TBK1_MOUSE
ID TBK1_MOUSE Reviewed; 729 AA.
AC Q9WUN2; Q9CT90; Q9DC03;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Serine/threonine-protein kinase TBK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9UHD2};
DE AltName: Full=T2K {ECO:0000303|Ref.2};
DE AltName: Full=TANK-binding kinase 1 {ECO:0000303|PubMed:10581243};
GN Name=Tbk1 {ECO:0000303|PubMed:10581243, ECO:0000312|MGI:MGI:1929658};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Spleen;
RX PubMed=10581243; DOI=10.1093/emboj/18.23.6694;
RA Pomerantz J.L., Baltimore D.;
RT "NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1,
RT a novel IKK-related kinase.";
RL EMBO J. 18:6694-6704(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster / NIH;
RA Wisniewski D., Marcy A.I.;
RT "Mus musculus homolog to human T2K cDNA.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=10990461; DOI=10.1093/emboj/19.18.4976;
RA Bonnard M., Mirtsos C., Suzuki S., Graham K., Huang J., Ng M., Itie A.,
RA Wakeham A., Shahinian A., Henzel W.J., Elia A.J., Shillinglaw W., Mak T.W.,
RA Cao Z., Yeh W.-C.;
RT "Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-
RT kappaB-dependent gene transcription.";
RL EMBO J. 19:4976-4985(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15210742; DOI=10.1084/jem.20040520;
RA Hemmi H., Takeuchi O., Sato S., Yamamoto M., Kaisho T., Sanjo H., Kawai T.,
RA Hoshino K., Takeda K., Akira S.;
RT "The roles of two IkappaB kinase-related kinases in lipopolysaccharide and
RT double stranded RNA signaling and viral infection.";
RL J. Exp. Med. 199:1641-1650(2004).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=14679297; DOI=10.1073/pnas.2237236100;
RA McWhirter S.M., Fitzgerald K.A., Rosains J., Rowe D.C., Golenbock D.T.,
RA Maniatis T.;
RT "IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-
RT deficient mouse embryonic fibroblasts.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:233-238(2004).
RN [7]
RP FUNCTION.
RX PubMed=15661922; DOI=10.4049/jimmunol.174.3.1602;
RA O'Connell R.M., Vaidya S.A., Perry A.K., Saha S.K., Dempsey P.W., Cheng G.;
RT "Immune activation of type I IFNs by Listeria monocytogenes occurs
RT independently of TLR4, TLR2, and receptor interacting protein 2 but
RT involves TNFR-associated NF kappa B kinase-binding kinase 1.";
RL J. Immunol. 174:1602-1607(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION IN ENERGY BALANCE, ACTIVITY REGULATION, AND PHOSPHORYLATION AT
RP SER-172.
RX PubMed=23396211; DOI=10.1038/nm.3082;
RA Reilly S.M., Chiang S.H., Decker S.J., Chang L., Uhm M., Larsen M.J.,
RA Rubin J.R., Mowers J., White N.M., Hochberg I., Downes M., Yu R.T.,
RA Liddle C., Evans R.M., Oh D., Li P., Olefsky J.M., Saltiel A.R.;
RT "An inhibitor of the protein kinases TBK1 and IKK-[?] improves obesity-
RT related metabolic dysfunctions in mice.";
RL Nat. Med. 19:313-321(2013).
RN [10]
RP INTERACTION WITH HNRNPA2B1.
RX PubMed=31320558; DOI=10.1126/science.aav0758;
RA Wang L., Wen M., Cao X.;
RT "Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to
RT DNA viruses.";
RL Science 0:0-0(2019).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 2-656 IN COMPLEX WITH INHIBITORS,
RP SUBUNIT, AND COILED-COIL.
RX PubMed=23746807; DOI=10.1016/j.str.2013.04.025;
RA Shu C., Sankaran B., Chaton C.T., Herr A.B., Mishra A., Peng J., Li P.;
RT "Structural insights into the functions of TBK1 in innate antimicrobial
RT immunity.";
RL Structure 21:1137-1148(2013).
CC -!- FUNCTION: Serine/threonine kinase that plays an essential role in
CC regulating inflammatory responses to foreign agents (PubMed:10581243,
CC PubMed:15210742, PubMed:15661922). Following activation of toll-like
CC receptors by viral or bacterial components, associates with TRAF3 and
CC TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and
CC IRF7 as well as DDX3X (By similarity). This activity allows subsequent
CC homodimerization and nuclear translocation of the IRFs leading to
CC transcriptional activation of pro-inflammatory and antiviral genes
CC including IFNA and IFNB (By similarity). In order to establish such an
CC antiviral state, TBK1 form several different complexes whose
CC composition depends on the type of cell and cellular stimuli (By
CC similarity). Thus, several scaffolding molecules including FADD, TRADD,
CC MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-
CC containing-complexes (By similarity). Plays a key role in IRF3
CC activation: acts by first phosphorylating innate adapter proteins MAVS,
CC STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3,
CC thereby licensing IRF3 for phosphorylation by TBK1 (By similarity).
