UniProtKB - Q9WUN2 (TBK1_MOUSE)
Serine/threonine-protein kinase TBK1
Tbk1
Functioni
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).
Phosphorylates and activates AKT1 (By similarity).
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 (PubMed:23396211).
By similarity4 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 38 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 135 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 15 – 23 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- nucleic acid binding Source: MGI
- phosphoprotein binding Source: MGI
- protein phosphatase binding Source: ARUK-UCL
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: ParkinsonsUK-UCL
- protein serine kinase activity Source: RHEA
GO - Biological processi
- activation of innate immune response Source: MGI
- defense response to Gram-positive bacterium Source: MGI
- defense response to virus Source: UniProtKB-KW
- dendritic cell proliferation Source: MGI
- innate immune response Source: UniProtKB
- negative regulation of gene expression Source: UniProtKB
- peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
- peptidyl-threonine phosphorylation Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
- positive regulation of interferon-alpha production Source: MGI
- positive regulation of interferon-beta production Source: MGI
- positive regulation of macroautophagy Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of type I interferon-mediated signaling pathway Source: UniProtKB
- positive regulation of xenophagy Source: ParkinsonsUK-UCL
- protein phosphorylation Source: UniProtKB
- regulation of gene expression Source: MGI
- regulation of type I interferon production Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Antiviral defense, Immunity, Innate immunity |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-168928, DDX58/IFIH1-mediated induction of interferon-alpha/beta R-MMU-3134975, Regulation of innate immune responses to cytosolic DNA R-MMU-3249367, STAT6-mediated induction of chemokines R-MMU-3270619, IRF3-mediated induction of type I IFN R-MMU-9008059, Interleukin-37 signaling R-MMU-936440, Negative regulators of DDX58/IFIH1 signaling R-MMU-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase TBK1Curated (EC:2.7.11.1By similarity)Alternative name(s): T2K1 Publication TANK-binding kinase 11 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1929658, Tbk1 |
VEuPathDBi | HostDB:ENSMUSG00000020115 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Note: Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2.By similarity
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: MGI
Other locations
- cytoplasm Source: UniProtKB
- intracellular membrane-bounded organelle Source: MGI
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Disruption phenotypei
Chemistry databases
ChEMBLi | CHEMBL2189160 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086744 | 1 – 729 | Serine/threonine-protein kinase TBK1Add BLAST | 729 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 30 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 172 | Phosphoserine; by autocatalysis and IKKB1 Publication | 1 | |
Cross-linki | 401 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 670 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 716 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q9WUN2 |
MaxQBi | Q9WUN2 |
PaxDbi | Q9WUN2 |
PRIDEi | Q9WUN2 |
ProteomicsDBi | 254666 |
PTM databases
iPTMneti | Q9WUN2 |
PhosphoSitePlusi | Q9WUN2 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000020115, Expressed in paneth cell and 330 other tissues |
Genevisiblei | Q9WUN2, MM |
Interactioni
Subunit structurei
Homodimer (PubMed:23746807).
Interacts with DDX3X, TIRAP and TRAF2 (By similarity).
Part of a ternary complex consisting of TANK, TRAF2 and TBK1 (By similarity).
Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation (By similarity).
Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation (By similarity).
Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation (By similarity).
Interacts with IRF3, leading to IRF3 phosphorylation (By similarity).
Interacts with DDX58/RIG-I (By similarity).
Interacts with CYLD (By similarity).
Interacts with OPTN and TRAF3 (By similarity).
Interacts with SRC (By similarity).
Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity (By similarity).
Interacts with STING1, leading to STING1 phosphorylation (By similarity).
Interacts with IFIT3 (via N-terminus) (By similarity).
Interacts with MAVS; interaction only takes place in the presence of IFIT3 and leads to MAVS phosphorylation (By similarity).
Interacts (via protein kinase domain) with TTLL12 (via TTL domain); the interaction prevents MAVS binding to TBK1 (By similarity).
Interacts with TICAM1; this interaction is enhanced in the presence of WDFY1 and leads to TICAM1 phosphorylation (By similarity).
Interacts with TRIM26 (By similarity).
Interacts with TRIM23 (By similarity).
Interacts with TTC4 and IKBKE (By similarity).
Interacts with HNRNPA2B1 (PubMed:31320558).
