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 297182065  10 INTVTLGD--NGGLIGMCCCPGRVEQHNDgvhrsRDLAEDLAVVSDWQPDLVISLVEQHEFDFLGVAQLPEEFKK-RFQW 86
Cdd:cd14505    1 IDWLPLSMlgNAGSLGLTPCPGCKFKDHR-----RDLQADLEELKDQGVDDVVTLCTDGELEELGVPDLLEQYQQaGITW 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  87 QHHPVRDLAATSEaTGENTVLGEWFASVYRGG-RVLLHCAAGLGRTGTVAARLLMMAGE--DADTAIKRVRAARPGTVES 163
Cdd:cd14505   76 HHLPIPDGGVPSD-IAQWQELLEELLSALENGkKVLIHCKGGLGRTGLIAACLLLELGDtlDPEQAIAAVRALRPGAIQT 154

                 ....*....
gi 297182065 164 GAQERFLHQ 172
Cdd:cd14505  155 PKQENFLHQ 163

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 297182065  10 INTVTLGD--NGGLIGMCCCPGRVEQHNDgvhrsRDLAEDLAVVSDWQPDLVISLVEQHEFDFLGVAQLPEEFKK-RFQW 86
Cdd:cd14505    1 IDWLPLSMlgNAGSLGLTPCPGCKFKDHR-----RDLQADLEELKDQGVDDVVTLCTDGELEELGVPDLLEQYQQaGITW 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  87 QHHPVRDLAATSEaTGENTVLGEWFASVYRGG-RVLLHCAAGLGRTGTVAARLLMMAGE--DADTAIKRVRAARPGTVES 163
Cdd:cd14505   76 HHLPIPDGGVPSD-IAQWQELLEELLSALENGkKVLIHCKGGLGRTGLIAACLLLELGDtlDPEQAIAAVRALRPGAIQT 154

                 ....*....
gi 297182065 164 GAQERFLHQ 172
Cdd:cd14505  155 PKQENFLHQ 163

Protein tyrosine phosphatase, catalytic domain motif;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 297182065   109 EWFASVYRGGRVLLHCAAGLGRTGTVAARLLMMAGEDADTA-------IKRVRAARPGTVESGAQERFLHQ 172
Cdd:smart00404  31 KNLNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGevdifdtVKELRSQRPGMVQTEEQYLFLYR 101

protein tyrosine phosphatase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 297182065 106 VLGEWF----ASVYRGGRVLLHCAAGLGRTGTVAARLLMMAGEDADTAIKRVRAARPGTVESgAQERFL 170
Cdd:PTZ00393 155 IVSNWLtivnNVIKNNRAVAVHCVAGLGRAPVLASIVLIEFGMDPIDAIVFIRDRRKGAINK-RQLQFL 222

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 297182065  10 INTVTLGD--NGGLIGMCCCPGRVEQHNDgvhrsRDLAEDLAVVSDWQPDLVISLVEQHEFDFLGVAQLPEEFKK-RFQW 86
Cdd:cd14505    1 IDWLPLSMlgNAGSLGLTPCPGCKFKDHR-----RDLQADLEELKDQGVDDVVTLCTDGELEELGVPDLLEQYQQaGITW 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  87 QHHPVRDLAATSEaTGENTVLGEWFASVYRGG-RVLLHCAAGLGRTGTVAARLLMMAGE--DADTAIKRVRAARPGTVES 163
Cdd:cd14505   76 HHLPIPDGGVPSD-IAQWQELLEELLSALENGkKVLIHCKGGLGRTGLIAACLLLELGDtlDPEQAIAAVRALRPGAIQT 154

                 ....*....
gi 297182065 164 GAQERFLHQ 172
Cdd:cd14505  155 PKQENFLHQ 163

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 297182065 116 RGGRVLLHCAAGLGRTGTVAARLLMMAGE-DADTAIKRVRAARPGTVESGAQERFLHQ 172
Cdd:cd14504   81 KNEAVLVHCLAGKGRTGTMLACYLVKTGKiSAVDAINEIRRIRPGSIETSEQEKFVIQ 138

