NFKB1
Nuclear factor NF-kappa-B p105 subunit
Also known as: KBF1, NF-kappaB, NF-kB1, NFkappaB, NFKB-p50, NFKB1_HUMAN, p105, p50
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P19838
- Gene
- NFKB1
- Ensembl
- ENSG00000109320
- Chromosome
- 4
- Canonical length
- 968 aa
- Protein class
- Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins, Transcription factors
- Subcellular location
- Nucleoplasm,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. NFKB is a critical regulator of the immediate-early response to viral infection. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Aug 2020]
Canonical amino-acid sequenceUniProt
968 residues, UniProt reviewed canonical sequence.
>P19838|NFKB1
1 MAEDDPYLGR PEQMFHLDPS LTHTIFNPEV FQPQMALPTD GPYLQILEQP KQRGFRFRYV
61 CEGPSHGGLP GASSEKNKKS YPQVKICNYV GPAKVIVQLV TNGKNIHLHA HSLVGKHCED
121 GICTVTAGPK DMVVGFANLG ILHVTKKKVF ETLEARMTEA CIRGYNPGLL VHPDLAYLQA
181 EGGGDRQLGD REKELIRQAA LQQTKEMDLS VVRLMFTAFL PDSTGSFTRR LEPVVSDAIY
241 DSKAPNASNL KIVRMDRTAG CVTGGEEIYL LCDKVQKDDI QIRFYEEEEN GGVWEGFGDF
301 SPTDVHRQFA IVFKTPKYKD INITKPASVF VQLRRKSDLE TSEPKPFLYY PEIKDKEEVQ
361 RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGTGST GPGYSFPHYG FPTYGGITFH
421 PGTTKSNAGM KHGTMDTESK KDPEGCDKSD DKNTVNLFGK VIETTEQDQE PSEATVGNGE
481 VTLTYATGTK EESAGVQDNL FLEKAMQLAK RHANALFDYA VTGDVKMLLA VQRHLTAVQD
541 ENGDSVLHLA IIHLHSQLVR DLLEVTSGLI SDDIINMRND LYQTPLHLAV ITKQEDVVED
601 LLRAGADLSL LDRLGNSVLH LAAKEGHDKV LSILLKHKKA ALLLDHPNGD GLNAIHLAMM
661 SNSLPCLLLL VAAGADVNAQ EQKSGRTALH LAVEHDNISL AGCLLLEGDA HVDSTTYDGT
721 TPLHIAAGRG STRLAALLKA AGADPLVENF EPLYDLDDSW ENAGEDEGVV PGTTPLDMAT
781 SWQVFDILNG KPYEPEFTSD DLLAQGDMKQ LAEDVKLQLY KLLEIPDPDK NWATLAQKLG
841 LGILNNAFRL SPAPSKTLMD NYEVSGGTVR ELVEALRQMG YTEAIEVIQA ASSPVKTTSQ
901 AHSLPLSPAS TRQQIDELRD SDSVCDSGVE TSFRKLSFTE SLTSGASLLT LNKMPHDYGQ
961 EGPLEGKILocalizationUniProt · AlphaFold · HPA
Whether an antibody against NFKB1 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)
- 0.4
- Highest tissue expression
- 48 nTPM
Expression across tissuesHPA
Tissue
- urinary bladder: 48 nTPM
- tonsil: 38 nTPM
- thymus: 34 nTPM
- lymph node: 29 nTPM
- appendix: 24 nTPM
- bone marrow: 23 nTPM
Single-cell type
- neutrophils: 3,105 nCPM
- monocytes: 2,371 nCPM
- mast cells: 2,182 nCPM
- innate lymphoid cells: 1,999 nCPM
- endometrial glandular cells: 1,554 nCPM
- endometrial luminal cells: 1,403 nCPM
Immune cell
- myeloid DC: 2.5 nTPM
- naive CD4 T-cell: 2.2 nTPM
- non-classical monocyte: 2.1 nTPM
- intermediate monocyte: 1.7 nTPM
- memory CD4 T-cell: 1.5 nTPM
- NK-cell: 1.5 nTPM
Brain region
- white matter: 11 nTPM
- medulla oblongata: 10 nTPM
- thalamus: 9.5 nTPM
- spinal cord: 9.4 nTPM
- pons: 9.3 nTPM
- basal ganglia: 9.2 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NFKB1.
Disease | AllUniProt
Conditions NFKB1 is implicated in, by any mechanism.
- Immunodeficiency, common variable, 12, with autoimmunity (CVID12) MIM:616576
Disease | GeneticClinVar
160 pathogenic / likely-pathogenic of 964 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Immunodeficiency, common variable, 12
- Inherited Immunodeficiency Diseases
- Common variable immunodeficiency
- NFKB1-related disorder
- Primary ciliary dyskinesia 3
Disease | ImmuneIEDB
Conditions an epitope on NFKB1 was assayed in.
- narcolepsy B cell
- multiple sclerosis B cell
- peripheral nervous system disease B cell
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)
- 0.14
- gnomAD pLI
- 1
- gnomAD missense Z
- 3.19
- DepMap mean gene effect
- 0
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antibacterial innate immune response
- apoptotic process
- B cell receptor signaling pathway
- canonical NF-kappaB signal transduction
- cellular response to angiotensin
- cellular response to dsRNA
- cellular response to interleukin-17
- cellular response to interleukin-6
- cellular response to lipopolysaccharide
- cellular response to mechanical stimulus
- cellular response to nicotine
- cellular response to virus
- inflammatory response
- JNK cascade
- mammary gland involution
- negative regulation of apoptotic process
- negative regulation of cytokine production involved in inflammatory response
- negative regulation of gene expression
- negative regulation of inflammatory response
- negative regulation of interleukin-12 production
- negative regulation of transcription by RNA polymerase II
- negative regulation of vitamin D biosynthetic process
- non-canonical NF-kappaB signal transduction
- positive regulation of canonical Wnt signaling pathway
- positive regulation of cholesterol efflux
- positive regulation of DNA-templated transcription
- positive regulation of hyaluronan biosynthetic process
- positive regulation of lipid storage
- positive regulation of macrophage derived foam cell differentiation
- positive regulation of miRNA metabolic process
- positive regulation of transcription by RNA polymerase II
- positive regulation of transcription initiation by RNA polymerase II
- regulation of transcription by RNA polymerase II
- response to muscle stretch
- transcription by RNA polymerase II
- tumor necrosis factor-mediated signaling pathway
Molecular functions
- actinin binding
- chromatin binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- identical protein binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- transcription cis-regulatory region binding
- transcription coregulator activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- NF-kappa-B/Dorsal
- Death domain
- Ankyrin repeat
- IPT domain
- p53-like transcription factor, DNA-binding domain superfamily
- Death-like domain superfamily
- Rel homology domain, DNA-binding domain
- Immunoglobulin-like fold
- Immunoglobulin E-set
- Rel homology domain, conserved site
- Rel homology dimerisation domain
- NFkappaB IPT domain
- Ankyrin repeat-containing domain superfamily
- Rel homology domain (RHD), DNA-binding domain superfamily
- Death domain
- Rel homology DNA-binding domain
- Ankyrin repeats (3 copies)
- Rel homology dimerisation domain
- Nuclear factor NF-kappa-B, p105 subunit, Rel homology domain, N-terminal
- Nuclear factor NF-kappa-B p105 subunit, death domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of NFKB1 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 NFKB1 as an antibody target. Whether an autoantibody or antibody against NFKB1 could matter depends on whether native NFKB1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NFKB1 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 NFKB1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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