NFKB2 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)

2002-01-01   Fei Chen 

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

Identity

HGNC
LOCATION
10q24.32
LOCUSID
ALIAS
CVID10,H2TF1,LYT-10,LYT10,NF-kB2,p100,p49/p100,p52
FUSION GENES

DNA/RNA

Description

The gene encoding human nfkb2 has 24 exons spanning 8 kb. The expression of nfkb2 can be regulated by two distinct promoters, P1 and P2, in which a number of consensus binding sites for transcription factors, including SP1, AP1 and putative NF-kappa B (kappa B sites), were identified.

Proteins

Atlas Image

Description

The human nfkb2 gene encodes a protein composed 900 amino acids with an approximately molecular weight of 100 kDa, which was considered as a precursor of p52 subunit of NF-kB complexes. The structural characteristics of NF-kB2 are much similar with that of NF-kB1: A N-terminal RHD; two nuclear localization sequences within the C-terminus of RHD, a putative GRR region that possibly contributes to the generation of NF-kB p52 from the precursor, NF-kB2. The C-terminal region of NF-kB2 also contains multiple copies of the so-called ankyrin repeats and one proline, glutamic acid, serine, and threonine (PEST) domain. Studies demonstrated that NF-kB2 was posttranslationally cleaved to produce the p52 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal 406-900 portion of NF-kB2. However, other studies revealed that the mechanism for the generation of NF-kB p52 is through cotranslational processing. Recent studies demonstrated that the processing of NF-kB p52 required IKKa- and/or NIK-dependent C-terminal phosphorylation of NF-kB2.

Expression

nfkb2 is expressed mainly in lymphoid cells and mononuclear cells.

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. Similar with NF-kB1, the full length of NF-kB2 can serve as an endogenous inhibitor for the NF-kB p50/ p65(RelA) or NF-kB p52/p65 heterodimer. The homodimer of NF-kB p52 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p52 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 p52 homodimer. Interaction with : members of IkB family and Rel family, Bcl3.

Implicated in

Entity name
hematological malignancies (see below) and other diseases: autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, cancer, HTLV-1 infection, and AIDS.
Disease
t(10;14)(q24;q11) or t(10;14)(q24;q32) in hematological malignancies
Cytogenetics
poor.
Oncogenesis
Unlike its relative nfkb1, rearrangement of nfkb2 gene locus has been found in many forms of lymophomas. The chromosomal translocations by t(10;14)(q24;q11) and t(10;14)(q24;q32) cause deletions of sequences encoding the ankyrin repeat motif of NF-kB2. Consequently, this carboxyl terminal truncated NF-kB2 is constitutively located in the nucleus of cells, which was found in small percentage of B-cell non-Hodgkins lymphoma, cutaneous lymphomas, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemias, and multiple myelomas. Chromosomal translocation generated a fusion NF-kB2- IGHA1 or NF-kB2- TCRa or TCRd transcriptional unit.

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
105972181999The generation of nfkb2 p52: mechanism and efficiency.Heusch M 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
17608391991B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50.Neri A et al
115209892001Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.Senftleben U et al
117265162001Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.Xiao G et al

Other Information

Locus ID:

NCBI: 4791
MIM: 164012
HGNC: 7795
Ensembl: ENSG00000077150

Variants:

dbSNP: 4791
ClinVar: 4791
TCGA: ENSG00000077150
COSMIC: NFKB2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000077150ENST00000189444Q00653
ENSG00000077150ENST00000369966Q00653
ENSG00000077150ENST00000428099Q00653
ENSG00000077150ENST00000601386M0QZX1
ENSG00000077150ENST00000652277Q00653
ENSG00000077150ENST00000661543Q00653

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
MAPK signaling pathwayKEGGhsa04010
Pathways in cancerKEGGhsa05200
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
LegionellosisKEGGko05134
LegionellosisKEGGhsa05134
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
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
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
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
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CLEC7A (Dectin-1) signalingREACTOMER-HSA-5607764
Dectin-1 mediated noncanonical NF-kB signalingREACTOMER-HSA-5607761
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-1 processingREACTOMER-HSA-448706
TNFR2 non-canonical NF-kB pathwayREACTOMER-HSA-5668541
NIK-->noncanonical NF-kB signalingREACTOMER-HSA-5676590
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

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

References

Pubmed IDYearTitleCitations
123529692002BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells.215
151408822004Induction of p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation.105
177034122007Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.100
172373702007Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes.85
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
236996542013NF-κB2/p52 induces resistance to enzalutamide in prostate cancer: role of androgen receptor and its variants.77
128081092003p53 represses cyclin D1 transcription through down regulation of Bcl-3 and inducing increased association of the p52 NF-kappaB subunit with histone deacetylase 1.76
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
263896652015Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation.61
119942702002Genetic evidence for the essential role of beta-transducin repeat-containing protein in the inducible processing of NF-kappa B2/p100.58

Citation

Fei Chen

NFKB2 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)

Atlas Genet Cytogenet Oncol Haematol. 2002-01-01

Online version: http://atlasgeneticsoncology.org/gene/362/nfkb2-nuclear-factor-of-kappa-light-polypeptide-gene-enhancer-in-b-cells-2-(p49-p100)