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 297182065 116 RGGRVLLHCAAGLGRTGT-VAARLLMMAGEDADTAIKRVRAARPG-TVESGAQERFLHQ 172
Cdd:cd14494   55 PGEPVLVHCKAGVGRTGTlVACYLVLLGGMSAEEAVRIVRLIRPGgIPQTIEQLDFLIK 113

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 297182065   109 EWFASVYRGGRVLLHCAAGLGRTGTVAARLLMMAGEDADTA-------IKRVRAARPGTVESGAQERFLHQ 172
Cdd:smart00012  31 KNLNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGevdifdtVKELRSQRPGMVQTEEQYLFLYR 101

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 297182065  116 RGGRVLLHCAAGLGRTGTVAARLLMMA-GEDADTAIKRVRAARPGTVESgaqERFLHQ 172
Cdd:pfam00782  68 KGGKVLVHCQAGISRSATLIIAYLMKTrNLSLNEAYSFVKERRPGISPN---FGFKRQ 122

C-terminal dual-specificity phosphatase domain of CDC14 family proteins; The cell division control protein 14 (CDC14) family is highly conserved in all eukaryotes, although the roles of its members seem to have diverged during evolution. Yeast Cdc14, the best characterized member of this family, is a dual-specificity phosphatase that plays key roles in cell cycle control. It preferentially dephosphorylates cyclin-dependent kinase (CDK) targets, which makes it the main antagonist of CDK in the cell. Cdc14 functions at the end of mitosis and it triggers the events that completely eliminates the activity of CDK and other mitotic kinases. It is also involved in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint, and in chromosome segregation. Cdc14 phosphatases also function in DNA replication, DNA damage checkpoint, and DNA repair. Vertebrates may contain more than one Cdc14 homolog; humans have three (CDC14A, CDC14B, and CDC14C). CDC14 family proteins contain a highly conserved N-terminal pseudophosphatase domain that contributes to substrate specificity and a C-terminal catalytic dual-specificity phosphatase domain with the PTP signature motif.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 297182065 117 GGRVLLHCAAGLGRTGTVAARLLM-MAGEDADTAIKRVRAARPGTVeSGAQERFLHQ 172
Cdd:cd14499  109 KGAIAVHCKAGLGRTGTLIACYLMkHYGFTAREAIAWLRICRPGSV-IGPQQQFLEE 164

catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11), also called SH2 domain-containing tyrosine phosphatase 2 (SHP-2 or SHP2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 promotes the activation of the RAS/Mitogen-Activated Protein Kinases (MAPK) Extracellular-Regulated Kinases 1/2 (ERK1/2) pathway, a canonical signaling cascade that plays key roles in various cellular processes, including proliferation, survival, differentiation, migration, or metabolism. It also regulates the phosphoinositide 3-kinase (PI3K)/AKT pathway, a fundamental cascade that functions in cell survival, proliferation, migration, morphogenesis, and metabolism. PTPN11 dysregulation is associated with several developmental diseases and malignancies, such as Noonan syndrome and juvenile myelomonocytic leukemia. It contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065 113 SVYRGGRVLLHCAAGLGRTGT-----VAARLLMMAGEDAD----TAIKRVRAARPGTVESGAQERFLHQS 173
Cdd:cd14605  177 SIMDAGPVVVHCSAGIGRTGTfividILIDIIREKGVDCDidvpKTIQMVRSQRSGMVQTEAQYRFIYMA 246

