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Protein

Serine/threonine-protein kinase TBK1

Gene

TBK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates and activates AKT1 (PubMed:21464307). 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 (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system (PubMed:22851595).22 Publications

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

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

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processAntiviral defense, Host-virus interaction, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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-9008059 Interleukin-37 signaling
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
R-HSA-918233 TRAF3-dependent IRF activation pathway
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
SABIO-RKiQ9UHD2
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

EuPathDBiHostDB:ENSG00000183735.9
HGNCiHGNC:11584 TBK1
MIMi604834 gene
neXtProtiNX_Q9UHD2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs770942184Ensembl.1
Natural variantiVAR_069755306L → I in FTDALS4; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs201970436Ensembl.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 dbSNP:rs758357594Ensembl.1
Natural variantiVAR_073943401K → E in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs756751089EnsemblClinVar.1
Natural variantiVAR_073944559M → R in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_073945571A → V in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs765035140Ensembl.1
Natural variantiVAR_073946598M → V in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs899858451EnsemblClinVar.1
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 dbSNP:rs748112833EnsemblClinVar.1
Encephalopathy, acute, infection-induced, herpes-specific, 8 (IIAE8)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA rare, often fatal complication of herpes simplex infection, caused by virus spreading in the central nervous system. Disease manifestations include low-grade fever, severe headache, nausea, vomiting, and lethargy. Neurological features include confusion, acute memory disturbances, disorientation, behavioral changes, hemiparesis and seizures.
See also OMIM:617900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08051750D → A in IIAE8; decreased expression levels. 1 PublicationCorresponds to variant dbSNP:rs1010930015Ensembl.1
Natural variantiVAR_080518159G → A in IIAE8; loss of kinase activity; loss of autophosphorylation at S-172. 1 Publication1
Natural variantiVAR_080519207I → V in IIAE8; unknown pathological significance. 1 Publication1

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. 4 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
617900 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 IKKB3 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. 'Lys-63'-linked polyubiquitination by RNF128 at Lys-30 and Lys-401 leads to the activation of antiviral responses.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UHD2
MaxQBiQ9UHD2
PaxDbiQ9UHD2
PeptideAtlasiQ9UHD2
PRIDEiQ9UHD2
ProteomicsDBi84323

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 Expressed in 233 organ(s), highest expression level in lateral nuclear group of thalamus
CleanExiHS_TBK1
ExpressionAtlasiQ9UHD2 baseline and differential
GenevisibleiQ9UHD2 HS

Organism-specific databases

HPAiHPA045797
HPA060211

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). Interacts with TRIM26 (PubMed:26611359). Interacts with TRIM23 (PubMed:28871090).21 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
(Microbial infection) Interacts with herpes simplex virus 1 protein ICP34.5.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118878, 131 interactors
CORUMiQ9UHD2
DIPiDIP-27529N
IntActiQ9UHD2, 93 interactors
MINTiQ9UHD2
STRINGi9606.ENSP00000329967

Chemistry databases

BindingDBiQ9UHD2

Structurei

Secondary structure

1729
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4250 Eukaryota
ENOG410XRMU LUCA
GeneTreeiENSGT00910000144033
HOGENOMiHOG000220867
HOVERGENiHBG008494
InParanoidiQ9UHD2
KOiK05410
OMAiFRGRHKK
OrthoDBiEOG091G0354
PhylomeDBiQ9UHD2
TreeFamiTF324269

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H206F5H206_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
98Annotation score:
F5GZI4F5GZI4_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
48Annotation score:
F5H1A3F5H1A3_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
103Annotation score:

