TBK1
entrez
29110
canonical
uniprot
Q9UHD2
canonical
ensembl
ENSG00000183735
resolver
ensp
ENSP00000329967
resolver
ensp
ENSP00000498995
resolver
ensp
ENSP00000581989
resolver
ensp
ENSP00000640178
resolver
enst
ENST00000331710
resolver
enst
ENST00000650790
resolver
enst
ENST00000911930
resolver
enst
ENST00000970119
resolver
genesymbol
TBK1
resolver
genesymbol_syn
NAK
resolver
hgnc
HGNC:11584
resolver
uniprot
A8K4S4
resolver
uniprot
Q8IYV3
resolver
uniprot
Q9NUJ5
resolver
uniprot_entry
TBK1_HUMAN
resolver
uniprot_sec
A8K4S4
resolver
uniprot_sec
Q8IYV3
resolver
uniprot_sec
Q9NUJ5
resolver
amino_acid_sequence
MQSTSNHLWLLSDILGQGATANVFRGRHKKTGDLFAIKVFNNISFLRPVDVQMREFEVLKKLNHKNIVKLFAIEEETTTRHKVLIMEFCPCGSLYTVLEEPSNAYGLPESEFLIVLRDVVGGMNHLRENGIVHRDIKPGNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLYGTEEYLHPDMYERAVLRKDHQKKYGATVDLWSIGVTFYHAATGSLPFRPFEGPRRNKEVMYKIITGKPSGAISGVQKAENGPIDWSGDMPVSCSLSRGLQVLLTPVLANILEADQEKCWGFDQFFAETSDILHRMVIHVFSLQQMTAHKIYIHSYNTATIFHELVYKQTKIISSNQELIYEGRRLVLEPGRLAQHFPKTTEENPIFVVSREPLNTIGLIYEKISLPKVHPRYDLDGDASMAKAITGVVCYACRIASTLLLYQELMRKGIRWLIELIKDDYNETVHKKTEVVITLDFCIRNIEKTVKVYEKLMKINLEAAELGEISDIHTKLLRLSSSQGTIETSLQDIDSRLSPGGSLADAWAHQEGTHPKDRNVEKLQVLLNCMTEIYYQFKKDKAERRLAYNEEQIHKFDKQKLYYHATKAMTHFTDECVKKYEAFLNKSEEWIRKMLHLRKQLLSLTNQCFDIEEEVSKYQEYTNELQETLPQKMFTASSGIKHTMTPIYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGSLTMDGGLRNVDCL
uniprot
proteins
disease_involvement
DISEASE: Glaucoma 1, open angle, P (GLC1P) [MIM:177700]: 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. {ECO:0000269|PubMed:21447600, ECO:0000269|PubMed:22306015}. Note=The disease may be caused by variants affecting the gene represented in this entry. A copy number variation on chromosome 12q14 consisting of a 300 kb duplication that includes TBK1, XPOT, RASSF3 and GNS has been found in individuals affected by glaucoma. TBK1 is the most likely candidate for the disorder (PubMed:21447600). {ECO:0000269|PubMed:21447600}.; DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4) [MIM:616439]: 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. {ECO:0000269|PubMed:25803835, ECO:0000269|PubMed:25943890}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Encephalopathy, acute, infection-induced, 8, herpes-specific (IIAE8) [MIM:617900]: 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. {ECO:0000269|PubMed:22851595, ECO:0000269|PubMed:26513235}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Autoinflammation with arthritis and vasculitis (AIARV) [MIM:620880]: An autosomal recessive disorder characterized by onset of chronic and systemic autoinflammation in infancy or early childhood. Affected individuals have recurrent fever, erythematous skin rashes, vasculitis, oral aphthous lesions, and polyarthritis. Additional variable features are poor overall growth, microcytic anemia, mild intellectual disability, and seizures. {ECO:0000269|PubMed:32447396, ECO:0000269|PubMed:34363755}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: 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, PubMed:32298923). 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, PubMed:37926288, PubMed:38917796). 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). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, which 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). Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR, leading to increased phosphorylation and activation of AKT1 (By similarity). Phosphorylates and activates AKT1 (PubMed:21464307). 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). Also participates in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed:27135603). {ECO:0000250|UniProtKB:Q9WUN2, ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:12692549, ECO:0000269|PubMed:12702806, ECO:0000269|PubMed:14703513, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:15489227, ECO:0000269|PubMed:16155125, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21270402, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:22851595, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:23746807, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:26611359, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27135603, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:31530866, ECO:0000269|PubMed:31709703, ECO:0000269|PubMed:32298923, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:34363755, ECO:0000269|PubMed:37926288, ECO:0000269|PubMed:38917796}.
