Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MAP3K4 contributors: mct/npt - updated : 17-04-2019
HGNC name mitogen-activated protein kinase kinase kinase 4
HGNC id 6856
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-terminal kinase catalytic domain, and a nonkinase domain that may contain a regulatory domain
  • a docking site, a stretch of about 20 amino acids immediately on the C-terminal side of the MAPKK catalytic domain (Takekawa 2005)
  • hybrid between those of serine/threonine and tyrosine protein kinases at the C-terminus
    • HOMOLOGY
    interspecies homolog to C.elegans B0414.7
    homolog to yeast S.cerevisiae SSK2
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP kinase kinase kinase subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    basic FUNCTION
  • activating the MAPK and JNK signal transduction pathway (see MAP4K4)
  • major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway
  • signaling hub for FGF4 activation of JNK that is required for maintenance of trophoblast stem cells in an undifferentiated state (Abell 2009)
  • coordinates the activity of the JNK and MAPK14 modules in trophoblast stem cells required for stem cell maintenance (Abell 2009)
  • MAP3K4-dependent signalling events are required for normal expression of SRY during testis development, and implicated in disorders of sexual development (Bogani 2009)
  • is a mitogen-activated protein kinase kinase kinase that regulates the activity of its downstream mitogen-activated kinases, MAPK14, and JUN N-terminal kinase (JNK)
  • plays an important role in the regulation of cell death and is also involved in the pathogenesis of heart failure
  • MAP3K4 expression is highly regulated during inner ear development and is critical to normal cytoarchitecture and function
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    MAP3K4 pathway is involved in FLNA regulation and periventricular heterotopia formation
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SH3KBP1-interacting partner (enhances the activation of MKK6 and of the downstream MAPK14 following oxidative stress and growth factor stimulation)
  • FLNA, impacts neuronal migration initiation and provides insight into the pathogenesis of periventricular heterotopia
  • link between MAPK signalling in proliferating gonadal somatic cells and regulation of SRY expression (Bogani 2009)
  • interacts with TRAF4 (MAP3K4 is the MAPK kinase kinase for TRAF4 regulation of the JNK pathway) (Abell 2005)
  • MAP3K4 controls the activity of the histone acetyltransferase CREBBP, and acetylation of histones H2A and H2B by CREBBP is required to maintain the epithelial phenotype
  • spatial regulation of MAPK14 by GADD45B/MAP3K4 negatively regulates the autophagic process
  • interaction of SH3KBP1 with MAP3K4 was increased during the late phase of TNFSF10 incubation, suggesting that sustained MAPK14 and HSPB1 phosphorylation protects cells by preventing further cell death
  • MAP3K4 and MAP3K10 are sufficient for mediating the TGFB1-induced activation of MAPK14
  • MAP3K4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence hair cells (HCs) development
  • GADD45A interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MAP3K4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy
  • MAP3K4 activity controls epithelial-to-mesenchymal transition (EMT) through the ubiquitination and degradation of HDAC6
    • cell & other
    REGULATION
    activated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice homozygous for a kinase-inactive Mekk4 mutation exhibit significant hearing loss