Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9UHD2 (TBK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase TBK1

EC=2.7.11.1
Alternative name(s):
NF-kappa-B-activating kinase
T2K
TANK-binding kinase 1
Gene names
Name:TBK1
Synonyms:NAK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length729 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. 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. 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. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. 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. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Phosphorylates and activates AKT1. 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. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates Borna disease virus (BDV) P protein. Ref.1 Ref.2 Ref.6 Ref.8 Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.21 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.44 Ref.45

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Homodimer. Interacts with DDX3X, TIRAP and TRAF2. Part of a ternary complex consisting of TANK, TRAF2 and TBK1. Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation. Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation. Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation. Interacts with TICAM1/TRIF, IRF3 and DDX58/RIG-I. Interacts with CYLD. Interacts with OPTN and TRAF3. Interacts with SRC. Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity. Interacts with TMEM173/MITA. Interacts with IFIT3 (via N-terminus). Interacts with MAVS only in the presence of IFIT3. Interacts with HCV NS3, Ebola virus VP35 and Borna disease virus protein P; these interactions lead to inhibition of cellular antiviral response by blocking necessary interactions between the TBK1 and its substrates IRF3 and IRF7. Ref.1 Ref.7 Ref.10 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.22 Ref.24 Ref.25 Ref.28 Ref.29 Ref.30 Ref.34 Ref.36 Ref.45

Subcellular location

Cytoplasm. Note: Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2. Ref.13 Ref.34

Tissue specificity

Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina. Ref.2 Ref.32

Domain

Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal leucine-zipper. Ref.20 Ref.39

Post-translational modification

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. Ref.6 Ref.25 Ref.29 Ref.40 Ref.41 Ref.45

'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.

Involvement in 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.
Note: The disease may be caused by mutations 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 (Ref.32). Ref.18 Ref.32 Ref.42

Miscellaneous

In cancer cells, pathological TBK1 activation promotes oncogenic transformation by suppressing programmed cell death. Mechanistically, the RALB-SEC5/EXOC2-TBK1 signaling cascade seems to participate in both innate immune signaling and cell transformation. Additionally, TBK1 supports oncogenesis by directly phosphorylating and activating AKT1 at the exocyst (Ref.39).

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Contains 1 protein kinase domain.

Contains 1 ubiquitin-like domain.

Sequence caution

The sequence BAA92129.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processAntiviral defense
Host-virus interaction
Immunity
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseGlaucoma
   DomainCoiled coil
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Traceable author statement Ref.39. Source: UniProtKB

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

inflammatory response

Traceable author statement Ref.39. Source: UniProtKB

innate immune response

Traceable author statement Ref.39. Source: UniProtKB

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern PubMed 12761501. Source: UniProtKB

positive regulation of interferon-alpha production

Inferred from direct assay PubMed 16127453. Source: BHF-UCL

positive regulation of interferon-beta biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-beta production

Inferred from direct assay PubMed 16127453. Source: BHF-UCL

positive regulation of peptidyl-serine phosphorylation

Non-traceable author statement PubMed 22412986. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16127453. Source: BHF-UCL

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

response to virus

Traceable author statement Ref.39. Source: UniProtKB

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

type I interferon production

Traceable author statement Ref.39. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.34. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

nucleic acid binding

Inferred from electronic annotation. Source: Ensembl

phosphoprotein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

protein kinase activity

Non-traceable author statement Ref.1. Source: ProtInc

protein serine/threonine kinase activity

Traceable author statement Ref.39. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 729729Serine/threonine-protein kinase TBK1
PRO_0000086743

Regions

Domain9 – 310302Protein kinase
Domain309 – 38577Ubiquitin-like
Nucleotide binding15 – 239ATP By similarity
Region621 – 6299Interaction with AZI2, TANK and TBKBP1
Coiled coil407 – 657251
Coiled coil658 – 71356 Potential

Sites

Active site1351Proton acceptor Probable
Binding site381ATP Probable

Amino acid modifications

Modified residue1721Phosphoserine; by autocatalysis and IKKB Ref.6 Ref.41
Cross-link30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.44
Cross-link401Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.44
Cross-link670Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.43

