Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:15210742, PubMed:15661922). Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X (By similarity). This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB (By similarity). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (By similarity). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (By similarity). Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (By similarity). Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus (By similarity). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (By similarity). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (By similarity). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (By similarity). Phosphorylates and activates AKT1 (By similarity). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity (PubMed:23396211). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Kinase activity is inhibited competitively by amlexanox. Homodimer (PubMed:23746807). Interacts with DDX3X, TIRAP and TRAF2 (By similarity). Part of a ternary complex consisting of TANK, TRAF2 and TBK1 (By similarity). Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation (By similarity). Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation (By similarity). Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation (By similarity). Interacts with IRF3, leading to IRF3 phosphorylation (By similarity). Interacts with DDX58/RIG-I (By similarity). Interacts with CYLD (By similarity). Interacts with OPTN and TRAF3 (By similarity). Interacts with SRC (By similarity). Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity (By similarity). Interacts with STING1, leading to STING1 phosphorylation (By similarity). Interacts with IFIT3 (via N-terminus) (By similarity). Interacts with MAVS; interaction only takes place in the presence of IFIT3 and leads to MAVS phosphorylation (By similarity). Interacts (via protein kinase domain) with TTLL12 (via TTL domain); the interaction prevents MAVS binding to TBK1 (By similarity). Interacts with TICAM1; this interaction is enhanced in the presence of WDFY1 and leads to TICAM1 phosphorylation (By similarity). Interacts with TRIM26 (By similarity). Interacts with TRIM23 (By similarity). Interacts with TTC4 and IKBKE (By similarity). Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with DDX3X (By similarity). Interacts with TRIM14 (By similarity). Interacts with CEP170; efficient complex formation may be dependent on the presence of CCDC61 (By similarity). Interacts with TRAF3IP3 (By similarity). Interacts with HSP90AA1; the interaction mediates TBK1 association with TOMM70 (By similarity). Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2. Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal coiled-coil region mediating homodimerization. Autophosphorylation at Ser-172 activates the kinase, and is an essential step for virus-triggered signaling. Phosphorylated by IKBKB/IKKB at Ser-172. Phosphorylation requires homodimerization and ubiquitination at Lys-30 and Lys-401. Dephosphorylated at Ser-172 by PPM1B and this negatively regulates its role in mediating antiviral response. 'Lys-63'-linked polyubiquitination by MIB1 after RNA virus infection, or by NRDP1 after LPS stimulation at Lys-30 and Lys-401, participates in kinase activation. 'Lys-48'-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation. 'Lys-48'-linked polyubiquitination by TRAIP also leads to proteasomal degradation. 'Lys-63'-linked polyubiquitination by RNF128 at Lys-30 and Lys-401 leads to the activation of antiviral responses. Mice display embryonic lethality at 14.5 dpc due to massive liver degeneration and apoptosis. Embryonic fibroblasts from mice lacking Tbk1 exhibit dramatically reduced transcription of NF-kappa-B, as well as marked defects in interferon alpha and beta, and RANTES gene expression after infection with Sendai or Newcastle disease virus. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.