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UniProtKB - Q9UHD2 (TBK1_HUMAN)

Entry version 189 (12 Aug 2020)
Sequence version 1 (01 May 2000)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:12692549, PubMed:14703513, PubMed:18583960, PubMed:12702806, PubMed:15367631, PubMed:10581243, PubMed:11839743, PubMed:15485837, PubMed:21138416, PubMed:25636800, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:26611359). 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 (PubMed:12692549, PubMed:14703513, PubMed:18583960, PubMed:12702806, PubMed:15367631, PubMed:25636800). 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 (PubMed:12702806, PubMed:15367631, PubMed:25636800). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:23453971, PubMed:23453972, PubMed:23746807). Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800, PubMed:30842653). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (PubMed:21931631). 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 (PubMed:10783893, PubMed:15489227). 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 (By similarity). 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).By similarity24 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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei38ATPCurated1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei135Proton acceptor3 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi15 – 23ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>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

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q9UHD2

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-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-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		Q9UHD2

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q9UHD2

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q9UHD2

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Serine/threonine-protein kinase TBK1Curated (EC:2.7.11.17 Publications)
Alternative name(s):
NF-kappa-B-activating kinase1 Publication
T2K
TANK-binding kinase 11 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TBK11 PublicationImported
Synonyms:NAK1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 12

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000183735.9

Human Gene Nomenclature Database

More...HGNCi		HGNC:11584, TBK1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		604834, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9UHD2

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
Related information in OMIM
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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_07393847R → H in FTDALS4; loss of kinase activity. 1 Publication1
Natural variantiVAR_073939105Y → C in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs1366668789Ensembl.1
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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08051750D → A in IIAE8; decreased expression levels. 1 PublicationCorresponds to variant dbSNP:rs1010930015EnsemblClinVar.1
Natural variantiVAR_080518159G → A in IIAE8; loss of kinase activity; loss of autophosphorylation at S-172. 1 PublicationCorresponds to variant dbSNP:rs1555202947EnsemblClinVar.1
Natural variantiVAR_080519207I → V in IIAE8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1555203557EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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. 4 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. Reduced phosphorylation of STING1. 2 Publications1
Mutagenesisi578N → A: Reduced phosphorylation of STING1. 1 Publication1
Mutagenesisi580E → A: Decreases kinase activity. 1 Publication1
Mutagenesisi581Q → A: Reduced phosphorylation of STING1. 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

DisGeNET

More...DisGeNETi		29110

MalaCards human disease database

More...MalaCardsi		TBK1
MIMi177700, phenotype
616439, phenotype
617900, phenotype

Open Targets

More...OpenTargetsi		ENSG00000183735

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		803, Amyotrophic lateral sclerosis
275872, Frontotemporal dementia with motor neuron disease
1930, Herpes simplex virus encephalitis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA36348

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q9UHD2, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL5408

Drug and drug target database

More...DrugBanki		DB12010, Fostamatinib

DrugCentral

More...DrugCentrali		Q9UHD2

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2237

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		TBK1

Domain mapping of disease mutations (DMDM)

More...DMDMi		74761953

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000867431 – 729Serine/threonine-protein kinase TBK1Add BLAST729

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki30Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

The CPTAC Assay portal

More...CPTACi		CPTAC-910
CPTAC-911

Encyclopedia of Proteome Dynamics

More...EPDi		Q9UHD2

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9UHD2

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q9UHD2

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q9UHD2

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9UHD2

PeptideAtlas

More...PeptideAtlasi		Q9UHD2

PRoteomics IDEntifications database

More...PRIDEi		Q9UHD2

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		84323

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9UHD2

MetOSite database of methionine sulfoxide sites

More...MetOSitei		Q9UHD2

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9UHD2

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000183735, Expressed in lateral nuclear group of thalamus and 243 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q9UHD2, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9UHD2, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000183735, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (PubMed:21145761).