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 297182065 118 GRVLLHCAAGLGRTGT----VAARLLMMAGEDADT--AIKRVRAARPGTVESGAQERFLHQ 172
Cdd:cd00047  140 GPIVVHCSAGVGRTGTfiaiDILLERLEAEGEVDVfeIVKALRKQRPGMVQTLEQYEFIYE 200

catalytic domain of receptor-type tyrosine-protein phosphatase H; Receptor-type tyrosine-protein phosphatase H (PTPRH or R-PTP-H), also known as stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRH 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 localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. It plays a role in intestinal immunity by regulating CEACAM20 through tyrosine dephosphorylation. It is also a negative regulator of integrin-mediated signaling and may contribute to contact inhibition of cell growth and motility.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 297182065 106 VLGEWFASVYRGGRVLLHCAAGLGRTGTVAARLLMMAGEDADTAI------KRVRAARPGTVESGAQERFLHQ 172
Cdd:cd14619  155 LLRQWLDQTMSGGPTVVHCSAGVGRTGTLIALDVLLQQLQSEGLLgpfsfvQKMRENRPLMVQTESQYVFLHQ 227

catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) and type 6 (PTPN6) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 and PTPN6, are also called SH2 domain-containing tyrosine phosphatase 2 (SHP2) and 1 (SHP1), respectively. They contain two tandem SH2 domains: a catalytic PTP domain, and a C-terminal tail with regulatory properties. Although structurally similar, they have different localization and different roles in signal transduction. PTPN11/SHP2 is expressed ubiquitously and plays a positive role in cell signaling, leading to cell activation, while PTPN6/SHP1 expression is restricted mainly to hematopoietic and epithelial cells and functions as a negative regulator of signaling events.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 297182065 118 GRVLLHCAAGLGRTGTVAARLLMM-----AGEDADT----AIKRVRAARPGTVESGAQERFLH 171
Cdd:cd14544  180 GPIVVHCSAGIGRTGTFIVIDMLLdqikrKGLDCDIdiqkTIQMVRSQRSGMVQTEAQYKFIY 242

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the first PTP domain (repeat 1).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 297182065 118 GRVLLHCAAGLGRTGT---VAARLLMMAGE---DADTAIKRVRAARPGTVESGAQERFLHQS 173
Cdd:cd14620  165 GPIVVHCSAGVGRTGTfivIDAMIDMMHAEqkvDVFEFVSRIRNQRPQMVQTDMQYSFIYQA 226

catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 1; Receptor-type tyrosine-protein phosphatase A (PTPRA), also known as receptor-type tyrosine-protein phosphatase alpha (R-PTP-alpha), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA is a positive regulator of Src and Src family kinases via dephosphorylation of the Src-inhibitory tyrosine 527. Thus, it affects transformation and tumorigenesis, inhibition of proliferation, cell cycle arrest, integrin signaling, neuronal differentiation and outgrowth, and ion channel activity. It is also involved in interleukin-1 signaling in fibroblasts through its interaction with the focal adhesion targeting domain of focal adhesion kinase. PTPRA comprises a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the first catalytic PTP domain (repeat 1).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 297182065 117 GGRVLLHCAAGLGRTGT---VAARLLMMAGE---DADTAIKRVRAARPGTVESGAQERFLHQS 173
Cdd:cd14621  222 AGAIVVHCSAGVGRTGTfivIDAMLDMMHAErkvDVYGFVSRIRAQRCQMVQTDMQYVFIYQA 284

protein tyrosine phosphatase 1 from Arabidopsis thaliana and similar plant PTPs; Arabidopsis thaliana protein tyrosine phosphatase 1 (AtPTP1) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. AtPTP1 dephosphorylates and inhibits MAP kinase 6 (MPK6) in non-oxidative stress conditions. Together with MAP kinase phosphatase 1 (MKP1) it expresses salicylic acid (SA) and camalexin biosynthesis, and therefore, modulating defense response.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065 118 GRVLLHCAAGLGRTGTVAA------RLLM--MAGEDADTAIKRVRAARPGTVESGAQERF 169
Cdd:cd17658  144 GPIVVHCSAGIGRTGAYCTihntirRILEgdMSAVDLSKTVRKFRSQRIGMVQTQDQYIF 203

