TBK1 gene

TANK binding kinase 1

The information on this page was automatically extracted from online scientific databases.

From NCBI Gene:

The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. [provided by RefSeq, Oct 2010]

From UniProt:

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). 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). 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).

Covered on Genetics Home Reference:

From NCBI Gene:

  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 4

From UniProt:

Glaucoma 1, open angle, P (GLC1P): A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. GLC1P is characterized by early onset, thin central corneas and low intraocular pressure. [MIM:177700]

Encephalopathy, acute, infection-induced, herpes-specific, 8 (IIAE8): A rare, often fatal complication of herpes simplex infection, caused by virus spreading in the central nervous system. Disease manifestations include low-grade fever, severe headache, nausea, vomiting, and lethargy. Neurological features include confusion, acute memory disturbances, disorientation, behavioral changes, hemiparesis and seizures. [MIM:617900]

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4): A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. [MIM:616439]

Cytogenetic Location: 12q14.2, which is the long (q) arm of chromosome 12 at position 14.2

Molecular Location: base pairs 64,452,105 to 64,502,114 on chromosome 12 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 12q14.2, which is the long (q) arm of chromosome 12 at position 14.2
  • IIAE8
  • NAK
  • T2K