TBK1
Description
The TBK1 (TANK binding kinase 1) is a protein-coding gene located on chromosome 12.
TBK1 may refer to:
TBK1 is a serine/threonine kinase that plays a crucial role in regulating inflammatory responses to foreign agents. It is activated by viral or bacterial components through toll-like receptors, leading to the phosphorylation of interferon regulatory factors (IRFs) IRF3 and IRF7, as well as DDX3X. This phosphorylation event triggers dimerization and nuclear translocation of IRFs, ultimately activating the transcription of pro-inflammatory and antiviral genes, including IFNA and IFNB. TBK1 forms various complexes depending on the cell type and stimuli to establish an antiviral state. It is also involved in IRF3 activation by phosphorylating innate adapter proteins MAVS, STING1, and TICAM1, leading to IRF3 recruitment and phosphorylation. Phosphorylated IRF3 then dissociates from the adapter proteins, dimerizes, and enters the nucleus to induce interferon expression. TBK1 can also act as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB, or RELA, resulting in NF-Kappa-B translocation to the nucleus. In addition, TBK1 restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin, enhancing LC3 binding affinity and promoting antibacterial autophagy. It also phosphorylates SMCR8, a component of the C9orf72-SMCR8 complex, promoting autophagosome maturation. TBK1 phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, preventing their delipidation and premature removal from nascent autophagosomes. Furthermore, TBK1 phosphorylates and activates AKT1, suggesting a role in energy balance regulation by sustaining chronic low-grade inflammation in obesity, which negatively impacts insulin sensitivity. TBK1 also attenuates retroviral budding by phosphorylating the ESCRT-I subunit VPS37C. TBK1 plays an essential role in controlling herpes virus HSV-1 and HSV-2 infections in the central nervous system. It acts as both a positive and negative regulator of the mTORC1 complex, activating mTORC1 in response to growth factors by phosphorylating MTOR, while limiting the mTORC1 complex by promoting phosphorylation of RPTOR.
TBK1 is also known as FTDALS4, IIAE8, NAK, T2K.
Associated Diseases
- Frontotemporal dementia with motor neuron disease
- Frontotemporal dementia and/or amyotrophic lateral sclerosis 4
- Herpes simplex virus encephalitis
- Amyotrophic lateral sclerosis
- Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8
