Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:
12692549, PubMed:
14703513, PubMed:
18583960, PubMed:
12702806, PubMed:
15367631, PubMed:
10581243, PubMed:
11839743, PubMed:
15485837, PubMed:
21138416, PubMed:
25636800, PubMed:
23453971, PubMed:
23453972, PubMed:
23746807, PubMed:
26611359, PubMed:
32404352). 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 (PubMed:
12692549, PubMed:
14703513, PubMed:
18583960, PubMed:
12702806, PubMed:
15367631, PubMed:
25636800). 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 (PubMed:
12702806, PubMed:
15367631, PubMed:
25636800, PubMed:
32972995). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:
23453971, PubMed:
23453972, PubMed:
23746807). 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 (PubMed:
25636800, PubMed:
30842653). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:
25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1- containing-complexes (PubMed:
21931631). 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 (PubMed:
10783893, PubMed:
15489227). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:
21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:
27103069). Phosphorylates and activates AKT1 (PubMed:
21464307). 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 (By similarity). Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:
21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:
16155125). Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system (PubMed:
22851595).
