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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
Location 19q13.2      Physical location : 40.697.650 - 40.721.481
Synonym name
  • mixed lineage kinase 2, dual (tyr and ser:thr) specificity
  • MKN28 derived nonreceptor_type serine/threonine kinase
  • MKN28 kinase
  • mixed lineage kinase 2
    • Synonym symbol(s) MLK2, MST, MEKK10
    EC.number 2.7.11.25
    DNA
    TYPE functioning gene
    STRUCTURE 23.83 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3453 - 954 - 1995 7731697
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Nervousbrain    
    Reproductivefemale systemuteruscervix highly
     male systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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