Nuclear factor NF-kappa-B p100 subunit

UniProt Q00653 Organism Homo sapiens Gene LYT10, NFKB2

Also known as: LYT10, NFKB2

Function

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer.

Classification

Family (Pfam): PF00023 Ank, PF12796 Ank_2, PF00531 Death, PF16179 RHD_dimer, PF00554 RHD_DNA_bind
InterPro: Ankyrin_rpt, Ankyrin_rpt-contain_sf, DEATH-like_dom_sf, Death_dom, Ig-like_fold, Ig_E-set, IPT_dom, IPT_NFkappaB, NFkB/Dor, NFkB_p100_RHD_N, p53-like_TF_DNA-bd_sf, RHD_CS, RHD_dimer, RHD_DNA_bind_dom, RHD_DNA_bind_dom_sf
Functional cluster: Eukaryotic Transcription Factors & related

Experimental structures · PDB · 11

1A3Q X-ray 2.10A
2D96 NMR
3DO7 X-ray 3.05A
4OT9 X-ray 3.35A
5ZMC X-ray 2.99A
7CLI X-ray 3.00A
7VUP X-ray 3.40A
7VUQ X-ray 3.10A
7W7L X-ray 3.00A
8G8Q X-ray 2.60A
8G8S X-ray 2.10A

A predicted model is available from AlphaFold.

Gene Ontology · 19

Disease associations

immunodeficiency, common variable, 10 MONDO:0014260

Drugs targeting this protein · 1

EDASALONEXENT inhibitor

Neighborhood · nearest proteins

Nearest neighbours of Nuclear factor NF-kappa-B p100 subunit: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Nuclear factor NF-kappa-B p100 subunit 1.00
Nuclear factor NF-kappa-B p100 subunit 0.94
Nuclear factor NF-kappa-B p105 subunit 0.79
Nuclear factor NF-kappa-B p105 subunit 0.78
Nuclear factor NF-kappa-B p105 subunit 0.77
Nuclear factor NF-kappa-B p105 subunit 0.75
Transcription factor p65 0.74
NF-kappa-B inhibitor beta 0.74
NF-kappa-B inhibitor beta 0.74
NF-kappa-B inhibitor beta 0.74
NF-kappa-B inhibitor alpha 0.70
Mitogen-activated protein kinase kinase kinase 10 0.69

Co-cited proteins · studied together in the literature

Mitogen-activated protein kinase kinase kinase 14 1 shared papers
B-cell lymphoma 3 protein 1 shared papers
Tripartite motif-containing 55 1 shared papers
Transcription factor RelB 1 shared papers
Transcription factor p65 4 shared papers
Proto-oncogene c-Rel 2 shared papers
Tripartite motif-containing protein 55 1 shared papers
Nuclear factor NF-kappa-B p105 subunit 3 shared papers
NF-kappa-B inhibitor epsilon 1 shared papers
Menin 1 shared papers

Literature · 30 cited papers

TRIM55 promotes noncanonical NF-kappaB signaling and B cell-mediated immune responses by coordinating p100 ubiquitination and processing. Sci. Signal. · 2023
Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies. BMC Med. Genet. · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the pathogenesis of common variable immunodeficiency. Am. J. Hum. Genet. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation. Proc. Natl. Acad. Sci. U.S.A. · 2006
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
… and 18 more in the literature graph

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