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FLASH GENE
Symbol MAP3K12 contributors: mct/npt - updated : 24-08-2012
HGNC name mitogen-activated protein kinase kinase kinase 12
HGNC id 6851
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
  • N terminal kinase catalytic domain, hybrid between those of serine/threonine and tyrosine protein kinases
  • a double leucine zipper domain
  • a large C terminal glycine and proline rich region
    • conjugated HemoP
    mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Map3k12
    Homologene
    FAMILY
  • MAP (mitogen activated protein) kinase family
  • Mixed lineage kinase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text phosphorylated and dephosphorylated in cytosol and dephosphorylated only when membrane-associated
    basic FUNCTION
  • serine/threonine protein kinase contributing in the developing brain to cytodifferentiation, apoptotic elimination, and migration
  • acting in the epidermis to promote the terminal differentiation of keratinocytes
  • acting as a signaling molecule implicated in the regulation of keratinocyte terminal differentiation and cornification
  • plays a significant role in the coordinated regulation of radial migration and axon projection by modulating JNK activity
  • potential role in PDGF signaling
  • potentially involved in regenerative responses of mammalian dorsal root ganglion neurons to axonal injury through activation of c-JUN
  • plays a significant role in the coordinated regulation of radial migration and axon projection by modulating JNK activity
  • key regulator of development, cell differentiation and apoptosis
  • critical role in naturally occurring programmed cell death of motoneurons
  • selectively regulates the JNK-based stress response pathway to mediate axon degeneration and neuronal apoptosis without influencing other aspects of JNK signaling
  • participates in cell proliferation and/or survival, at least in part, by modulating the expression of cell cycle regulatory proteins
  • appears to be important for proper cell proliferation and/or cell survival
  • cell cycle-regulated protein whose depletion by RNA interference causes proliferation arrest concomitantly with senescence
  • essential component of the neuronal response to axon damage, broadly regulating the transcriptional response to axonal injury
  • is required for both the proapoptotic and proregenerative responses that occur after optic nerve lesion through broad regulation of injury-induced alterations in gene expression
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
  • JNK cascade
  • MAP3K12-JNK pathway facilitates axon formation in neocortical neurons via stage-specific regulation of microtubule stability
  • MAP3K12-ERK signaling pathway may act as a regulator of the interaction that occurs between HSPB1 and the cytoskeleton during the formation of the cornified cell envelope, a process conferring to the skin its crucial barrier function (PMIDS:
    • a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Mg2+
    • protein
  • interacting with the GTP bound form of RAC and CDC42, regulators of JNK pathway
  • induces activation of c-Jun N-terminal kinase (JNK), a molecule that regulates morphogenesis in various organisms
  • its expression, is sufficient by itself to induce HSPB1 phosphorylation, cell periphery localization, and redistribution to the insoluble protein fraction (cytoskeleton) in poorly differentiated keratinocytes (PMIDS:
  • novel transcriptional target of PPARG with functional PPARG-binding sites in its promoter
    • cell & other
    REGULATION
    activated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    MAP3K12 depletion interrupts progression of the cell cycle from the G1 to S phase
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularspinal muscular atrophy 
    could become a strategic therapeutic target in motor neuron diseases in which aberrant activation of the apoptogenic cascade is involved
    ANIMAL & CELL MODELS
  • Map3k12-null mice displayed reduced apoptosis in multiple neuronal populations during development, demonstrating that prodegenerative Map3k12 signaling is required in vivo