dual specificity phosphatase domain of laforin and similar domains; This family is composed of glucan phosphatases including vertebrate dual specificity protein phosphatase laforin, also called lafora PTPase (LAFPTPase), and plant starch excess4 (SEX4). Laforin is a glycogen phosphatase; its gene is mutated in Lafora progressive myoclonus epilepsy or Lafora disease (LD), a fatal autosomal recessive neurodegenerative disorder characterized by the presence of progressive neurological deterioration, myoclonus, and epilepsy. One characteristic of LD is the accumulation of insoluble glucans. Laforin prevents LD by at least two mechanisms: by preventing hyperphosphorylation of glycogen by dephosphorylating it, allowing proper glycogen formation, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with malin. Laforin contains an N-terminal CBM20 (carbohydrate-binding module, family 20) domain and a C-terminal catalytic dual specificity phosphatase (DSP) domain. Plant SEX4 regulate starch metabolism by selectively dephosphorylating glucose moieties within starch glucan chains. It contains an N-terminal catalytic DSP domain and a C-terminal Early (E) set domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  59 VISLVEQHEFDFLGVaqLPEEFKKRFQ-----WQHHPVRDLAATSEATGENTVLGEWFASVYRGGRVLLHCAAGLGR-TG 132
Cdd:cd14526   33 VLNLQTDSDMEYWGV--DIDSIRKACKesgirYVRLPIRDFDTEDLRQKLPQAVALLYRLLKNGGTVYVHCTAGLGRaPA 110

                         90       100
                 ....*....|....*....|....*.
gi 297182065 133 TVAARLLMMAGEDADTAIKRVRAARP 158
Cdd:cd14526  111 TVIAYLYWVLGYSLDEAYYLLTSKRP 136

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  68 FDFLGVAQL-------PEEFKKRFQWQHHPVRDLAATSEATGENTVLgEWFASVY-RGGRVLLHCAAGLGRTGTVAARLL 139
Cdd:cd14638   22 LDTLGITALinvsancPNHFEGHYQYKSIPVEDNHKADISSWFNEAI-DFIDSVKnAGGRVFVHCQAGISRSATICLAYL 100

                 .
gi 297182065 140 M 140
Cdd:cd14638  101 M 101

dual specificity phosphatase domain of dual specificity protein phosphatase 22, 15, and similar proteins; Dual specificity protein phosphatase 22 (DUSP22, also known as VHX) and 15 (DUSP15, also known as VHY) function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). They 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. The both contain N-terminal myristoylation recognition sequences and myristoylation regulates their subcellular location. DUSP22 negatively regulates the estrogen receptor-alpha-mediated signaling pathway and the IL6-leukemia inhibitory factor (LIF)-STAT3-mediated signaling pathway. DUSP15 has been identified as a regulator of oligodendrocyte differentiation. DUSP22 is a single domain protein containing only the catalytic dual specificity phosphatase domain while DUSP15 contains a short C-terminal tail.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 297182065 116 RGGRVLLHCAAGLGRTGTVAARLLM----MAGEDadtAIKRVRAARP 158
Cdd:cd14519   76 NGGNVLVHCLAGVSRSVTIVAAYLMtvtdLGWRD---ALKAVRAARP 119

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 297182065  75 QLPEEFKKRFQWQHHPVRDLaatseatgENTVLGEWFASVYR-------------------GGRVLLHCAAGLGRTGT-V 134
Cdd:cd14518   37 DVPEEYFKGYEHKQIEIDDV--------EDENILQHFPETNRfidsalfgngkdedeekkhGGAVLVHCAMGKSRSVTvV 108

