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FLASH GENE
Symbol IKBKE contributors: mct/shn - updated : 19-01-2022
HGNC name inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
HGNC id 14552
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal kinase domain
  • a leucine zipper and a potential helix-loop-helix domain at the C terminus
    • HOMOLOGY
    interspecies ortholog to Ikbke, Mus musculus
    ortholog to Ikbke, Rattus norvegicus
    ortholog to ikbke, Danio rerio
    intraspecies homolog to IKBKA,IKBKB,TBK1
    Homologene
    FAMILY IKK family
    CATEGORY adaptor , signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    basic FUNCTION
  • playing a key role in integrating signals induced by pro-inflammatory stimuli
  • serine-threonine kinase activating the transcription factors NFkappaB, interferon regulatory factor-3 (IRF3) and CCAAA/enhancer-binding protein (C/EBPdelta)
  • playing a role in controlling proliferation of certain cancer cells through regulation of constitutive NF-kappaB activity
  • plays a critical role in the IFN-inducible antiviral transcriptional response
  • essential for regulating antiviral signaling pathways and is a recently discovered breast cancer oncoprotein
  • IKBKE and CYLD are an oncogene-tumor suppressor network that participates in tumorigenesis (phosphorylation of CYLD at serine 418 decreases its deubiquitinase activity and is necessary for IKBKE-driven)
  • oncogenic kinase participating in malignant transformation and tumor development
  • role of IKBKE as a mediator protecting from DNA-damage-induced cell death
  • pivotal for an efficient innate immune response to viral infections and recognized as breast cancer oncogene
  • antiviral function of IKBKE involves activation of the transcription factors IFN regulatory factor 3 (IRF3) and NFKB, thus inducing the expression of type I IFN
  • IKBKE/TBK1 mediate the activation of PELI1 E3 ligase activity, as well as inducing the transcription of its gene and protein expression in response to TLR3 and TLR4 agonists
  • physiological function of IKBKE/TBK1 in AKT1 regulation and a possible mechanism of IKBKE/TBK1 in oncogenesis by activating AKT1
  • plays a role in the regulation of NFKB activity
  • modulates inflammatory nociceptive sensitivity by activation of NFKB-dependent gene transcription
  • activates AKT1 through a PI3K-independent pathway
  • plays an important role in the regulation of inflammatory signaling pathway
  • critical regulator of AKT1
  • FOXO3 is a new IKBKE-controlled check-point of regulation of IFNB1 expression
  • phosphorylates STAT1
  • plays a critical role in regulating the balance between the IFN-I and IFN-II signaling pathways
  • is implicated in inflammation-driven tumorigenes
  • IKBKE-dependent autophagy is necessary for breast cancer cell proliferation, suggesting an important supporting role for this oncogene and autophagy in these tumors
  • role of IKBKE in the regulation of the stem cell phenotype in breast cancer cells
  • contributes to the clinical characteristics of systemic lupus erythematosus
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    NF-kappa B, JNK signaling pathway
    a component component of a PMA-inducible complex with IKB complex
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • I-TRAF
  • TANK
  • NAP1
  • A20
  • Suppressor of IKKepsilon, SIKE
  • Ret finger protein, RFP
  • C-terminal region of MAVS
  • ABIN1
  • RNF11
  • cIAP1/cIAP2/TRAF2 E3 ligase complex
  • DDX3X is a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKBKE and might thus be involved in pathway-specific activation of IRF3
  • CDK2AP1 is a substrate for IKBKE
  • IKBKE promotes NFATC1 phosphorylation and inhibits T cell responses, identifying IKBKE as a crucial negative regulator of T cell activation
  • adaptor molecule CRADD coordinates IKBKE and IRF7 interaction to ensure efficient expression of type I interferon
  • cytoplasmic localization of PELP1 up-regulates pro-tumorigenic IKBKE and secreted inflammatory signals, which through paracrine macrophage activation regulates the migratory phenotype associated with breast cancer initiation
  • TBK1 acts redundantly with IKBKE to drive NFKB1 upon STING1 activation
    • cell & other
    REGULATION
    activated by IFNbeta
    induced by liposaccharides of bacterial walls via proinflammatory cytokines such as TNF,IL1,IL6
    Other SUMO modification of IKBKE is required to trigger phosphorylation of nuclear substrates including NF-kappaB RELA, thereby contributing to the antiapoptotic function of NF-kappaB in response to DNA damage
    regulated by K63-linked polyubiquitination
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in breast cancer cell lines and patient-derived tumors
    tumoral     --over  
    in breast cancer, ovarian cancer and prostate cancer
    tumoral     --over  
    in glioma and contributes to resistance of glioma cells to apoptosis via activating NFKB
    constitutional     --low  
    in SLE patients compared with healthy controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • a possible therapeutic target for obesity, insulin resistance and diabetes
    • SystemTypeDisorderPubmed
    cancer  
    therapeutic target for cancer intervention
    miscelleaneouspain 
    may be useful as a therapeutic target in the treatment of inflammatory pain
    cancer  
    MCCK1 is an IKBKE inhibitor with anti-tumor activity and could be a potential anti-cancer agent for patients with tumors over expressing IKBKE
    ANIMAL & CELL MODELS
  • mice lacking IKKepsilon produce normal amounts of IFNbeta but are hypersusceptible to viral infection