TBK1 TANK binding kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TBK1provided by HGNC
Official Full Name: TANK binding kinase 1provided by HGNC
Primary source: HGNC:HGNC:11584
See related: Ensembl:ENSG00000183735 MIM:604834; AllianceGenome:HGNC:11584
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NAK; T2K; IIAE8; FTDALS4
Summary: The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. The protein is also an important kinase for antiviral innate immunity response. [provided by RefSeq, Sep 2021]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Ubiquitous expression in testis (RPKM 15.8), bone marrow (RPKM 10.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q14.2

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (64452120..64502114)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (64430747..64480735)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (64845900..64895894)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A TBK1 variant causes autophagolysosomal and motoneuron pathology without neuroinflammation in mice.
Title: A TBK1 variant causes autophagolysosomal and motoneuron pathology without neuroinflammation in mice.
AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer.
Title: AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer.
Optineurin provides a mitophagy contact site for TBK1 activation.
Title: Optineurin provides a mitophagy contact site for TBK1 activation.
Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.
Title: Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma.
STING upregulation mediates ferroptosis and inflammatory response in lupus nephritis by upregulating TBK1 and activating NF-kappaB signal pathway.
Title: STING upregulation mediates ferroptosis and inflammatory response in lupus nephritis by upregulating TBK1 and activating NF-κB signal pathway.
Activating STING/TBK1 suppresses tumor growth via degrading HPV16/18 E7 oncoproteins in cervical cancer.
Title: Activating STING/TBK1 suppresses tumor growth via degrading HPV16/18 E7 oncoproteins in cervical cancer.
Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1.
Title: Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1.
NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.
Title: NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.
ATG4B antagonizes antiviral immunity by GABARAP-directed autophagic degradation of TBK1.
Title: ATG4B antagonizes antiviral immunity by GABARAP-directed autophagic degradation of TBK1.
CDK12 loss inhibits cell proliferation by regulating TBK1 in non-small cell lung cancer cells.
Title: CDK12 loss inhibits cell proliferation by regulating TBK1 in non-small cell lung cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (247)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8 MedGen: C4693542 OMIM: 617900 GeneReviews: Not available	Compare labs
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 MedGen: C4225325 OMIM: 616439 GeneReviews: Amyotrophic Lateral Sclerosis Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif co-immunoprecipitates with TBK1 suggesting an interaction between Vif and TBK1	PubMed
Vpr	vpr	HIV-1 Vpr co-immunoprecipitates with TBK1 suggesting an interaction between Vpr and TBK1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH77769 (e-PCR)
- UniSTS:6428

WI-20972 (e-PCR)
- UniSTS:27934

TBK1_1450 (e-PCR)
- UniSTS:277794

TBK1_v491 (e-PCR)
- UniSTS:277794

RH15751 (e-PCR)
- UniSTS:73371

D5S2649 (e-PCR)
- UniSTS:70890

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables nucleic acid binding	IEA Inferred from Electronic Annotation more info
enables phosphoprotein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	NAS Non-traceable Author Statement more info	PubMed
enables protein phosphatase binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in antiviral innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in cGAS/STING signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in canonical NF-kappaB signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in cytoplasmic pattern recognition receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to Gram-positive bacterium	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	NAS Non-traceable Author Statement more info	PubMed
involved_in dendritic cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of interferon-alpha production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macroautophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-serine phosphorylation	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type I interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type I interferon production	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of type I interferon-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of xenophagy	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of type I interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in type I interferon-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
part_of serine/threonine protein kinase complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase TBK1

Names: NF-kB-activating kinase; NF-kappa-B-activating kinase

NP_037386.1

EC 2.7.11.1

XP_005268866.1

EC 2.7.11.1

XP_005268867.1

EC 2.7.11.1

XP_054227832.1

EC 2.7.11.1

XP_054227833.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_046906.1 RefSeqGene

Range

5061..55055

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1306

mRNA and Protein(s)

NM_013254.4 → NP_037386.1 serine/threonine-protein kinase TBK1

See identical proteins and their annotated locations for NP_037386.1

Status: REVIEWED

Source sequence(s)

AA970899, AC135279, AC136977, BC034950

Consensus CDS

CCDS8968.1

UniProtKB/Swiss-Prot

A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2

UniProtKB/TrEMBL

A0A7I2V646

Related

ENSP00000329967.5, ENST00000331710.10

Conserved Domains (3) summary

smart00220
Location:9 → 242

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd12219
Location:297 → 385

UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins

cd13988
Location:15 → 330

STKc_TBK1; Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

64452120..64502114

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005268810.2 → XP_005268867.1 serine/threonine-protein kinase TBK1 isoform X1

See identical proteins and their annotated locations for XP_005268867.1

UniProtKB/Swiss-Prot

A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2

UniProtKB/TrEMBL

A0A7I2V646

Conserved Domains (3) summary

smart00220
Location:9 → 242

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd12219
Location:297 → 385

UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins

cd13988
Location:15 → 330

STKc_TBK1; Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1
XM_005268809.2 → XP_005268866.1 serine/threonine-protein kinase TBK1 isoform X1

See identical proteins and their annotated locations for XP_005268866.1

UniProtKB/Swiss-Prot

A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2

UniProtKB/TrEMBL

A0A7I2V646

Conserved Domains (3) summary

smart00220
Location:9 → 242

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd12219
Location:297 → 385

UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins

cd13988
Location:15 → 330

STKc_TBK1; Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1

RNA

XR_007063071.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

64430747..64480735

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054371858.1 → XP_054227833.1 serine/threonine-protein kinase TBK1 isoform X1

UniProtKB/Swiss-Prot

A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2
XM_054371857.1 → XP_054227832.1 serine/threonine-protein kinase TBK1 isoform X1

UniProtKB/Swiss-Prot

A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2