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FLASH GENE
Symbol TBK1 contributors: mct/npt - updated : 26-10-2017
HGNC name TANK-binding kinase 1
HGNC id 11584
Corresponding disease
FTDALS4 frontotemporal dementia and/or amyotrophic lateral sclerosis 4
Location 12q14.1      Physical location : 64.845.936 - 64.895.891
Synonym name
  • NF-kB-activating kinase
  • TRAF family member-associated NF-kappaB activator (TANK)-binding kinase 1
  • serine/threonine-protein kinase TBK1
  • Synonym symbol(s) NAK, T2K, FLJ11330, FTDALS4
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 50.06 kb     21 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
    21 - 3098 83.6 729 - 2007 17823124
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a protein kinase domain
  • OPTN-binding domain localised to AAs 601-729
  • HOMOLOGY
    intraspecies homolog to IKBKE
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • IKK-related kinase family
  • CATEGORY adaptor , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    text
  • TBK1 partly co-localizes with CDON along cellular processes in puncta-like structures
  • basic FUNCTION
  • activator of NF-kappa B, in a TRAF2 dependent manner
  • mediating NFKB activation in response to certain growth factors
  • involved in the signaling cascade converging to the activation of the transcription factor NF-kappa-B
  • may function as an IKK kinase, playing an essential role
  • in the transcription of a subset of TNF-alpha-induced genes
  • acting synergistically with DDX3X to stimulate the IFN promoter
  • critically involved in virus-triggered type I IFN signaling
  • plays an inhibitory role in virus-triggered IFN-beta signaling pathways
  • requirement for the TBK1-IRF3 pathway in host defense against a DNA virus infection
  • may play a role in the HBx-mediated activation of the NF-kappaB signaling pathway and the development of hepatocellular carcinoma
  • 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
  • controls cell survival through SERPINB2 and transglutaminase 2 (TGM2)
  • plays essential roles in mammalian cell division
  • TBK1 functions likely as a mitotic kinase necessary for microtubule dynamics and mitosis
  • TBK1 activation is a central event in type I interferon production in anti-virus innate immunity
  • positive feedback loop between PEBP1 and TBK1 that is essential for type I interferon production in anti-viral innate immunity
  • master innate immune kinase, that is an important regulator of dendritic cells (DC) function
  • DC-specific function of TBK1 in the maintenance of immune homeostasis and tolerance
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
    NF-kappa B, JNK signaling
    a component
  • component of a signaling ternary complex with TRAF2 and TANK
  • complexing with IRF3 and playing a role in innate immune reactions
  • a CDON-TBK1 complex is associated with AKT1 phosphorylation and early OLG differentiation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TANK binding
  • associating with Borna disease virus protein (repressing its IFN-inducing kinase activity)
  • interacts with AZI2, SIKE, TICAM1/TRIF, IRF3 and DDX58
  • binding partner for Optineurin (OPTN)
  • interacting with DDX3X
  • interacting with AKT1 (regulatory mechanism for AKT1 activation mediated by TBK1 and role of AKT1 in TLR-mediated immune responses)
  • 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
  • AKT1 is a direct TBK1 substrate that connects TBK1 to prosurvival signaling
  • physiological function of IKBKE/TBK1 in AKT1 regulation and a possible mechanism of IKBKE/TBK1 in oncogenesis by activating AKT1
  • SERPINB2 and TGM2 are downstream mediators in the antiapoptotic response triggered upon TBK1 activation
  • TRAF6, was critical for IL17A-induced TRAF3IP2 phosphorylation, and for IL17A-induced TBK1 activation, its association with TRAF3IP2, and consequent TRAF3IP2 phosphorylation
  • negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NFKB1, an action that involved TBK1-mediated phosphorylation
  • TBK1 kinase addiction in lung cancer cells is mediated via autophagy of TAX1BP1/CALCOCO2 and non-canonical NFKB1 signalling
  • TRIM11 and TBK1, a key kinase that phosphorylates IRF3 in the DDX58 pathway, interacted with each other through CC and CC2 domain, respectively
  • in the presence of cytosolic DNA, rapidly traffics with TBK1 via VPS34-related autophagosomes to associate with endosomal compartments containing NFKB and IRF3
  • TBK1 is a downstream kinase controlling dsDNA-mediated IRF3 and NFKB1 signaling dependent on TMEM173
  • DOK3 was shown to bind TRAF3, and the binding of TRAF3 and TBK1 to DOK3 required the tyrosine-rich C-terminal domain of DOK3
  • SIGLEC1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27
  • TBK1 binds to the centrosomal protein CEP170 and to the mitotic apparatus protein NUMA1, and both CEP170 and NUMA1 are TBK1 substrates
  • constitutive interaction of TBK1 with OPTN and the ability of OPTN to bind to ubiquitin chains are essential for TBK1 recruitment and kinase activation on mitochondria
  • OPTN is a positive regulator TBK1 via a bipartite interaction between these molecules
  • SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its N-terminal Sec63 domain (Sec63-1) to bind RNA and to interact with TBK1
  • PEBP1 is essential for TBK1 activation and type I interferon production triggered by viral infection
  • TBK1 negatively regulates the induction of a subset of genes by type I interferon receptor (IFNAR1)
  • TRIM23 mediates virus-induced autophagy via activation of TBK1
  • unique innate immune activation cascade in which TBK1-IKBKB formed a positive feedback loop to assure robust cytokine production during CGAS-TMEM173 activation
  • through interacting with TBK1, HERPUD1 amplifies the MAVS signaling and facilitates the phosphorylation and nuclear translocation of IRF3 and NFKB1 to enhance the expression of IFNs, which leads to a broad inhibition of the replication of RNA viruses
  • mechanistically, USP1 and WDR48 bound to TBK1, removed its K48-linked polyubiquitination, and then reversed the degradation process of TBK1
  • cell & other
    REGULATION
    activated by hepatitis B viral X protein (HBx)at the transcriptional level
    ASSOCIATED DISORDERS
    corresponding disease(s) FTDALS4
    Susceptibility to amyotrophic lateral sclerosis
    Variant & Polymorphism other TBK1 variants associated to ALS
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    TBK1 could be involved in the insulin resistance mechanism related with IR Ser994 phosphorylation in a genetic model of diabetes