背景介绍
domain:Glycine-rich region (GRR) appears to be a critical element in the generation of p50.,domain:The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription activation.,function:NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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.,induction:By phorbol ester and TNF-alpha.,PTM:Phosphorylation at 'Ser-903' and 'Ser-907' primes p105 for proteolytic processing in response to TNF-alpha stimulation. Phosphorylation at 'Ser-927' and 'Ser-932' are required for BTRC/BTRCP-mediated proteolysis.,PTM:Polyubiquitination seems to allow p105 processing.,PTM:S-nitrosylation of Cys-61 affects DNA binding.,PTM:While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing.,similarity:Contains 1 death domain.,similarity:Contains 1 RHD (Rel-like) domain.,similarity:Contains 7 ANK repeats.,subcellular location:Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).,subunit:Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-p50 complex. 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. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Also interacts with MAP3K8. NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity. Interacts with DSIPI; this interaction prevents nuclear translocation and DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50. NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. Interacts with GSK3B; the interaction prevents processing of p105 to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with NFKBIZ. Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID.,
功能
negative regulation of transcription from RNA polymerase II promoter,?regulation of cytokine production,?negative regulation of cytokine production,?transcription,?transcription, DNA-dependent,?regulation of transcription, DNA-dependent,?regulation of transcription from RNA polymerase II promoter,?transcription from RNA polymerase II promoter,?proteolysis,?apoptosis,?anti-apoptosis,?defense response,?inflammatory response,?cell death,?macromolecule catabolic process,?response to wounding,?negative regulation of biosynthetic process,?positive regulation of biosynthetic process,?regulation of specific transcription from RNA polymerase II promoter,?negative regulation of specific transcription from RNA polymerase II promoter,?positive regulation of macromolecule biosynthetic process,negative regulation of macromolecule biosynthetic process,?positive regulation of macromolecule metabolic process,negative regulation of macromolecule metabolic process,?positive regulation of gene expression,?negative regulation of gene expression,?regulation of foam cell differentiation,?positive regulation of foam cell differentiation,?regulation of lipid storage,?positive regulation of lipid storage,?negative regulation of steroid biosynthetic process,?regulation of cell death,?negative regulation of calcidiol 1-monooxygenase activity,?negative regulation of vitamin D biosynthetic process,?programmed cell death,?death,?negative regulation of transcription,?regulation of lipid metabolic process,regulation of steroid metabolic process,?protein catabolic process,?regulation of vitamin metabolic process,?membrane protein intracellular domain proteolysis,?negative regulation of cellular biosynthetic process,?positive regulation of cellular biosynthetic process,?regulation of cellular protein metabolic process,?negative regulation of cellular protein metabolic process,?regulation of lipid transport,?negative regulation of lipid transport,?regulation of sterol transport,negative regulation of sterol transport,?regulation of cholesterol transport,?negative regulation of cholesterol transport,?negative regulation of gene-specific transcription,?regulation of gene-specific transcription,?regulation of monooxygenase activity,?negative regulation of monooxygenase activity,?RNA biosynthetic process,?membrane protein proteolysis,?regulation of apoptosis,?negative regulation of apoptosis,?regulation of programmed cell death,?negative regulation of programmed cell death,?negative regulation of catalytic activity,?negative regulation of molecular function,cellular protein catabolic process,?cellular macromolecule catabolic process,?regulation of transcription,?positive regulation of cell differentiation,?negative regulation of lipid metabolic process,?negative regulation of transcription, DNA-dependent,?positive regulation of transcription, DNA-dependent,?negative regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process,?positive regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process,?negative regulation of steroid metabolic process,?positive regulation of transcription,?positive regulation of transcription from RNA polymerase II promoter,?negative regulation of vitamin metabolic process,regulation of lipid biosynthetic process,?regulation of steroid biosynthetic process,?negative regulation of transport,negative regulation of lipid biosynthetic process,?positive regulation of developmental process,?negative regulation of nitrogen compound metabolic process,?positive regulation of nitrogen compound metabolic process,?negative regulation of multicellular organismal process,?negative regulation of protein metabolic process,?regulation of RNA metabolic process,?negative regulation of RNA metabolic process,?positive regulation of RNA metabolic process,regulation of oxidoreductase activity,?negative regulation of oxidoreductase activity,?proteolysis involved in cellular protein catabolic process,?negative regulation of cell death,?regulation of vitamin D biosynthetic process,?regulation of calcidiol 1-monooxygenase activity,
