RELA
NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene.
Full Name
RELA Proto-Oncogene, NF-KB Subunit
Alternative Names
RELA Proto-Oncogene, NF-KB Subunit; Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells 3; V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A; Nuclear Factor NF-Kappa-B P65 Subunit; NFKB3; V-Rel Reticuloendotheliosis Viral Oncogene Homolog A;
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 heterodimeric RELA-NFKB1 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. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. 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. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells. The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection.
Biological Process
Acetaldehyde metabolic process
Aging
Animal organ morphogenesis
Cellular defense response
Cellular response to angiotensin
Cellular response to hepatocyte growth factor stimulus
Cellular response to hydrogen peroxide
Cellular response to interleukin-1
Cellular response to interleukin-6
Cellular response to lipopolysaccharide
Cellular response to lipoteichoic acid
Cellular response to nicotine
Cellular response to peptidoglycan
Cellular response to tumor necrosis factor
Cellular response to vascular endothelial growth factor stimulus
Chromatin organization
Cytokine-mediated signaling pathway
Defense response to virus
Fc-epsilon receptor signaling pathway
Hair follicle development
I-kappaB kinase/NF-kappaB signaling
Inflammatory response
Innate immune response
Interleukin-1-mediated signaling pathway
Liver development
Membrane protein intracellular domain proteolysis
Negative regulation of apoptotic process
Negative regulation of extrinsic apoptotic signaling pathway
Negative regulation of insulin receptor signaling pathway
Negative regulation of NIK/NF-kappaB signaling
Negative regulation of pri-miRNA transcription by RNA polymerase II
Negative regulation of protein catabolic process
Negative regulation of protein sumoylationNegative regulation of transcription, DNA-templated
Negative regulation of transcription by RNA polymerase II
NIK/NF-kappaB signaling Source: GO_Central
Nucleotide-binding oligomerization domain containing 2 signaling pathway
Positive regulation of amyloid-beta formation
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of interleukin-12 production
Positive regulation of interleukin-8 production
Positive regulation of leukocyte adhesion to vascular endothelial cell
Positive regulation of miRNA metabolic process
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of pri-miRNA transcription by RNA polymerase II
Positive regulation of Schwann cell differentiation
Positive regulation of T cell receptor signaling pathway
Positive regulation of transcription, DNA-templated
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
Positive regulation of type I interferon production
Postsynapse to nucleus signaling pathway
Regulation of DNA-templated transcription in response to stress
Regulation of inflammatory response
Regulation of NIK/NF-kappaB signaling
Regulation of transcription, DNA-templated
Regulation of transcription by RNA polymerase II
Regulation of transcription initiation from RNA polymerase II promoter
Response to amino acid
Response to cAMP
Response to cobalamin
Response to cytokine
Response to drug
Response to insulin
Response to interleukin-1
Response to morphine
Response to muramyl dipeptide
Response to muscle stretch
Response to organic substance
Response to progesterone
Response to UV-B
Stimulatory C-type lectin receptor signaling pathway
T cell receptor signaling pathway
Transcription, DNA-templated
Tumor necrosis factor-mediated signaling pathway
Viral process
Cellular Location
Nucleus; Cytoplasm. Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). Colocalized with DDX1 in the nucleus upon TNF-alpha induction. Colocalizes with GFI1 in the nucleus after LPS stimulation. Translocation to the nucleus is impaired in L.monocytogenes infection.
Involvement in disease
Mucocutaneous ulceration, chronic (CMCU): An autosomal dominant, mucocutaneous disease characterized by chronic mucosal lesions, in absence of recurrent infections.
PTM
Ubiquitinated by RNF182, leading to its proteasomal degradation. Degradation is required for termination of NF-kappa-B response.
Monomethylated at Lys-310 by SETD6. Monomethylation at Lys-310 is recognized by the ANK repeats of EHMT1 and promotes the formation of repressed chromatin at target genes, leading to down-regulation of NF-kappa-B transcription factor activity. Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes (By similarity).
Phosphorylation at Ser-311 disrupts the interaction with EHMT1 and promotes transcription factor activity (By similarity). Phosphorylation on Ser-536 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity. Phosphorylation at Ser-276 by RPS6KA4 and RPS6KA5 promotes its transactivation and transcriptional activities.
Reversibly acetylated; the acetylation seems to be mediated by CBP, the deacetylation by HDAC3 and SIRT2. Acetylation at Lys-122 enhances DNA binding and impairs association with NFKBIA. Acetylation at Lys-310 is required for full transcriptional activity in the absence of effects on DNA binding and NFKBIA association. Acetylation at Lys-310 promotes interaction with BRD4. Acetylation can also lower DNA-binding and results in nuclear export. Interaction with BRMS1 promotes deacetylation of Lys-310. Lys-310 is deacetylated by SIRT2.
S-nitrosylation of Cys-38 inactivates the enzyme activity.
Sulfhydration at Cys-38 mediates the anti-apoptotic activity by promoting the interaction with RPS3 and activating the transcription factor activity.
Sumoylation by PIAS3 negatively regulates DNA-bound activated NF-kappa-B.
Proteolytically cleaved within a conserved N-terminus region required for base-specific contact with DNA in a CPEN1-mediated manner, and hence inhibits NF-kappa-B transcriptional activity.
Loading...
Datasheet