Property Summary

NCBI Gene PubMed Count 77
PubMed Score 169.53
PubTator Score 114.93

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Disease Target Count Z-score Confidence
Klinefelter's syndrome 59 0.0 4.0
Disease Target Count Z-score Confidence
Cancer 2346 3.761 1.9

Expression

  Differential Expression (34)

Disease log2 FC p
glioblastoma 3.200 2.7e-03
gastric carcinoma 2.100 1.4e-02
hepatocellular carcinoma 2.300 2.0e-06
pancreatic cancer 2.100 2.2e-03
Waldenstrons macroglobulinemia 1.469 2.0e-02
Multiple myeloma 1.940 8.7e-03
Barrett's esophagus 1.800 1.5e-02
esophageal adenocarcinoma 1.400 1.8e-02
cutaneous lupus erythematosus 1.400 8.8e-03
osteosarcoma 1.290 3.2e-02
group 4 medulloblastoma -2.100 3.1e-03
cystic fibrosis 2.919 3.4e-07
astrocytoma 2.200 3.8e-02
medulloblastoma, large-cell -2.300 4.8e-03
Duchenne muscular dystrophy 1.143 7.5e-06
autosomal dominant Emery-Dreifuss muscul... 1.310 3.6e-03
juvenile dermatomyositis 2.100 2.1e-12
primary pancreatic ductal adenocarcinoma 1.353 1.2e-02
non-small cell lung cancer -1.270 1.8e-08
intraductal papillary-mucinous neoplasm ... 2.100 1.6e-02
Hydrolethalus syndrome 3.079 6.2e-03
diabetes mellitus -1.200 1.8e-02
pediatric high grade glioma 1.300 2.8e-02
pilocytic astrocytoma 1.200 1.1e-02
posterior fossa group B ependymoma -1.200 4.0e-03
pancreatic carcinoma 2.100 2.2e-03
aldosterone-producing adenoma -1.311 1.5e-02
inflammatory breast cancer -2.000 7.9e-03
lung carcinoma -1.400 2.4e-11
breast carcinoma -1.500 2.8e-27
ulcerative colitis 2.200 8.0e-08
ovarian cancer 3.100 1.3e-06
pituitary cancer -1.700 5.8e-07
dermatomyositis 1.500 9.2e-03

Gene RIF (60)

