Q9UHD2 (TBK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	729 AA.
Sequence status	Complete.
Protein existence	Evidence 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 IFN-alpha and IFN-beta. 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 or 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. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1. 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.34 Ref.35 Ref.36 Ref.38
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Self-associates. Interacts with TIRAP, TANK and TRAF2. Part of a ternary complex consisting of TANK, TRAF2 and TBK1. Interacts with AZI2; this interaction mediates 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 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. 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. 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.33
Subcellular location	Cytoplasm. Note: Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2. Ref.13 Ref.33
Tissue specificity	Ubiquitous with higher expression in testis. Ref.2
Domain	Comprises A N-terminal kinase domain, an ubiquitin-like domain and a C-terminal leucine-zipper. Ref.20 Ref.37
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. Ref.6 Ref.29 Ref.38 'Lys-63'-linked polyubiquitination by MIB1 after RNA virus infection, or by NRDP1 after LPS stimulation, may participate in kinase activation. 'Lys-48'-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation.
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.37).
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 process	Antiviral defense Host-virus interaction Immunity Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Traceable author statement Ref.37. Source: UniProtKB TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome defense response to Gram-positive bacterium Inferred from electronic annotation. Source: Compara defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Traceable author statement Ref.37. Source: UniProtKB innate immune response Traceable author statement Ref.37. Source: UniProtKB negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of type I interferon production Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade 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: Compara 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 response to virus Traceable author statement Ref.37. Source: UniProtKB toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome type I interferon production Traceable author statement Ref.37. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome endosome membrane Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid binding Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Traceable author statement Ref.37. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P27958	4	EBI-356402,EBI-3649474	From a different organism.
ATG9A	Q7Z3C6	2	EBI-356402,EBI-727146
CALCOCO2	Q13137	5	EBI-356402,EBI-739580
CDC42BPG	Q6DT37	2	EBI-356402,EBI-689124
CYorf15B	Q9BZA4	2	EBI-356402,EBI-6115828
EIF2C2	Q9UKV8	2	EBI-356402,EBI-528269
IRF3	Q14653	4	EBI-356402,EBI-2650369
MIB1	Q86YT6	2	EBI-356402,EBI-2129148
MIB2	Q96AX9	2	EBI-356402,EBI-2130249
MTPAP	Q9NVV4	2	EBI-356402,EBI-2556166
OPTN	Q96CV9	3	EBI-356402,EBI-748974
STAT6	P42226	7	EBI-356402,EBI-1186478
TANK	Q92844	3	EBI-356402,EBI-356349
TXLNA	P40222	4	EBI-356402,EBI-359793
Txlng	Q8BHN1	2	EBI-356402,EBI-6116854	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 729

729

Serine/threonine-protein kinase TBK1

PRO_0000086743

Regions

Domain

9 – 310

302

Protein kinase

Domain

309 – 385

77

Ubiquitin-like

Nucleotide binding

15 – 23

9

ATP By similarity

Coiled coil

626 – 713

88

Potential

Sites

Active site

135

1

Proton acceptor By similarity

Binding site

38

1

ATP By similarity

Amino acid modifications

Modified residue

172

1

Phosphoserine; by autocatalysis and IKKB Ref.6

Cross-link

670

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.39

Natural variations

Natural variant

271

1

R → Q. Ref.40
Corresponds to variant rs56196591 [ dbSNP | Ensembl ].

VAR_041208

Natural variant

291

1

K → E. Ref.40
Corresponds to variant rs34774243 [ dbSNP | Ensembl ].

VAR_041209

Natural variant

296

1

D → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.40

VAR_041210

Natural variant

388

1

N → D. Ref.5
Corresponds to variant rs17857028 [ dbSNP | Ensembl ].

VAR_024746

Natural variant

410

1

G → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.40

VAR_041211

Natural variant

464

1

V → A. Ref.40
Corresponds to variant rs35635889 [ dbSNP | Ensembl ].

VAR_041212

Natural variant

570

1

K → Q. Ref.5
Corresponds to variant rs17853341 [ dbSNP | Ensembl ].