Natural variations

Natural variant1511S → F. Ref.32
Corresponds to variant rs55824172 [ dbSNP | Ensembl ].
VAR_069754
Natural variant2711R → Q. Ref.46
Corresponds to variant rs56196591 [ dbSNP | Ensembl ].
VAR_041208
Natural variant2911K → E. Ref.46
Corresponds to variant rs34774243 [ dbSNP | Ensembl ].
VAR_041209
Natural variant2961D → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.46
VAR_041210
Natural variant3061L → I. Ref.32
Corresponds to variant rs201970436 [ dbSNP | Ensembl ].
VAR_069755
Natural variant3881N → D. Ref.5
Corresponds to variant rs17857028 [ dbSNP | Ensembl ].
VAR_024746
Natural variant4101G → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.46
VAR_041211
Natural variant4641V → A. Ref.32 Ref.46
Corresponds to variant rs35635889 [ dbSNP | Ensembl ].
VAR_041212
Natural variant5701K → Q. Ref.5
Corresponds to variant rs17853341 [ dbSNP | Ensembl ].
VAR_024747

Experimental info

Mutagenesis301K → R: Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-401. Ref.44
Mutagenesis331D → A: Decreases phosphorylation and kinase activity. Ref.44
Mutagenesis381K → A: Loss of kinase activity. Ref.1 Ref.44 Ref.45
Mutagenesis1351D → N: Loss of kinase activity. Ref.36 Ref.44 Ref.45
Mutagenesis1721S → A: Loss of kinase activity. No effect on dimerization. Ref.6 Ref.45
Mutagenesis1721S → E: Decreased kinase activity. Ref.6 Ref.45
Mutagenesis3161L → E: Decreases kinase activity. No effect on phosphorylation. Ref.45
Mutagenesis3251Y → E: Abolishes phosphorylation and kinase activity. Ref.45
Mutagenesis3551E → R: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with A-357 or R-448. Ref.44 Ref.45
Mutagenesis3571R → A: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355. Ref.44
Mutagenesis4011K → R: Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-30. Ref.44
Mutagenesis4481E → R: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355. Ref.45
Mutagenesis4591H → E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-466 and E-470. Ref.45
Mutagenesis4661I → E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-470. Ref.45
Mutagenesis4701F → E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-466. Ref.45
Mutagenesis5471R → D: Decreases phosphorylation and kinase activity. Abolishes dimerization. Ref.44
Mutagenesis5771Y → A: Decreases kinase activity. Ref.44
Mutagenesis5801E → A: Decreases kinase activity. Ref.44
Mutagenesis5821I → A: Decreases kinase activity. Ref.44
Mutagenesis5891K → D: Decreases phosphorylation and kinase activity. Ref.44
Mutagenesis6901M → A: Decreases interaction with TANK. Ref.36
Mutagenesis6931L → A: Almost abolishes interaction with TANK. Ref.36
Mutagenesis6941K → E: Strongly decreases interaction with TANK and TBKBP1. No effect on phosphorylation. Ref.36
Mutagenesis7041L → A: Strongly decreases interaction with AZI2, TANK and TBKBP1. No effect on phosphorylation. Ref.36
Mutagenesis7081N → A: Decreases interaction with TANK. Ref.36
Mutagenesis7111L → A: Almost abolishes interaction with TANK. Ref.36

Secondary structure

.............................................................................................. 729
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UHD2 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: B58E4FE1B502276D

FASTA72983,642
        10         20         30         40         50         60 
MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLFAIKVF NNISFLRPVD VQMREFEVLK 

        70         80         90        100        110        120 
KLNHKNIVKL FAIEEETTTR HKVLIMEFCP CGSLYTVLEE PSNAYGLPES EFLIVLRDVV 

       130        140        150        160        170        180 
GGMNHLRENG IVHRDIKPGN IMRVIGEDGQ SVYKLTDFGA ARELEDDEQF VSLYGTEEYL 

