TBK1, Serine/threonine-protein kinase TBK1
Enzyme Classification 22.214.171.124
Also Known as
TBK1_HUMAN, TBK1, NAK
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. 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. 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. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. 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. 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. 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). Homodimer. Interacts with DDX3X, TIRAP and TRAF2. Part of a ternary complex consisting of TANK, TRAF2 and TBK1. Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation. Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation. Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation. Interacts with IRF3 and DDX58/RIG-I. Interacts with CYLD. Interacts with OPTN and TRAF3. Interacts with SRC. Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity. Interacts with TMEM173/MITA. Interacts with IFIT3 (via N-terminus). Interacts with MAVS only in the presence of IFIT3. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). Interacts with TRIM26 (PubMed:26611359). Interacts with TRIM23 (PubMed:28871090).