TANK-binding kinase 1

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TANK-binding kinase 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TBK1 ; NAK; T2K
External IDs OMIM604834 MGI1929658 HomoloGene22742 ChEMBL: 5408 GeneCards: TBK1 Gene
EC number 2.7.11.1
RNA expression pattern
PBB GE TBK1 218520 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 29110 56480
Ensembl ENSG00000183735 ENSMUSG00000020115
UniProt Q9UHD2 Q9WUN2
RefSeq (mRNA) NM_013254 NM_019786
RefSeq (protein) NP_037386 NP_062760
Location (UCSC) Chr 12:
64.85 – 64.9 Mb
Chr 10:
121.55 – 121.59 Mb
PubMed search [1] [2]

Serine/threonine-protein kinase TBK1 is an enzyme that in humans is encoded by the TBK1 gene.[1][2][3]

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.[3]

Interactions[edit]

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

Transcriptional factors activated upon TBK1 activation include IRF3, IRF7 [7] and ZEB1. [8]


Clinical significance[edit]

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.[9]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b "Entrez Gene: TBK1 TANK-binding kinase 1". 
  4. ^ 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. PMID 7706279. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ Ikeda F (Jun 2017). "Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes.". Embo J. 26. PMID 17599067. 
  8. ^ 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. PMID 24468793. 
  9. ^ 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. 

Further reading[edit]