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FLASH GENE
Symbol MAPK6 contributors: mct - updated : 16-03-2018
HGNC name mitogen-activated protein kinase 6
HGNC id 6879
Location 15q21.2      Physical location : 52.311.410 - 52.358.461
Synonym name
  • extracellular signal-regulated kinase 3
  • MAP kinase isoform p97
  • Synonym symbol(s) ERK3, PRKM6, p97MAPK, HsT17250
    EC.number 2.7.1.37/2.7.11.24
    DNA
    TYPE functioning gene
    STRUCTURE 47.05 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 4225 - 721 - 2003 12915405
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   moderately
    Digestiveesophagus   moderately
     mouthtongue  moderately
     salivary gland   predominantly
     stomach   moderately
    Hearing/Equilibriumear   highly
    Nervousbrainhindbrain   
    Reproductivefemale systemuterus  moderately
    Respiratoryrespiratory tracttrachea  highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connective    
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
     digestive
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies ortholog to murine Mapk6 (94.9pc)
    intraspecies homolog to MAPK4
    Homologene
    FAMILY
  • SER/THR family of protein kinases
  • MAP kinase subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • translocated to the nucleus after activation
  • basic FUNCTION
  • acting as a serine/threonine kinase
  • playing a pivotal role in converting tyrosine phosphorylation
  • involved in TNFA and tyrosine phosphorylated in response to insulin NGF and other signals
  • atypical mitogen-activated protein kinase (MAPK), which is regulated by protein stability
  • phosphorylating microtubule-associated protein 2 (MAP2)
  • may promote entry in the cell cycle
  • contrary to most protein kinases, MAPK6 is a highly unstable protein that is subject to dynamic regulation by the ubiquitin-proteasome system
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • activation loop phosphorylation of MAPK4 and MAPK6 stimulates their intrinsic catalytic activity and is required for the formation of stable active complexes with MAPKAPK5 and, consequently, for efficient cytoplasmic redistribution of MAPK4/MAPK6/MAPKAPK5 complexes
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • Mg2+
  • ATP
  • protein
  • specific interaction between MAPK6 and MAPKAPK5 (binding results in nuclear exclusion of both MAPK6 and MAPKAPK5 and is accompanied by MAPK6-dependent phosphorylation and activation of MAPKAPK5)
  • is a potential PAK2 substrate
  • interacted with and phosphorylated steroid receptor NCOA3, an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857)
  • several new UBE3A-interacting proteins, including HIF1AN, NEURL4, and mitogen-activated protein kinase 6 (MAPK6)
  • MAPK6, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against TOP2A inhibitors-induced DNA damage and growth inhibition
  • USP20 is a novel MAPK6 regulator (USP20 interacts with and deubiquitinates MAPK6 both in vitro and in intact cells)
  • cell & other
    REGULATION
    activated by TNFA
    treatment with serum or phorbol esters in fibroblasts
    in response to BRAF signaling
    Other its phosphorylation can be modulated indirectly by interaction with the substrate MAP kinase-activated protein kinase 5 (MAPKAPK5)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerskin 
    potential pharmacodynamic marker for targeting BRAF signaling in melanoma
    ANIMAL & CELL MODELS