NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1)

2002-01-01   Fei Chen 

Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA

Identity

HGNC
LOCATION
4q24
LOCUSID
ALIAS
CVID12,EBP-1,KBF1,NF-kB,NF-kB1,NF-kappa-B1,NF-kappaB,NF-kappabeta,NFKB-p105,NFKB-p50,NFkappaB
FUSION GENES

DNA/RNA

Description

The gene encoding human nfkb1 has 24 exons spanning 156 kb. The expression of nfkb1 can be positively regulated by NF-kB itself and possibly Ets family transcription factors.

Proteins

Atlas Image

Description

The nfkb1 gene encodes a protein composed 968 amino acids with an approximately molecular weight of 105 kDa, which was considered as a precursor of p50 subunit of NF-kB complexes. In the N-terminal region of NF-kB1, there is a Rel homology domain (RHD) composed of ~300 amino acids that are responsible for DNA binding, dimerization with other Rel family members, and interaction with IkB proteins. The C-terminal region of NF-kB1 contains multiple copies of the so-called ankyrin repeats which is found in IkB family members, including IkBa, IkBb, IkBe, Bcl3, and Drosophila cactus. The earlier studies by several groups demonstrated that NF-kB1 was posttranslationally cleaved to produce the p50 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal portion of NF-kB1. Further studies by Lin and Ghosh suggested that a glycine-rich region (GRR) within the region of 375 to 400 of NF-kB1 is necessary and sufficient for directing the cleavage of NF-kB1. However, recent studies challenged this model and revealed a novel mechanism in which p50 is generated by a unique cotranslational processing event involving the 26S proteasome. In other words, NF-kB1 is not the precursor of p50.

Expression

nfkb1 is widely expressed in virtually all type of cells in both adults and in the embryo.

Localisation

cytosol, nuclei after activation.

Function

regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, and initiation or acceleration of tumorigenesis. The full length of NF-kB1 can serve as an endogenous inhibitor for the NF-kB p50/p65(RelA) heterodimer. It has been proposed that the homodimer of NF-kB p50 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p50 homodimer may function to competitively inhibit B binding by transactivating NF- B dimers. The Bcl3 protein can form a complex with this homodimer at B sites and act as a transactivator of NF-kB p50 homodimer. Interaction with : members of IkB family and Rel family, LYL1 , Bcl3, NCOA1a(V).

Implicated in

Entity name
cancer (see below), autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, HTLV-1 infection, and AIDS.
Oncogenesis
overexpression of nfkb1 has been found in a number of human cancer including non-small cell lung carcinoma, colon cancer, prostate cancer, breast cancer, bone cancer and brain cancer. The rearrangement of nfkb1 gene, however, only has been identified in certain acute lymphoblastic leukemias.

Bibliography

Pubmed IDLast YearTitleAuthors
87175281996The NF-kappa B and I kappa B proteins: new discoveries and insights.Baldwin AS Jr et al
98953311999New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases.Chen F et al
95971301998NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.Ghosh S et al
95292571998Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome.Lin L et al
16125891992Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2.Liptay S et al

Other Information

Locus ID:

NCBI: 4790
MIM: 164011
HGNC: 7794
Ensembl: ENSG00000109320

Variants:

dbSNP: 4790
ClinVar: 4790
TCGA: ENSG00000109320
COSMIC: NFKB1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000109320ENST00000226574P19838
ENSG00000109320ENST00000394820P19838
ENSG00000109320ENST00000394820A0A024RDJ4
ENSG00000109320ENST00000505458P19838
ENSG00000109320ENST00000505458A0A024RDJ4
ENSG00000109320ENST00000507079D6RH30
ENSG00000109320ENST00000508584D6RF93
ENSG00000109320ENST00000509165D6RC45
ENSG00000109320ENST00000511926D6RDI9
ENSG00000109320ENST00000600343P19838
ENSG00000109320ENST00000652569A0A494C157
ENSG00000109320ENST00000652619A0A494C1E9