Interacts with DDX3X (By similarity).
Interacts with TRIM14 (By similarity).
Interacts with CEP170; efficient complex formation may be dependent on the presence of CCDC61 (By similarity).
Interacts with TRAF3IP3 (By similarity).
Interacts with HSP90AA1; the interaction mediates TBK1 association with TOMM70 (By similarity).
By similarity2 PublicationsBinary interactionsi
Q9WUN2
GO - Molecular functioni
- identical protein binding Source: IntAct
- phosphoprotein binding Source: MGI
- protein phosphatase binding Source: ARUK-UCL
Protein-protein interaction databases
BioGRIDi | 208009, 36 interactors |
DIPi | DIP-29880N |
IntActi | Q9WUN2, 18 interactors |
MINTi | Q9WUN2 |
STRINGi | 10090.ENSMUSP00000020316 |
Chemistry databases
BindingDBi | Q9WUN2 |
Miscellaneous databases
RNActi | Q9WUN2, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q9WUN2 |
SMRi | Q9WUN2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 9 – 310 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 302 | |
Domaini | 309 – 385 | Ubiquitin-likeAdd BLAST | 77 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 621 – 729 | Interaction with AZI2, TANK and TBKBP1By similarityAdd BLAST | 109 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 407 – 657 | 1 PublicationAdd BLAST | 251 | |
Coiled coili | 658 – 713 | Sequence analysisAdd BLAST | 56 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG4250, Eukaryota |
GeneTreei | ENSGT00950000182937 |
HOGENOMi | CLU_000288_101_1_1 |
InParanoidi | Q9WUN2 |
OMAi | DWSADMP |
OrthoDBi | 563981at2759 |
PhylomeDBi | Q9WUN2 |
TreeFami | TF324269 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR041309, TBK1_CCD1 IPR041087, TBK1_ULD |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit PF18394, TBK1_CCD1, 1 hit PF18396, TBK1_ULD, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLYAVKVF NNISFLRPVD
60 70 80 90 100
VQMREFEVLK KLNHKNIVKL FAIEEETTTR HKVLIMEFCP CGSLYTVLEE
110 120 130 140 150
PSNAYGLPES EFLIVLRDVV GGMNHLRENG IVHRDIKPGN IMRVIGEDGQ
160 170 180 190 200
SVYKLTDFGA ARELEDDEQF VSLYGTEEYL HPDMYERAVL RKDHQKKYGA
210 220 230 240 250
TVDLWSVGVT FYHAATGSLP FRPFEGPRRN KEVMYKIITG KPSGAISGVQ
260 270 280 290 300
KAENGPIDWS GDMPLSCSLS QGLQALLTPV LANILEADQE KCWGFDQFFA
310 320 330 340 350
ETSDVLHRMV IHVFSLQHMT AHKIYIHSYN TAAVFHELVY KQTKIVSSNQ
360 370 380 390 400
ELIYEGRRLV LELGRLAQHF PKTTEENPIF VTSREQLNTV GLRYEKISLP
410 420 430 440 450
KIHPRYDLDG DASMAKAVTG VVCYACRTAS TLLLYQELMR KGVRWLVELV
460 470 480 490 500
KDDYNETVHK KTEVVITLDF CIRNIEKTVK VYEKLMKVNL EAAELGEISD
510 520 530 540 550
IHTKLLRLSS SQGTIESSLQ DISSRLSPGG LLADTWAHQE GTHPRDRNVE
560 570 580 590 600
KLQVLLNCIT EIYYQFKKDK AERRLAYNEE QIHKFDKQKL YYHATKAMSH
610 620 630 640 650
FSEECVRKYE AFKDKSEEWM RKMLHLRKQL LSLTNQCFDI EEEVSKYQDY
660 670 680 690 700
TNELQETLPQ KMLAASGGVK HAMAPIYPSS NTLVEMTLGM KKLKEEMEGV
710 720
VKELAENNHI LERFGSLTMD GGLRNVDCL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1W2P6W7 | A0A1W2P6W7_MOUSE | Serine/threonine-protein kinase TBK... | Tbk1 | 121 | Annotation score: | ||
A0A1W2P835 | A0A1W2P835_MOUSE | Serine/threonine-protein kinase TBK... | Tbk1 | 108 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 468 | L → V in BAB23440 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 594 | A → S in BAB23244 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 631 | L → S in BAB23440 (PubMed:16141072).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF191839 mRNA Translation: AAF05990.1 AF145705 mRNA Translation: AAD34590.1 AK004269 mRNA Translation: BAB23244.1 AK004649 mRNA Translation: BAB23440.1 |
