NF-kappa B TF proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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NF-κB transcription factors (TFs) are homo- or heterodimeric complexes containing NFKB1/p105, NFKB1/p50, NFKB2/p52, REL, RELA/p65, and/or RELB proteins. They bind to κ-B sites in the DNA of their target genes to regulate the expression of genes that influence biological process including immune and inflammatory responses (cytokine production), development, growth, survival, and apoptosis. The different dimers are selective for κ-B sites, and act as transcriptional repressors or activators. The most abundant NF-κB transcriptional activator is the heterodimer containing NFKB1 and RELA. The RELA-REL complex is also an activator.
NF-κB activity is tightly regulated. An inactive state is maintained by interactions between transcriptionally active complexes and inhibitory proteins of the NF-κB inhibitor (I-κB) family. In turn the I-κBs are regulated by phosphorylation (catalysed by kinases IKKα and IKKβ) which promotes ubiquitin dependent degradation. Removal of the I-κBs disinhibits NF-κB TFs which then translocate into the nucleus to drive transcription of target genes. Dysregulated NF-κB pathway activity is associated with human diseases.

Targets

Targets of relevance to immunopharmacology are highlighted in blue

nuclear factor kappa B subunit 1 Show summary »« Hide summary

Target Id	3281
Nomenclature	nuclear factor kappa B subunit 1
Previous and unofficial names	NF-kB1 \| NFKB-p50 \| Nuclear factor NF-kappa-B p105 subunit
Genes	NFKB1 (Hs), Nfkb1 (Mm), Nfkb1 (Rn)
Ensembl ID	ENSG00000109320 (Hs), ENSMUSG00000028163 (Mm), ENSRNOG00000023258 (Rn)
UniProtKB AC	P19838 (Hs), P25799 (Mm)
Comment	The human gene encodes a 105 kD protein. This is cotranslationally processed to produce an active 50 kD protein, but both isoforms have independent functions [2,2,5]. NF-κB p50 dimerises with RELA (p65) to form the most abundant of the NF-κB transcription factors that promotes expression of genes involved in immune response and acute phase responses to infection and tissue trauma.

nuclear factor kappa B subunit 2 Show summary »« Hide summary

Target Id	3282
Nomenclature	nuclear factor kappa B subunit 2
Previous and unofficial names	NF-kB2 \| NF-kB-p105
Genes	NFKB2 (Hs), Nfkb2 (Mm), Nfkb2 (Rn)
Ensembl ID	ENSG00000077150 (Hs), ENSMUSG00000025225 (Mm), ENSRNOG00000019311 (Rn)
UniProtKB AC	Q00653 (Hs), Q9WTK5 (Mm)
Comment	The full length protein encoded by this gene is cotranslationally processed into a 52 kD active form (p52). Depending on its dimerisation partner this protein can behave as either a transcriptional activator or repressor of genes involved in inflammation and the immune response.

REL proto-oncogene, NF-kB subunit Show summary »« Hide summary

Target Id	3283
Nomenclature	REL proto-oncogene, NF-kB subunit
Previous and unofficial names	c-Rel \| v-rel avian reticuloendotheliosis viral oncogene homolog
Genes	REL (Hs), Rel (Mm), Rel (Rn)
Ensembl ID	ENSG00000162924 (Hs), ENSMUSG00000020275 (Mm), ENSRNOG00000054437 (Rn)
UniProtKB AC	Q04864 (Hs), P15307 (Mm)
Comment	The Rel protein regulates the expression of genes involved in apoptosis, inflammation and the immune response. It has oncogenic activity in some B cell malignancies.