CC Under particular conditions, functions as a NF-kappa-B effector by
CC phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to
CC translocate NF-Kappa-B to the nucleus (By similarity). Restricts
CC bacterial proliferation by phosphorylating the autophagy receptor
CC OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and
CC antibacterial autophagy (By similarity). Phosphorylates SMCR8 component
CC of the C9orf72-SMCR8 complex, promoting autophagosome maturation (By
CC similarity). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2,
CC thereby preventing their delipidation and premature removal from
CC nascent autophagosomes (By similarity). Phosphorylates and activates
CC AKT1 (By similarity). Seems to play a role in energy balance regulation
CC by sustaining a state of chronic, low-grade inflammation in obesity,
CC wich leads to a negative impact on insulin sensitivity
CC (PubMed:23396211). {ECO:0000250|UniProtKB:Q9UHD2,
CC ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:15210742,
CC ECO:0000269|PubMed:15661922, ECO:0000269|PubMed:23396211}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q9UHD2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9UHD2};
CC -!- ACTIVITY REGULATION: Kinase activity is inhibited competitively by
CC amlexanox. {ECO:0000269|PubMed:23396211}.
CC -!- SUBUNIT: Homodimer (PubMed:23746807). Interacts with DDX3X, TIRAP and
CC TRAF2 (By similarity). Part of a ternary complex consisting of TANK,
CC TRAF2 and TBK1 (By similarity). Interacts with AZI2, TANK and TBKBP1;
CC these interactions are mutually exclusive and mediate TBK1 activation
CC (By similarity). Interacts with GSK3B; this interaction promotes TBK1
CC self-association and autophosphorylation (By similarity). Interacts
CC with SIKE1; SIKE1 is associated with TBK1 under physiological condition
CC and dissociated from TBK1 upon viral infection or TLR3 stimulation (By
CC similarity). Interacts with IRF3, leading to IRF3 phosphorylation (By
CC similarity). Interacts with DDX58/RIG-I (By similarity). Interacts with
CC CYLD (By similarity). Interacts with OPTN and TRAF3 (By similarity).
CC Interacts with SRC (By similarity). Interacts with the exocyst complex
CC subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1
CC activity (By similarity). Interacts with STING1, leading to STING1
CC phosphorylation (By similarity). Interacts with IFIT3 (via N-terminus)
CC (By similarity). Interacts with MAVS; interaction only takes place in
CC the presence of IFIT3 and leads to MAVS phosphorylation (By
CC similarity). Interacts (via protein kinase domain) with TTLL12 (via TTL
CC domain); the interaction prevents MAVS binding to TBK1 (By similarity).
CC Interacts with TICAM1; this interaction is enhanced in the presence of
CC WDFY1 and leads to TICAM1 phosphorylation (By similarity). Interacts
CC with TRIM26 (By similarity). Interacts with TRIM23 (By similarity).
CC Interacts with TTC4 and IKBKE (By similarity). Interacts with HNRNPA2B1
CC (PubMed:31320558). Interacts with DDX3X (By similarity). Interacts with
CC TRIM14 (By similarity). Interacts with CEP170; efficient complex
CC formation may be dependent on the presence of CCDC61 (By similarity).
CC Interacts with TRAF3IP3 (By similarity). Interacts with HSP90AA1; the
CC interaction mediates TBK1 association with TOMM70 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UHD2, ECO:0000269|PubMed:23746807,
CC ECO:0000269|PubMed:31320558}.
CC -!- INTERACTION:
CC Q9WUN2; Q3TBT3: Sting1; NbExp=3; IntAct=EBI-764193, EBI-3862093;
CC Q9WUN2; P70347: Tank; NbExp=7; IntAct=EBI-764193, EBI-646116;
CC Q9WUN2; Q9WUN2: Tbk1; NbExp=5; IntAct=EBI-764193, EBI-764193;
CC Q9WUN2; A2A9T0: Tbkbp1; NbExp=2; IntAct=EBI-764193, EBI-7987134;
CC Q9WUN2; Q80UF7: Ticam1; NbExp=2; IntAct=EBI-764193, EBI-3649271;
CC Q9WUN2; O41932: GAMMAHV.ORF11; Xeno; NbExp=3; IntAct=EBI-764193, EBI-9544132;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UHD2}.
CC Note=Upon mitogen stimulation or triggering of the immune system, TBK1
CC is recruited to the exocyst by EXOC2. {ECO:0000250|UniProtKB:Q9UHD2}.
