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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
    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
    Physical map
    LOC144583 12q14.1 hypothetical gene supported by AK025388 USP15 12q14 ubiquitin specific protease 15 KIAA1040 12q14.1 KIAA1040 protein FLJ25590 12q14.1 hypothetical protein FLJ25590 ARHCL1 12q14.1 ras homolog gene family, member C like 1 LOC390337 12 similar to RIKEN cDNA A430075L18 gene LOC144581 12q14.1 similar to ribosomal protein L14; 60S ribosomal protein L14 LOC121498 12q14.1 similar to lactate dehydrogenase A -like AVPR1A 12q14 arginine vasopressin receptor 1A FLJ32949 12q14.1 hypothetical protein FLJ32949 LOC390338 12 similar to T-box transcription factor TBX20 TMEM5 12q14.1 transmembrane protein 5 LOC341315 12q14.1 similar to Polyadenylate-binding protein 1 (Poly(A)-binding protein 1) (PABP 1) SRGAP1 12q13.13 SLIT-ROBO Rho GTPase activating protein 1 FLJ32549 12q14.1 hypothetical protein FLJ32549 LOC115749 12q14.1 hypothetical protein LOC115749 LOC390339 12 similar to 40S ribosomal protein S11 XPOT 12q14 exportin, tRNA (nuclear export receptor for tRNAs) TBK1 13q14.2-q14.3 TANK-binding kinase 1 RASSF3 12q14.1 Ras association (RalGDS/AF-6) domain family 3 GNS 12q14 glucosamine (N-acetyl)-6-sulfatase (Sanfilippo disease IIID) KIAA0984 12q13.13 glucosamine (N-acetyl)-6-sulfatase (Sanfilippo disease IIID) WIF1 12q13.13 WNT inhibitory factor 1 MAN1 12q14 WNT inhibitory factor 1 LOC253827 12q14.1 hypothetical protein LOC253827 LOC387865 12 LOC387865 LOC204010 12q14.2 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) HMGA2 12q14-q15 high mobility group AT-hook 2 LOC341321 12q14.2 similar to 60S ribosomal protein L21 MGC14817 12q14.2 hypothetical protein MGC14817 CGI-119 12q14.1-q15 CGI-119 protein IRAK3 12q13.13 interleukin-1 receptor-associated kinase 3 RBMS1P 12q14.2 RNA binding motif, single stranded interacting protein 1, pseudogene LOC387866 12 LOC387866 LOC390340 12 similar to IAP-associated factor VIAF1; phosducin-like 2 HELB 12q14.2 helicase (DNA) B GRIP1 12q14.1-q14.2 glutamate receptor interacting protein 1
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3098 83.6 729 - 2007 17823124
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    at STAGE
  • a protein kinase domain
  • OPTN-binding domain localised to AAs 601-729
    intraspecies homolog to IKBKE
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • IKK-related kinase family
  • CATEGORY adaptor , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
  • 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
    PHYSIOLOGICAL PROCESS immunity/defense
    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
    small molecule
  • 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
    activated by hepatitis B viral X protein (HBx)at the transcriptional level
    corresponding disease(s) FTDALS4
    Susceptibility to amyotrophic lateral sclerosis
    Variant & Polymorphism other TBK1 variants associated to ALS
    Candidate gene
    Therapy target
    TBK1 could be involved in the insulin resistance mechanism related with IR Ser994 phosphorylation in a genetic model of diabetes