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FLASH GENE
Symbol MAP3K11 contributors: mct/ - updated : 20-05-2016
HGNC name mitogen-activated protein kinase kinase kinase 11
HGNC id 6850
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  highly
 salivary gland   highly
Lymphoid/Immunespleen   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
  • glycine rich and N-terminal Src-homology 3 (SH3) domain (is autoinhibited through its SH3 domain)
  • a kinase domain
  • a leucine zipper
  • a Cdc42/Rac interactive binding (CRIB) motif
  • a catalytic domain (in MLK1 domain)
  • C-terminal proline–serine–threonine rich domain, with signature sequences of both Ser/Thr and Tyr kinases in the catalytic domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Map3k11
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP (mitogen activated protein) kinase family
  • mixed-lineage kinase family
  • CATEGORY enzyme , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    basic FUNCTION
  • serine/threonine protein kinase that may contribute to promoting microtubule instability, a hallmark of M phase entry
  • contributing to the TNF signaling pathway that activates JNK
  • required for mitogen activation of BRAF and cell proliferation
  • activates multiple mitogen-activated protein kinase (MAPK) pathways in response to growth factors, stresses and the pro-inflammatory cytokine, tumor necrosis factor (TNF)
  • regulates the MAPKinase pathway activating ERK, MAPK14 and JNK, in response to extracellular signals
  • scaffolding protein, involved in the formation of a multiprotein complex containing MAP3K11/BRAF/RAF1
  • required for optimal activation of stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling by TNFA
  • activates multiple MAPK pathways, including the JNK (c-Jun N-terminal kinase) pathway
  • crucial requirement in the migration of invasive breast cancer cells
  • induces luminal repopulation and suppresses the expression of the pro-apoptotic protein BCL2L11 in breast cancer
  • having both a proliferative and antiapoptotic role in the acquisition of a malignant phenotype in mammary epithelial cells
  • is an important regulator of MMP expression and invasion in ovarian cancer cells
  • plays a crucial role in compromising mitochondrial integrity and functions as a proapoptotic competence factor in the early stages of cytokine-induced pancreatic beta cell death
  • promotes saturated fatty acid-induced JNK activation and diet-induced metabolic dysfunction.
  • mitogen-activated protein kinase kinase kinase that activates multiple mitogen-activated protein kinase pathways and has been implicated in regulating proliferation in several cell types
  • is a critical factor controlling the activity of kinase networks that control the cellular responses to different concentrations of ROS
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • JNK cascade
  • MAP3K11-PIN1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis
  • a component
  • MAP3K11-JNK-AP1 signaling is critical for breast cancer cell migration and invasion
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting specifically with the GTP bound form of RAC and CDC42, regulators of JNK pathway
  • interacting with GSK3B (cell death induced by GSK3B was mediated by MAP3K11 in a manner dependent on its phosphorylation of the specific residues within the C-terminal domain by GSK3B)
  • activation of MAP3K11 specifically by FGD1/CDC42 is important for skeletal mineralization
  • associates with and uniquely phosphorylates S138 within the PPIase domain of PIN1
  • promotes neointima formation through increased activation of the RHOA pathway in vascular smooth muscle cells
  • direct interaction between PRKAA1 subunit and MAP3K11, and MAP3K11 serves as a common upstream kinase of AMPK and JNK and functions as a direct upstream kinase for AMPK independent of STK11
  • serves as a common upstream kinase of PRKAA1 and JNK and functions as a direct upstream kinase for PRKAA1 independent of STK11
  • ERBB2 activation inhibits the pro-apoptotic function of MAP3K11, which plays a mechanistic role in mediating anti-tumor activities of ERBB2-directed therapies
  • cell & other
    REGULATION
    activated by phosphorylation
    Other activation of MAP3K11 specifically by FGD1/CDC42 is important for skeletal mineralization
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in MSI gastrointestinal carcinomas
    tumoral     --over  
    in breast cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    therapeutics that target MAP3K11 or PIN1 could prove beneficial for a subset of cancers where the MAP3K11-PIN1 pathway is dysregulated
    cancerreproductivebreast
    may be an important therapeutic target for the treatment of invasive breast cancer
    ANIMAL & CELL MODELS