uniprot
proteins
mass_dalton
83642
uniprot
proteins
mutagenesis
MUTAGEN 30; /note="K->R: Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-401."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 33; /note="D->A: Decreases phosphorylation and kinase activity."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 38; /note="K->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:22851595, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:31530866, ECO:0000269|PubMed:31709703"; MUTAGEN 135; /note="D->N: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:30842653"; MUTAGEN 172; /note="S->A: Loss of kinase activity. No effect on dimerization. Loss of USP38-mediated degradation."; /evidence="ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:27692986"; MUTAGEN 172; /note="S->E: Decreased kinase activity."; /evidence="ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:23453972"; MUTAGEN 316; /note="L->E: Decreases kinase activity. No effect on phosphorylation."; /evidence="ECO:0000269|PubMed:23453972"; MUTAGEN 325; /note="Y->E: Abolishes phosphorylation and kinase activity."; /evidence="ECO:0000269|PubMed:23453972"; MUTAGEN 355; /note="E->R: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with A-357 or R-448."; /evidence="ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972"; MUTAGEN 357; /note="R->A: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 401; /note="K->R: Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-30."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 448; /note="E->R: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355."; /evidence="ECO:0000269|PubMed:23453972"; MUTAGEN 459; /note="H->E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-466 and E-470."; /evidence="ECO:0000269|PubMed:23453972"; MUTAGEN 466; /note="I->E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-470."; /evidence="ECO:0000269|PubMed:23453972"; MUTAGEN 470; /note="F->E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-466."; /evidence="ECO:0000269|PubMed:23453972"; MUTAGEN 547; /note="R->D: Decreases phosphorylation and kinase activity. Abolishes dimerization."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 577; /note="Y->A: Decreases kinase activity. Reduced phosphorylation of STING1."; /evidence="ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:30842653"; MUTAGEN 578; /note="N->A: Reduced phosphorylation of STING1."; /evidence="ECO:0000269|PubMed:30842653"; MUTAGEN 580; /note="E->A: Decreases kinase activity."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 581; /note="Q->A: Reduced phosphorylation of STING1."; /evidence="ECO:0000269|PubMed:30842653"; MUTAGEN 582; /note="I->A: Decreases kinase activity."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 584; /note="K->A: Decreased IFNB1 promoter activation."; /evidence="ECO:0000269|PubMed:37926288"; MUTAGEN 589; /note="K->D: Decreases phosphorylation and kinase activity."; /evidence="ECO:0000269|PubMed:23453971"; MUTAGEN 607; /note="K->A,R: Attenuated homodimerization during Sendai virus infection; decreased interaction with IRF3 or MAVS; decreased IFNB1 promoter activation."; /evidence="ECO:0000269|PubMed:37926288"; MUTAGEN 670; /note="K->R: Abrogates both 'Lys-48'-linked and 'Lys-33'-linked ubiquitination."; /evidence="ECO:0000269|PubMed:27692986"; MUTAGEN 690; /note="M->A: Decreases interaction with TANK."; /evidence="ECO:0000269|PubMed:21931631"; MUTAGEN 693; /note="L->A: Almost abolishes interaction with TANK."; /evidence="ECO:0000269|PubMed:21931631"; MUTAGEN 694; /note="K->E: Strongly decreases interaction with TANK and TBKBP1. No effect on phosphorylation."; /evidence="ECO:0000269|PubMed:21931631"; MUTAGEN 704; /note="L->A: Strongly decreases interaction with AZI2, TANK and TBKBP1. No effect on phosphorylation."; /evidence="ECO:0000269|PubMed:21931631"; MUTAGEN 708; /note="N->A: Decreases interaction with TANK."; /evidence="ECO:0000269|PubMed:21931631"; MUTAGEN 711; /note="L->A: Almost abolishes interaction with TANK."; /evidence="ECO:0000269|PubMed:21931631
uniprot
proteins
post_translational_modification
PTM: Autophosphorylation at Ser-172 activates the kinase, and is an essential step for virus-triggered signaling. Phosphorylated by IKBKB/IKKB at Ser-172. Phosphorylation requires homodimerization and ubiquitination at Lys-30 and Lys-401. Dephosphorylated at Ser-172 by PPM1B and this negatively regulates its role in mediating antiviral response. {ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23746807}.; PTM: 'Lys-63'-linked polyubiquitination by MIB1 after RNA virus infection, or by NRDP1 after LPS stimulation at Lys-30 and Lys-401, participates in kinase activation (PubMed:23453971). 'Lys-48'-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation (PubMed:22388039). 'Lys-48'-linked polyubiquitination by TRAIP also leads to proteasomal degradation (PubMed:32366851). 'Lys-48'-linked polyubiquitination by TRAF7; leading to proteasomal degradation (PubMed:38917796). 'Lys-63'-linked polyubiquitination by RNF128 at Lys-30 and Lys-401 leads to the activation of antiviral responses (PubMed:27776110). 'Lys-48'-linked polyubiquitination after 'lys-33'-linked deubiquitination by USP38 promotes TBK1 degradation (PubMed:27692986). 'Lys-63'-linked polyubiquitination by PELI2 inhibits cGAS-STING signaling (PubMed:38917796). {ECO:0000269|PubMed:22388039, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:27692986, ECO:0000269|PubMed:27776110, ECO:0000269|PubMed:32366851, ECO:0000269|PubMed:37086853, ECO:0000269|PubMed:38917796}.; PTM: (Microbial infection) Interaction with SARS-CoV-2 M protein induces 'Lys-48'-linked ubiquitination which leads to proteasomal degradation. {ECO:0000269|PubMed:34084167}.; PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to inhibition of type I interfewron production. {ECO:0000269|PubMed:36802409}.; PTM: Monomethylation at Lys-607 by SETD4 maximizes TBK1 activation and promotes efficient interferon signaling. {ECO:0000269|PubMed:37926288}.
