NFKB2 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)
2002-01-01 Fei Chen   AffiliationHealth 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

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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8717528 | 1996 | The NF-kappa B and I kappa B proteins: new discoveries and insights. | Baldwin AS Jr et al |
| 9895331 | 1999 | New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. | Chen F et al |
| 9597130 | 1998 | NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. | Ghosh S et al |
| 10597218 | 1999 | The generation of nfkb2 p52: mechanism and efficiency. | Heusch M et al |
| 1612589 | 1992 | Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. | Liptay S et al |
| 1760839 | 1991 | B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. | Neri A et al |
| 11520989 | 2001 | Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. | Senftleben U et al |
| 11726516 | 2001 | Retroviral 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
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA134992438 | CAMK1D | Gene | Pathway | associated | |||
| PA24684 | AKT1 | Gene | Pathway | associated | |||
| PA24685 | AKT2 | Gene | Pathway | associated | |||
| PA24686 | AKT3 | Gene | Pathway | associated | |||
| PA26048 | CAMK1 | Gene | Pathway | associated | |||
| PA26049 | CAMK1G | Gene | Pathway | associated | |||
| PA283 | MAPK8 | Gene | Pathway | associated | |||
| PA30616 | MAPK1 | Gene | Pathway | associated | |||
| PA30622 | MAPK3 | Gene | Pathway | associated | |||
| PA33678 | PPP3CA | Gene | Pathway | associated | 23922006 | ||
| PA33679 | PPP3CB | Gene | Pathway | associated | 23922006 | ||
| PA33680 | PPP3CC | Gene | Pathway | associated | 23922006 | ||
| PA33681 | PPP3R1 | Gene | Pathway | associated | 23922006 | ||
| PA33682 | PPP3R2 | Gene | Pathway | associated | 23922006 | ||
| PA337 | STAT3 | Gene | Pathway | associated | |||
| PA33759 | PRKCA | Gene | Pathway | associated | |||
| PA33761 | PRKCB | Gene | Pathway | associated | |||
| PA33766 | PRKCG | Gene | Pathway | associated | |||
| PA338 | STAT5A | Gene | Pathway | associated | |||
| PA36183 | STAT1 | Gene | Pathway | associated | |||
| PA36184 | STAT2 | Gene | Pathway | associated | |||
| PA36185 | STAT4 | Gene | Pathway | associated | |||
| PA36186 | STAT5B | Gene | Pathway | associated | |||
| PA90 | CAMK2A | Gene | Pathway | associated | |||
| PA91 | CAMK2B | Gene | Pathway | associated | |||
| PA92 | CAMK2D | Gene | Pathway | associated | |||
| PA93 | CAMK2G | Gene | Pathway | associated |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38092960 | 2024 | RUNX1-IT1 acts as a scaffold of STAT1 and NuRD complex to promote ROS-mediated NF-κB activation and ovarian cancer progression. | 4 |
| 38092960 | 2024 | RUNX1-IT1 acts as a scaffold of STAT1 and NuRD complex to promote ROS-mediated NF-κB activation and ovarian cancer progression. | 4 |
| 36706462 | 2023 | How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity? | 1 |
| 36773447 | 2023 | Analysis of NFKB1 and NFKB2 gene expression in the blood of patients with sudden sensorineural hearing loss. | 2 |
| 37087499 | 2023 | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression. | 2 |
| 37191755 | 2023 | Novel NFKB2 Pathogenic Variants in Two Unrelated Patients with Common Variable Immunodeficiency. | 0 |
| 36706462 | 2023 | How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity? | 1 |
| 36773447 | 2023 | Analysis of NFKB1 and NFKB2 gene expression in the blood of patients with sudden sensorineural hearing loss. | 2 |
| 37087499 | 2023 | NF-κB/p52 augments ETS1 binding genome-wide to promote glioma progression. | 2 |
| 37191755 | 2023 | Novel NFKB2 Pathogenic Variants in Two Unrelated Patients with Common Variable Immunodeficiency. | 0 |
| 34023356 | 2021 | NFKB2 inhibits NRG1 transcription to affect nucleus pulposus cell degeneration and inflammation in intervertebral disc degeneration. | 8 |
| 34155144 | 2021 | An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module. | 22 |
| 34023356 | 2021 | NFKB2 inhibits NRG1 transcription to affect nucleus pulposus cell degeneration and inflammation in intervertebral disc degeneration. | 8 |
| 34155144 | 2021 | An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module. | 22 |
| 32813180 | 2020 | A Nonsense N -Terminus NFKB2 Mutation Leading to Haploinsufficiency in a Patient with a Predominantly Antibody Deficiency. | 1 |
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)
