Anti-NAK/TBK1 antibody

Target data

Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed : 10581243, PubMed : 11839743, PubMed : 12692549, PubMed : 12702806, PubMed : 14703513, PubMed : 15367631, PubMed : 15485837, PubMed : 18583960, PubMed : 21138416, PubMed : 23453971, PubMed : 23453972, PubMed : 23746807, PubMed : 25636800, PubMed : 26611359, PubMed : 32404352, PubMed : 34363755). 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 : 12702806, PubMed : 14703513, PubMed : 15367631, PubMed : 18583960, 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 ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (PubMed : 31709703). 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). Acts both as a positive and negative regulator of the mTORC1 complex, depending on the context : activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR, while it limits the mTORC1 complex by promoting phosphorylation of RPTOR (PubMed : 29150432, PubMed : 31530866). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (PubMed : 34363755). Participates also in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed : 27135603).