RELA proto-oncogene, NF-kB subunit Show summary »« Hide summary

Target Id

3280

Nomenclature

RELA proto-oncogene, NF-kB subunit

Previous and unofficial names

NF-κB p65 | NFKB3 | v-rel avian reticuloendotheliosis viral oncogene homolog A | RELA proto-oncogene

Genes

RELA (Hs), Rela (Mm), Rela (Rn)

Ensembl ID

ENSG00000173039 (Hs), ENSMUSG00000024927 (Mm), ENSRNOG00000030888 (Rn)

UniProtKB AC

Q04206 (Hs), Q04207 (Mm)

Inhibitors

RelA inhibitor A55 (Binding) pK_d 5.5 [8]

compound 11 [PMID: 30694059] pIC₅₀ 5.1 [3] - Mouse

Comment

This protein is a component of the most abundant NF-κB transcription complex formed as a heterodimer with NFKB1 (p50). Following viral RNA detection by the RIG-I-like receptor MDA5, the RELA homodimeric NF-κB transcription factor is key to regulating the interferon response to SARS-CoV-2 infection [9].

RELB proto-oncogene, NF-kB subunit Show summary »« Hide summary

Target Id	3284
Nomenclature	RELB proto-oncogene, NF-kB subunit
Previous and unofficial names	REL-B \| v-rel avian reticuloendotheliosis viral oncogene homolog B (nuclear factor of kappa light polypeptide gene enhancer in B-cells 3)
Genes	RELB (Hs), Relb (Mm), Relb (Rn)
Ensembl ID	ENSG00000104856 (Hs), ENSMUSG00000002983 (Mm), ENSRNOG00000033235 (Rn)
UniProtKB AC	Q01201 (Hs), Q04863 (Mm)
Comment	RelB-NFκB/p50 and RelB-NFκB/p52 heterodimers are transcriptional activators [6]. RelB has no DNA binding activity and it does not dimerise with the other two related proteins RelA or Rel. RelB is involved in T and B lymphocyte maturation and function [7], and circadian clock regulation [1,4].

References

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1. Bellet MM, Zocchi L, Sassone-Corsi P. (2012) The RelB subunit of NFκB acts as a negative regulator of circadian gene expression. Cell Cycle, 11 (17): 3304-11. [PMID:22894897]

2. Hansen SK, Nerlov C, Zabel U, Verde P, Johnsen M, Baeuerle PA, Blasi F. (1992) A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene. EMBO J, 11 (1): 205-13. [PMID:1740106]

3. Jaidee W, Andersen RJ, Chavez MAG, Wang YA, Patrick BO, Pyne SG, Muanprasat C, Borwornpinyo S, Laphookhieo S. (2019) Amides and Flavonoids from the Fruit and Leaf Extracts of Melodorum siamensis. J Nat Prod, 82 (2): 283-292. [PMID:30694059]

4. Millet P, McCall C, Yoza B. (2013) RelB: an outlier in leukocyte biology. J Leukoc Biol, 94 (5): 941-51. [PMID:23922380]

5. Rice NR, MacKichan ML, Israël A. (1992) The precursor of NF-kappa B p50 has I kappa B-like functions. Cell, 71 (2): 243-53. [PMID:1423592]

6. Ryseck RP, Bull P, Takamiya M, Bours V, Siebenlist U, Dobrzanski P, Bravo R. (1992) RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B. Mol Cell Biol, 12 (2): 674-84. [PMID:1732739]

7. Sharfe N, Merico D, Karanxha A, Macdonald C, Dadi H, Ngan B, Herbrick JA, Roifman CM. (2015) The effects of RelB deficiency on lymphocyte development and function. J Autoimmun, 65: 90-100. [PMID:26385063]

8. Shiroma Y, Fujita G, Yamamoto T, Takahashi RU, Kumar A, Zhang KYJ, Ito A, Osada H, Yoshida M, Tahara H. (2020) Identification of a Selective RelA Inhibitor Based on DSE-FRET Screening Methods. Int J Mol Sci, 21 (23). [PMID:33266352]

9. Yin X, Riva L, Pu Y, Martin-Sancho L, Kanamune J, Yamamoto Y, Sakai K, Gotoh S, Miorin L, De Jesus PD et al.. (2021) MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells. Cell Rep, 34 (2): 108628. [PMID:33440148]

How to cite this family page

Database page citation:

NF-kappa B TF proteins. Accessed on 11/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1099.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.