RELA
entrez
5970
canonical
uniprot
Q04206
canonical
ensembl
ENSG00000173039
resolver
ensp
ENSP00000311508
resolver
ensp
ENSP00000384273
resolver
ensp
ENSP00000483705
resolver
ensp
ENSP00000601912
resolver
ensp
ENSP00000630026
resolver
enst
ENST00000612991
resolver
genesymbol
RELA
resolver
genesymbol_syn
NFKB3
resolver
hgnc
HGNC:9955
resolver
uniprot
A0A087X0W8
resolver
uniprot
Q6GTV1
resolver
uniprot
Q6SLK1
resolver
uniprot_entry
A0A087X0W8_HUMAN
resolver
uniprot_entry
TF65_HUMAN
resolver
uniprot_sec
Q6GTV1
resolver
uniprot_sec
Q6SLK1
resolver
amino_acid_sequence
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving ZFTA is found in more than two-thirds of supratentorial ependymomas. Translocation with ZFTA produces a ZFTA-RELA fusion protein. ZFTA-RELA translocations are potent oncogenes that probably transform neural stem cells by driving an aberrant NF-kappa-B transcription program (PubMed:24553141). {ECO:0000269|PubMed:24553141}.; DISEASE: Autoinflammatory disease, familial, Behcet-like 3 (AIFBL3) [MIM:618287]: An autosomal dominant, mucocutaneous disease characterized by chronic mucosal lesions, in absence of recurrent infections. {ECO:0000269|PubMed:28600438}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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. Besides 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). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:41747053}.
uniprot
proteins
mass_dalton
60219
uniprot
proteins
mutagenesis
MUTAGEN 254; /note="T->A: Abolishes interaction with PIN1."; /evidence="ECO:0000269|PubMed:14690596"; MUTAGEN 276; /note="S->C: Loss of phosphorylation."; /evidence="ECO:0000269|PubMed:12628924"; MUTAGEN 536; /note="S->A: Decreased transactivation function of NF-kappa-B."; /evidence="ECO:0000269|PubMed:16840782
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by RNF182, leading to its proteasomal degradation (PubMed:31432514). Degradation is required for termination of NF-kappa-B response. Polyubiquitinated via 'Lys-29'-linked ubiquitin; leading to lysosomal degradation (PubMed:21518757). {ECO:0000269|PubMed:15226358, ECO:0000269|PubMed:21518757, ECO:0000269|PubMed:31432514}.; PTM: Monomethylated at Lys-310 by SETD6 (PubMed:21515635). 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). {ECO:0000250|UniProtKB:Q04207, ECO:0000269|PubMed:21515635}.; PTM: Phosphorylation at Ser-468 and Ser-536 by IKKB/IKBKB and IKKE/IKBKE promotes NF-kappa-B activity (PubMed:10521409, PubMed:11931769, PubMed:16046471, PubMed:16407239, PubMed:16840782). Phosphorylation on Ser-536 by IKKB/IKBKB and IKKE/IKBKE stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity (PubMed:10521409, PubMed:11931769). Phosphorylation at Ser-276 by RPS6KA4 and RPS6KA5 promotes its transactivation and transcriptional activities (PubMed:12628924). Phosphorylation at Ser-311 disrupts the interaction with EHMT1 and promotes transcription factor activity (By similarity). {ECO:0000250|UniProtKB:Q04207, ECO:0000269|PubMed:10521409, ECO:0000269|PubMed:11931769, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:16046471, ECO:0000269|PubMed:16407239, ECO:0000269|PubMed:16840782}.; PTM: (Microbial infection) Phosphorylation at Ser-75 by herpes simplex virus 1/HHV-1 inhibits NF-kappa-B activation. {ECO:0000269|PubMed:24807716}.; PTM: 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. {ECO:0000269|PubMed:12419806, ECO:0000269|PubMed:12456660, ECO:0000269|PubMed:16135789, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:19103749}.; PTM: S-nitrosylation of Cys-38 inactivates the enzyme activity. {ECO:0000250}.; PTM: Sulfhydration at Cys-38 mediates the anti-apoptotic activity by promoting the interaction with RPS3 and activating the transcription factor activity. {ECO:0000250}.; PTM: Sumoylation by PIAS3 negatively regulates DNA-bound activated NF-kappa-B. {ECO:0000269|PubMed:22649547}.; PTM: 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 (PubMed:18212740). {ECO:0000269|PubMed:18212740}.; PTM: Ubiquitinated by the SCF-FBXO16 E3 ubiquitin ligase, leading to proteasomal degradation. {ECO:0000269|PubMed:40529355}.
