TANK-binding kinase 1

TBK1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4EFO, 4EUT, 4EUU, 4IM0, 4IM2, 4IM3, 4IW0, 4IWO, 4IWP, 4IWQ
Identifiers
Aliases	TBK1, Tbk1, 1200008B05Rik, AI462036, AW048562, NAK, T2K, FTDALS4, TANK binding kinase 1, IIAE8
External IDs	OMIM: 604834; MGI: 1929658; HomoloGene: 22742; GeneCards: TBK1; OMA:TBK1 - orthologs
Gene location (Human)
Chr.	Chromosome 12 (human)
End	64,502,114 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	121,422,692 bp
RNA expression pattern
	Top expressed in
	epithelium of colon; ; Achilles tendon; ; lateral nuclear group of thalamus; ; secondary oocyte; ; sperm; ; monocyte; ; sural nerve; ; ventricular zone; ; tonsil; ; bone marrow cells;
	Top expressed in
	Paneth cell; ; facial motor nucleus; ; condyle; ; Epithelium of choroid plexus; ; fossa; ; substantia nigra; ; conjunctival fornix; ; iris; ; stroma of bone marrow; ; vestibular membrane of cochlear duct;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	transferase activity; nucleotide binding; kinase activity; protein serine/threonine kinase activity; phosphoprotein binding; protein binding; nucleic acid binding; ATP binding; protein kinase activity; identical protein binding; protein phosphatase binding;
Cellular component	cytoplasm; cytosol; endosome membrane; nucleoplasm; aggresome;
Biological process	phosphorylation; positive regulation of interferon-alpha production; immune system process; response to virus; positive regulation of xenophagy; negative regulation of gene expression; positive regulation of peptidyl-serine phosphorylation; TRIF-dependent toll-like receptor signaling pathway; type I interferon production; defense response to virus; peptidyl-serine phosphorylation; regulation of neuron death; activation of innate immune response; positive regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of type I interferon production; innate immune response; viral process; inflammatory response; I-kappaB kinase/NF-kappaB signaling; positive regulation of type I interferon production; positive regulation of transcription by RNA polymerase II; dendritic cell proliferation; defense response to Gram-positive bacterium; positive regulation of interferon-beta production; regulation of type I interferon production; positive regulation of macroautophagy; peptidyl-threonine phosphorylation; protein phosphorylation; cellular response to cytokine stimulus; regulation of gene expression; regulation of cellular metabolic process; positive regulation of type I interferon-mediated signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	29110
	56480
	ENSG00000183735
	ENSMUSG00000020115
	Q9UHD2
	Q9WUN2
	NM_013254
	NM_019786
	NP_037386
	NP_062760
	Wikidata
View/Edit Human	View/Edit Mouse

Serine/threonine-protein kinase TBK1 is an enzyme that in humans is encoded by the TBK1 gene.^[5]^[6]^[7]

Template:PBB Summary

Interactions

TANK-binding kinase 1 has been shown to interact with:

Transcriptional factors activated upon TBK1 activation include IRF3, IRF7 ^[11] and ZEB1. ^[12]

Clinical significance

Inhibition of IκB kinase (IKK) and IKK-related kinases, IKBKE (IKKε) and TANK-binding kinase 1 (TBK1), has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer.^[13]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000183735 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020115 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Pomerantz JL, Baltimore D (January 2000). "NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase". EMBO J. 18 (23): 6694–704. doi:10.1093/emboj/18.23.6694. PMC 1171732. PMID 10581243.
^ Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M (May 2000). "NAK is an IkappaB kinase-activating kinase". Nature. 404 (6779): 778–82. doi:10.1038/35008109. PMID 10783893.
^ "Entrez Gene: TBK1 TANK-binding kinase 1".
^ Chou MM, Hanafusa H (March 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^a ^b Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 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.
^ Bonnard M, Mirtsos C, Suzuki S, Graham K, Huang J, Ng M, Itié A, Wakeham A, Shahinian A, Henzel WJ, Elia AJ, Shillinglaw W, Mak TW, Cao Z, Yeh WC (September 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.
^ Ikeda F (Jun 2007). "Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes". EMBO J. 26 (14). doi:10.1038/sj.emboj.7601773. PMC 1933404. PMID 17599067.
^ Liu W (Apr 2014). "Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3β and repression of ZEB1". Lab Invest. 94 (4): 362–370. doi:10.1038/labinvest.2013.153. PMID 24468793.
^ Llona-Minguez S, Baiget J, Mackay SP (2013). "Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases". Pharm Pat Anal. 2 (4): 481–98. doi:10.4155/ppa.13.31. PMID 24237125.

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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.
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. doi:10.4049/jimmunol.171.8.4304. 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.
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.
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
{{Cite journal |vauthors=Buss H, Dörrie A, Schmitz ML, etal |title=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. |journal=J. Biol. Chem. |volume=279 |issue= 53 |pages= 55633–43 |year= 2005 |pmid= 15489227 |doi= 10.1074/jbc.M409825200 }}

}}

Template:PBB Controls

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000183735 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020115 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10581243-5] Pomerantz JL, Baltimore D (January 2000). "NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase". EMBO J. 18 (23): 6694–704. doi:10.1093/emboj/18.23.6694. PMC 1171732. PMID 10581243.

[pmid10783893-6] Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M (May 2000). "NAK is an IkappaB kinase-activating kinase". Nature. 404 (6779): 778–82. doi:10.1038/35008109. PMID 10783893.

[entrez-7] "Entrez Gene: TBK1 TANK-binding kinase 1".

[pmid7706279-8] Chou MM, Hanafusa H (March 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[pmid14743216-9] Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 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.

[pmid10990461-10] Bonnard M, Mirtsos C, Suzuki S, Graham K, Huang J, Ng M, Itié A, Wakeham A, Shahinian A, Henzel WJ, Elia AJ, Shillinglaw W, Mak TW, Cao Z, Yeh WC (September 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.

[pmid_=_17599067-11] Ikeda F (Jun 2007). "Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes". EMBO J. 26 (14). doi:10.1038/sj.emboj.7601773. PMC 1933404. PMID 17599067.

[pmid_=_24468793-12] Liu W (Apr 2014). "Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3β and repression of ZEB1". Lab Invest. 94 (4): 362–370. doi:10.1038/labinvest.2013.153. PMID 24468793.

[pmid24237125-13] Llona-Minguez S, Baiget J, Mackay SP (2013). "Small-molecule inhibitors of IκB kinase (IKK) and IKK-related kinases". Pharm Pat Anal. 2 (4): 481–98. doi:10.4155/ppa.13.31. PMID 24237125.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Interactions

Clinical significance

References

Further reading