CC -!- DOMAIN: Comprises A N-terminal kinase domain, a ubiquitin-like domain
CC and a C-terminal coiled-coil region mediating homodimerization.
CC {ECO:0000269|PubMed:23746807}.
CC -!- PTM: Autophosphorylation at Ser-172 activates the kinase, and is an
CC essential step for virus-triggered signaling. Phosphorylated by
CC IKBKB/IKKB at Ser-172. Phosphorylation requires homodimerization and
CC ubiquitination at Lys-30 and Lys-401. Dephosphorylated at Ser-172 by
CC PPM1B and this negatively regulates its role in mediating antiviral
CC response. {ECO:0000250|UniProtKB:Q9UHD2}.
CC -!- PTM: 'Lys-63'-linked polyubiquitination by MIB1 after RNA virus
CC infection, or by NRDP1 after LPS stimulation at Lys-30 and Lys-401,
CC participates in kinase activation. 'Lys-48'-linked polyubiquitination
CC at Lys-670 by DTX4 leads to proteasomal degradation. 'Lys-48'-linked
CC polyubiquitination by TRAIP also leads to proteasomal degradation.
CC 'Lys-63'-linked polyubiquitination by RNF128 at Lys-30 and Lys-401
CC leads to the activation of antiviral responses.
CC {ECO:0000250|UniProtKB:Q9UHD2}.
CC -!- DISRUPTION PHENOTYPE: Mice display embryonic lethality at 14.5 dpc due
CC to massive liver degeneration and apoptosis. Embryonic fibroblasts from
CC mice lacking Tbk1 exhibit dramatically reduced transcription of NF-
CC kappa-B, as well as marked defects in interferon alpha and beta, and
CC RANTES gene expression after infection with Sendai or Newcastle disease
CC virus. {ECO:0000269|PubMed:10990461, ECO:0000269|PubMed:14679297,
CC ECO:0000269|PubMed:15210742}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. I-kappa-B kinase subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AF191839; AAF05990.1; -; mRNA.
DR EMBL; AF145705; AAD34590.1; -; mRNA.
DR EMBL; AK004269; BAB23244.1; -; mRNA.
DR EMBL; AK004649; BAB23440.1; -; mRNA.
DR CCDS; CCDS24212.1; -.
DR RefSeq; NP_062760.3; NM_019786.4.
DR PDB; 4JL9; X-ray; 3.10 A; A=2-656.
DR PDB; 4JLC; X-ray; 3.00 A; A=2-656.
DR PDB; 6O8C; X-ray; 3.17 A; A/B=2-657.
DR PDBsum; 4JL9; -.
DR PDBsum; 4JLC; -.
DR PDBsum; 6O8C; -.
DR AlphaFoldDB; Q9WUN2; -.
DR SMR; Q9WUN2; -.
DR BioGRID; 208009; 37.
DR DIP; DIP-29880N; -.
DR IntAct; Q9WUN2; 18.
DR MINT; Q9WUN2; -.
DR STRING; 10090.ENSMUSP00000020316; -.
DR BindingDB; Q9WUN2; -.
DR ChEMBL; CHEMBL2189160; -.
DR iPTMnet; Q9WUN2; -.
DR PhosphoSitePlus; Q9WUN2; -.
DR EPD; Q9WUN2; -.
DR MaxQB; Q9WUN2; -.
DR PaxDb; Q9WUN2; -.
DR PRIDE; Q9WUN2; -.
DR ProteomicsDB; 254666; -.
DR Antibodypedia; 16584; 629 antibodies from 46 providers.
DR DNASU; 56480; -.
DR Ensembl; ENSMUST00000020316; ENSMUSP00000020316; ENSMUSG00000020115.
DR GeneID; 56480; -.
DR KEGG; mmu:56480; -.
DR UCSC; uc007hft.3; mouse.
DR CTD; 29110; -.
DR MGI; MGI:1929658; Tbk1.
DR VEuPathDB; HostDB:ENSMUSG00000020115; -.
DR eggNOG; KOG4250; Eukaryota.
DR GeneTree; ENSGT00950000182937; -.
DR HOGENOM; CLU_000288_101_1_1; -.
DR InParanoid; Q9WUN2; -.
DR OMA; DWSADMP; -.
DR OrthoDB; 563981at2759; -.
DR PhylomeDB; Q9WUN2; -.
DR TreeFam; TF324269; -.
DR Reactome; R-MMU-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-MMU-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-MMU-3249367; STAT6-mediated induction of chemokines.
DR Reactome; R-MMU-3270619; IRF3-mediated induction of type I IFN.
DR Reactome; R-MMU-9008059; Interleukin-37 signaling.
DR Reactome; R-MMU-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR BioGRID-ORCS; 56480; 21 hits in 76 CRISPR screens.