VAR_024747

Experimental info

Mutagenesis

38

1

K → A: Loss of TANK-mediated NF-kappa-B activation. Ref.1

Mutagenesis

172

1

S → A: Loss of kinase activity. Ref.6

Mutagenesis

172

1

S → E: Decreased kinase activity. Ref.6

Secondary structure

1

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729

Helix Strand Turn

Details...

Beta strand

5 – 17

13

Beta strand

19 – 28

10

Turn

29 – 31

3

Beta strand

34 – 40

7

Helix

42 – 46

5

Helix

49 – 61

13

Beta strand

70 – 75

6

Turn

77 – 79

3

Beta strand

82 – 87

6

Helix

94 – 99

6

Helix

101 – 103

3

Helix

109 – 128

20

Helix

138 – 140

3

Beta strand

141 – 145

5

Beta strand

151 – 155

5

Helix

167 – 169

3

Beta strand

173 – 175

3

Helix

177 – 179

3

Helix

182 – 188

7

Helix

202 – 216

15

Beta strand

220 – 222

3

Helix

227 – 229

3

Helix

231 – 240

10

Beta strand

247 – 250

4

Beta strand

257 – 262

6

Helix

271 – 284

14

Turn

289 – 291

3

Helix

305 – 307

3

Beta strand

308 – 315

8

Turn

316 – 319

4

Beta strand

320 – 327

8

Helix

332 – 343

12

Helix

347 – 349

3

Beta strand

350 – 354

5

Beta strand

357 – 359

3

Helix

367 – 369

3

Beta strand

375 – 377

3

Beta strand

379 – 383

5

Sequences

	Sequence		Length	Mass (Da)
	Q9UHD2 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: B58E4FE1B502276D	FASTA	729	83,642
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
[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]	"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.
[33]	"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.
[34]	"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.
[35]	"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.
[36]	"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.
[37]	"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.
[38]	"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.
[39]	"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.
[40]	"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. , 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.

IPI

IPI00293613.

RefSeq

NP_037386.1. NM_013254.3.

UniGene

Hs.505874.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4EFO	X-ray	1.77	A/B	302-383	[»]
4EUT	X-ray	2.60	A/B	2-385	[»]
4EUU	X-ray	1.80	A/B	2-308	[»]
4IM0	X-ray	2.40	A	1-657	[»]
4IM2	X-ray	2.50	A	1-657	[»]
4IM3	X-ray	3.34	A	1-657	[»]
4IW0	X-ray	4.00	A	2-657	[»]
4IWO	X-ray	2.61	A	2-657	[»]
4IWP	X-ray	3.06	A	2-657	[»]
4IWQ	X-ray	3.00	A	2-657	[»]

ProteinModelPortal

Q9UHD2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27529N.

IntAct

Q9UHD2. 41 interactions.

MINT

MINT-1131333.

STRING

9606.ENSP00000329967.

PTM databases

PhosphoSite

Q9UHD2.

Polymorphism databases

DMDM

74761953.

Proteomic databases

PaxDb

Q9UHD2.

PeptideAtlas

Q9UHD2.

PRIDE

Q9UHD2.

Protocols and materials databases

DNASU

29110.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331710; ENSP00000329967; ENSG00000183735.

GeneID

29110.

KEGG

hsa:29110.

UCSC

uc001ssc.2. human.

Organism-specific databases

CTD

29110.

GeneCards

GC12P064845.

HGNC

HGNC:11584. TBK1.

HPA

HPA045797.

MIM

604834. gene.

neXtProt

NX_Q9UHD2.

PharmGKB

PA36348.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000220867.

HOVERGEN

HBG008494.

InParanoid

Q9UHD2.

KO

K05410.

OMA

LLYQELM.

OrthoDB

EOG4229J4.

PhylomeDB

Q9UHD2.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9UHD2.

Bgee

Q9UHD2.

CleanEx

HS_TBK1.

Genevestigator

Q9UHD2.

GermOnline

ENSG00000183735. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
PS00299. UBIQUITIN_1. False negative.
PS50053. UBIQUITIN_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9UHD2.

ChEMBL

CHEMBL5408.

GenomeRNAi

29110.

NextBio

52179.

SOURCE

Search...

Entry information

Entry name

TBK1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.