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Protein

Serine/threonine-protein kinase TBK1

Gene

TBK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.18 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei38ATPCurated1
Active sitei135Proton acceptor2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 23ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • nucleic acid binding Source: Ensembl
  • phosphoprotein binding Source: UniProtKB
  • protein kinase activity Source: Reactome
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • defense response to Gram-positive bacterium Source: Ensembl
  • defense response to virus Source: UniProtKB-KW
  • dendritic cell proliferation Source: Ensembl
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • negative regulation of gene expression Source: Ensembl
  • negative regulation of type I interferon production Source: Reactome
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interferon-alpha production Source: BHF-UCL
  • positive regulation of interferon-beta biosynthetic process Source: Ensembl
  • positive regulation of interferon-beta production Source: BHF-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of type I interferon production Source: Reactome
  • positive regulation of xenophagy Source: Ensembl
  • regulation of neuron death Source: ParkinsonsUK-UCL
  • response to virus Source: UniProtKB
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  • type I interferon production Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00020-MONOMER.
ReactomeiR-HSA-1606341. IRF3 mediated activation of type 1 IFN.
R-HSA-3134975. Regulation of innate immune responses to cytosolic DNA.
R-HSA-3249367. STAT6-mediated induction of chemokines.
R-HSA-3270619. IRF3-mediated induction of type I IFN.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
R-HSA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
SABIO-RKQ9UHD2.
SignaLinkiQ9UHD2.
SIGNORiQ9UHD2.

Names & Taxonomyi

Protein namesi
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 namesi
Name:TBK1
Synonyms:NAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11584. TBK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endosome membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Glaucoma 1, open angle, P (GLC1P)2 Publications
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 (PubMed:21447600).1 Publication
Disease descriptionA 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.
See also OMIM:177700
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis.
See also OMIM:616439
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07393847R → H in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_073939105Y → C in FTDALS4. 1 Publication1
Natural variantiVAR_073940305I → T in FTDALS4. 1 PublicationCorresponds to variant rs770942184dbSNPEnsembl.1
Natural variantiVAR_069755306L → I in FTDALS4; unknown pathological significance. 2 PublicationsCorresponds to variant rs201970436dbSNPEnsembl.1
Natural variantiVAR_073941308R → Q in FTDALS4; reduced kinase activity. 1 Publication1
Natural variantiVAR_073942357R → Q in FTDALS4; reduced kinase activity. 1 PublicationCorresponds to variant rs758357594dbSNPEnsembl.1
Natural variantiVAR_073943401K → E in FTDALS4. 1 PublicationCorresponds to variant rs756751089dbSNPEnsembl.1
Natural variantiVAR_073944559M → R in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_073945571A → V in FTDALS4. 1 PublicationCorresponds to variant rs765035140dbSNPEnsembl.1
Natural variantiVAR_073946598M → V in FTDALS4. 1 Publication1
Natural variantiVAR_073947643Missing in FTDALS4. 1 Publication1
Natural variantiVAR_073948696E → K in FTDALS4; loss of kinase activity; impairs binding to OPTN. 2 PublicationsCorresponds to variant rs748112833dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi30K → R: Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-401. 1 Publication1
Mutagenesisi33D → A: Decreases phosphorylation and kinase activity. 1 Publication1
Mutagenesisi38K → A: Loss of kinase activity. 3 Publications1
Mutagenesisi135D → N: Loss of kinase activity. 3 Publications1
Mutagenesisi172S → A: Loss of kinase activity. No effect on dimerization. 2 Publications1
Mutagenesisi172S → E: Decreased kinase activity. 2 Publications1
Mutagenesisi316L → E: Decreases kinase activity. No effect on phosphorylation. 1 Publication1
Mutagenesisi325Y → E: Abolishes phosphorylation and kinase activity. 1 Publication1
Mutagenesisi355E → R: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with A-357 or R-448. 2 Publications1
Mutagenesisi357R → A: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355. 1 Publication1
Mutagenesisi401K → R: Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-30. 1 Publication1
Mutagenesisi448E → R: Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355. 1 Publication1
Mutagenesisi459H → E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-466 and E-470. 1 Publication1
Mutagenesisi466I → E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-470. 1 Publication1
Mutagenesisi470F → E: Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-466. 1 Publication1
Mutagenesisi547R → D: Decreases phosphorylation and kinase activity. Abolishes dimerization. 1 Publication1
Mutagenesisi577Y → A: Decreases kinase activity. 1 Publication1
Mutagenesisi580E → A: Decreases kinase activity. 1 Publication1
Mutagenesisi582I → A: Decreases kinase activity. 1 Publication1
Mutagenesisi589K → D: Decreases phosphorylation and kinase activity. 1 Publication1
Mutagenesisi690M → A: Decreases interaction with TANK. 1 Publication1
Mutagenesisi693L → A: Almost abolishes interaction with TANK. 1 Publication1
Mutagenesisi694K → E: Strongly decreases interaction with TANK and TBKBP1. No effect on phosphorylation. 1 Publication1
Mutagenesisi704L → A: Strongly decreases interaction with AZI2, TANK and TBKBP1. No effect on phosphorylation. 1 Publication1
Mutagenesisi708N → A: Decreases interaction with TANK. 1 Publication1
Mutagenesisi711L → A: Almost abolishes interaction with TANK. 1 Publication1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Glaucoma, Neurodegeneration

