The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TBK1  -  TANK-binding kinase 1

Homo sapiens

Synonyms: NAK, NF-kappa-B-activating kinase, Serine/threonine-protein kinase TBK1, T2K
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TBK1


High impact information on TBK1

  • RalB GTPase-Mediated Activation of the IkappaB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival [6].
  • In tumor cells the RalB/TBK1 pathway inhibits apoptosis and in nontumorigenic cells it stimulates an innate immune response [7].
  • B-DNA signaling by this pathway conferred resistance to viral infection in a way dependent on both TBK1 and IKKi [8].
  • IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway [9].
  • These include the kinase TBK1 as well as Toll-like receptor adaptor molecule and IFN regulatory factor 3 [10].

Chemical compound and disease context of TBK1


Biological context of TBK1


Anatomical context of TBK1

  • This pattern of expression and the decreased expression of angiogenic factors in cultured cells upon RNA-interference-mediated ablation suggests that TBK1 is important for vascularization and subsequent tumor growth and a target for cancer therapy [10].
  • These data suggest that intracellular RNP formation contributes to the early recognition of VSV infection, activates the catalytic activity of TBK1, and induces transcriptional upregulation of IKKepsilon in epithelial cells [1].
  • In addition, no degradation of IRF-3 was observed in TBK1(-/-) mouse embryonic fibroblasts [15].
  • Virus-induced Viperin expression was not attenuated in macrophages deficient in either TBK1 or IKKepsilon alone [16].
  • We further showed that NAK is recruited to TNFR1 in a temporally regulated and TNFalpha-dependent manner and that it mediates the TNFalpha-induced production of the chemokine RANTES (regulated on activation normal T cell expressed and secreted) [17].

Associations of TBK1 with chemical compounds


Enzymatic interactions of TBK1

  • IKK-related kinases TBK1 and IKKepsilon have been shown to phosphorylate and activate IRF-3 and IRF-7, leading to the production of type 1 interferons and the development of a cellular antiviral state [21].

Regulatory relationships of TBK1

  • NAP1 activates NAK and facilitates its oligomerization [22].
  • NAK has been identified as an IkappaB-kinase activating-kinase that plays an important role in NF-kappaB activation in response to several pro-inflammatory cytokines such as TNF-alpha [3].
  • The importance of the ULD of TBK1 in LPS- or poly(I:C)-stimulated IFN-beta production was demonstrated by reconstitution experiments in TBK1-IKK-i-deficient cells [23].