Interacts with DDX3X, TIRAP and TRAF2 (PubMed:10581243, PubMed:14530355).

Part of a ternary complex consisting of TANK, TRAF2 and TBK1 (PubMed:10581243).

Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation (PubMed:14560022, PubMed:21931631, PubMed:23453972, PubMed:10581243, PubMed:29251827).

Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation (PubMed:21145761).

Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation (PubMed:16281057).

Interacts with IRF3, leading to IRF3 phosphorylation (PubMed:14703513, PubMed:25636800).

Interacts with DDX58/RIG-I (PubMed:16281057).

Interacts with CYLD (PubMed:18636086).

Interacts with OPTN and TRAF3 (PubMed:20174559).

Interacts with SRC (PubMed:19419966).

Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity (PubMed:17018283).

Interacts with STING1, leading to STING1 phosphorylation (PubMed:19416887, PubMed:25636800, PubMed:30842653).

Interacts with IFIT3 (via N-terminus) (PubMed:21813773).

Interacts with MAVS; interaction only takes place in the presence of IFIT3 and leads to MAVS phosphorylation (PubMed:21813773, PubMed:25636800, PubMed:28011935).

Interacts (via protein kinase domain) with TTLL12 (via TTL domain); the interaction prevents MAVS binding to TBK1 (PubMed:28011935).

Interacts with TICAM1; this interaction is enhanced in the presence of WDFY1 and leads to TICAM1 phosphorylation (PubMed:14530355, PubMed:14739303, PubMed:25736436, PubMed:25636800).

Interacts with TRIM26 (PubMed:26611359).

Interacts with TRIM23 (PubMed:28871090).

Interacts with TTC4 and IKBKE (PubMed:29251827).

Interacts with HNRNPA2B1 (PubMed:31320558).

Interacts with DDX3X (PubMed:20375222).

24 Publications

(Microbial infection) Interacts with Borna disease virus (BDV) P protein leading to its phosphorylation.

1 Publication

(Microbial infection) Interacts with Ebola virus protein VP35.

1 Publication

(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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details
Q9UHD2
With#Exp.IntAct
AGO2 [Q9UKV8]2EBI-356402,EBI-528269
ATG9A [Q7Z3C6]2EBI-356402,EBI-727146
AZI2 [Q9H6S1]6EBI-356402,EBI-359973
CALCOCO2 [Q13137]6EBI-356402,EBI-739580
CDC42BPG [Q6DT37]2EBI-356402,EBI-689124
HSP90AB1 [P08238]2EBI-356402,EBI-352572
ICOS [Q9Y6W8]5EBI-356402,EBI-3922712
IKBKE [Q14164]5EBI-356402,EBI-307369
IKBKG [Q9Y6K9]4EBI-356402,EBI-81279
IRF3 [Q14653]10EBI-356402,EBI-2650369
IRF7 [Q92985]2EBI-356402,EBI-968267
MAVS [Q7Z434]2EBI-356402,EBI-995373
MIB1 [Q86YT6]2EBI-356402,EBI-2129148
MIB2 [Q96AX9]2EBI-356402,EBI-2130249
MTPAP [Q9NVV4]2EBI-356402,EBI-2556166
OPTN [Q96CV9]15EBI-356402,EBI-748974
RIOK3 [O14730]3EBI-356402,EBI-1047061
STAT6 [P42226]7EBI-356402,EBI-1186478
STING1 [Q86WV6]8EBI-356402,EBI-2800345
TANK [Q92844]12EBI-356402,EBI-356349
TBKBP1 [A7MCY6]8EBI-356402,EBI-359969
TICAM1 [Q8IUC6]3EBI-356402,EBI-525995
TRAF2 [Q12933]6EBI-356402,EBI-355744
TTC4 [O95801]5EBI-356402,EBI-1050890
TXLNA [P40222]5EBI-356402,EBI-359793
Ddx3x [Q62167] from Mus musculus.8EBI-356402,EBI-773173
GAMMAHV.ORF11 [O41932] from Murid herpesvirus 4.4EBI-356402,EBI-9544132
Txlng [Q8BHN1] from Mus musculus.2EBI-356402,EBI-6116854
VP35 [Q05127] from Zaire ebolavirus (strain Mayinga-76).2EBI-356402,EBI-6148294
I0DF37 from Phlebovirus WCH/97/HN/China/2011.3EBI-356402,EBI-9543922
I6W9F2 from Phlebovirus JS2010-014.6EBI-356402,EBI-9518472
K7Y1A2 from Hepacivirus C.2EBI-356402,EBI-8788634
Protease NS2-3 (PRO_0000037572) from Hepatitis C virus genotype 1a (isolate H).2EBI-356402,EBI-6919131
Serine protease NS3 (PRO_0000037573) from Hepatitis C virus genotype 1a (isolate H).4EBI-356402,EBI-3649474

