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FLASH GENE
Symbol MAPK6 contributors: mct - updated : 16-03-2018
HGNC name mitogen-activated protein kinase 6
HGNC id 6879
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
  • biomarker for thyroid cancer exhibiting differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power
    • Therapy target
    SystemTypeDisorderPubmed
    cancerskin 
    potential pharmacodynamic marker for targeting BRAF signaling in melanoma
    ANIMAL & CELL MODELS