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ApoptosisKEGGko04210
Toll-like receptor signaling pathwayKEGGko04620
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Adipocytokine signaling pathwayKEGGko04920
Epithelial cell signaling in Helicobacter pylori infectionKEGGko05120
Pancreatic cancerKEGGko05212
Prostate cancerKEGGko05215
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Small cell lung cancerKEGGko05222
MAPK signaling pathwayKEGGhsa04010
ApoptosisKEGGhsa04210
Toll-like receptor signaling pathwayKEGGhsa04620
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Adipocytokine signaling pathwayKEGGhsa04920
Epithelial cell signaling in Helicobacter pylori infectionKEGGhsa05120
ShigellosisKEGGhsa05131
Pathways in cancerKEGGhsa05200
Pancreatic cancerKEGGhsa05212
Prostate cancerKEGGhsa05215
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Small cell lung cancerKEGGhsa05222
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
RIG-I-like receptor signaling pathwayKEGGko04622
RIG-I-like receptor signaling pathwayKEGGhsa04622
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Cytosolic DNA-sensing pathwayKEGGko04623
Cytosolic DNA-sensing pathwayKEGGhsa04623
LeishmaniasisKEGGko05140
LeishmaniasisKEGGhsa05140
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
AmoebiasisKEGGko05146
AmoebiasisKEGGhsa05146
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
MeaslesKEGGko05162
MeaslesKEGGhsa05162
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Influenza AKEGGko05164
Influenza AKEGGhsa05164
PertussisKEGGko05133
PertussisKEGGhsa05133
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
LegionellosisKEGGko05134
LegionellosisKEGGhsa05134
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Cocaine addictionKEGGhsa05030
Cocaine addictionKEGGko05030
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
HIF-1 signaling pathwayKEGGhsa04066
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Inflammatory bowel disease (IBD)KEGGhsa05321
Inflammatory bowel disease (IBD)KEGGko05321
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Ras signaling pathwayKEGGhsa04014
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Toll-like receptor signalingKEGGhsa_M00686
Toll-like receptor signalingKEGGM00686
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
DiseaseREACTOMER-HSA-1643685
Diseases of Immune SystemREACTOMER-HSA-5260271
Diseases associated with the TLR signaling cascadeREACTOMER-HSA-5602358
IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)REACTOMER-HSA-5603027
IkBA variant leads to EDA-IDREACTOMER-HSA-5603029
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
TCR signalingREACTOMER-HSA-202403
Downstream TCR signalingREACTOMER-HSA-202424
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
Activation of NF-kappaB in B cellsREACTOMER-HSA-1169091
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
TAK1 activates NFkB by phosphorylation and activation of IKKs complexREACTOMER-HSA-445989
MAP kinase activation in TLR cascadeREACTOMER-HSA-450294
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathwaysREACTOMER-HSA-168928
TRAF6 mediated NF-kB activationREACTOMER-HSA-933542
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
ZBP1(DAI) mediated induction of type I IFNsREACTOMER-HSA-1606322
RIP-mediated NFkB activation via ZBP1REACTOMER-HSA-1810476
DEx/H-box helicases activate type I IFN and inflammatory cytokines productionREACTOMER-HSA-3134963
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated NF-kB activationREACTOMER-HSA-2871837
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CLEC7A (Dectin-1) signalingREACTOMER-HSA-5607764
CLEC7A/inflammasome pathwayREACTOMER-HSA-5660668
CD209 (DC-SIGN) signalingREACTOMER-HSA-5621575
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-1 processingREACTOMER-HSA-448706
Interleukin-1 signalingREACTOMER-HSA-446652
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
p75 NTR receptor-mediated signallingREACTOMER-HSA-193704
p75NTR signals via NF-kBREACTOMER-HSA-193639
NF-kB is activated and signals survivalREACTOMER-HSA-209560
Regulated proteolysis of p75NTRREACTOMER-HSA-193692
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of white adipocyte differentiationREACTOMER-HSA-381340
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
Senescence-Associated Secretory Phenotype (SASP)REACTOMER-HSA-2559582
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841
Insulin resistanceKEGGhsa04931
MAP3K8 (TPL2)-dependent MAPK1/3 activationREACTOMER-HSA-5684264
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Longevity regulating pathwayKEGGhsa04211
Antifolate resistanceKEGGko01523
Antifolate resistanceKEGGhsa01523
Neutrophil degranulationREACTOMER-HSA-6798695
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
IL-17 signaling pathwayKEGGko04657
Fluid shear stress and atherosclerosisKEGGko05418
IL-17 signaling pathwayKEGGhsa04657
Fluid shear stress and atherosclerosisKEGGhsa05418

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA10268flupenthixolChemicalVariantAnnotationassociatedPD27992301
PA134992438CAMK1DGenePathwayassociated
PA24684AKT1GenePathwayassociated
PA24685AKT2GenePathwayassociated
PA24686AKT3GenePathwayassociated
PA26048CAMK1GenePathwayassociated
PA26049CAMK1GGenePathwayassociated
PA283MAPK8GenePathwayassociated
PA30616MAPK1GenePathwayassociated
PA30622MAPK3GenePathwayassociated
PA33678PPP3CAGenePathwayassociated23922006
PA33679PPP3CBGenePathwayassociated23922006
PA33680PPP3CCGenePathwayassociated23922006
PA33681PPP3R1GenePathwayassociated23922006
PA33682PPP3R2GenePathwayassociated23922006
PA337STAT3GenePathwayassociated
PA33759PRKCAGenePathwayassociated
PA33761PRKCBGenePathwayassociated
PA33766PRKCGGenePathwayassociated
PA338STAT5AGenePathwayassociated
PA36183STAT1GenePathwayassociated
PA36184STAT2GenePathwayassociated
PA36185STAT4GenePathwayassociated
PA36186STAT5BGenePathwayassociated
PA447216SchizophreniaDiseaseVariantAnnotationassociatedPD27992301
PA90CAMK2AGenePathwayassociated
PA91CAMK2BGenePathwayassociated
PA92CAMK2DGenePathwayassociated
PA93CAMK2GGenePathwayassociated

References

Pubmed IDYearTitleCitations
195708222009Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression.636
198789812009An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation.594
200660922009The NF-kappaB family of transcription factors and its regulation.552
191692542009Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.410
194121642009Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma.379
176928052007Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma.369
200661132009NF-kappaB as a critical link between inflammation and cancer.297
153277702004TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains.285
194110702009Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion.283
193038522009Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation.280

Citation

Fei Chen

NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1)

Atlas Genet Cytogenet Oncol Haematol. 2002-01-01

Online version: http://atlasgeneticsoncology.org/gene/323/nfkb1-(nuclear-factor-of-kappa-light-polypeptide-gene-enhancer-in-b-cells-1)