TANK Binding Kinase 1 (TBK1)

NAK; T2K; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1

SPN	P682
HGNC	11584
MGI	1929658
PubMed	21329883
RGD	1588588
UniProt	Q9UHD2
Wiki	TBK1

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. TANK-Binding Kinase 1 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.The cDNA encodes a deduced 730-amino acid protein that contains a leucine zipper and a helix-loop-helix motif within its C-terminal half. Unlike IKBKA and IKBKB, which each contain 2 serines in their respective activation loops, NAK contains a glutamic acid (glu168) and a serine, which must be phosphorylated for activation. Northern blot analysis revealed ubiquitous expression of a 2.2-kb transcript, with highest expression in testis.

Reference

"NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, a novel IKK-related kinase."
EMBO J. 18:6694-6704(1999) [PubMed] [Europe PMC] [Abstract]

"NAK is an IkappaB kinase-activating kinase."
Nature 404:778-782(2000) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"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. 277:13840-13847(2002) [PubMed] [Europe PMC] [Abstract]

"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. 171:4304-4310(2003) [PubMed] [Europe PMC] [Abstract]

"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway."
Nat. Immunol. 4:491-496(2003) [PubMed] [Europe PMC] [Abstract]

"Triggering the interferon antiviral response through an IKK-related pathway."
Science 300:1148-1151(2003) [PubMed] [Europe PMC] [Abstract]

"Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling."
Mol. Cell. Biol. 23:7780-7793(2003) [PubMed] [Europe PMC] [Abstract]

"Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation."
J. Biol. Chem. 279:9698-9702(2004) [PubMed] [Europe PMC] [Abstract]

"Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways."
J. Biol. Chem. 279:15652-15661(2004) [PubMed] [Europe PMC] [Abstract]

"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. 279:53266-53271(2004) [PubMed] [Europe PMC] [Abstract]

"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. 279:55633-55643(2004) [PubMed] [Europe PMC] [Abstract]

"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. 78:10636-10649(2004) [PubMed] [Europe PMC] [Abstract]

"SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways."
EMBO J. 24:4018-4028(2005) [PubMed] [Europe PMC] [Abstract]

"Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses."
Hepatology 41:1004-1012(2005) [PubMed] [Europe PMC] [Abstract]

"Viral targeting of the interferon-beta-inducing Traf family member-associated NF-kappa-B activator (TANK)-binding kinase-1."
Proc. Natl. Acad. Sci. U.S.A. 102:13640-13645(2005) [PubMed] [Europe PMC] [Abstract]

"RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival."
Cell 127:157-170(2006) [PubMed] [Europe PMC] [Abstract]

"Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes."
EMBO J. 26:3451-3462(2007) [PubMed] [Europe PMC] [Abstract]

"The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response."
EMBO J. 27:2135-2146(2008) [PubMed] [Europe PMC] [Abstract]

"The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response."
EMBO Rep. 9:930-936(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling."
J. Biol. Chem. 284:19122-19131(2009) [PubMed] [Europe PMC] [Abstract]

"Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1."
J. Virol. 83:3069-3077(2009) [PubMed] [Europe PMC] [Abstract]

"Large-scale proteomics analysis of the human kinome."
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]

"The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon."
Nat. Immunol. 10:744-752(2009) [PubMed] [Europe PMC] [Abstract]

"ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response."
Proc. Natl. Acad. Sci. U.S.A. 106:7945-7950(2009) [PubMed] [Europe PMC] [Abstract]

"Glycogen synthase kinase 3beta regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1."
Immunity 33:878-889(2010) [PubMed] [Europe PMC] [Abstract]

"Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection."
PLoS Pathog. 6:E1000778-E1000778(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Copy number variations on chromosome 12q14 in patients with normal tension glaucoma."
Hum. Mol. Genet. 20:2482-2494(2011) [PubMed] [Europe PMC] [Abstract]

"Mapping a dynamic innate immunity protein interaction network regulating type I interferon production."
Immunity 35:426-440(2011) [PubMed] [Europe PMC] [Abstract]

"IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1."
J. Immunol. 187:2559-2568(2011) [PubMed] [Europe PMC] [Abstract]

"TANK-binding kinase 1 attenuates PTAP-dependent retroviral budding through targeting endosomal sorting complex required for transport-I."
J. Immunol. 186:3023-3030(2011) [PubMed] [Europe PMC] [Abstract]

"Functional dissection of the TBK1 molecular network."
PLoS ONE 6:E23971-E23971(2011) [PubMed] [Europe PMC] [Abstract]

"IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth."
Science 333:228-233(2011) [PubMed] [Europe PMC] [Abstract]

"Emerging roles for the non-canonical IKKs in cancer."
Oncogene 30:631-641(2011) [PubMed] [Europe PMC] [Abstract]

"Novel cross-talk within the IKK family controls innate immunity."
Biochem. J. 434:93-104(2011) [PubMed] [Europe PMC] [Abstract]

"PPM1B negatively regulates antiviral response via dephosphorylating TBK1."
Cell. Signal. 24:2197-2204(2012) [PubMed] [Europe PMC] [Abstract]

"Confirmation of TBK1 duplication in normal tension glaucoma."
Exp. Eye Res. 96:178-180(2012) [PubMed] [Europe PMC] [Abstract]

"TRAF-interacting protein (TRIP) negatively regulates IFN-beta production and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1."
J. Exp. Med. 209:1703-1711(2012) [PubMed] [Europe PMC] [Abstract]

"NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4."
Nat. Immunol. 13:387-395(2012) [PubMed] [Europe PMC] [Abstract]

"Crystal structure and mechanism of activation of TANK-binding kinase 1."
Cell Rep. 3:734-746(2013) [PubMed] [Europe PMC] [Abstract]

"Structure and ubiquitination-dependent activation of TANK-binding kinase 1."
Cell Rep. 3:747-758(2013) [PubMed] [Europe PMC] [Abstract]

"Structural insights into the functions of TBK1 in innate antimicrobial immunity."
Structure 21:1137-1148(2013) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]