Property Summary

NCBI Gene PubMed Count 60
PubMed Score 53.03
PubTator Score 47.67

Knowledge Summary

Patent (7,681)

TINX Plot

  Disease (2)

Disease Target Count
Esophageal Neoplasms 67
Disease Target Count P-value
non-small cell lung cancer 2798 1.0e-27
ovarian cancer 8491 1.2e-08
osteosarcoma 7933 9.6e-07

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma -1.968 9.6e-07
non-small cell lung cancer -1.190 1.0e-27
ovarian cancer -1.800 1.2e-08

 GWAS Trait (1)

Protein-protein Interaction (2)

MLP Assay (6)

AID Type Active / Inconclusive / Inactive Description
1529 screening 4159 / 151 / 285664 Multiplex HTS Assay for Inhibitors of MEK Kinase PB1 Domains, specifically MEK5 MEK Kinase3 Wildtype
1894 screening 105 / 0 / 5837 Single Concentration Confirmation Screen via Multiplex HTS Assay for Inhibitors of MEK Kinase PB1 Domains, specifically MEK5 MEK Kinase3 Wildtype
1896 confirmatory 33 / 0 / 153 Dose Response Confirmation Screen via Multiplex HTS Assay for Inhibitors of MEK Kinase PB1 Domains, specifically MEK5 binding to MEK Kinase 3 Wildtype
1982 other 0 / 0 / 0 Kinase inhibition selectivity assay for compound SID-48409448
2145 confirmatory 0 / 0 / 13 SAR Compounds tested by Dose Response Screen via Multiplex HTS Assay for Inhibitors of MEK Kinase PB1 Domains, specifically MEK5 binding to MEK Kinase 3 Wildtype.
588725 other 0 / 0 / 1 Late stage counterscreen results from the probe development effort to identify inhibitors of kruppel-like factor 5 (KLF5): Radioactivity-based biochemical assay to identify modulators of a panel of 48 kinases

Gene RIF (32)