DR ChiTaRS; Tbk1; mouse.
DR PRO; PR:Q9WUN2; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9WUN2; protein.
DR Bgee; ENSMUSG00000020115; Expressed in paneth cell and 273 other tissues.
DR ExpressionAtlas; Q9WUN2; baseline and differential.
DR Genevisible; Q9WUN2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003676; F:nucleic acid binding; IDA:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:ARUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0002218; P:activation of innate immune response; IMP:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0044565; P:dendritic cell proliferation; IGI:MGI.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISO:MGI.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
DR GO; GO:0032479; P:regulation of type I interferon production; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR041309; TBK1_CCD1.
DR InterPro; IPR041087; TBK1_ULD.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF18394; TBK1_CCD1; 1.
DR Pfam; PF18396; TBK1_ULD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; ATP-binding; Coiled coil; Cytoplasm;
KW Immunity; Innate immunity; Isopeptide bond; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1..729
FT /note="Serine/threonine-protein kinase TBK1"
FT /id="PRO_0000086744"
FT DOMAIN 9..310
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 309..385
FT /note="Ubiquitin-like"
FT REGION 621..729
FT /note="Interaction with AZI2, TANK and TBKBP1"
FT /evidence="ECO:0000250|UniProtKB:Q9UHD2"
FT COILED 407..657
FT /evidence="ECO:0000269|PubMed:23746807"
FT COILED 658..713
FT /evidence="ECO:0000255"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 172
FT /note="Phosphoserine; by autocatalysis and IKKB"
FT /evidence="ECO:0000269|PubMed:23396211"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHD2"
FT CROSSLNK 30
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9UHD2"
FT CROSSLNK 401
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9UHD2"
FT CROSSLNK 670
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9UHD2"
FT CONFLICT 468
FT /note="L -> V (in Ref. 3; BAB23440)"
FT /evidence="ECO:0000305"
FT CONFLICT 594
FT /note="A -> S (in Ref. 3; BAB23244)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="L -> S (in Ref. 3; BAB23440)"
FT /evidence="ECO:0000305"
FT STRAND 5..14
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 22..28
FT /evidence="ECO:0007829|PDB:4JLC"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:6O8C"
FT HELIX 49..60
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:4JLC"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 94..98
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 109..127
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 203..216
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 226..229
FT /evidence="ECO:0007829|PDB:6O8C"
FT HELIX 231..239
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 271..284
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 289..292
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 295..307
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:4JLC"
FT TURN 316..319
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 320..326
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 332..343
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 351..354
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 408..483
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 491..494
FT /evidence="ECO:0007829|PDB:6O8C"
FT HELIX 495..524
FT /evidence="ECO:0007829|PDB:4JLC"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 536..539
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 544..546
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 548..571
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 577..644
FT /evidence="ECO:0007829|PDB:4JLC"
FT HELIX 645..647
FT /evidence="ECO:0007829|PDB:4JLC"
SQ SEQUENCE 729 AA; 83425 MW; 978ADDE3061DACD1 CRC64;
MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLYAVKVF NNISFLRPVD VQMREFEVLK
KLNHKNIVKL FAIEEETTTR HKVLIMEFCP CGSLYTVLEE PSNAYGLPES EFLIVLRDVV
GGMNHLRENG IVHRDIKPGN IMRVIGEDGQ SVYKLTDFGA ARELEDDEQF VSLYGTEEYL
HPDMYERAVL RKDHQKKYGA TVDLWSVGVT FYHAATGSLP FRPFEGPRRN KEVMYKIITG
KPSGAISGVQ KAENGPIDWS GDMPLSCSLS QGLQALLTPV LANILEADQE KCWGFDQFFA
ETSDVLHRMV IHVFSLQHMT AHKIYIHSYN TAAVFHELVY KQTKIVSSNQ ELIYEGRRLV
LELGRLAQHF PKTTEENPIF VTSREQLNTV GLRYEKISLP KIHPRYDLDG DASMAKAVTG
VVCYACRTAS TLLLYQELMR KGVRWLVELV KDDYNETVHK KTEVVITLDF CIRNIEKTVK
VYEKLMKVNL EAAELGEISD IHTKLLRLSS SQGTIESSLQ DISSRLSPGG LLADTWAHQE
GTHPRDRNVE KLQVLLNCIT EIYYQFKKDK AERRLAYNEE QIHKFDKQKL YYHATKAMSH
FSEECVRKYE AFKDKSEEWM RKMLHLRKQL LSLTNQCFDI EEEVSKYQDY TNELQETLPQ
KMLAASGGVK HAMAPIYPSS NTLVEMTLGM KKLKEEMEGV VKELAENNHI LERFGSLTMD
GGLRNVDCL