Organism-specific databases

DisGeNETi29110.
MalaCardsiTBK1.
MIMi177700. phenotype.
616439. phenotype.
OpenTargetsiENSG00000183735.
Orphaneti1930. Herpetic encephalitis.
PharmGKBiPA36348.

Chemistry databases

ChEMBLiCHEMBL5408.
GuidetoPHARMACOLOGYi2237.

Polymorphism and mutation databases

BioMutaiTBK1.
DMDMi74761953.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867431 – 729Serine/threonine-protein kinase TBK1Add BLAST729

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei172Phosphoserine; by autocatalysis and IKKB2 Publications1
Cross-linki401Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki670Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei716PhosphoserineCombined sources1

Post-translational modificationi

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.4 Publications
'Lys-63'-linked polyubiquitination by MIB1 after RNA virus infection, or by NRDP1 after LPS stimulation at Lys-30 and Lys-401, participates in kinase activation. 'Lys-48'-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation. 'Lys-48'-linked polyubiquitination by TRAIP also leads to proteasomal degradation.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UHD2.
MaxQBiQ9UHD2.
PaxDbiQ9UHD2.
PeptideAtlasiQ9UHD2.
PRIDEiQ9UHD2.

PTM databases

iPTMnetiQ9UHD2.
PhosphoSitePlusiQ9UHD2.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000183735.
CleanExiHS_TBK1.
ExpressionAtlasiQ9UHD2. baseline and differential.
GenevisibleiQ9UHD2. HS.

Organism-specific databases

HPAiHPA045797.

Interactioni

Subunit structurei

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 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 TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436).19 Publications
(Microbial infection) Interacts with HCV NS3; this interaction leads to inhibition of cellular antiviral response by blocking necessary interactions between the TBK1 and its substrates IRF3 and IRF7.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
I0DF373EBI-356402,EBI-9543922From a different organism.
I6W9F26EBI-356402,EBI-9518472From a different organism.
K7Y1A22EBI-356402,EBI-8788634From a different organism.
P279584EBI-356402,EBI-3649474From a different organism.
AGO2Q9UKV82EBI-356402,EBI-528269
ATG9AQ7Z3C62EBI-356402,EBI-727146
AZI2Q9H6S13EBI-356402,EBI-359973
CALCOCO2Q131375EBI-356402,EBI-739580
CDC42BPGQ6DT372EBI-356402,EBI-689124
Ddx3xQ621678EBI-356402,EBI-773173From a different organism.
GAMMAHV.ORF11O419324EBI-356402,EBI-9544132From a different organism.
HSP90AB1P082382EBI-356402,EBI-352572
IKBKEQ141642EBI-356402,EBI-307369
IKBKGQ9Y6K92EBI-356402,EBI-81279
IRF3Q146538EBI-356402,EBI-2650369
IRF7Q929852EBI-356402,EBI-968267
MAVSQ7Z4342EBI-356402,EBI-995373
MIB1Q86YT62EBI-356402,EBI-2129148
MIB2Q96AX92EBI-356402,EBI-2130249
MTPAPQ9NVV42EBI-356402,EBI-2556166
OPTNQ96CV911EBI-356402,EBI-748974
STAT6P422267EBI-356402,EBI-1186478
TANKQ928447EBI-356402,EBI-356349
TBKBP1A7MCY68EBI-356402,EBI-359969
TMEM173Q86WV63EBI-356402,EBI-2800345
TRAF2Q129333EBI-356402,EBI-355744
TXLNAP402224EBI-356402,EBI-359793
TxlngQ8BHN12EBI-356402,EBI-6116854From a different organism.
VP35Q051272EBI-356402,EBI-6148294From a different organism.