                         90       100
                 ....*....|....*....|....
gi 297182065 135 AARLLMMAGEDADTAIKRVRAARP 158
Cdd:cd14518  109 IAYLMYKYNLSVSQALHAVRRKRP 132

catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), type 18 (PTPN18) and type 12 (PTPN12) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signaling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signaling molecules. TPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 297182065 120 VLLHCAAGLGRTGTVAA----RLLMMAGEDAD-----TAIKRVRAARPGTVESGAQERFLHQ 172
Cdd:cd14542  141 ICVHCSAGCGRTGTICAidyvWNLLKTGKIPEefslfDLVREMRKQRPAMVQTKEQYELVYR 202

catalytic domain of receptor-type tyrosine-protein phosphatase C, repeat 1; Receptor-type tyrosine-protein phosphatase C (PTPRC), also known as CD45, leukocyte common antigen (LCA) or GP180, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRC/CD45 is found in all nucleated hematopoietic cells and is an essential regulator of T- and B-cell antigen receptor signaling. It controls immune response, both positively and negatively, by dephosphorylating a number of signaling molecules such as the Src family kinases, the CD3zeta chain of TCY, and ZAP-70 kinase. Mutations in the human PTPRC/CD45 gene are associated with severe combined immunodeficiency (SCID) and multiple sclerosis. PTPRC/CD45 contains an extracellular receptor-like region with fibronectin type III (FN3) repeats, a short transmembrane segment, and a cytoplasmic region comprising of a membrane proximal catalytically active PTP domain (repeat 1 or D1) and a membrane distal catalytically impaired PTP-like domain (repeat 2, or D2). This model represents repeat 1.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 297182065 118 GRVLLHCAAGLGRTGTVAARLLMMAGEDADTAIK------RVRAARPGTVESGAQERFLHQ 172
Cdd:cd14557  141 GPIVVHCSAGVGRTGTYIGIDAMLEGLEAEGRVDvygyvvKLRRQRCLMVQVEAQYILIHQ 201

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 297182065 117 GGRVLLHCAAGLGRTGT-VAARLLMMAGEDADTAIKRVRAAR 157
Cdd:cd14515   88 GGKVLVHCVEGVSRSATlVLAYLMIYQNMTLEEAIRTVRKKR 129

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  68 FDFLGVAQL-------PEEFKKRFQWQHHPVRDlaatseatGENTVLGEWFASVYR--------GGRVLLHCAAGLGRTG 132
Cdd:cd14640   22 LDALGITALlnvssdcPNHFEGHYQYKCIPVED--------NHKADISSWFMEAIEyidsvkdcNGRVLVHCQAGISRSA 93

                         90       100
                 ....*....|....*....|..
gi 297182065 133 TVAARLLMMAgedadtaiKRVR 154
Cdd:cd14640   94 TICLAYLMMK--------KRVR 107

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 297182065 118 GRVLLHCAAGLGRTGT-VAARLLMMAGEDADTA-----IKRVRAARPGTVESGAQERFLHQS 173
Cdd:cd14612  182 GPIVVHCSAGIGRTGCfIATSIGCQQLKDTGKVdilgiVCQLRLDRGGMIQTSEQYQFLHHT 243

Tyrosine phosphatase family; This family is closely related to the pfam00102 and pfam00782 families.

                          10        20
                  ....*....|....*....|....*....
gi 297182065  120 VLLHCAAGLGRTGTVAARLLMMAGEDADT 148
Cdd:pfam13350 132 VLFHCTAGKDRTGVAAALLLSLLGVPEDT 160

catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type tyrosine-protein phosphatase J (PTPRJ or R-PTP-J), also known as receptor-type tyrosine-protein phosphatase eta (R-PTP-eta) or density-enhanced phosphatase 1 (DEP-1) OR CD148, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRJ 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 (eight in PTPRJ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed in various cell types including epithelial, hematopoietic, and endothelial cells. It plays a role in cell adhesion, migration, proliferation and differentiation. It dephosphorylates or contributes to the dephosphorylation of various substrates including protein kinases such as FLT3, PDGFRB, MET, RET (variant MEN2A), VEGFR-2, LYN, SRC, MAPK1, MAPK3, and EGFR, as well as PIK3R1 and PIK3R2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 297182065 116 RGGRVLLHCAAGLGRTGT-VAARLLMMAGEDADTA-----IKRVRAARPGTVESGAQERFLHQ 172
Cdd:cd14615  163 PNSPILVHCSAGVGRTGTfIAIDRLIYQIENENVVdvygiVYDLRMHRPLMVQTEDQYVFLNQ 225

