TANK-binding kinase 1

TANK-binding kinase 1
Identifiers
Symbols	TBK1; FLJ11330; NAK; T2K
External IDs	OMIM: 604834 MGI: 1929658 HomoloGene: 22742 GeneCards: TBK1 Gene
EC number	2.7.11.1
Gene Ontology Molecular function • nucleotide binding • protein kinase activity • protein serine/threonine kinase activity • protein binding • ATP binding • phosphoprotein binding Cellular component • cytoplasm • cytosol • cytosol • plasma membrane • endosome membrane • endosome membrane Biological process • activation of innate immune response • MyD88-independent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • protein phosphorylation • I-kappaB kinase/NF-kappaB cascade • Toll signaling pathway • response to virus • negative regulation of gene expression • negative regulation of type I interferon production • positive regulation of interferon-alpha production • positive regulation of interferon-beta production • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • positive regulation of I-kappaB kinase/NF-kappaB cascade • interspecies interaction between organisms • innate immune response • positive regulation of interferon-beta biosynthetic process • positive regulation of transcription from RNA polymerase II promoter • defense response to Gram-positive bacterium Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	29110	56480
Ensembl	ENSG00000183735	ENSMUSG00000020115
UniProt	Q9UHD2	Q3THP3
RefSeq (mRNA)	NM_013254	NM_019786.4
RefSeq (protein)	NP_037386	NP_062760.3
Location (UCSC)	Chr 12: 64.85 – 64.9 Mb	Chr 10: 120.98 – 121.02 Mb
PubMed search	[1]	[2]

Serine/threonine-protein kinase TBK1 is an enzyme that in humans is encoded by the TBK1 gene.

The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. For example, the protein can form a complex with the IKB protein TANK and TRAF2 and release the NFKB inhibition caused by TANK.

Interactions

TANK-binding kinase 1 has been shown to interact with NCK1, TRAF2 and TANK.

Further reading

• Chou MM, Hanafusa H (1995). "A novel ligand for SH3 domains. The Nck adaptor protein binds to a serine/threonine kinase via an SH3 domain.". J. Biol. Chem. 270 (13): 7359–64. doi:10.1074/jbc.270.13.7359. PMID 7706279. 
• Chen ZJ, Parent L, Maniatis T (1996). "Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity.". Cell 84 (6): 853–62. doi:10.1016/S0092-8674(00)81064-8. PMID 8601309. 
• Zandi E, Chen Y, Karin M (1998). "Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate.". Science 281 (5381): 1360–3. doi:10.1126/science.281.5381.1360. PMID 9721103. 
• Bonnard M, Mirtsos C, Suzuki S, et al. (2000). "Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription.". EMBO J. 19 (18): 4976–85. doi:10.1093/emboj/19.18.4976. PMC 314216. PMID 10990461. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=314216. 
• Kishore N, Huynh QK, Mathialagan S, et al. (2002). "IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2.". J. Biol. Chem. 277 (16): 13840–7. doi:10.1074/jbc.M110474200. PMID 11839743. 
• Chariot A, Leonardi A, Muller J, et al. (2002). "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.". J. Biol. Chem. 277 (40): 37029–36. doi:10.1074/jbc.M205069200. PMID 12133833. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Li SF, Fujita F, Hirai M, et al. (2003). "Genomic structure and characterization of the promoter region of the human NAK gene.". Gene 304: 57–64. doi:10.1016/S0378-1119(02)01179-4. PMID 12568715. 
• Fitzgerald KA, McWhirter SM, Faia KL, et al. (2003). "IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.". Nat. Immunol. 4 (5): 491–6. doi:10.1038/ni921. PMID 12692549. 
• Sharma S, tenOever BR, Grandvaux N, et al. (2003). "Triggering the interferon antiviral response through an IKK-related pathway.". Science 300 (5622): 1148–51. doi:10.1126/science.1081315. PMID 12702806. 
• Matsuda A, Suzuki Y, Honda G, et al. (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.". Oncogene 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501. 
• Sato S, Sugiyama M, Yamamoto M, et al. (2004). "Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling.". J. Immunol. 171 (8): 4304–10. PMID 14530355. 
• Fujita F, Taniguchi Y, Kato T, et al. (2003). "Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling.". Mol. Cell. Biol. 23 (21): 7780–93. doi:10.1128/MCB.23.21.7780-7793.2003. PMC 207563. PMID 14560022. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=207563. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. 
• tenOever BR, Sharma S, Zou W, et al. (2004). "Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity.". J. Virol. 78 (19): 10636–49. doi:10.1128/JVI.78.19.10636-10649.2004. PMC 516426. PMID 15367631. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=516426. 
• Kuai J, Wooters J, Hall JP, et al. (2005). "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.". J. Biol. Chem. 279 (51): 53266–71. doi:10.1074/jbc.M411037200. PMID 15485837. 
• Buss H, Dörrie A, Schmitz ML, et al. (2005). "Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription.". J. Biol. Chem. 279 (53): 55633–43. doi:10.1074/jbc.M409825200. PMID 15489227.