Tbk1
entrez
56480
canonical
uniprot
Q9WUN2
canonical
ensembl
ENSMUSG00000020115
resolver
ensp
ENSMUSP00000020316
resolver
enst
ENSMUST00000020316
resolver
genesymbol
Tbk1
resolver
uniprot
A1L361
resolver
uniprot
Q9CT90
resolver
uniprot
Q9DC03
resolver
uniprot_entry
A1L361_MOUSE
resolver
uniprot_entry
TBK1_MOUSE
resolver
uniprot_sec
Q9CT90
resolver
uniprot_sec
Q9DC03
resolver
activity_regulation
ACTIVITY REGULATION: Kinase activity is inhibited competitively by amlexanox. {ECO:0000269|PubMed:23396211}.
uniprot
proteins
amino_acid_sequence
MQSTSNHLWLLSDILGQGATANVFRGRHKKTGDLYAVKVFNNISFLRPVDVQMREFEVLKKLNHKNIVKLFAIEEETTTRHKVLIMEFCPCGSLYTVLEEPSNAYGLPESEFLIVLRDVVGGMNHLRENGIVHRDIKPGNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLYGTEEYLHPDMYERAVLRKDHQKKYGATVDLWSVGVTFYHAATGSLPFRPFEGPRRNKEVMYKIITGKPSGAISGVQKAENGPIDWSGDMPLSCSLSQGLQALLTPVLANILEADQEKCWGFDQFFAETSDVLHRMVIHVFSLQHMTAHKIYIHSYNTAAVFHELVYKQTKIVSSNQELIYEGRRLVLELGRLAQHFPKTTEENPIFVTSREQLNTVGLRYEKISLPKIHPRYDLDGDASMAKAVTGVVCYACRTASTLLLYQELMRKGVRWLVELVKDDYNETVHKKTEVVITLDFCIRNIEKTVKVYEKLMKVNLEAAELGEISDIHTKLLRLSSSQGTIESSLQDISSRLSPGGLLADTWAHQEGTHPRDRNVEKLQVLLNCITEIYYQFKKDKAERRLAYNEEQIHKFDKQKLYYHATKAMSHFSEECVRKYEAFKDKSEEWMRKMLHLRKQLLSLTNQCFDIEEEVSKYQDYTNELQETLPQKMLAASGGVKHAMAPIYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGSLTMDGGLRNVDCL
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:15210742, PubMed:15661922). 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 (By similarity). 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 (By similarity). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (By similarity). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (By similarity). 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 (By similarity). 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 (By similarity). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (By similarity). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (By similarity). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (By similarity). 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 (PubMed:23396211). 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 (By similarity). Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR, leading to increased phosphorylation and activation of AKT1 (PubMed:34245780). Phosphorylates and activates AKT1 (By similarity). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (By similarity). Also participates in the differentiation of T follicular regulatory cells together with the receptor ICOS (By similarity). {ECO:0000250|UniProtKB:Q9UHD2, ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:15210742, ECO:0000269|PubMed:15661922, ECO:0000269|PubMed:23396211, ECO:0000269|PubMed:34245780}.
uniprot
proteins
mass_dalton
83425
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:0000250|UniProtKB:Q9UHD2}.; 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. 'Lys-48'-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation. 'Lys-48'-linked polyubiquitination by TRAIP also leads to proteasomal degradation. 'Lys-48'-linked polyubiquitination by TRAF7; leading to proteasomal degradation. 'Lys-63'-linked polyubiquitination by RNF128 at Lys-30 and Lys-401 leads to the activation of antiviral responses. 'Lys-48'-linked polyubiquitination after 'lys-33'-linked deubiquitination by USP38 promotes TBK1 degradation. 'Lys-63'-linked polyubiquitination by PELI2 inhibits cGAS-STING signaling. {ECO:0000250|UniProtKB:Q9UHD2}.
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
10990461
uniprot
proteins
pubmed
14679297
uniprot
proteins
pubmed
15210742
uniprot
proteins
pubmed
15661922
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23376065
uniprot
proteins
pubmed
23396211
uniprot
proteins
pubmed
23746807
uniprot
proteins
pubmed
31320558
uniprot
proteins
pubmed
34245780
uniprot
proteins
sequence_length
729
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UHD2}. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2. {ECO:0000250|UniProtKB:Q9UHD2}.
uniprot
proteins