Seroatlas · Human Serome Atlas

TBK1

Serine/threonine-protein kinase TBK1

Also known as: NAK, TBK1_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9UHD2
Gene: TBK1
Ensembl: ENSG00000183735
Chromosome: 12
Canonical length: 729 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, RAS pathway related proteins
Subcellular location: Nucleoplasm,Vesicles
Quaternary structure: Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

729 residues, UniProt reviewed canonical sequence.

>Q9UHD2|TBK1
     1  MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLFAIKVF NNISFLRPVD VQMREFEVLK
    61  KLNHKNIVKL FAIEEETTTR HKVLIMEFCP CGSLYTVLEE PSNAYGLPES EFLIVLRDVV
   121  GGMNHLRENG IVHRDIKPGN IMRVIGEDGQ SVYKLTDFGA ARELEDDEQF VSLYGTEEYL
   181  HPDMYERAVL RKDHQKKYGA TVDLWSIGVT FYHAATGSLP FRPFEGPRRN KEVMYKIITG
   241  KPSGAISGVQ KAENGPIDWS GDMPVSCSLS RGLQVLLTPV LANILEADQE KCWGFDQFFA
   301  ETSDILHRMV IHVFSLQQMT AHKIYIHSYN TATIFHELVY KQTKIISSNQ ELIYEGRRLV
   361  LEPGRLAQHF PKTTEENPIF VVSREPLNTI GLIYEKISLP KVHPRYDLDG DASMAKAITG
   421  VVCYACRIAS TLLLYQELMR KGIRWLIELI KDDYNETVHK KTEVVITLDF CIRNIEKTVK
   481  VYEKLMKINL EAAELGEISD IHTKLLRLSS SQGTIETSLQ DIDSRLSPGG SLADAWAHQE
   541  GTHPKDRNVE KLQVLLNCMT EIYYQFKKDK AERRLAYNEE QIHKFDKQKL YYHATKAMTH
   601  FTDECVKKYE AFLNKSEEWI RKMLHLRKQL LSLTNQCFDI EEEVSKYQEY TNELQETLPQ
   661  KMFTASSGIK HTMTPIYPSS NTLVEMTLGM KKLKEEMEGV VKELAENNHI LERFGSLTMD
   721  GGLRNVDCL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TBK1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.28
Highest tissue expression: 22 nTPM

Expression across tissuesHPA

Tissue

testis: 22 nTPM
bone marrow: 16 nTPM
liver: 16 nTPM
skeletal muscle: 15 nTPM
urinary bladder: 15 nTPM
duodenum: 14 nTPM

Single-cell type

neutrophils: 492 nCPM
monocytes: 170 nCPM
neutrophil progenitors: 162 nCPM
syncytiotrophoblasts: 157 nCPM
extravillous trophoblasts: 130 nCPM
endometrial glandular cells: 126 nCPM

Immune cell

basophil: 42 nTPM
NK-cell: 27 nTPM
eosinophil: 25 nTPM
neutrophil: 19 nTPM
intermediate monocyte: 18 nTPM
MAIT T-cell: 16 nTPM

Brain region

white matter: 9.8 nTPM
cerebral cortex: 9.6 nTPM
midbrain: 9.2 nTPM
thalamus: 8.9 nTPM
medulla oblongata: 8.7 nTPM
pons: 8.2 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TBK1.

Disease | AllUniProt

Conditions TBK1 is implicated in, by any mechanism.

Glaucoma 1, open angle, P (GLC1P) MIM:177700
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4) MIM:616439
Encephalopathy, acute, infection-induced, 8, herpes-specific (IIAE8) MIM:617900
Autoinflammation with arthritis and vasculitis (AIARV) MIM:620880

Disease | GeneticClinVar

83 pathogenic / likely-pathogenic of 617 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4
TBK1-related disorder
Amyotrophic lateral sclerosis
Autoinflammation with arthritis and vasculitis
Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.42
gnomAD pLI: 0.08
gnomAD missense Z: 1.93
DepMap mean gene effect: -0.11
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of TBK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads TBK1 as an antibody target. Whether an autoantibody or antibody against TBK1 could matter depends on whether native TBK1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TBK1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label TBK1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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