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
                 ....*....|....*....|....*....|....*....|....
gi 297182065 117 GGRVLLHCAAGLGRTGTVAARLLMM-AGEDADTAIKRVRAARPG 159
Cdd:cd14523   79 DGVVLVHCNAGVSRSASIVIGYLMAtENLSFEDAFSLVKNARPS 122

PTP-like domain of receptor-type tyrosine-protein phosphatase C, repeat 2; Receptor-type tyrosine-protein phosphatase C (PTPRC), also known as CD45, leukocyte common antigen (LCA) or GP180, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRC/CD45 is found in all nucleated hematopoietic cells and is an essential regulator of T- and B-cell antigen receptor signaling. It controls immune response, both positively and negatively, by dephosphorylating a number of signaling molecules such as the Src family kinases, the CD3zeta chain of TCY, and ZAP-70 kinase. Mutations in the human PTPRC/CD45 gene are associated with severe combined immunodeficiency (SCID) and multiple sclerosis. PTPRC/CD45 contains an extracellular receptor-like region with fibronectin type III (FN3) repeats, a short transmembrane segment, and a cytoplasmic region comprising of a membrane proximal catalytically active PTP domain (repeat 1 or D1) and a membrane distal catalytically impaired PTP-like domain (repeat 2, or D2). This model represents repeat 2.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065 120 VLLHCAAGLGRTGTVAARLLMMagEDADT--------AIKRVRAARPGTVESGAQERFLH 171
Cdd:cd14558  145 IVVHCSDGSSRTGIFCALWNLL--ESAETekvvdvfqVVKALRKQRPGMVSTLEQYQFLY 202

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065  77 PEEFKKRFQWQHHPVRD--LAATSEATGENTVLGEWFASvyRGGRVLLHCAAGLGRTGTVAARLLMMAG----EDADTAI 150
Cdd:cd14641   41 PNYFEGQFQYKSIPVEDshMADISAWFQEAIDFIDSVKN--SGGRVLVHCQAGISRSATICLAYLIQSQrvrlDEAFDFV 118

                 ....
gi 297182065 151 KRVR 154
Cdd:cd14641  119 KQRR 122

catalytic domain of tyrosine-protein phosphatase non-receptor type 2; Tyrosine-protein phosphatase non-receptor type 2 (PTPN2), also called T-cell protein-tyrosine phosphatase (TCPTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN2, a tumor suppressor, dephosphorylates and inactivates EGFRs, Src family kinases, Janus-activated kinases (JAKs)-1 and -3, and signal transducer and activators of transcription (STATs)-1, -3 and -5, in a cell type and context-dependent manner. It is deleted in 6% of all T-cell acute lymphoblastic leukemias and is associated with constitutive JAK1/STAT5 signaling and tumorigenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 297182065 118 GRVLLHCAAGLGRTGT---VAARLLMMAGEDADTA-IKRV----RAARPGTVESGAQERF 169
Cdd:cd14607  193 GPAVVHCSAGIGRSGTfslVDTCLVLMEKKDPDSVdIKQVlldmRKYRMGLIQTPDQLRF 252

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and type 14 (PTPN14) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Both PTPN21 and PTPN14 contain an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 297182065 120 VLLHCAAGLGRTGTVAARLLMMA----GEDADtaIKRV----RAARPGTVESGAQERFLHQS 173
Cdd:cd14540  155 TLVHCSAGVGRTGVVILADLMLYcldhNEELD--IPRVlallRHQRMLLVQTLAQYKFVYNV 214

