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Symbol MAP3K8 contributors: mct - updated : 16-01-2019
HGNC name mitogen-activated protein kinase kinase kinase 8
HGNC id 6860
Location 10p11.23      Physical location : 30.722.865 - 30.750.761
Synonym name
  • Ewing sarcoma transformant
  • cancer osaka thyroid oncogene
  • COT (cancer osaka thyroid) oncogene
  • proto-oncogene serine/threonine-protein kinase
  • tumor progression locus 2
  • Synonym symbol(s) COT, TPL2, EST, ESTF, MEKK8, Tpl-2, c-COT, FLJ10486
    TYPE functioning gene
    STRUCTURE 27.90 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    MAPPING cloned Y linked   status confirmed
    Map pter - D10S1684 - MAP3K8 - D10S1695 - D10S193 - qter
    Physical map
    LOC347806 10p12.1 similar to hypothetical protein FLJ10817 LOC340913 10p12.1 similar to breast cancer antigen NY-BR-1 LOC338617 10p12.1 similar to HSPC132 FLJ44037 10p12.1 FLJ44037 protein RAB18 10p12.1 RAB18, member RAS oncogene family C10orf48 10p12.1 chromosome 10 open reading frame 48 FLJ10817 MRPS21P5 10p12.1 mitochondrial ribosomal protein S21 pseudogene 5 FLJ32798 LOC389945 10 similar to zinc finger protein 12 LOC340917 10p12.1 similar to laminin-binding protein WAC 10p12.1-p11.2 similar to laminin-binding protein NMA 10p12.3-p11.2 similar to laminin-binding protein MGC45541 10p12.1 hypothetical protein MGC45541 LOC256457 10p12.1 similar to 60S ribosomal protein L21 MGC33408 10p12.1 similar to lysozyme C-1 (1,4-beta-N-acylmuramidase C, EC LOC387647 10 hypothetical gene supported by BC014163 SVIL 10p11.2 supervillin bA192N10.2 10q11.1 cell division control protein CKS1 pseudogene KIAA1462 10p12.1 KIAA1462 FLJ10486 10p12.1 hypothetical protein FLJ10486 LOC389946 10 similar to G1/S-specific cyclin D3 MAP3K8 10p11.2 mitogen-activated protein kinase kinase kinase 8 LOC119180 10p11.23 lysozyme 2 LOC143110 10p11.23 similar to supervillin isoform 2; membrane-associated F-actin binding protein p205; archvillin LOC387648 10 similar to supervillin isoform 2; membrane-associated F-actin binding protein p205; archvillin LOC220929 10p11.23 hypothetical protein LOC220929 TCF8 10p11.2 transcription factor 8 (represses interleukin 2 expression) LOC387649 10 LOC387649 ARHGAP12 10pter-cen Rho GTPase activating protein 12 KIF5B 10p11.2 kinesin family member 5B LOC387650 10 hypothetical gene supported by BC000689; NM_021130; NR_000030 EPC1 10p11 enhancer of polycomb homolog 1, (Drosophila) FLJ32762 FLJ13031 ITGB1 10p11.2 integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) LOC340933 10p11.23 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) NRP1 10p12 neuropilin 1
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 3096 58 467 - 1993 8226782
  • 397 common Aas
  • 70 specific C-terminal Aas
  • - splicing - 52 415 - 1993 8226782
    397 + 18 C-terminal Aas
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   moderately
     liver   lowly
    Lymphoid/Immunethymus   highly
    Nervousnervecranial nerve  moderately
    Reproductivefemale systemplacenta   
     female systembreastmammary gland lowly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period neonatal, pregnancy
    cell cycle     cell cycle, S, checkpoint, G2M
    Text umbilical cord
  • a serine proteine kinase domain
  • conjugated PhosphoP
    interspecies homolog to rattus Map3k8 (94.00 pc)
    homolog to murine Map3k8 (93.36 pc)
  • serine/threonine protein kinase family
  • MAP kinase kinase kinase subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • playing a role in the cell cycle
  • can activate both the MAP kinase and JNK kinase pathways
  • activates IKappaB kinases and thus induces the nuclear production of NF-KappaB
  • promotes the production of TNF-alpha and IL-2 during T lymphocyte activation
  • regulates IL8 production, which is markedly reduced in presence of KSR2
  • required for TLR4 activation of the MEK/ERK pathway
  • able to activate NF-KappaB1 by stimulating proteasome-mediated proteolysis of NF-KappaB1/p105
  • may be an important mediator of intracellular mechanotransduction in mesenchymal stem cells
  • regulator of T helper cell lineage decisions and important functional role in the regulation of Th1 responses
  • functioning as a promoter of apoptosis in ischemia/reperfusion injury
  • inducing cell migration upon COX2 expression and Erk1/Erk2 activity
  • can phosphorylate histone H3 and thus induces cellular transformation through up-regulation of c-fos transcriptional activity
  • CELLULAR PROCESS cell cycle, checkpoint
    signaling signal transduction
    a component
  • forming a ternary complex with NFKB1 and TNIP2
    small molecule metal binding, cofactor, nucleotide,
  • Mg2+ as a cofactor
  • ATP binding
  • protein
  • NFKB1/p105
  • interacting with TNIP2
  • IKBKB directly phosphorylated MAP3K8 on three serines, including the critical MAP3K8 phosphorylation following LPS stimulation of macrophages
  • cell & other
    activated by IL1 stimulated activation of the MAP3K8 catalytic subunit
    through the phosphorylation of Thr290 and Ser62
    induced by IL12 in a Stat4-dependent manner
    Other up-regulated by BCL11B
    activated specifically during the S and G2/M phases of the cell cycle
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cancer Osaka thyroid
    Variant & Polymorphism
    Candidate gene
  • could be a prognostic factor in breast cancer
  • Marker
    Therapy target
    miscelleaneousvascularischemic injury
    could be a possible therapeutic target in ischemia/reperfusion injury