIVFIRDRRKGAINKRQLQFL 222

Protein-tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  56 PETYIPYFKNHNVTTIIRLN-KRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLD-ICENVK--GAIAVHCKAGLGR 131
Cdd:COG2453   14 PGGGEADLKREGIDAVVSLTeEEELLLGLLEEAGLEYLHLPIPDFGAPDDEQLQEAVDfIDEALRegKKVLVHCRGGIGR 93

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568983315 132 TGTLIGCYLMKHyRMTAAESIAWLRICRPGSVIGPQQQ 169
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 568983315  62 YFKNHNVTTIIRLNKR----MYDA----KRFTDAGFDHHDLFFPDGSTPaeSIVQEFLDICENVKGA------IAVHCKA 127
Cdd:cd14505   38 ELKDQGVDDVVTLCTDgeleELGVpdllEQYQQAGITWHHLPIPDGGVP--SDIAQWQELLEELLSAlengkkVLIHCKG 115

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568983315 128 GLGRTGTLIGCYLM-KHYRMTAAESIAWLRICRPGSVIGP-QQQFL 171
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 568983315  63 FKNHNVTTIIRLNKrmYDAKRFTDAGFDHHDLFFPDGSTpaESIVQEF-----------------LDICENVKGAIAVHC 125
Cdd:cd14518   22 LKAENITHILSVIP--GDVPEEYFKGYEHKQIEIDDVED--ENILQHFpetnrfidsalfgngkdEDEEKKHGGAVLVHC 97

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568983315 126 KAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPgsVIGPQQQFlvMKQSSLWLE 181
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 568983315  105 SIVQEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGsvIGPQQQFlvMKQSSLW 179
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 568983315  54 HSP-----ETYIPYFKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLDI-----CENVKGAIAV 123
Cdd:cd18535   19 HNPtnatlSTFIEDLKKYGATTVVRVCEVTYDKTPLEKDGITVVDWPFDDGAPPPGKVVEDWLSLlktkfCEDPGCCVAV 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 568983315 124 HCKAGLGRTGTLIGCYLMKHyRMTAAESIAWLRICRPGSVIGPQQQFL 171
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 568983315  28 NWIIPE-RFLAFCGPhsrsrLESGYHQHSPETYIpyF-----------KNHNVTTIIRLN--KRMYDAKRFTDAGFDHHD 93
Cdd:cd17665    9 GQRIPGtRFIAFKVP-----LRKSFFANLPPEQR--FtpkdlveqvekRGEKLGLVIDLTntTRYYDPRDLTNHGVYYKK 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568983315  94 LFFPDGSTPAESIVQEFLDI-------CENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESI 152
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 568983315  97 PDGSTPAEsiVQEFLDICENVK-------GAIAVHCKAGLGRTGTLIG-CYLMKHYRMTAAESIAW----LRICRPGSV 163
Cdd:cd00047  113 PDHGVPSS--PEDLLALVRRVRkearkpnGPIVVHCSAGVGRTGTFIAiDILLERLEAEGEVDVFEivkaLRKQRPGMV 189

Protein tyrosine phosphatase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  97 PDGSTPAESIVQEFLD-------ICENVKGAIAVHCKAGLGRTGTLIGCY-LMKH------YRMTAAESIAWLRICRPGS 162
Cdd:COG5599  178 PDHGAISAEALKNLADlidkkekIKDPDKLLPVVHCRAGVGRTGTLIACLaLSKSinalvqITLSVEEIVIDMRTSRNGG 257

                         90
                 ....*....|..
gi 568983315 163 VIGPQQQFLVMK 174
Cdd:COG5599  258 MVQTSEQLDVLV 269

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 568983315  63 FKNHNVTTIIRLNKRMYDAKRFTDAGFDHHDLFFPDGSTPAESIVQEFLDIC-----ENVKGAIAVHCKAGLGRTGTLIG 137
Cdd:cd18536   34 LKKYGVTTLVRVCDATYDKAPVEKEGIQVLDWPFDDGAPPPNQIVDDWLNLLktkfrEEPGCCVAVHCVAGLGRAPVLVA 113

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568983315 138 CYLMKhYRMTAAESIAWLRICRPGSVIGPQQQFL 171
Cdd:cd18536  114 LALIE-CGMKYEDAVQFIRQKRRGAFNSKQLLYL 146

dual specificity protein phosphatases 18 and 21; This subfamily contains dual specificity protein phosphatase 18 (DUSP18), dual specificity protein phosphatase 21 (DUSP21), and similar proteins. They function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48), and are atypical DUSPs. They contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP18, also called low molecular weight dual specificity phosphatase 20 (LMW-DSP20), is a catalytically active phosphatase with a preference for phosphotyrosine over phosphoserine/threonine oligopeptides in vitro. In vivo, it has been shown to interact and dephosphorylate SAPK/JNK, and may play a role in regulating the SAPK/JNK pathway. DUSP21 is also called low molecular weight dual specificity phosphatase 21 (LMW-DSP21). Its gene has been identified as a potential therapeutic target in human hepatocellular carcinoma. DUSP18 and DUSP21 target to opposing sides of the mitochondrial inner membrane.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  97 PDGSTPAESIVQEFLDICENVK------GAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPgsVIGPQQQF 170
Cdd:cd14573   52 PVADSPDTRLRDYFDPIADKIHtveargGRTLLHCVAGVSRSATLCLAYLMKYHAMSLLDAHTWVKSCRP--IIRPNNGF 129

