NFKB2
NFKB2 (nuclear factor kappa B subunit 2, also known as p100, p52, LYT-10 and NF-kB2) encodes a subunit of the NF-kappa-B transcription factor family. The full-length p100 protein is processed into p52, and the gene acts as both an NF-kappa-B inhibitor and a source of an active DNA-binding subunit. Browse Assay Genie's current range of NFKB2 research reagents below, or read on for the biology behind the target.
NF-kappa-B is a pleiotropic transcription factor found in almost all cell types. It is the endpoint of signalling events triggered by stimuli linked to inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. Active complexes are homo- or heterodimers of Rel-like domain-containing proteins: RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. Dimers bind kappa-B sites in target gene DNA, each with distinct site preferences, and different combinations act as transcriptional activators or repressors. The RelB-p52 heterodimer is an activator, whereas the p52-p52 homodimer is a repressor.
The NFKB2 protein has dual functions. As p100, it retains attached NF-kappa-B proteins in the cytoplasm; through co-translational processing it also generates p52. Proteasome-mediated processing ensures that both p52 and p100 are produced and keep their independent functions. p100 is the major form and p52 the minor form, because processing is relatively poor. In the non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates p100 associated with RelB, inducing processing to p52 and formation of RelB-p52 complexes. p52 binds the kappa-B consensus sequence 5'-GGRNNYYCC-3' in the enhancer region of genes involved in immune response and acute phase reactions. Isoform p49 is a subunit that stimulates the HIV enhancer in synergy with p65. With RELB, NFKB2 also helps regulate the circadian clock by repressing CLOCK-BMAL1 activity.
HGNC places the NFKB2 gene in the ankyrin repeat domain containing, NF-kappa-B complex subunits, IPT domain containing and NFKB inhibitor families. Its previous name was nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100). Chromosomal rearrangements and translocations at this locus have been observed in B cell lymphomas, some producing fusion proteins. A pseudogene exists on chromosome 18, and alternative splicing yields multiple transcript variants. The mouse ortholog is Nfkb2.
NFKB2 p100 is processed to p52 after MAP3K14-activated CHUK/IKKA phosphorylation, forming RelB-p52 transcriptional activator complexes.
NF-kappa-B complexes containing NFKB2 regulate genes involved in immune response and acute phase reactions, as well as inflammation.
Chromosomal rearrangements and translocations of the NFKB2 locus have been observed in B cell lymphomas, some forming fusion proteins.
With RELB, NFKB2 represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer, linking NF-kappa-B biology to circadian control.
NFKB2 encodes p100, which retains NF-kappa-B proteins in the cytoplasm, and its processed form p52, which binds kappa-B DNA sites. Depending on its dimerisation partner, p52 can activate transcription (with RelB) or repress it (as a p52-p52 homodimer).
NFKB2 is also called LYT-10, NF-kB2, p100, p52, p105 and p49/p100. Its former HGNC name was nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100). p100 is the full-length protein, p52 the processed form, and isoform p49 is also described.
NCBI Gene reports chromosomal rearrangements and translocations of NFKB2 in B cell lymphomas. The mouse ortholog is Nfkb2. Researchers should check the datasheet of any product for its validated reactivity before choosing a reagent for a given species.
Other NF-kappa-B subunits and NF-kappa-B inhibitor family members that act alongside NFKB2 in canonical and non-canonical signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q00653; product specifications from Assay Genie datasheets.