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		118878, 166 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q9UHD2

Database of interacting proteins

More...DIPi		DIP-27529N

Protein interaction database and analysis system

More...IntActi		Q9UHD2, 107 interactors

Molecular INTeraction database

More...MINTi		Q9UHD2

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000329967

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q9UHD2

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q9UHD2, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

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

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9UHD2

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini9 – 310Protein kinasePROSITE-ProRule annotationAdd BLAST302
Domaini309 – 385Ubiquitin-likeAdd BLAST77

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni621 – 729Interaction with AZI2, TANK and TBKBP11 PublicationAdd BLAST109

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and domains' section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili407 – 657By similarityAdd BLAST251
Coiled coili658 – 713Sequence analysisAdd BLAST56

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>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

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG4250, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00950000182937

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_101_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9UHD2

KEGG Orthology (KO)

More...KOi		K05410

Identification of Orthologs from Complete Genome Data

More...OMAi		MRKGVRW

Database of Orthologous Groups

More...OrthoDBi		563981at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9UHD2

TreeFam database of animal gene trees

More...TreeFami		TF324269

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR011009, Kinase-like_dom_sf
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR041309, TBK1_CCD1
IPR041087, TBK1_ULD

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00069, Pkinase, 1 hit
PF18394, TBK1_CCD1, 1 hit
PF18396, TBK1_ULD, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00107, PROTEIN_KINASE_ATP, 1 hit
PS50011, PROTEIN_KINASE_DOM, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 13 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB58E4FE1B502276D
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A494C045A0A494C045_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
731Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C0X2A0A494C0X2_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
643Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C148A0A494C148_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
705Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C167A0A494C167_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
677Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C079A0A494C079_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
519Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C0A8A0A494C0A8_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
551Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C0R4A0A494C0R4_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
542Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C1M6A0A494C1M6_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
575Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5GZI4F5GZI4_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
48Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5H1A3F5H1A3_HUMAN
Serine/threonine-protein kinase TBK...
TBK1
103Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
There are more potential isoformsShow all

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAA92129 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.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:rs1010930015EnsemblClinVar.1
Natural variantiVAR_073939105Y → C in FTDALS4. 1 PublicationCorresponds to variant dbSNP:rs1366668789Ensembl.1
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 PublicationCorresponds to variant dbSNP:rs1555202947EnsemblClinVar.1
Natural variantiVAR_080519207I → V in IIAE8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1555203557EnsemblClinVar.1
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:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS8968.1

NCBI Reference Sequences

More...RefSeqi		NP_037386.1, NM_013254.3
XP_005268866.1, XM_005268809.1
XP_005268867.1, XM_005268810.1

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000331710; ENSP00000329967; ENSG00000183735
ENST00000650790; ENSP00000498995; ENSG00000183735