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315    91 HHDLFFPDGSTPAESI-VQEFLDICENV------KGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRIC----- 158
Cdd:smart00404   5 YHYTGWPDHGVPESPDsILELLRAVKKNlnqsesSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGEVDIFDTVkelrs 84

                   ....*.
gi 568983315   159 -RPGSV 163
Cdd:smart00404  85 qRPGMV 90

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 568983315  63 FKNHnvTTIIRL-NKRMYDAKRFtdagfdHHDL---FFPDGSTPAesiVQEFLDICENVKG--------AIAVHCKAGLG 130
Cdd:cd14510   52 HPDH--YKVYNLcSERGYDPKYF------HNRVervPIDDHNVPT---LDEMLSFTAEVREwmaadpknVVAIHCKGGKG 120

                         90
                 ....*....|.
gi 568983315 131 RTGTLIGCYLM 141
Cdd:cd14510  121 RTGTMVCAWLI 131

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 568983315  88 GFDHHDLFFPDgsTPAESIVQEF---LDICENVK---GAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRP 160
Cdd:cd14514   43 GIEYLRVPVED--SPHADLSPHFdevADKIHQVKrrgGRTLVHCVAGVSRSATLCLAYLMKYEGMTLREAYKHVKAARP 119

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 568983315  96 FPDGSTP--AESIVQEFLDICEN-----VKGAIAVHCKAGLGRTG----TLIGCYLMKHYRMTAAESIA-WLRICRPGSV 163
Cdd:cd14611  136 WPDHKTPdsAQPLLQLMLDVEEDrlaspGRGPVVVHCSAGIGRTGcfiaTTIGCQQLKEEGVVDVLSIVcQLRVDRGGMV 215

                 ....*
gi 568983315 164 IGPQQ 168
Cdd:cd14611  216 QTSEQ 220

dual specificity phosphatase-like domain of serine/threonine/tyrosine-interacting protein; Serine/threonine/tyrosine-interacting protein (STYX), also called protein tyrosine phosphatase-like protein, is a catalytically inactive member of the protein tyrosine phosphatase family that plays an integral role in regulating pathways by competing with active phosphatases for binding to MAPKs. It acts as a nuclear anchor for MAPKs, affecting their nucleocytoplasmic shuttling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  30 IIPERFLafcGPHS---RSRLESgyhqhspetyipyFKNHNVTTI--IRLNKRmydaKRFTDAGFDHH--DLFFPDGSTP 102
Cdd:cd14522    8 ILPGLYL---GPYSaamKSKLEV-------------LLKHGITHIvcVRQNIE----ANFIKPNFPDHfrYLVLDVADNP 67

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568983315 103 AESIVQ------EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWL---RICrpgsvIGPQQQFL 171
Cdd:cd14522   68 TENIIRhfptvkEFIDDCLQTGGKVLVHGNAGISRSAALVIAYIMETYGLSYRDAFAYVqqrRFC-----INPNEGFV 140

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 568983315 109 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPgsVIGPQQQFL 171
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 568983315 109 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGP 166
Cdd:cd18534   64 DFIEQCRKDKARVLVHCMSGQSRSPAVVIAYLMKHKGWRLAESYQWVKERRPSINLSP 121

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568983315  90 DHHDlffPDGSTPAESIVQE--FLDICENVKGAIAVHCKAGLGRTG----TLIGC 138
Cdd:cd14547  136 DHKT---PEAAQPLLSLVQEveEARQTEPHRGPIVVHCSAGIGRTGcfiaTSIGC 187

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
                 ....*....|....*....|....*....|....
gi 568983315 119 GAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESI 152
Cdd:cd14578   85 GKILVHCAVGVSRSATLVLAYLMIHHHMTLVEAI 118