uniprot
proteins
pubmed
10498867
uniprot
proteins
pubmed
10521409
uniprot
proteins
pubmed
10660609
uniprot
proteins
pubmed
10928981
uniprot
proteins
pubmed
10938077
uniprot
proteins
pubmed
11526476
uniprot
proteins
pubmed
11533489
uniprot
proteins
pubmed
11931769
uniprot
proteins
pubmed
12398897
uniprot
proteins
pubmed
12419806
uniprot
proteins
pubmed
12456660
uniprot
proteins
pubmed
12628924
uniprot
proteins
pubmed
12748188
uniprot
proteins
pubmed
12871932
uniprot
proteins
pubmed
14690596
uniprot
proteins
pubmed
14769797
uniprot
proteins
pubmed
1493333
uniprot
proteins
pubmed
15029197
uniprot
proteins
pubmed
15073167
uniprot
proteins
pubmed
15125834
uniprot
proteins
pubmed
15226358
uniprot
proteins
pubmed
15355351
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15516339
uniprot
proteins
pubmed
15629770
uniprot
proteins
pubmed
15775976
uniprot
proteins
pubmed
15790681
uniprot
proteins
pubmed
15799966
uniprot
proteins
pubmed
16046471
uniprot
proteins
pubmed
16135789
uniprot
proteins
pubmed
16214042
uniprot
proteins
pubmed
16407239
uniprot
proteins
pubmed
16452207
uniprot
proteins
pubmed
16477006
uniprot
proteins
pubmed
16497732
uniprot
proteins
pubmed
16840782
uniprot
proteins
pubmed
17000776
uniprot
proteins
pubmed
1732726
uniprot
proteins
pubmed
1740106
uniprot
proteins
pubmed
17467953
uniprot
proteins
pubmed
17620405
uniprot
proteins
pubmed
17785205
uniprot
proteins
pubmed
18178962
uniprot
proteins
pubmed
18212740
uniprot
proteins
pubmed
18405956
uniprot
proteins
pubmed
18577712
uniprot
proteins
pubmed
19058135
uniprot
proteins
pubmed
19103749
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
2006423
uniprot
proteins
pubmed
20164180
uniprot
proteins
pubmed
20547752
uniprot
proteins
pubmed
20855622
uniprot
proteins
pubmed
21081649
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21515635
uniprot
proteins
pubmed
21518757
uniprot
proteins
pubmed
21697472
uniprot
proteins
pubmed
22649547
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24553141
uniprot
proteins
pubmed
24807716
uniprot
proteins
pubmed
25355951
uniprot
proteins
pubmed
26041281
uniprot
proteins
pubmed
27736973
uniprot
proteins
pubmed
28600438
uniprot
proteins
pubmed
29044191
uniprot
proteins
pubmed
29305315
uniprot
proteins
pubmed
29813070
uniprot
proteins
pubmed
30867312
uniprot
proteins
pubmed
31432514
uniprot
proteins
pubmed
33314660
uniprot
proteins
pubmed
33440148
uniprot
proteins
pubmed
40529355
uniprot
proteins
pubmed
41747053
uniprot
proteins
pubmed
7907305
uniprot
proteins
pubmed
8152812
uniprot
proteins
pubmed
8281153
uniprot
proteins
pubmed
9056676
uniprot
proteins
pubmed
9315679
uniprot
proteins
pubmed
9751059
uniprot
proteins
pubmed
9865693
uniprot
proteins
sequence_length
551
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:15799966, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:25355951, ECO:0000269|PubMed:40529355}. Cytoplasm {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:24807716, ECO:0000269|PubMed:27736973}. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B) (PubMed:1493333). Colocalized with DDX1 in the nucleus upon TNF induction (PubMed:19058135). Colocalizes with GFI1 in the nucleus after LPS stimulation (PubMed:20547752). Translocation to the nucleus is impaired in L.monocytogenes infection (PubMed:20855622). {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:20855622}.
uniprot
proteins