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_08051750D → A in IIAE8; decreased expression levels. 1 PublicationCorresponds to variant dbSNP:rs1010930015Ensembl.1
Natural variantiVAR_073939105Y → C in FTDALS4. 1 Publication1
Natural variantiVAR_069754151S → F1 PublicationCorresponds to variant dbSNP:rs55824172EnsemblClinVar.1
Natural variantiVAR_080518159G → A in IIAE8; loss of kinase activity; loss of autophosphorylation at S-172. 1 Publication1
Natural variantiVAR_080519207I → V in IIAE8; unknown pathological significance. 1 Publication1
Natural variantiVAR_041208271R → Q1 PublicationCorresponds to variant dbSNP:rs56196591EnsemblClinVar.1
Natural variantiVAR_041209291K → E1 PublicationCorresponds to variant dbSNP:rs34774243EnsemblClinVar.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 dbSNP:rs770942184Ensembl.1
Natural variantiVAR_069755306L → I in FTDALS4; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs201970436Ensembl.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 dbSNP:rs758357594Ensembl.1
Natural variantiVAR_024746388N → D1 PublicationCorresponds to variant dbSNP:rs17857028Ensembl.1
Natural variantiVAR_073943401K → E in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs756751089EnsemblClinVar.1
Natural variantiVAR_041211410G → R in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1262765773Ensembl.1
Natural variantiVAR_041212464V → A2 PublicationsCorresponds to variant dbSNP:rs35635889EnsemblClinVar.1
Natural variantiVAR_073944559M → R in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_024747570K → Q1 PublicationCorresponds to variant dbSNP:rs17853341Ensembl.1
Natural variantiVAR_073945571A → V in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs765035140Ensembl.1
Natural variantiVAR_073946598M → V in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs899858451EnsemblClinVar.1
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 dbSNP:rs748112833EnsemblClinVar.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

Similar proteinsi

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[»]
5W5VX-ray3.65A1-657[»]
ProteinModelPortaliQ9UHD2
SMRiQ9UHD2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118878, 131 interactors
CORUMiQ9UHD2
DIPiDIP-27529N
IntActiQ9UHD2, 93 interactors
MINTiQ9UHD2
STRINGi9606.ENSP00000329967

Chemistry databases

BindingDBiQ9UHD2
ChEMBLiCHEMBL5408
GuidetoPHARMACOLOGYi2237

PTM databases

iPTMnetiQ9UHD2
PhosphoSitePlusiQ9UHD2

Polymorphism and mutation databases

BioMutaiTBK1
DMDMi74761953

Proteomic databases

EPDiQ9UHD2
MaxQBiQ9UHD2
PaxDbiQ9UHD2
PeptideAtlasiQ9UHD2
PRIDEiQ9UHD2
ProteomicsDBi84323

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
EuPathDBiHostDB:ENSG00000183735.9
GeneCardsiTBK1
HGNCiHGNC:11584 TBK1
HPAiHPA045797
HPA060211
MalaCardsiTBK1
MIMi177700 phenotype
604834 gene
616439 phenotype
617900 phenotype
neXtProtiNX_Q9UHD2
OpenTargetsiENSG00000183735
Orphaneti1930 Herpetic encephalitis
PharmGKBiPA36348
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4250 Eukaryota
ENOG410XRMU LUCA
GeneTreeiENSGT00910000144033
HOGENOMiHOG000220867
HOVERGENiHBG008494
InParanoidiQ9UHD2
KOiK05410
OMAiFRGRHKK
OrthoDBiEOG091G0354
PhylomeDBiQ9UHD2
TreeFamiTF324269

Enzyme and pathway databases

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-9008059 Interleukin-37 signaling
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
R-HSA-918233 TRAF3-dependent IRF activation pathway
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
SABIO-RKiQ9UHD2
SignaLinkiQ9UHD2
SIGNORiQ9UHD2

Miscellaneous databases

ChiTaRSiTBK1 human
GeneWikiiTANK-binding_kinase_1
GenomeRNAii29110
PROiPR:Q9UHD2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183735 Expressed in 233 organ(s), highest expression level in lateral nuclear group of thalamus
CleanExiHS_TBK1
ExpressionAtlasiQ9UHD2 baseline and differential
GenevisibleiQ9UHD2 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTBK1_HUMAN
AccessioniPrimary (citable) accession number: Q9UHD2
Secondary accession number(s): A8K4S4, Q8IYV3, Q9NUJ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: May 1, 2000
Last modified: October 10, 2018
This is version 172 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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