CCDSi | CCDS24212.1 |
RefSeqi | NP_062760.3, NM_019786.4 |
Genome annotation databases
Ensembli | ENSMUST00000020316; ENSMUSP00000020316; ENSMUSG00000020115 |
GeneIDi | 56480 |
KEGGi | mmu:56480 |
UCSCi | uc007hft.3, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF191839 mRNA Translation: AAF05990.1 AF145705 mRNA Translation: AAD34590.1 AK004269 mRNA Translation: BAB23244.1 AK004649 mRNA Translation: BAB23440.1 |
CCDSi | CCDS24212.1 |
RefSeqi | NP_062760.3, NM_019786.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4JL9 | X-ray | 3.10 | A | 2-656 | [»] | |
4JLC | X-ray | 3.00 | A | 2-656 | [»] | |
6O8C | X-ray | 3.17 | A/B | 2-657 | [»] | |
AlphaFoldDBi | Q9WUN2 | |||||
SMRi | Q9WUN2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 208009, 36 interactors |
DIPi | DIP-29880N |
IntActi | Q9WUN2, 18 interactors |
MINTi | Q9WUN2 |
STRINGi | 10090.ENSMUSP00000020316 |
Chemistry databases
BindingDBi | Q9WUN2 |
ChEMBLi | CHEMBL2189160 |
PTM databases
iPTMneti | Q9WUN2 |
PhosphoSitePlusi | Q9WUN2 |
Proteomic databases
EPDi | Q9WUN2 |
MaxQBi | Q9WUN2 |
PaxDbi | Q9WUN2 |
PRIDEi | Q9WUN2 |
ProteomicsDBi | 254666 |
Protocols and materials databases
Antibodypediai | 16584, 617 antibodies from 45 providers |
DNASUi | 56480 |
Genome annotation databases
Ensembli | ENSMUST00000020316; ENSMUSP00000020316; ENSMUSG00000020115 |
GeneIDi | 56480 |
KEGGi | mmu:56480 |
UCSCi | uc007hft.3, mouse |
Organism-specific databases
CTDi | 29110 |
MGIi | MGI:1929658, Tbk1 |
VEuPathDBi | HostDB:ENSMUSG00000020115 |
Phylogenomic databases
eggNOGi | KOG4250, Eukaryota |
GeneTreei | ENSGT00950000182937 |
HOGENOMi | CLU_000288_101_1_1 |
InParanoidi | Q9WUN2 |
OMAi | DWSADMP |
OrthoDBi | 563981at2759 |
PhylomeDBi | Q9WUN2 |
TreeFami | TF324269 |
Enzyme and pathway databases
Reactomei | R-MMU-168928, DDX58/IFIH1-mediated induction of interferon-alpha/beta R-MMU-3134975, Regulation of innate immune responses to cytosolic DNA R-MMU-3249367, STAT6-mediated induction of chemokines R-MMU-3270619, IRF3-mediated induction of type I IFN R-MMU-9008059, Interleukin-37 signaling R-MMU-936440, Negative regulators of DDX58/IFIH1 signaling R-MMU-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon |
Miscellaneous databases
BioGRID-ORCSi | 56480, 21 hits in 76 CRISPR screens |
ChiTaRSi | Tbk1, mouse |
PROi | PR:Q9WUN2 |
RNActi | Q9WUN2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000020115, Expressed in paneth cell and 330 other tissues |
Genevisiblei | Q9WUN2, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR041309, TBK1_CCD1 IPR041087, TBK1_ULD |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit PF18394, TBK1_CCD1, 1 hit PF18396, TBK1_ULD, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TBK1_MOUSE | |
Accessioni | Q9WUN2Primary (citable) accession number: Q9WUN2 Secondary accession number(s): Q9CT90, Q9DC03 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | November 1, 1999 | |
Last modified: | May 25, 2022 | |
This is version 176 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families