uniprot
proteins
protein_family
I-kappa-B kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
10581243
uniprot
proteins
pubmed
10783893
uniprot
proteins
pubmed
11839743
uniprot
proteins
pubmed
12692549
uniprot
proteins
pubmed
12702806
uniprot
proteins
pubmed
14530355
uniprot
proteins
pubmed
14560022
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14703513
uniprot
proteins
pubmed
14739303
uniprot
proteins
pubmed
15367631
uniprot
proteins
pubmed
15485837
uniprot
proteins
pubmed
15489227
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15841462
uniprot
proteins
pubmed
16155125
uniprot
proteins
pubmed
16281057
uniprot
proteins
pubmed
17018283
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17599067
uniprot
proteins
pubmed
18583960
uniprot
proteins
pubmed
18636086
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19010780
uniprot
proteins
pubmed
19153231
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19416887
uniprot
proteins
pubmed
19419966
uniprot
proteins
pubmed
19483718
uniprot
proteins
pubmed
20174559
uniprot
proteins
pubmed
20375222
uniprot
proteins
pubmed
20628368
uniprot
proteins
pubmed
21042276
uniprot
proteins
pubmed
21138416
uniprot
proteins
pubmed
21145761
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21270402
uniprot
proteins
pubmed
21447600
uniprot
proteins
pubmed
21464307
uniprot
proteins
pubmed
21617041
uniprot
proteins
pubmed
21813773
uniprot
proteins
pubmed
21903422
uniprot
proteins
pubmed
21931631
uniprot
proteins
pubmed
22306015
uniprot
proteins
pubmed
22388039
uniprot
proteins
pubmed
22750291
uniprot
proteins
pubmed
22851595
uniprot
proteins
pubmed
22945920
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23453971
uniprot
proteins
pubmed
23453972
uniprot
proteins
pubmed
23746807
uniprot
proteins
pubmed
24478431
uniprot
proteins
pubmed
24706939
uniprot
proteins
pubmed
25636800
uniprot
proteins
pubmed
25736436
uniprot
proteins
pubmed
25803835
uniprot
proteins
pubmed
25943890
uniprot
proteins
pubmed
26513235
uniprot
proteins
pubmed
26611359
uniprot
proteins
pubmed
27103069
uniprot
proteins
pubmed
27135603
uniprot
proteins
pubmed
27692986
uniprot
proteins
pubmed
27776110
uniprot
proteins
pubmed
28011935
uniprot
proteins
pubmed
28373913
uniprot
proteins
pubmed
28680969
uniprot
proteins
pubmed
28848048
uniprot
proteins
pubmed
28871090
uniprot
proteins
pubmed
28904192
uniprot
proteins
pubmed
29150432
uniprot
proteins
pubmed
29251827
uniprot
proteins
pubmed
30021900
uniprot
proteins
pubmed
30354798
uniprot
proteins
pubmed
30842653
uniprot
proteins
pubmed
31320558
uniprot
proteins
pubmed
31509299
uniprot
proteins
pubmed
31530866
uniprot
proteins
pubmed
31709703
uniprot
proteins
pubmed
32185393
uniprot
proteins
pubmed
32209697
uniprot
proteins
pubmed
32298923
uniprot
proteins
pubmed
32366851
uniprot
proteins
pubmed
32404352
uniprot
proteins
pubmed
32447396
uniprot
proteins
pubmed
32466380
uniprot
proteins
pubmed
32972995
uniprot
proteins
pubmed
32979938
uniprot
proteins
pubmed
33226137
uniprot
proteins
pubmed
34084167
uniprot
proteins
pubmed
34363755
uniprot
proteins
pubmed
36802409
uniprot
proteins
pubmed
37086853
uniprot
proteins
pubmed
37926288
uniprot
proteins
pubmed
38917796
uniprot
proteins
sequence_length
729
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:21813773, ECO:0000269|PubMed:29251827, ECO:0000269|PubMed:32298923}. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2. {ECO:0000269|PubMed:17018283}.
uniprot
proteins