GO - Molecular functioni

  • phosphoprotein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118878. 114 interactors.
DIPiDIP-27529N.
IntActiQ9UHD2. 77 interactors.
MINTiMINT-1131333.
STRINGi9606.ENSP00000329967.

Chemistry databases

BindingDBiQ9UHD2.

Structurei

Secondary structure

1729
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1 – 3Combined sources3
Beta strandi5 – 17Combined sources13
Beta strandi19 – 28Combined sources10
Turni29 – 31Combined sources3
Beta strandi34 – 40Combined sources7
Helixi42 – 46Combined sources5
Helixi49 – 61Combined sources13
Beta strandi65 – 67Combined sources3
Beta strandi70 – 75Combined sources6
Turni77 – 79Combined sources3
Beta strandi82 – 87Combined sources6
Helixi94 – 99Combined sources6
Helixi101 – 103Combined sources3
Helixi109 – 128Combined sources20
Helixi138 – 140Combined sources3
Beta strandi141 – 145Combined sources5
Beta strandi151 – 155Combined sources5
Turni161 – 163Combined sources3
Helixi167 – 169Combined sources3
Beta strandi173 – 175Combined sources3
Helixi177 – 179Combined sources3
Helixi182 – 188Combined sources7
Helixi202 – 216Combined sources15
Beta strandi220 – 222Combined sources3
Helixi227 – 229Combined sources3
Helixi231 – 240Combined sources10
Beta strandi247 – 250Combined sources4
Beta strandi257 – 262Combined sources6
Helixi271 – 284Combined sources14
Beta strandi285 – 287Combined sources3
Turni289 – 291Combined sources3
Helixi305 – 307Combined sources3
Beta strandi308 – 315Combined sources8
Turni316 – 319Combined sources4
Beta strandi320 – 327Combined sources8
Helixi332 – 343Combined sources12
Helixi347 – 349Combined sources3
Beta strandi350 – 354Combined sources5
Beta strandi357 – 359Combined sources3
Helixi367 – 369Combined sources3
Beta strandi375 – 377Combined sources3
Beta strandi379 – 383Combined sources5
Helixi408 – 480Combined sources73
Helixi498 – 526Combined sources29
Beta strandi530 – 532Combined sources3
Helixi535 – 539Combined sources5
Helixi544 – 546Combined sources3
Helixi548 – 571Combined sources24
Helixi577 – 603Combined sources27
Helixi605 – 647Combined sources43
Turni648 – 651Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5EOAX-ray2.50C/D677-729[»]
5EOFX-ray2.05C/D677-729[»]
5EP6X-ray1.45B/D677-729[»]
ProteinModelPortaliQ9UHD2.
SMRiQ9UHD2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 310Protein kinasePROSITE-ProRule annotationAdd BLAST302
Domaini309 – 385Ubiquitin-likeAdd BLAST77

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni621 – 629Interaction with AZI2, TANK and TBKBP11 Publication9

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili407 – 657Add BLAST251
Coiled coili658 – 713Sequence analysisAdd BLAST56

Domaini

Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal coiled-coil region mediating homodimerization.2 Publications

