Basic gene annotations are collected from Uniprot and displayed with links to original sources. A quick link to explore the genomic context with Uniprot Browser is available.
RELA - RELA proto-oncogene, NF-kB subunit
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 (PubMed:15790681). 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 (PubMed:33440148).
Uniprot Browser| Entrez ID | EnsEMBL ID | Preferred Name | Uniprot ID |
|---|---|---|---|
| 5970 | ENSG00000173039 | RELA | Q04206 |
Causal Flows are statistically significant links between putative causal events (somatic mutations, copy number variations, chromosomal translocations, etc.) and the activity levels of regulators and regulons. In the causal flow, a mutation may causally activate or deactivate a downstream regulator which then might up- down-regulates a regulonthat contains genes with similar expression profiles and binding sites.
Causal Mechanistic Flows with ENSG00000173039 as Regulator
| ID | Mutation | Role | Regulator | Role | Regulon | # downstream regulons | # diffexp regulons | Drugs |
|---|---|---|---|---|---|---|---|---|
| CMF-00697 | HMCN1 | up-regulates | RELA | activates | R-3149 | 3 | 1 | Drugs (2) |
| CMF-01253 | RNF168 | up-regulates | RELA | activates | R-3149 | 3 | 1 | Drugs (2) |
| CMF-13852 | ADAMTS8 | down-regulates | RELA | activates | R-3149 | 3 | 2 | Drugs (2) |
| CMF-15742 | FN1 | up-regulates | RELA | activates | R-3149 | 3 | 1 | Drugs (2) |
| CMF-23273 | RNF17 | up-regulates | RELA | activates | R-3149 | 3 | 1 | Drugs (2) |
| CMF-24547 | SEMA3C | down-regulates | RELA | activates | R-3149 | 3 | 1 | Drugs (2) |
| CMF-27344 | CHD5 | up-regulates | RELA | activates | R-3149 | 3 | 1 | Drugs (2) |