Database of genes from NCBI RefSeq genomes

More...GeneIDi		29110

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:29110

UCSC genome browser

More...UCSCi		uc001ssc.3, human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...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[»]
6BNYX-ray3.34A1-657[»]
6BODX-ray3.20A1-657[»]
6BOEX-ray3.60A1-657[»]
6CQ0X-ray3.19A1-657[»]
6CQ4X-ray3.20A1-657[»]
6CQ5X-ray3.35A1-657[»]
6NT9electron microscopy3.3A/B1-729[»]
6O8BX-ray3.40A/B2-657[»]
6RSRX-ray3.15A2-657[»]
6RSTX-ray3.29A2-657[»]
6RSUX-ray2.75A2-657[»]
SMRiQ9UHD2
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi118878, 166 interactors
CORUMiQ9UHD2
DIPiDIP-27529N
IntActiQ9UHD2, 107 interactors
MINTiQ9UHD2
STRINGi9606.ENSP00000329967

Chemistry databases

BindingDBiQ9UHD2
ChEMBLiCHEMBL5408
DrugBankiDB12010, Fostamatinib
DrugCentraliQ9UHD2
GuidetoPHARMACOLOGYi2237

PTM databases

iPTMnetiQ9UHD2
MetOSiteiQ9UHD2
PhosphoSitePlusiQ9UHD2

Polymorphism and mutation databases

BioMutaiTBK1
DMDMi74761953

Proteomic databases

CPTACiCPTAC-910
CPTAC-911
EPDiQ9UHD2
jPOSTiQ9UHD2
MassIVEiQ9UHD2
MaxQBiQ9UHD2
PaxDbiQ9UHD2
PeptideAtlasiQ9UHD2
PRIDEiQ9UHD2
ProteomicsDBi84323

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		16584, 592 antibodies

The DNASU plasmid repository

More...DNASUi		29110

Genome annotation databases

EnsembliENST00000331710; ENSP00000329967; ENSG00000183735
ENST00000650790; ENSP00000498995; ENSG00000183735
GeneIDi29110
KEGGihsa:29110
UCSCiuc001ssc.3, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		29110
DisGeNETi29110
EuPathDBiHostDB:ENSG00000183735.9

GeneCards: human genes, protein and diseases

More...GeneCardsi		TBK1
HGNCiHGNC:11584, TBK1
HPAiENSG00000183735, Low tissue specificity
MalaCardsiTBK1
MIMi177700, phenotype
604834, gene
616439, phenotype
617900, phenotype
neXtProtiNX_Q9UHD2
OpenTargetsiENSG00000183735
Orphaneti803, Amyotrophic lateral sclerosis
275872, Frontotemporal dementia with motor neuron disease
1930, Herpes simplex virus encephalitis
PharmGKBiPA36348

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG4250, Eukaryota
GeneTreeiENSGT00950000182937
HOGENOMiCLU_000288_101_1_1
InParanoidiQ9UHD2
KOiK05410
OMAiMRKGVRW
OrthoDBi563981at2759
PhylomeDBiQ9UHD2
TreeFamiTF324269

Enzyme and pathway databases

PathwayCommonsiQ9UHD2
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

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		29110, 15 hits in 908 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		TBK1, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		TANK-binding_kinase_1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		29110
PharosiQ9UHD2, Tchem

Protein Ontology

More...PROi		PR:Q9UHD2
RNActiQ9UHD2, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000183735, Expressed in lateral nuclear group of thalamus and 243 other tissues
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
IPR041309, TBK1_CCD1
IPR041087, TBK1_ULD
PfamiView protein in Pfam
PF00069, Pkinase, 1 hit
PF18394, TBK1_CCD1, 1 hit
PF18396, TBK1_ULD, 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

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTBK1_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9UHD2
Secondary accession number(s): A8K4S4, Q8IYV3, Q9NUJ5
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: May 1, 2000
Last modified: August 12, 2020
This is version 189 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, 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. SIMILARITY comments
    Index of protein domains and families
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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