PMID Text
27156317 DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs
26097584 Suppression of the FOXA1/DUSP6 signaling pathway may contribute to the development of Hirschsprung disease.
25499223 These observations led us to conclude that increased TSH signaling overcomes OIS and is essential for B-RafV600E-induced papillary thyroid carcinogenesis.
25451692 Dusp6 expression was higher in progestin-sensitive atypical endometrial hyperplasia groups compared with progestin-resistant groups. After treatment, Dusp6 expression was upregulated in progestin-sensitive groups, but not in progestin-resistant groups.
25414256 These results therefore indicate that p53-mediated up-regulation of MKP-3 contributes to the establishment of the senescent cellular phenotype through dephosphorylating ERK1/2
25344212 Our results suggest that DUSP6 gene expression in tumour samples may be a prognostic marker in NSCLC
25241655 DUSP6 downregulated the expression of matrix metallopeptidase 3.
24709168 Higher expression of DUSP6 in tumor tissue, than in peritumor tissue, is associated with the recurrence after curative resection of HCC, and the relative tumor DUSP6 expression has good power to predict the recurrence of HCC.
24681741 Downregulation of Dusp6, Sprouty4, and Sef--negative modulators of FGF2/ERK1/2 signaling--was present in eutopic endometria of adenomyosis, which may play critical roles in the development of adenomyosis.
24222120 Increased DUSP6 expression is associated with papillary thyroid carcinoma.
23965468 missense mutation, c.545C>T (p.Ser182Phe), in the DUSP6 gene may be genetically linked to the Class III malocclusion
23839489 Depletion of DUSP6 reduced the viability of cancer cell lines and increased the cytotoxicity of EGFR and other targeted inhibitors, and cytotoxic agents.
23419500 Dusp6 overexpression is involved in the pathogenesis and development of human endometrial adenocarcinoma.
23246965 suggest an important role for DeltaNp63alpha in preventing cancer metastasis by inhibition of Erk2 signaling via MKP3 subscribing
23132790 DUSP6 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells.
23108049 The results provide insights on the modulatory role of p53 in the survival pathway by up-regulating DUSP6.
23023500 study reports that naive CD4 T cells from elderly individuals have reduced signaling capacity of the ERK pathway; the underlying mechanism is an age-related decline in miR-181a expression and associated rise in levels of DUSP6 expression
22848708 ischemia/reperfusion inhibited eNOS expression by inactivation of ERK1/2, leading to decreased NO formation through a MKP-3-dependent mechanism in endothelial cells
22812510 Studies indicate that dual-specificity MAP kinase phosphatases (MKPs) DUSP6/MKP-3 and DUSP5 are localized in the cytoplasm and nuclear compartments.
22744456 MESP2, HES7 and DUSP6 genes may not be involved in the etiopathogenesis of sporadic and non-syndromic CS in Chinese Han population.
22535643 A link between DUSP6 expression and high-risk features of papillary thyroid carcinoma suggested that DUSP6 is an important independent factor affecting the signaling pathways in established papillary thyroid carcinoma.
22504224 caspase-3 cleavage of MKP3 down-regulates MKP3 full length and renders active MKP3 fragments, which may participate in novel regulatory pathways controlling the subcellular localization and activation of ERK1/2 during apoptosis.
22171919 DUSP6 is important in melanoma and it plays a different role in the distinct subtype of mouse melanoma compared with that in classic human melanoma.
22169769 Studies identified a single gene DUSP6, whose expression was associated with sensitivity to GSK1120212.
22155192 DUSP6 plays an important role in the pathogenesis of bipolar disorder, particularly in women.
22028468 Studies indicate that ERKs stimulate their own dephosphorylation by directly binding to phosphatases, such as MKP-3, and activating them.
21680106 DUSP6 plays an important role in cancer resistance in different subtypes of non-small cell lung carcinoma.
21610072 ERK cascade can act as a coincidence detector to decode the simultaneous engagement of a receptor tyrosine kinase and of LRP-1 and as a signal integrator that encodes this information in a spatially and temporally distinct biological signal
21499306 upregulation of DUSP6 exerts a tumor-promoting role in human glioblastomas exacerbating the malignant phenotype.
21454500 MKP3 not only controls the activities of ERK2 and p38alpha but also mediates cross-talk between these two MAPK pathways.
21387288 Loss of DUSP6 is associated with esophageal squamous cell carcinoma and nasopharyngeal carcinoma.
20806045 DUSP5 and DUSP6 selectively control ERK pathway activity and proliferation.
20800603 Observational study of gene-disease association. (HuGE Navigator)
20665674 This study shows that post-transcriptional regulation is a key process in the control of DUSP6 expression.
20638106 DUSP6 methylation is a rare event in endometrial cancer. Silencing of the DUSP6 phosphatase is unlikely to contribute to constitutive activation of the ERK kinase cascade in endometrial cancer.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20554528 the differential up-regulation of MKP3 by Ets2 and of DUSP5 by c-Jun may converge in similar functional roles for these MAP kinase phosphatases in the growth arrest versus proliferation decisions of breast cancer cells
20097731 Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19608870 These results suggest that DUSP6 is a growth suppressor whose inactivation could promote the progression of lung cancer.
19328558 Observational study of gene-disease association. (HuGE Navigator)
19106095 MKP3 is an important regulator of PDGF-induced Erk phosphorylation acting in both a rapid positive feed-forward and a later negative feed-back loop.
19091959 Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3.
18848526 These results indicate that intron 1 of DUSP6 plays a crucial role in transcriptional regulation of DUSP6 in a feedback loop manner responding to MAPK1 via ETS2 in human cells.
18771677 regulation of ERK1/2 by MKP-3 is countered by the complex regulation of MKP-3 by ERK1/2.
18694935 mitogen-activated protein kinase phosphatase 3 activity is inhibited by interdomain binding
18644985 WT1 transactivates another important negative regulator of the Ras/MAPK pathway, MAPK phosphatase 3 (MKP3).
18632752 Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer
18434601 MKP3 can act to enhance DAT function and is a phosphatase involved in regulating dynamin-dependent endocysis
18280112 even upon over-expression DUSP6 fails to inactivate ERK5, confirming that it is indeed an ERK1/2-specific DUSP
17569113 Nuclear matrix proteins such as mutant Pyst1 and nucleophosmin 1 were downregulated, whereas eIF6 and beta-tubulin were upregulated during cell differentiation in hepatocarcinoma cells.
17131384 These results suggest the existence of an ERK1/2-driven negative feed-back regulation of ERK5 signaling in epidermal growth factor-stimulated HK-2 cells, which is mediated by MKP-3, DUSP5 and/or MKP-1.
16491131 Results demonstrate that in the Korean population DUSP6 may contribute to the etiology of bipolar disorder, but not schizophrenia.
15832194 Results suggest that the abrogation of DUSP6 is associated exclusively with progression from pancreatic intraepithelial neoplasia to the invasive ductal carcinoma.
15824892 Hypermethylation with modification of histone deacetylation play an important role in transcriptional suppression of DUSP6 in human pancreatic cancer
15269220 cytoplasmic localization of MKP3 is mediated by a chromosome region maintenance-1 (CRM1)-dependent nuclear export pathway; the ability of MKP3 to cause the cytoplasmic retention of ERK2 requires both a functional kinase interaction motif and NES
14690430 Study gives first direct evidence that the N-terminal domain of MKP3 mediates intramolecular dephosphorylation between the monomeric form of phosphorylated extracellular signal-regulated kinase and a monomer of MKP3.
12840032 Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence.
12759238 Results show that DUSP6 exerts apparent tumor-suppressive effects in vitro and suggest that DUSP6 is a strong candidate tumor suppressor gene at 12q22 locus.
11998972 Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis

AA Sequence

MIDTLRPVPFASEMAISKTVAWLNEQLELGNERLLLMDCRPQELYESSHIESAINVAIPGIMLRRLQKGN      1 - 70
LPVRALFTRGEDRDRFTRRCGTDTVVLYDESSSDWNENTGGESVLGLLLKKLKDEGCRAFYLEGGFSKFQ     71 - 140
AEFSLHCETNLDGSCSSSSPPLPVLGLGGLRISSDSSSDIESDLDRDPNSATDSDGSPLSNSQPSFPVEI    141 - 210
LPFLYLGCAKDSTNLDVLEEFGIKYILNVTPNLPNLFENAGEFKYKQIPISDHWSQNLSQFFPEAISFID    211 - 280
EARGKNCGVLVHCLAGISRSVTVTVAYLMQKLNLSMNDAYDIVKMKKSNISPNFNFMGQLLDFERTLGLS    281 - 350
SPCDNRVPAQQLYFTTPSNQNVYQVDSLQST                                           351 - 381
//

Text Mined References (78)

PMID Year Title
27156317 2016 Dual Specificity Phosphatase 6 (DUSP6) Polymorphism Predicts Prognosis of Inoperable Non-Small Cell Lung Cancer after Chemoradiotherapy.
26097584 2015 Differential expression of FOXA1, DUSP6, and HA117 in colon segments of Hirschsprung's disease.
25499223 2014 TSH signaling overcomes B-RafV600E-induced senescence in papillary thyroid carcinogenesis through regulation of DUSP6.
25451692 2015 Dual-specificity phosphatase 6 predicts the sensitivity of progestin therapy for atypical endometrial hyperplasia.
25414256 2015 p53 protein-mediated up-regulation of MAP kinase phosphatase 3 (MKP-3) contributes to the establishment of the cellular senescent phenotype through dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2).
25344212 2015 Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer.
25241655 2014 Dual specificity phosphatase 6 suppresses the growth and metastasis of prostate cancer cells.
24709168 2014 Higher intratumor than peritumor expression of DUSP6/MKP-3 is associated with recurrence after curative resection of hepatocellular carcinoma.
24681741 2014 Loss of expressions of Dusp6, Sprouty4, and Sef, negative regulators of FGF2/ERK1/2 signaling, in the endometrium of women with adenomyosis.
24222120 2013 DNA methylation of MAPK signal-inhibiting genes in papillary thyroid carcinoma.
23965468 2013 A missense mutation in DUSP6 is associated with Class III malocclusion.
23839489 2013 DUSP6 regulates drug sensitivity by modulating DNA damage response.
23643382 2013 Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.
23419500 2013 Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17?-estradiol-induced cell growth in endometrial adenocarcinoma cell.
23246965 2014 ?Np63? regulates Erk signaling via MKP3 to inhibit cancer metastasis.
23132790 2013 DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells.
23108049 2012 DUSP6 is a novel transcriptional target of p53 and regulates p53-mediated apoptosis by modulating expression levels of Bcl-2 family proteins.
23023500 2012 Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity.
22848708 2012 Ischemia/reperfusion-induced MKP-3 impairs endothelial NO formation via inactivation of ERK1/2 pathway.
22812510 2013 Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling.
22744456 2012 Mutation analysis of MESP2, HES7 and DUSP6 gene exons in patients with congenital scoliosis.
22535643 2012 Dual specificity phosphatase 6 as a predictor of invasiveness in papillary thyroid cancer.
22504224 2012 Caspase-3 cleavage of DUSP6/MKP3 at the interdomain region generates active MKP3 fragments that regulate ERK1/2 subcellular localization and function.
22171919 2012 Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype.
22169769 2012 Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212.
22155192 2012 The genetic association of DUSP6 with bipolar disorder and its effect on ERK activity.
22028468 2011 Working without kinase activity: phosphotransfer-independent functions of extracellular signal-regulated kinases.
21680106 2011 Differential expression of DUSP6 with expression of ERK and Ki-67 in non-small cell lung carcinoma.
21610072 2011 Signal integration and coincidence detection in the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) cascade: concomitant activation of receptor tyrosine kinases and of LRP-1 leads to sustained ERK phosphorylation via down-regulation of dual specificity phosphatases (DUSP1 and -6).
21499306 2011 Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas.
21454500 2011 Mitogen-activated protein kinase (MAPK) phosphatase 3-mediated cross-talk between MAPKs ERK2 and p38alpha.
21387288 2012 Tumor suppressor dual-specificity phosphatase 6 (DUSP6) impairs cell invasion and epithelial-mesenchymal transition (EMT)-associated phenotype.
20806045 2010 DUSP5 and DUSP6 modulate corneal epithelial cell proliferation.
20800603 2010 Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
20665674 2011 Post-transcriptional regulation of the DUSP6/MKP-3 phosphatase by MEK/ERK signaling and hypoxia.
20638106 2010 Infrequent methylation of the DUSP6 phosphatase in endometrial cancer.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20554528 2010 Differential up-regulation of MAP kinase phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun converge in the control of the growth arrest versus proliferation response of MCF-7 breast cancer cells to phorbol ester.
20097731 2010 Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19608870 2009 Down-regulation of DUSP6 expression in lung cancer: its mechanism and potential role in carcinogenesis.
19328558 2009 Case-control association study of 65 candidate genes revealed a possible association of a SNP of HTR5A to be a factor susceptible to bipolar disease in Bulgarian population.
19106095 2009 Negative and positive regulation of MAPK phosphatase 3 controls platelet-derived growth factor-induced Erk activation.
19091959 2009 Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3.
18848526 2008 Feedback regulation of DUSP6 transcription responding to MAPK1 via ETS2 in human cells.
18771677 2008 Reciprocal regulation of extracellular signal regulated kinase 1/2 and mitogen activated protein kinase phosphatase-3.
18694935 2008 Inhibition of mitogen-activated protein kinase phosphatase 3 activity by interdomain binding.
18644985 2008 WT1 induction of mitogen-activated protein kinase phosphatase 3 represents a novel mechanism of growth suppression.
18632752 2008 Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells.
18434601 2008 Genetic complementation screen identifies a mitogen-activated protein kinase phosphatase, MKP3, as a regulator of dopamine transporter trafficking.
18280112 2008 DUSP6/MKP-3 inactivates ERK1/2 but fails to bind and inactivate ERK5.
17569113 2007 Alteration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation.
17322878 2007 A module of negative feedback regulators defines growth factor signaling.
17131384 2007 ERK1/2-driven and MKP-mediated inhibition of EGF-induced ERK5 signaling in human proximal tubular cells.
16491131 2006 The association of DUSP6 gene with schizophrenia and bipolar disorder: its possible role in the development of bipolar disorder.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15832194 2005 Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas.
15824892 2005 Abrogation of DUSP6 by hypermethylation in human pancreatic cancer.
15632084 2005 Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15276183 2004 MD-2: the Toll 'gatekeeper' in endotoxin signalling.
15269220 2004 Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14690430 2003 Intramolecular dephosphorylation of ERK by MKP3.
12840032 2003 Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence.
12759238 2003 Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11998972 2002 Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis.
10846176 2000 Nitric oxide down-regulates MKP-3 mRNA levels: involvement in endothelial cell protection from apoptosis.
10048930 1999 Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation.
9858808 1998 Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer.
9788880 1998 Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases.
9535927 1998 The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity.
9205128 1997 Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7).
8670865 1996 Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase.
8626780 1996 MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.