Other interactions of TBK1


  1. Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. tenOever, B.R., Sharma, S., Zou, W., Sun, Q., Grandvaux, N., Julkunen, I., Hemmi, H., Yamamoto, M., Akira, S., Yeh, W.C., Lin, R., Hiscott, J. J. Virol. (2004) [Pubmed]
  2. Roles of an IkappaB kinase-related pathway in human cytomegalovirus-infected vascular smooth muscle cells: a molecular link in pathogen-induced proatherosclerotic conditions. Gravel, S.P., Servant, M.J. J. Biol. Chem. (2005) [Pubmed]
  3. Genomic structure and characterization of the promoter region of the human NAK gene. Li, S.F., Fujita, F., Hirai, M., Lu, R., Niida, H., Nakanishi, M. Gene (2003) [Pubmed]
  4. p21-activated kinase 1 plays a critical role in cellular activation by Nef. Fackler, O.T., Lu, X., Frost, J.A., Geyer, M., Jiang, B., Luo, W., Abo, A., Alberts, A.S., Peterlin, B.M. Mol. Cell. Biol. (2000) [Pubmed]
  5. Identification of the Nef-associated kinase as p21-activated kinase 2. Renkema, G.H., Manninen, A., Mann, D.A., Harris, M., Saksela, K. Curr. Biol. (1999) [Pubmed]
  6. RalB GTPase-Mediated Activation of the IkappaB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival. Chien, Y., Kim, S., Bumeister, R., Loo, Y.M., Kwon, S.W., Johnson, C.L., Balakireva, M.G., Romeo, Y., Kopelovich, L., Gale, M., Yeaman, C., Camonis, J.H., Zhao, Y., White, M.A. Cell (2006) [Pubmed]
  7. RalB Signaling: A Bridge between Inflammation and Cancer. Mantovani, A., Balkwill, F. Cell (2006) [Pubmed]
  8. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Ishii, K.J., Coban, C., Kato, H., Takahashi, K., Torii, Y., Takeshita, F., Ludwig, H., Sutter, G., Suzuki, K., Hemmi, H., Sato, S., Yamamoto, M., Uematsu, S., Kawai, T., Takeuchi, O., Akira, S. Nat. Immunol. (2006) [Pubmed]
  9. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Fitzgerald, K.A., McWhirter, S.M., Faia, K.L., Rowe, D.C., Latz, E., Golenbock, D.T., Coyle, A.J., Liao, S.M., Maniatis, T. Nat. Immunol. (2003) [Pubmed]
  10. Identification of proangiogenic genes and pathways by high-throughput functional genomics: TBK1 and the IRF3 pathway. Korherr, C., Gille, H., Schäfer, R., Koenig-Hoffmann, K., Dixelius, J., Egland, K.A., Pastan, I., Brinkmann, U. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Infectivity enhancement by human immunodeficiency virus type 1 Nef is independent of its association with a cellular serine/threonine kinase. Luo, T., Livingston, R.A., Garcia, J.V. J. Virol. (1997) [Pubmed]
  12. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. McWhirter, S.M., Fitzgerald, K.A., Rosains, J., Rowe, D.C., Golenbock, D.T., Maniatis, T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  13. Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells. Yang, K., Shi, H., Qi, R., Sun, S., Tang, Y., Zhang, B., Wang, C. Mol. Biol. Cell (2006) [Pubmed]
  14. Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. Han, K.J., Su, X., Xu, L.G., Bin, L.H., Zhang, J., Shu, H.B. J. Biol. Chem. (2004) [Pubmed]
  15. Involvement of the I{kappa}B Kinase (IKK)-Related Kinases Tank-Binding Kinase 1/IKKi and Cullin-Based Ubiquitin Ligases in IFN Regulatory Factor-3 Degradation. Bibeau-Poirier, A., Gravel, S.P., Cl??ment, J.F., Rolland, S., Rodier, G., Coulombe, P., Hiscott, J., Grandvaux, N., Meloche, S., Servant, M.J. J. Immunol. (2006) [Pubmed]
  16. Toll-like receptor-dependent and -independent Viperin gene expression and counter-regulation by PRDI-binding factor-1/BLIMP1. Severa, M., Coccia, E.M., Fitzgerald, K.A. J. Biol. Chem. (2006) [Pubmed]
  17. NAK is recruited to the TNFR1 complex in a TNFalpha-dependent manner and mediates the production of RANTES: identification of endogenous TNFR-interacting proteins by a proteomic approach. Kuai, J., Wooters, J., Hall, J.P., Rao, V.R., Nickbarg, E., Li, B., Chatterjee-Kishore, M., Qiu, Y., Lin, L.L. J. Biol. Chem. (2004) [Pubmed]
  18. Proteomic characterization of the angiogenesis inhibitor SU6668 reveals multiple impacts on cellular kinase signaling. Godl, K., Gruss, O.J., Eickhoff, J., Wissing, J., Blencke, S., Weber, M., Degen, H., Brehmer, D., Orfi, L., Horváth, Z., Kéri, G., Müller, S., Cotten, M., Ullrich, A., Daub, H. Cancer Res. (2005) [Pubmed]
  19. CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Lu, X., Wu, X., Plemenitas, A., Yu, H., Sawai, E.T., Abo, A., Peterlin, B.M. Curr. Biol. (1996) [Pubmed]
  20. The nature and properties of squirrel lens yellow pigment. Zigman, S., Paxhia, T. Exp. Eye Res. (1988) [Pubmed]
  21. A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization. Lin, R., Yang, L., Arguello, M., Penafuerte, C., Hiscott, J. J. Biol. Chem. (2005) [Pubmed]
  22. Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling. Fujita, F., Taniguchi, Y., Kato, T., Narita, Y., Furuya, A., Ogawa, T., Sakurai, H., Joh, T., Itoh, M., Delhase, M., Karin, M., Nakanishi, M. Mol. Cell. Biol. (2003) [Pubmed]
  23. Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. Ikeda, F., Hecker, C.M., Rozenknop, A., Nordmeier, R.D., Rogov, V., Hofmann, K., Akira, S., Dötsch, V., Dikic, I. EMBO J. (2007) [Pubmed]
  24. Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. Chariot, A., Leonardi, A., Muller, J., Bonif, M., Brown, K., Siebenlist, U. J. Biol. Chem. (2002) [Pubmed]
  25. The NF-kappaB pathway in human endometrium and first trimester decidua. King, A.E., Critchley, H.O., Kelly, R.W. Mol. Hum. Reprod. (2001) [Pubmed]
WikiGenes - Universities