       190        200        210        220        230        240 
HPDMYERAVL RKDHQKKYGA TVDLWSIGVT FYHAATGSLP FRPFEGPRRN KEVMYKIITG 

       250        260        270        280        290        300 
KPSGAISGVQ KAENGPIDWS GDMPVSCSLS RGLQVLLTPV LANILEADQE KCWGFDQFFA 

       310        320        330        340        350        360 
ETSDILHRMV IHVFSLQQMT AHKIYIHSYN TATIFHELVY KQTKIISSNQ ELIYEGRRLV 

       370        380        390        400        410        420 
LEPGRLAQHF PKTTEENPIF VVSREPLNTI GLIYEKISLP KVHPRYDLDG DASMAKAITG 

       430        440        450        460        470        480 
VVCYACRIAS TLLLYQELMR KGIRWLIELI KDDYNETVHK KTEVVITLDF CIRNIEKTVK 

       490        500        510        520        530        540 
VYEKLMKINL EAAELGEISD IHTKLLRLSS SQGTIETSLQ DIDSRLSPGG SLADAWAHQE 

       550        560        570        580        590        600 
GTHPKDRNVE KLQVLLNCMT EIYYQFKKDK AERRLAYNEE QIHKFDKQKL YYHATKAMTH 

       610        620        630        640        650        660 
FTDECVKKYE AFLNKSEEWI RKMLHLRKQL LSLTNQCFDI EEEVSKYQEY TNELQETLPQ 

       670        680        690        700        710        720 
KMFTASSGIK HTMTPIYPSS NTLVEMTLGM KKLKEEMEGV VKELAENNHI LERFGSLTMD 


