lmmol · Proteins

Nuclear factor NF-kappa-B p105 subunit

UniProt P19838 Organism Homo sapiens Gene NFKB1

Also known as: NFKB1

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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.

Classification

Family (Pfam)
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, NF-kB_p105_DD, NF-kB_p105_RHD_N, NFkB/Dor, p53-like_TF_DNA-bd_sf, RHD_CS, RHD_dimer, RHD_DNA_bind_dom, RHD_DNA_bind_dom_sf
Functional cluster
Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 15

A predicted model is available from AlphaFold.

Gene Ontology · 54

Disease associations

Drugs targeting this protein · 1

Neighborhood · nearest proteins

NFKB1NFKB1Nfkb1Nfkb1RELMap3k8BCL3
Nearest neighbours of Nuclear factor NF-kappa-B p105 subunit: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 51 cited papers

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