PTP domain of receptor-type tyrosine-protein phosphatase U, repeat 2; Receptor-type tyrosine-protein phosphatase U (PTPRU), also known as pancreatic carcinoma phosphatase 2 (PCP-2), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRU/PCP-2 is the most distant member of the type IIb subfamily and may have a distinct biological function other than cell-cell aggregation. It localizes to the adherens junctions and directly binds and dephosphorylates beta-catenin, and regulates the balance between signaling and adhesive beta-catenin. It plays an important role in the maintenance of epithelial integrity. PTPRU contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 297182065 116 RGGRVLLHCAAGLGRTGTVAARLLMMAG------EDADTAIKRVRAARPGTVESGAQERFLHQ 172
Cdd:cd14637  141 GEGRTVVHCLNGGGRSGTYCASAMILEMirchniVDVFYAVKTLRNYKPNMVETLEQYRFCYE 203

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), 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. DUSP3 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 favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 297182065 116 RGGRVLLHCAAGLGRTGT-VAARLLMMAGEDADTAIKRVRAARpgtvESGAQERFLHQ 172
Cdd:cd14579  107 KNGRVLVHCREGYSRSPTlVIAYLMLRQKMDVKSALSTVRQKR----EIGPNDGFLKQ 160

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 297182065 106 VLGEWFASVYR------GGRVLLHCAAGLGRTGTVAARLLMMAGEDADTAIKRVRAARPGTVES 163
Cdd:cd18535   76 VVEDWLSLLKTkfcedpGCCVAVHCVAGLGRAPVLVALALIESGMKYEDAIQFIRQKRRGAINS 139

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
                 ....*....|....*....|....*....|....*....|
gi 297182065 120 VLLHCAAGLGRTGTVAARLLMMAGE--DADTAIKRVRAAR 157
Cdd:cd14509   97 AAVHCKAGKGRTGVMICCYLLYLGKfpSAKEALDFYGAKR 136

catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 1; Receptor-type tyrosine-protein phosphatase Z (PTPRZ), also called receptor-type tyrosine-protein phosphatase zeta (R-PTP-zeta), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Three isoforms are generated by alternative splicing from a single PTPRZ gene: two transmembrane isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S (also known as phosphacan); all are preferentially expressed in the central nervous system (CNS) as chondroitin sulfate (CS) proteoglycans. PTPRZ isoforms play important roles in maintaining oligodendrocyte precursor cells in an undifferentiated state. PTPRZ is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the catalytic PTP domain (repeat 1).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 297182065 118 GRVLLHCAAGLGRTGT--VAARLLMMAGEDADTAI----KRVRAARPGTVESGAQERFLHQS 173
Cdd:cd17668  146 GPVVVHCSAGVGRTGTyiVLDSMLQQIQHEGTVNIfgflKHIRSQRNYLVQTEEQYVFIHDA 207

catalytic domain of tyrosine-protein phosphatase non-receptor type 9; Tyrosine-protein phosphatase non-receptor type 9 (PTPN9), also called protein-tyrosine phosphatase MEG2, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN9 plays an important role in promoting intracellular secretary vesicle fusion in hematopoietic cells and promotes the dephosphorylation of ErbB2 and EGFR in breast cancer cells, leading to impaired activation of STAT5 and STAT3. It also directly dephosphorylates STAT3 at the Tyr705 residue, resulting in its inactivation. PTPN9 has been found to be dysregulated in various human cancers, including breast, colorectal, and gastric cancer.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 297182065 116 RGGRVLLHCAAGLGRTGTVA------ARLLMMAGEDADTAIKRVRAARPGTVESGAQERFLH 171
Cdd:cd14543  209 PGPPIVVHCSAGIGRTGTFCtldiclSQLEDVGTLNVMQTVRRMRTQRAFSIQTPDQYYFCY 270

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 2; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 297182065 120 VLLHCAAGLGRTGTVAA------RLLMMAGEDADTAIKRVRAARPGTVESGAQERFLHQ 172
Cdd:cd14622  142 IVVHCSAGAGRTGTFIAlsnileRVKAEGLLDVFQTVKSLRLQRPHMVQTLEQYEFCYR 200