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 568983315 109 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRpgSVIGPQQQFL 171
Cdd:cd14638   69 DFIDSVKNAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRR--SIISPNFSFM 129

dual specificity phosphatase domain of class II mitogen-activated protein kinase phosphatase; Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are eukaryotic dual-specificity phosphatases (DUSPs) that act on MAPKs and function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). They deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. Based on sequence homology, subcellular localization and substrate specificity, 10 MKPs can be subdivided into three subfamilies (class I-III). Class II MKPs consist of DUSP6/MKP-3, DUSP7/MKP-X and DUSP9/MKP-4, and are ERK-selective cytoplasmic MKPs. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  90 DH--HDL--FFPdgstpaESIvqEFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGsvIG 165
Cdd:cd14566   56 DHwsQNLsaFFP------EAI--SFIDEARSKKCGVLVHCLAGISRSVTVTVAYLMQKLHLSLNDAYDFVKKRKSN--IS 125

                 ....*.
gi 568983315 166 PQQQFL 171
Cdd:cd14566  126 PNFNFM 131

Protein-tyrosine phosphatase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315   97 PDGSTPAESivQEFLDICENVK--------GAIAVHCKAGLGRTGTLIGCYLMkHYRMTA------AESIAWLRICRPGS 162
Cdd:pfam00102 142 PDHGVPESP--NSLLDLLRKVRkssldgrsGPIVVHCSAGIGRTGTFIAIDIA-LQQLEAegevdiFQIVKELRSQRPGM 218

                          90
                  ....*....|..
gi 568983315  163 VIGPQQ-QFLVM 173
Cdd:pfam00102 219 VQTLEQyIFLYD 230

catalytic domain of tyrosine-protein phosphatase non-receptor type 7; Tyrosine-protein phosphatase non-receptor type 7 (PTPN7), also called hematopoietic protein-tyrosine phosphatase (HePTP) or LC-PTP. belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN7/HePTP 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. PTPN7/HePTP is found exclusively in the white blood cells in bone marrow, thymus, spleen, lymph nodes and all myeloid and lymphoid cell lines. It negatively regulates T-cell activation and proliferation, and is often dysregulated in the preleukemic disorder myelodysplastic syndrome, as well as in acute myelogenous leukemia.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983315  92 HDLF--FPDGSTP--AESIVQEFLDICENVK-----GAIAVHCKAGLGRTG----TLIGCYLMKHyrmTAAESI----AW 154
Cdd:cd14612  146 HYWFssWPDHQTPesAGPLLRLVAEVEESRQtaaspGPIVVHCSAGIGRTGcfiaTSIGCQQLKD---TGKVDIlgivCQ 222

                         90
                 ....*....|....*...
gi 568983315 155 LRICRPGSVIGPQQ-QFL 171
Cdd:cd14612  223 LRLDRGGMIQTSEQyQFL 240

dual specificity phosphatase domain of dual specificity protein phosphatase 5; Dual specificity protein phosphatase 5 (DUSP5) functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other mitogen-activated protein kinase (MAPK) phosphatases (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. DUSP5 preferentially dephosphorylates extracellular signal-regulated kinase (ERK), and is involved in ERK signaling and ERK-dependent inflammatory gene expression in adipocytes. It also plays a role in regulating pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain. DUSP5 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 568983315 108 QEFLDICENVK---GAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRpgSVIGPQQQFL 171
Cdd:cd14639   65 QEAIDFIDCVRragGKVLVHCEAGISRSPTICMAYLMKTKRFRLEEAFDYIKQRR--SLISPNFGFM 129

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568983315 109 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRPGSVIGPQQQFL 171
Cdd:cd14516  107 DFIQKARLLGGKTLVHCRVGVSRSATVVIAEVMKHLRMSLVDAYLFVRVRRLNIIIQPNLRFF 169

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568983315 123 VHCKAGLGRTGTLIGCY-LMKHYRMTAAESI-AWLRICRPGSVIGPQQQFLVMKQ 175
Cdd:cd14559  173 IHCRAGVGRTGQLAAAMeLNKSPNNLSVEDIvSDMRTSRNGKMVQKDEQLDTLKE 227

dual specificity phosphatase domain of dual specificity protein phosphatase 2; Dual specificity protein phosphatase 2 (DUSP2), also called dual specificity protein phosphatase PAC-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 mitogen-activated protein kinase (MAPK) phosphatases (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. DUSP2 can preferentially dephosphorylate ERK1/2 and p38, but not JNK in vitro. It is predominantly expressed in hematopoietic tissues with high T-cell content, such as thymus, spleen, lymph nodes, peripheral blood and other organs such as the brain and liver. It has a critical and positive role in inflammatory responses. DUSP2 mRNA and protein are significantly reduced in most solid cancers including breast, colon, lung, ovary, kidney and prostate, and the suppression of DUSP2 is associated with tumorigenesis and malignancy. DUSP2 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 568983315 109 EFLDICENVKGAIAVHCKAGLGRTGTLIGCYLMKHYRMTAAESIAWLRICRpgSVIGPQQQFL 171
Cdd:cd14641   72 DFIDSVKNSGGRVLVHCQAGISRSATICLAYLIQSQRVRLDEAFDFVKQRR--GVISPNFSFM 132