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 ubiquitin-like domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000220867.
HOVERGENiHBG008494.
InParanoidiQ9UHD2.
KOiK05410.
OMAiFRGRHKK.
OrthoDBiEOG091G0354.
PhylomeDBiQ9UHD2.
TreeFamiTF324269.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9UHD2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLFAIKVF NNISFLRPVD
60 70 80 90 100
VQMREFEVLK KLNHKNIVKL FAIEEETTTR HKVLIMEFCP CGSLYTVLEE
110 120 130 140 150
PSNAYGLPES EFLIVLRDVV GGMNHLRENG IVHRDIKPGN IMRVIGEDGQ
160 170 180 190 200
SVYKLTDFGA ARELEDDEQF VSLYGTEEYL HPDMYERAVL RKDHQKKYGA
210 220 230 240 250
TVDLWSIGVT FYHAATGSLP FRPFEGPRRN KEVMYKIITG KPSGAISGVQ
260 270 280 290 300
KAENGPIDWS GDMPVSCSLS RGLQVLLTPV LANILEADQE KCWGFDQFFA
310 320 330 340 350
ETSDILHRMV IHVFSLQQMT AHKIYIHSYN TATIFHELVY KQTKIISSNQ
360 370 380 390 400
ELIYEGRRLV LEPGRLAQHF PKTTEENPIF VVSREPLNTI GLIYEKISLP
410 420 430 440 450
KVHPRYDLDG DASMAKAITG VVCYACRIAS TLLLYQELMR KGIRWLIELI
460 470 480 490 500
KDDYNETVHK KTEVVITLDF CIRNIEKTVK VYEKLMKINL EAAELGEISD
510 520 530 540 550
IHTKLLRLSS SQGTIETSLQ DIDSRLSPGG SLADAWAHQE GTHPKDRNVE
560 570 580 590 600
KLQVLLNCMT EIYYQFKKDK AERRLAYNEE QIHKFDKQKL YYHATKAMTH
610 620 630 640 650
FTDECVKKYE AFLNKSEEWI RKMLHLRKQL LSLTNQCFDI EEEVSKYQEY
660 670 680 690 700
TNELQETLPQ KMFTASSGIK HTMTPIYPSS NTLVEMTLGM KKLKEEMEGV
710 720
VKELAENNHI LERFGSLTMD GGLRNVDCL
Length:729
Mass (Da):83,642
Last modified:May 1, 2000 - v1
Checksum:iB58E4FE1B502276D
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07393847R → H in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_073939105Y → C in FTDALS4. 1 Publication1
Natural variantiVAR_069754151S → F.1 PublicationCorresponds to variant rs55824172dbSNPEnsembl.1
Natural variantiVAR_041208271R → Q.1 PublicationCorresponds to variant rs56196591dbSNPEnsembl.1
Natural variantiVAR_041209291K → E.1 PublicationCorresponds to variant rs34774243dbSNPEnsembl.1
Natural variantiVAR_041210296D → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_073940305I → T in FTDALS4. 1 PublicationCorresponds to variant rs770942184dbSNPEnsembl.1
Natural variantiVAR_069755306L → I in FTDALS4; unknown pathological significance. 2 PublicationsCorresponds to variant rs201970436dbSNPEnsembl.1
Natural variantiVAR_073941308R → Q in FTDALS4; reduced kinase activity. 1 Publication1
Natural variantiVAR_073942357R → Q in FTDALS4; reduced kinase activity. 1 PublicationCorresponds to variant rs758357594dbSNPEnsembl.1
Natural variantiVAR_024746388N → D.1 PublicationCorresponds to variant rs17857028dbSNPEnsembl.1
Natural variantiVAR_073943401K → E in FTDALS4. 1 PublicationCorresponds to variant rs756751089dbSNPEnsembl.1
Natural variantiVAR_041211410G → R in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041212464V → A.2 PublicationsCorresponds to variant rs35635889dbSNPEnsembl.1
Natural variantiVAR_073944559M → R in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_024747570K → Q.1 PublicationCorresponds to variant rs17853341dbSNPEnsembl.1
Natural variantiVAR_073945571A → V in FTDALS4. 1 PublicationCorresponds to variant rs765035140dbSNPEnsembl.1
Natural variantiVAR_073946598M → V in FTDALS4. 1 Publication1
Natural variantiVAR_073947643Missing in FTDALS4. 1 Publication1
Natural variantiVAR_073948696E → K in FTDALS4; loss of kinase activity; impairs binding to OPTN. 2 PublicationsCorresponds to variant rs748112833dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8968.1.
RefSeqiNP_037386.1. NM_013254.3.
XP_005268866.1. XM_005268809.1.
XP_005268867.1. XM_005268810.1.
UniGeneiHs.505874.