GGLRNVDCL 

« Hide

References

« Hide 'large scale' references
[1]"NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, a novel IKK-related kinase."
Pomerantz J.L., Baltimore D.
EMBO J. 18:6694-6704(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH TANK AND TRAF2, MUTAGENESIS OF LYS-38.
Tissue: Spleen.
[2]"NAK is an IkappaB kinase-activating kinase."
Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K., Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M., Nakanishi M.
Nature 404:778-782(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN PHOSPHORYLATION OF NFKBIA AND IKBKB, TISSUE SPECIFICITY.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ASP-388 AND GLN-570.
Tissue: Testis.
[6]"IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2."
Kishore N., Huynh Q.K., Mathialagan S., Hall T., Rouw S., Creely D., Lange G., Caroll J., Reitz B., Donnelly A., Boddupalli H., Combs R.G., Kretzmer K., Tripp C.S.
J. Biol. Chem. 277:13840-13847(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-172, PHOSPHORYLATION AT SER-172.
[7]"Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling."
Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., Akira S.
J. Immunol. 171:4304-4310(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TIRAP AND TICAM1.
[8]"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway."
Fitzgerald K.A., McWhirter S.M., Faia K.L., Rowe D.C., Latz E., Golenbock D.T., Coyle A.J., Liao S.-M., Maniatis T.
Nat. Immunol. 4:491-496(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Triggering the interferon antiviral response through an IKK-related pathway."
Sharma S., tenOever B.R., Grandvaux N., Zhou G.-P., Lin R., Hiscott J.
Science 300:1148-1151(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Identification of NAP1, a regulatory subunit of IkappaB kinase-related kinases that potentiates NF-kappaB signaling."
Fujita F., Taniguchi Y., Kato T., Narita Y., Furuya A., Ogawa T., Sakurai H., Joh T., Itoh M., Delhase M., Karin M., Nakanishi M.
Mol. Cell. Biol. 23:7780-7793(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AZI2.
[11]"Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation."
Mori M., Yoneyama M., Ito T., Takahashi K., Inagaki F., Fujita T.
J. Biol. Chem. 279:9698-9702(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF IRF3.
[12]"Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways."
Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.
J. Biol. Chem. 279:15652-15661(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TICAM1.
[13]"NAK is recruited to the TNFR1 complex in a TNFalpha-dependent manner and mediates the production of RANTES: identification of endogenous TNFR-interacting proteins by a proteomic approach."
Kuai J., Wooters J., Hall J.P., Rao V.R., Nickbarg E., Li B., Chatterjee-Kishore M., Qiu Y., Lin L.-L.
J. Biol. Chem. 279:53266-53271(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription."
Buss H., Dorrie A., Schmitz M.L., Hoffmann E., Resch K., Kracht M.
J. Biol. Chem. 279:55633-55643(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RELA.
[15]"Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity."
tenOever B.R., Sharma S., Zou W., Sun Q., Grandvaux N., Julkunen I., Hemmi H., Yamamoto M., Akira S., Yeh W.C., Lin R., Hiscott J.
J. Virol. 78:10636-10649(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF IRF7.
[16]"SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways."
Huang J., Liu T., Xu L.-G., Chen D., Zhai Z., Shu H.-B.
EMBO J. 24:4018-4028(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIKE1; IRF3; TICAM1 AND DDX58.
[17]"Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses."
Otsuka M., Kato N., Moriyama M., Taniguchi H., Wang Y., Dharel N., Kawabe T., Omata M.
Hepatology 41:1004-1012(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HCV NS3.
[18]"Viral targeting of the interferon-beta-inducing Traf family member-associated NF-kappa-B activator (TANK)-binding kinase-1."
Unterstab G., Ludwig S., Anton A., Planz O., Dauber B., Krappmann D., Heins G., Ehrhardt C., Wolff T.
Proc. Natl. Acad. Sci. U.S.A. 102:13640-13645(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BORNA DISEASE VIRUS P PROTEIN.
[19]"RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival."
Chien Y., Kim S., Bumeister R., Loo Y.M., Kwon S.W., Johnson C.L., Balakireva M.G., Romeo Y., Kopelovich L., Gale M. Jr., Yeaman C., Camonis J.H., Zhao Y., White M.A.
Cell 127:157-170(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EXOC2.
[20]"Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes."
Ikeda F., Hecker C.M., Rozenknop A., Nordmeier R.D., Rogov V., Hofmann K., Akira S., Dotsch V., Dikic I.
EMBO J. 26:3451-3462(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[21]"The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response."
Soulat D., Burckstummer T., Westermayer S., Goncalves A., Bauch A., Stefanovic A., Hantschel O., Bennett K.L., Decker T., Superti-Furga G.
EMBO J. 27:2135-2146(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF DDX3X.
[22]"The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response."
Friedman C.S., O'Donnell M.A., Legarda-Addison D., Ng A., Cardenas W.B., Yount J.S., Moran T.M., Basler C.F., Komuro A., Horvath C.M., Xavier R., Ting A.T.
EMBO Rep. 9:930-936(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CYLD.
[23]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling."
Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W.
J. Biol. Chem. 284:19122-19131(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRC.
[25]"Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1."
Prins K.C., Cardenas W.B., Basler C.F.
J. Virol. 83:3069-3077(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EBOLAVIRUS PROTEIN VP35, AUTOPHOSPHORYLATION.
[26]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon."
Wang C., Chen T., Zhang J., Yang M., Li N., Xu X., Cao X.
Nat. Immunol. 10:744-752(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY NRDP1.
[28]"ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response."
