FEATURES

DESCRIPTION

Also known as NFKB1_HUMAN, NFKB1. 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. Component of the NF-kappa-B p65-p50 complex (PubMed:1740106). Homodimer; component of the NF-kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 complex. Component of the NF-kappa-B p50-c-Rel complex (PubMed:15102766, PubMed:8152812). Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 (PubMed:10469655). Also interacts with MAP3K8 (PubMed:9950430, PubMed:15485931). NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity (PubMed:11094166). Interacts with DSIPI; this interaction prevents nuclear translocation and DNA-binding (PubMed:11468175, PubMed:12393603). Interacts with SPAG9 and UNC5CL (PubMed:14769797, PubMed:14743216). NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50 (PubMed:13679070). NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2 (PubMed:15169888). Interacts with GSK3B; the interaction prevents processing of p105 to p50 (PubMed:12871932). NFKB1/p50 interacts with NFKBIE (PubMed:9315679). NFKB1/p50 interacts with NFKBIZ (By similarity). Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID (By similarity). Directly interacts with MEN1 (PubMed:11526476). Interacts with HIF1AN (PubMed:17003112). Interacts with FEM1A; interaction is direct (By similarity).

EXTERNAL LINKS

NFKB1

Mutations

Mutation(s) distribution

Mutations table