Genome annotation databases

EnsembliENST00000331710; ENSP00000329967; ENSG00000183735.
GeneIDi29110.
KEGGihsa:29110.
UCSCiuc001ssc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8968.1.
RefSeqiNP_037386.1. NM_013254.3.
XP_005268866.1. XM_005268809.1.
XP_005268867.1. XM_005268810.1.
UniGeneiHs.505874.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5EOAX-ray2.50C/D677-729[»]
5EOFX-ray2.05C/D677-729[»]
5EP6X-ray1.45B/D677-729[»]
ProteinModelPortaliQ9UHD2.
SMRiQ9UHD2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118878. 114 interactors.
DIPiDIP-27529N.
IntActiQ9UHD2. 77 interactors.
MINTiMINT-1131333.
STRINGi9606.ENSP00000329967.

Chemistry databases

BindingDBiQ9UHD2.
ChEMBLiCHEMBL5408.
GuidetoPHARMACOLOGYi2237.

PTM databases

iPTMnetiQ9UHD2.
PhosphoSitePlusiQ9UHD2.

Polymorphism and mutation databases

BioMutaiTBK1.
DMDMi74761953.

Proteomic databases

EPDiQ9UHD2.
MaxQBiQ9UHD2.
PaxDbiQ9UHD2.
PeptideAtlasiQ9UHD2.
PRIDEiQ9UHD2.

Protocols and materials databases

DNASUi29110.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331710; ENSP00000329967; ENSG00000183735.
GeneIDi29110.
KEGGihsa:29110.
UCSCiuc001ssc.3. human.

Organism-specific databases

CTDi29110.
DisGeNETi29110.
GeneCardsiTBK1.
HGNCiHGNC:11584. TBK1.
HPAiHPA045797.
MalaCardsiTBK1.
MIMi177700. phenotype.
604834. gene.
616439. phenotype.
neXtProtiNX_Q9UHD2.
OpenTargetsiENSG00000183735.
Orphaneti1930. Herpetic encephalitis.
PharmGKBiPA36348.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000220867.
HOVERGENiHBG008494.
InParanoidiQ9UHD2.
KOiK05410.
OMAiFRGRHKK.
OrthoDBiEOG091G0354.
PhylomeDBiQ9UHD2.
TreeFamiTF324269.

Enzyme and pathway databases

BioCyciZFISH:HS00020-MONOMER.
ReactomeiR-HSA-1606341. IRF3 mediated activation of type 1 IFN.
R-HSA-3134975. Regulation of innate immune responses to cytosolic DNA.
R-HSA-3249367. STAT6-mediated induction of chemokines.
R-HSA-3270619. IRF3-mediated induction of type I IFN.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
R-HSA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
SABIO-RKQ9UHD2.
SignaLinkiQ9UHD2.
SIGNORiQ9UHD2.

Miscellaneous databases

GeneWikiiTANK-binding_kinase_1.
GenomeRNAii29110.
PROiQ9UHD2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183735.
CleanExiHS_TBK1.
ExpressionAtlasiQ9UHD2. baseline and differential.
GenevisibleiQ9UHD2. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTBK1_HUMAN
AccessioniPrimary (citable) accession number: Q9UHD2
Secondary accession number(s): A8K4S4, Q8IYV3, Q9NUJ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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 (PubMed:21042276).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.