Li Y., Li C., Xue P., Zhong B., Mao A.P., Ran Y., Chen H., Wang Y.Y., Yang F., Shu H.B.
Proc. Natl. Acad. Sci. U.S.A. 106:7945-7950(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMEM173/MITA.
[29]"Glycogen synthase kinase 3beta regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1."
Lei C.Q., Zhong B., Zhang Y., Zhang J., Wang S., Shu H.B.
Immunity 33:878-889(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH GSK3B.
[30]"Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection."
Mankouri J., Fragkoudis R., Richards K.H., Wetherill L.F., Harris M., Kohl A., Elliott R.M., Macdonald A.
PLoS Pathog. 6:E1000778-E1000778(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OPTN AND TRAF3.
[31]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"Copy number variations on chromosome 12q14 in patients with normal tension glaucoma."
Fingert J.H., Robin A.L., Stone J.L., Roos B.R., Davis L.K., Scheetz T.E., Bennett S.R., Wassink T.H., Kwon Y.H., Alward W.L., Mullins R.F., Sheffield V.C., Stone E.M.
Hum. Mol. Genet. 20:2482-2494(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN GLC1P, TISSUE SPECIFICITY, VARIANTS PHE-151; ILE-306 AND ALA-464.
[33]"Mapping a dynamic innate immunity protein interaction network regulating type I interferon production."
Li S., Wang L., Berman M., Kong Y.Y., Dorf M.E.
Immunity 35:426-440(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY MIB1.
[34]"IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1."
Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.
J. Immunol. 187:2559-2568(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH IFIT3 AND MAVS.
[35]"TANK-binding kinase 1 attenuates PTAP-dependent retroviral budding through targeting endosomal sorting complex required for transport-I."
Da Q., Yang X., Xu Y., Gao G., Cheng G., Tang H.
J. Immunol. 186:3023-3030(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF VPS37C.
[36]"Functional dissection of the TBK1 molecular network."
Goncalves A., Burckstummer T., Dixit E., Scheicher R., Gorna M.W., Karayel E., Sugar C., Stukalov A., Berg T., Kralovics R., Planyavsky M., Bennett K.L., Colinge J., Superti-Furga G.
PLoS ONE 6:E23971-E23971(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AZI2; TANK AND TBKBP1, MUTAGENESIS OF ASP-135; MET-690; LEU-693; LYS-694; LEU-704; ASN-708 AND LEU-711.
[37]"IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation."
Xie X., Zhang D., Zhao B., Lu M.K., You M., Condorelli G., Wang C.Y., Guan K.L.
Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1.
[38]"Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth."
Wild P., Farhan H., McEwan D.G., Wagner S., Rogov V.V., Brady N.R., Richter B., Korac J., Waidmann O., Choudhary C., Dotsch V., Bumann D., Dikic I.
Science 333:228-233(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF OPTN.
[39]"Emerging roles for the non-canonical IKKs in cancer."
Shen R.R., Hahn W.C.
Oncogene 30:631-641(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, DOMAIN.
[40]"Novel cross-talk within the IKK family controls innate immunity."
Clark K., Peggie M., Plater L., Sorcek R.J., Young E.R., Madwed J.B., Hough J., McIver E.G., Cohen P.
Biochem. J. 434:93-104(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION BY IKBKB/IKKB.
[41]"PPM1B negatively regulates antiviral response via dephosphorylating TBK1."
Zhao Y., Liang L., Fan Y., Sun S., An L., Shi Z., Cheng J., Jia W., Sun W., Mori-Akiyama Y., Zhang H., Fu S., Yang J.
Cell. Signal. 24:2197-2204(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: DEPHOSPHORYLATION AT SER-172.
[42]"Confirmation of TBK1 duplication in normal tension glaucoma."
Kawase K., Allingham R.R., Meguro A., Mizuki N., Roos B., Solivan-Timpe F.M., Robin A.L., Ritch R., Fingert J.H.
Exp. Eye Res. 96:178-180(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN GLC1P.
[43]"NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4."
Cui J., Li Y., Zhu L., Liu D., Songyang Z., Wang H.Y., Wang R.F.
Nat. Immunol. 13:387-395(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-670 BY DTX4.
[44]"Crystal structure and mechanism of activation of TANK-binding kinase 1."
Larabi A., Devos J.M., Ng S.L., Nanao M.H., Round A., Maniatis T., Panne D.
Cell Rep. 3:734-746(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-657 IN COMPLEX WITH INHIBITORS, FUNCTION, ACTIVE SITE, HOMODIMER, UBIQUITINATION AT LYS-30 AND LYS-401, MUTAGENESIS OF LYS-30; ASP-33; LYS-38; ASP-135; GLU-355; ARG-357; LYS-401; ARG-547; TYR-577; GLU-580; ILE-582 AND LYS-589.
[45]"Structure and ubiquitination-dependent activation of TANK-binding kinase 1."
Tu D., Zhu Z., Zhou A.Y., Yun C.H., Lee K.E., Toms A.V., Li Y., Dunn G.P., Chan E., Thai T., Yang S., Ficarro S.B., Marto J.A., Jeon H., Hahn W.C., Barbie D.A., Eck M.J.
Cell Rep. 3:747-758(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 1-657 IN COMPLEX WITH INHIBITORS, FUNCTION, ACTIVE SITE, AUTOPHOSPHORYLATION, HOMODIMER, INTERACTION WITH AZI2, MUTAGENESIS OF LYS-38; ASP-135; SER-172; LEU-316; TYR-325; GLU-355; GLU-448; HIS-459; ILE-466 AND PHE-470.
[46]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-271; GLU-291; HIS-296; ARG-410 AND ALA-464.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF191838 mRNA. Translation: AAF05989.1.
AF174536 mRNA. Translation: AAF69106.1.
AK002192 mRNA. Translation: BAA92129.1. Different initiation.
AK291039 mRNA. Translation: BAF83728.1.
CH471054 Genomic DNA. Translation: EAW97133.1.
BC034950 mRNA. Translation: AAH34950.1.
RefSeqNP_037386.1. NM_013254.3.
XP_005268866.1. XM_005268809.1.
XP_005268867.1. XM_005268810.1.
UniGeneHs.505874.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4EFOX-ray1.77A/B302-383[»]
4EUTX-ray2.60A/B2-385[»]
4EUUX-ray1.80A/B2-308[»]
4IM0X-ray2.40A1-657[»]
4IM2X-ray2.50A1-657[»]
4IM3X-ray3.34A1-657[»]
4IW0X-ray4.00A2-657[»]
4IWOX-ray2.61A2-657[»]
4IWPX-ray3.06A2-657[»]
4IWQX-ray3.00A2-657[»]
ProteinModelPortalQ9UHD2.
SMRQ9UHD2. Positions 2-657.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118878. 77 interactions.
DIPDIP-27529N.
IntActQ9UHD2. 54 interactions.
MINTMINT-1131333.
STRING9606.ENSP00000329967.