PMID Text
27027284 studies identify gain of MEKK3 signalling and KLF2/4 function as causal mechanisms for cerebral cavernous malformations pathogenesis that may be targeted to develop new CCM therapeutics
26997451 MAP3K3 overexpression is an independent poor prognostic indicator in ovarian carcinoma.
26304632 Polymorphisms in MAP3K3, MMP24 and IGF1R are associated with greater height and act additively on height in children of an admixed population.
26088427 MAP3K3 may potentially not only serve as diagnostic/prognostic markers for patients with lung cancer but also provide an indicator for future investigations into immunomodulatory therapies for lung cancer.
25824786 High MEKK3 expression is associated with renal clear cell carcinoma.
25728774 Our finding that Verrucous venous malformation contains a MAP3K3 mutation supports our impression that this lesion is a venous anomaly.
25388155 MEKK3 expression was significantly higher in patients with renal clear cell carcinoma than in controls.
25043814 This study identified an NBR1-MEKK3 complex as a key regulator of JNK signaling and adipose tissue inflammation in obesity.
25040987 MEKK3 expression was positively correlated with survivin.
24975362 Inhibitors of apoptosis proteins regulate myogenic differentiation by directly suppressing MEKK2/3-MEK5-ERK5 signaling.
24418622 We provide evidence for an intimate mutual control of the IKK complex by mitogen-activated protein kinase kinase kinase 3 (MEKK3) and transforming growth factor beta activated kinase 1 (TAK1).
24383423 Alterations in MEKK3 expression occur in early stages of development of esophageal squamous cell carcinoma and are sustained during disease progression.
22105580 Proliferation of human IVD cells is regulated by exogenous and autocrine growth factors mainly via the MEK/ERK and PI-3K/Akt pathways.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20615764 The regulation of NHEJ by EGFR was only blocked when ERK was affected by siRNA but not when AKT was knocked down. These data indicate that EGFR modulates DSB repair by regulating NHEJ via MAPK signalling.
20495538 EGFR and MAPK are actively involved in the pathobiology of serous cystic neoplasms of the pancreas.
20448038 PP2A plays an important role in the termination of LPA-mediated NF-kappaB activation through dephosphorylating and inactivating MEKK3
20068038 we report the identification of two regulatory phosphorylation sites at Thr-516 and Ser-520 within the kinase activation loop that is essential for MEKK3-mediated IkappaB kinase beta (IKKbeta)/NF-kappaB activation
19913121 Observational study of gene-disease association. (HuGE Navigator)
19903815 The rear end acidic cluster of the p62 PB1 domain is used to organize cytosolic aggregates or speckles-associated TRAF6-p62-MEKK3 complex for control of NF-kappaB activation.
19560753 These results strongly suggested that Hsp90 could work as the molecular chaperone of MEKK3.
19265138 Specific ablation of MEKK3 in T cells of conditional knockout mice does not significantly alter thymic T cell development, but leads to a peripheral T cell homeostasis defect.
18308725 identifies a potentially important regulatory step in MEKK3 signaling via dephosphorylation of Thr(294), which reduces 14-3-3 binding correlating with MEKK3 pathway activation
17985933 structural details of MEKK3 PB1 and its binding properties with mitogen-activated protein kinase kinase 5, human PB1.
16737960 TLR8-mediated MEKK3-dependent IKKgamma phosphorylation might play an important role in the activation of IKK complex, leading to IkappaBalpha phosphorylation
16407301 Serine526 is the only phosphorylation site within the activation loop of MEKK3; phosphorylation occurs in response to exogenous stimuli like osmotic stress.
16260783 TAK1 is recruited to the TNF-R1 complex via RIP and likely cooperates with MEKK3 to activate NF-kappaB in TNF-alpha signaling
16039990 We find that while hKSR-2 blocks MEKK3 activation, it has little to no effect on other members of the MAP3K family, including MEKK4, TAK1, and Ras-Raf, suggesting that its effects are selective.
15572679 RIP-dependent recruitment of MEKK3 plays a specific role in TNF-alpha signaling.
15047705 MEKK3 has a role in NF-kappaB activation by the chemopreventive dithiolethione oltipraz
15001576 MEKK3 signaling and apoptosis is potentiated by TRAF7
14662759 results established that elevated expression of mitogen-activated protein kinase kinase kinase 3(MEKK3) appears to be a frequent occurrence in breast and ovarian cancers

AA Sequence

MDEQEALNSIMNDLVALQMNRRHRMPGYETMKNKDTGHSNRQSDVRIKFEHNGERRIIAFSRPVKYEDVE      1 - 70
HKVTTVFGQPLDLHYMNNELSILLKNQDDLDKAIDILDRSSSMKSLRILLLSQDRNHNSSSPHSGVSRQV     71 - 140
RIKASQSAGDINTIYQPPEPRSRHLSVSSQNPGRSSPPPGYVPERQQHIARQGSYTSINSEGEFIPETSE    141 - 210
QCMLDPLSSAENSLSGSCQSLDRSADSPSFRKSRMSRAQSFPDNRQEYSDRETQLYDKGVKGGTYPRRYH    211 - 280
VSVHHKDYSDGRRTFPRIRRHQGNLFTLVPSSRSLSTNGENMGLAVQYLDPRGRLRSADSENALSVQERN    281 - 350
VPTKSPSAPINWRRGKLLGQGAFGRVYLCYDVDTGRELASKQVQFDPDSPETSKEVSALECEIQLLKNLQ    351 - 420
HERIVQYYGCLRDRAEKTLTIFMEYMPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDI    421 - 490
KGANILRDSAGNVKLGDFGASKRLQTICMSGTGMRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEM    491 - 560
LTEKPPWAEYEAMAAIFKIATQPTNPQLPSHISEHGRDFLRRIFVEARQRPSAEELLTHHFAQLMY        561 - 626
//

Text Mined References (69)

PMID Year Title
27027284 2016 Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling.
26997451 2016 MAP3K3 overexpression is associated with poor survival in ovarian carcinoma.
26304632 2015 Association Study of GWAS-Derived Loci with Height in Brazilian Children: Importance of MAP3K3, MMP24 and IGF1R Polymorphisms for Height Variation.
26088427 2015 MAP3K3 expression in tumor cells and tumor-infiltrating lymphocytes is correlated with favorable patient survival in lung cancer.
25824786 2015 Expression and prognostic role of MEKK3 and pERK in patients with renal clear cell carcinoma.
25728774 2015 A somatic MAP3K3 mutation is associated with verrucous venous malformation.
25429064 2015 Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
25388155 2015 The expression and role of MEKK3 in renal clear cell carcinoma.
25241761 2014 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
25043814 2014 A macrophage NBR1-MEKK3 complex triggers JNK-mediated adipose tissue inflammation in obesity.
25040987 2014 MEKK3 and survivin expression in cervical cancer: association with clinicopathological factors and prognosis.
24975362 2014 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1.
24418622 2014 MEKK3 and TAK1 synergize to activate IKK complex in Helicobacter pylori infection.
24383423 2014 Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22105580 2012 Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways.
22021425 2012 Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe).
21998595 2011 Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
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.
20615764 2010 The epidermal growth factor receptor modulates DNA double-strand break repair by regulating non-homologous end-joining.
20495538 2010 Association of epidermal growth factor receptor and mitogen-activated protein kinase with cystic neoplasms of the pancreas.
20448038 2010 Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3) phosphatase to inhibit lysophosphatidic acid-induced IkappaB kinase beta/nuclear factor-kappaB activation.
20068038 2010 Phosphorylation of Thr-516 and Ser-520 in the kinase activation loop of MEKK3 is required for lysophosphatidic acid-mediated optimal IkappaB kinase beta (IKKbeta)/nuclear factor-kappaB (NF-kappaB) activation.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19903815 2010 PB1 domain interaction of p62/sequestosome 1 and MEKK3 regulates NF-kappaB activation.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19560753 2009 Heat shock protein 90 regulates the stability of MEKK3 in HEK293 cells.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19265138 2009 MEKK3 is essential for lymphopenia-induced T cell proliferation and survival.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18391951 2008 Many sequence variants affecting diversity of adult human height.
18308725 2008 Phosphorylation of MEKK3 at threonine 294 promotes 14-3-3 association to inhibit nuclear factor kappaB activation.
17985933 2007 Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
16737960 2006 TLR8-mediated NF-kappaB and JNK activation are TAK1-independent and MEKK3-dependent.
16625196 2006 DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.
16407301 2006 Phosphorylation of serine 526 is required for MEKK3 activity, and association with 14-3-3 blocks dephosphorylation.
16381901 2006 The LIFEdb database in 2006.
16260783 2005 TAK1 is recruited to the tumor necrosis factor-alpha (TNF-alpha) receptor 1 complex in a receptor-interacting protein (RIP)-dependent manner and cooperates with MEKK3 leading to NF-kappaB activation.
16039990 2005 hKSR-2 inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation.
15572679 2004 Restoration of NF-kappaB activation by tumor necrosis factor alpha receptor complex-targeted MEKK3 in receptor-interacting protein-deficient cells.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15146197 2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.
15047705 2004 NF-kappaB activation by the chemopreventive dithiolethione oltipraz is exerted through stimulation of MEKK3 signaling.
15001576 2004 TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis.
14743216 2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14662759 2004 Overexpression of MEKK3 confers resistance to apoptosis through activation of NFkappaB.
14661019 2004 Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3.
12912994 2003 PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway.
12761501 2003 Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.
12761204 2003 Inhibition of mitogen-activated kinase kinase kinase 3 activity through phosphorylation by the serum- and glucocorticoid-induced kinase 1.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12392720 2002 Phosphorylation of the stress-activated protein kinase, MEKK3, at serine 166.
12391307 2002 JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors.
12065326 2002 Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression.
11429546 2001 The essential role of MEKK3 in TNF-induced NF-kappaB activation.
11256614 2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
11076863 2000 DNA cloning using in vitro site-specific recombination.
11073940 2001 MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway.
10700190 2000 Mekk3 is essential for early embryonic cardiovascular development.
10593883 1999 MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway.
9452471 1998 14-3-3 proteins interact with specific MEK kinases.
9006902 1997 Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.