DegronMD - Q04206(RELA)

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). {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}. View more >>

GO - Biological processes (BP): animal organ morphogenesis [GO:0009887]; cellular defense response [GO:0006968]; cellular response to angiotensin [GO:1904385]; cellular response to hepatocyte growth factor stimulus [GO:0035729]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to interleukin-1 [GO:0071347]; cellular response to interleukin-6 [GO:0071354]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to lipoteichoic acid [GO:0071223]; cellular response to nicotine [GO:0071316]; cellular response to peptidoglycan [GO:0071224]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to vascular endothelial growth factor stimulus [GO:0035924]; chromatin organization [GO:0006325]; cytokine-mediated signaling pathway [GO:0019221]; defense response to tumor cell [GO:0002357]; defense response to virus [GO:0051607]; hair follicle development [GO:0001942]; I-kappaB kinase/NF-kappaB signaling [GO:0007249]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; interleukin-1-mediated signaling pathway [GO:0070498]; liver development [GO:0001889]; negative regulation of apoptotic process [GO:0043066]; negative regulation of extrinsic apoptotic signaling pathway [GO:2001237]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of NIK/NF-kappaB signaling [GO:1901223]; negative regulation of protein catabolic process [GO:0042177]; negative regulation of protein sumoylation [GO:0033234]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neuropeptide signaling pathway [GO:0007218]; NIK/NF-kappaB signaling [GO:0038061]; nucleotide-binding oligomerization domain containing 2 signaling pathway [GO:0070431]; positive regulation of amyloid-beta formation [GO:1902004]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of gene expression [GO:0010628]; positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123]; positive regulation of interleukin-12 production [GO:0032735]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of leukocyte adhesion to vascular endothelial cell [GO:1904996]; positive regulation of miRNA metabolic process [GO:2000630]; positive regulation of miRNA transcription [GO:1902895]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of NIK/NF-kappaB signaling [GO:1901224]; positive regulation of T cell receptor signaling pathway [GO:0050862]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus [GO:1901522]; postsynapse to nucleus signaling pathway [GO:0099527]; regulation of DNA-templated transcription in response to stress [GO:0043620]; regulation of inflammatory response [GO:0050727]; regulation of NIK/NF-kappaB signaling [GO:1901222]; regulation of transcription, DNA-templated [GO:0006355]; regulation of transcription by RNA polymerase II [GO:0006357]; response to cytokine [GO:0034097]; response to interleukin-1 [GO:0070555]; response to muramyl dipeptide [GO:0032495]; response to muscle stretch [GO:0035994]; response to organic substance [GO:0010033]; response to UV-B [GO:0010224]; transcription, DNA-templated [GO:0006351]; tumor necrosis factor-mediated signaling pathway [GO:0033209] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D347Y	DO51612	CESC	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.25
p.S364R	DO230326	COCA	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.0556
p.S364R	DO233295	NACA	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.0556
p.S358I	DO50323	ESAD	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.2222
p.P350H	DO228948	LICA	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation altering degron motif	0.7694
p.L355M	DO229038	LICA	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.3056
p.S351F	DO220906	MELA	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation altering degron motif	0.7982
p.L362P	DO50127	STAD	ICGC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.1111
p.P350L	SIDM00545	Melanoma	GDSC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation altering degron motif	0.7582
p.P350L	ACH-000987	Skin Cancer	CCLE	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation altering degron motif	0.7582
p.P350L	Mewo	skin	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation altering degron motif	0.7582
p.S340F	SIDM01617	Endometrial Carcinoma	GDSC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.0556
p.S340F	ACH-000994	Endometrial/Uterine Cancer	CCLE	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.0556
p.Q361H	KMH-2	thyroid	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.1389
p.Q361H	KURAMOCHI	ovary	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.1389
p.S359F	KURAMOCHI	ovary	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.1944
p.S359F	KMH-2	thyroid	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.1944
p.P347L	Mewo	skin	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.25
p.T362A	CCK-81	large intestine	COSMIC	PFTSS	DEG_SPOP_SBC_1	350:354	Mutation rewiring degron network	0.1111

DegronMD: protein-targeted degradation, mutation and drug response to degrons

RELA

UniProt ID: Q04206

Entrez ID: 5970

Protein name: Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RELA in