Chemistry

BindingDBQ9UHD2.
ChEMBLCHEMBL5408.
GuidetoPHARMACOLOGY2237.

PTM databases

PhosphoSiteQ9UHD2.

Polymorphism databases

DMDM74761953.

Proteomic databases

PaxDbQ9UHD2.
PeptideAtlasQ9UHD2.
PRIDEQ9UHD2.

Protocols and materials databases

DNASU29110.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331710; ENSP00000329967; ENSG00000183735.
GeneID29110.
KEGGhsa:29110.
UCSCuc001ssc.2. human.

Organism-specific databases

CTD29110.
GeneCardsGC12P064845.
HGNCHGNC:11584. TBK1.
HPAHPA045797.
MIM177700. phenotype.
604834. gene.
neXtProtNX_Q9UHD2.
Orphanet1930. Herpetic encephalitis.
PharmGKBPA36348.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000220867.
HOVERGENHBG008494.
InParanoidQ9UHD2.
KOK05410.
OMALLYQELM.
OrthoDBEOG7Z95KH.
PhylomeDBQ9UHD2.
TreeFamTF324269.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SABIO-RKQ9UHD2.
SignaLinkQ9UHD2.

Gene expression databases

ArrayExpressQ9UHD2.
BgeeQ9UHD2.
CleanExHS_TBK1.
GenevestigatorQ9UHD2.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTANK-binding_kinase_1.
GenomeRNAi29110.
NextBio52179.
PROQ9UHD2.
SOURCESearch...

Entry information

Entry nameTBK1_HUMAN
AccessionPrimary (citable) accession number: Q9UHD2
Secondary accession number(s): A8K4S4, Q8IYV3, Q9NUJ5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM