NFKB2

Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)
PDB rendering based on 1a3q.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1A3Q​, 2D96​, 3DO7​, 4OT9​
Identifiers
Symbols	NFKB2 ; CVID10; H2TF1; LYT-10; LYT10; NF-kB2; p100; p52
External IDs	OMIM: 164012 MGI: 1099800 HomoloGene: 1873 ChEMBL: 3003 GeneCards: NFKB2 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • transcription coactivator activity • protein binding Cellular component • nucleus • nucleoplasm • cytoplasm • cytosol • Bcl3/NF-kappaB2 complex Biological process • negative regulation of transcription from RNA polymerase II promoter • stimulatory C-type lectin receptor signaling pathway • toll-like receptor signaling pathway • follicular dendritic cell differentiation • germinal center formation • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • inflammatory response • I-kappaB kinase/NF-kappaB signaling • aging • extracellular matrix organization • positive regulation of type I interferon production • response to lipopolysaccharide • response to cytokine • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • TRIF-dependent toll-like receptor signaling pathway • NIK/NF-kappaB signaling • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • innate immune response • positive regulation of transcription from RNA polymerase II promoter • rhythmic process • spleen development • positive regulation of NF-kappaB transcription factor activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4791	18034
Ensembl	ENSG00000077150	ENSMUSG00000025225
UniProt	Q00653	Q9WTK5
RefSeq (mRNA)	NM_001077494	NM_001177369
RefSeq (protein)	NP_001070962	NP_001170840
Location (UCSC)	Chr 10: 102.39 – 102.4 Mb	Chr 19: 46.3 – 46.31 Mb
PubMed search

Nuclear factor NF-kappa-B p100 subunit is a protein that in humans is encoded by the NFKB2 gene.^[1]

Function

NFKB has been detected in numerous cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and in various disease states. NFKB is activated by a wide variety of stimuli such as cytokines, oxidant-free radicals, inhaled particles, ultraviolet irradiation, and bacterial or viral products. Inappropriate activation of NF-kappa-B has been linked to inflammatory events associated with autoimmune arthritis, asthma, septic shock, lung fibrosis, glomerulonephritis, atherosclerosis, and AIDS. In contrast, complete and persistent inhibition of NF-kappa-B has been linked directly to apoptosis, inappropriate immune cell development, and delayed cell growth. For reviews, see Chen et al. (1999) and Baldwin (1996).[supplied by OMIM]^[2]

Clinical significance

Mutation of the NFKB2 gene has been linked to Common variable immunodeficiency (CVID) as the cause of the disease. Other genes might also be responsible. The frequency of NFKB2 mutation in CVID population is yet to be established.^[3]

Interactions

NFKB2 has been shown to interact with:

• BCL3,^[4][5]
• BTRC,^[6][7]
• MAP3K8,^[8]
• NFKB1,^[8]
• NFKBIE,^[9]
• RELA,^[8][10]
• RELB,^[4][8]
• REL,^[8][10] and
• TSC22D3.^[11]

See also

• NF-κB

References

1. Schmid RM, Perkins ND, Duckett CS, Andrews PC, Nabel GJ (Aug 1991). "Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65". Nature 352 (6337): 733–6. doi:10.1038/352733a0. PMID 1876189.
2. "Entrez Gene: NFKB2 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)".
3. Chen K, Coonrod EM, Kumánovics A, Franks ZF, Durtschi JD, Margraf RL, Wu W, Heikal NM, Augustine NH, Ridge PG, Hill HR, Jorde LB, Weyrich AS, Zimmerman GA, Gundlapalli AV, Bohnsack JF, Voelkerding KV (Nov 2013). "Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency". American Journal of Human Genetics 93 (5): 812–24. doi:10.1016/j.ajhg.2013.09.009. PMID 24140114.
4. Thornburg NJ, Pathmanathan R, Raab-Traub N (Dec 2003). "Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma". Cancer Research 63 (23): 8293–301. PMID 14678988.
5. Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, Siebenlist U (Mar 1993). "The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers". Cell 72 (5): 729–39. doi:10.1016/0092-8674(93)90401-b. PMID 8453667.
6. Fong A, Sun SC (Jun 2002). "Genetic evidence for the essential role of beta-transducin repeat-containing protein in the inducible processing of NF-kappa B2/p100". The Journal of Biological Chemistry 277 (25): 22111–4. doi:10.1074/jbc.C200151200. PMID 11994270.
7. Vatsyayan J, Qing G, Xiao G, Hu J (Sep 2008). "SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing". EMBO Reports 9 (9): 885–90. doi:10.1038/embor.2008.122. PMC 2529344. PMID 18617892.
8. Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
9. Li Z, Nabel GJ (Oct 1997). "A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription". Molecular and Cellular Biology 17 (10): 6184–90. doi:10.1128/mcb.17.10.6184. PMC 232469. PMID 9315679.
10. Scheinman RI, Beg AA, Baldwin AS (Oct 1993). "NF-kappa B p100 (Lyt-10) is a component of H2TF1 and can function as an I kappa B-like molecule". Molecular and Cellular Biology 13 (10): 6089–101. doi:10.1128/mcb.13.10.6089. PMC 364669. PMID 8413211.
11. Ayroldi E, Migliorati G, Bruscoli S, Marchetti C, Zollo O, Cannarile L, D'Adamio F, Riccardi C (Aug 2001). "Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB". Blood 98 (3): 743–53. doi:10.1182/blood.v98.3.743. PMID 11468175.

Further reading

• Schreck R, Albermann K, Baeuerle PA (1993). "Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review)". Free Radical Research Communications 17 (4): 221–37. doi:10.3109/10715769209079515. PMID 1473734.
• Baldwin AS (1996). "The NF-kappa B and I kappa B proteins: new discoveries and insights". Annual Review of Immunology 14 (1): 649–83. doi:10.1146/annurev.immunol.14.1.649. PMID 8717528.
• Chen F, Castranova V, Shi X, Demers LM (Jan 1999). "New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases". Clinical Chemistry 45 (1): 7–17. PMID 9895331.
• Bottex-Gauthier C, Pollet S, Favier A, Vidal DR (Apr 2002). "[The Rel/NF-kappa-B transcription factors: complex role in cell regulation]". Pathologie-Biologie 50 (3): 204–11. doi:10.1016/s0369-8114(02)00289-4. PMID 11980335.
• Garg A, Aggarwal BB (Jun 2002). "Nuclear transcription factor-kappaB as a target for cancer drug development". Leukemia 16 (6): 1053–68. doi:10.1038/sj.leu.2402482. PMID 12040437.

External links

• NFKB2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)