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NAK / TBK1
TANK-binding kinase 1
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. Phosphorylates and activates AKT1. 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. Phosphorylates Borna disease virus (BDV) P protein.
TBK1 does not play a role in the control of in vitro Burkholderia pseudomallei growth. Panomket P, Splitter G, Harms J, Sermswan RW, Chedchotisakd P, Wongratanacheewin S. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2008 S95-100. (WB)
Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease. Pottier C, Bieniek KF, Finch N, van de Vorst M, Baker M, Perkersen R, Brown P, Ravenscroft T, van Blitterswijk M, Nicholson AM, DeTure M, Knopman DS, Josephs KA, Parisi JE, Petersen RC, Boylan KB, Boeve BF, Graff-Radford NR, Veltman JA, Gilissen C, Murray ME, Dickson DW, Rademakers R. Acta neuropathologica. 2015 130:77-92. (IHC; Human)[Full Text Article]
Related Antibodies: LS-B1317.