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FLASH GENE
Symbol MAP3K10 contributors: mct - updated : 11-04-2023
HGNC name mitogen-activated protein kinase kinase kinase 10
HGNC id 6849
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
  • SH3 N terminal motif
  • a catalytic domain (in MLK1 domain)
  • two leucine zipper domains
  • a basic sequence
  • a protein kinase domain
  • a C terminal proline-rich domain
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Map3k10
    homolog to C.elegans F20b6.8
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP kinase kinase kinase subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • co-localizes with activated JNK along microtubules
  • localized both in the cytoplasm and cell nucleus
    • basic FUNCTION
  • induction of apoptosis
  • serine/threonine protein kinase involved in nerve growth factor (NGF) induced neuronal apoptosis
  • activating the JUN N-terminal pathway
  • playing a role in the neuronal death mechanism
  • role for MAP3K10 and the stress-signaling pathway at sites of clathrin activity in vesicle formation or trafficking
  • regulates NTRK2 expression through phosphorylation of an activation domain of TCF3
  • both hippocalcin and MAP3K10 may be associated with the pathogenesis of Parkinson disease
  • upstream activator of JNKs and activation of MAP3K10-mediated signaling cascades play roles in neurodegenerative and apoptotic mechanisms in the central nervous system
  • able to phosphorylate COPS2 in immune-kinase assays
  • MAP3K10 is an upstream activating kinase of JUN N-terminal kinase (JNK), which regulates adult neurogenesis
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    JNK cascade
    a component
  • homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • normal huntingtin, NEUROD1, HAP1
  • clathrin is a binding partner for MAP3K10 in mammalian brain (clathrin binding requires a motif (LLDMD) located near the MLK2 C terminus, which is similar to "clathrin box" motifs important for binding of clathrin coat assembly and accessory proteins to the clathrin heavy chain)
  • interacting partner for the corepressor COPS2
  • interacting with TCF3 (enhances phosphorylation of the AD2 activation domain of TCF3)
  • MAP3K4 and MAP3K10 are sufficient for mediating the TGFB1-induced activation of MAPK14
  • MAP3K10 is a novel NCALD interacting partner
  • WBP2 is a target of the Hippo/MAP3K10, and MAP3K10 is identified as yet another rheostat in the regulation of WBP2 and its oncogenic function
    • cell & other
    REGULATION
    activated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    upregulated in pancreatic ductal adenocarcinoma tissues and cell lines
    constitutional     --over  
    MAP3K10 methylation in patients with intracranial aneurysm (IA) was significantly lower than that in controls, and this phenomenon was more significant in women
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • MAP3K10 methylation may be a potential predictor of intracranial aneurysm risk, particularly low in women
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    targeting MAP3K10 is a potential strategy for the development of alternative therapies for pancreatic cancers
    ANIMAL & CELL MODELS