RELA (RELA proto-oncogene, NF-kB subunit)

Gene

• Entrez ID: 5970
• Gene name: RELA proto-oncogene, NF-kB subunit
• Gene symbol: RELA
• Synonyms: CMCU, NFKB3, p65
• Chromosome: 11
• Chromosome location: 11q13.1
• Summary: 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. [provided by RefSeq, Sep 2011]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1565191003	C>T	Pathogenic	Splice donor variant
rs1590931704	T>G	Likely-pathogenic	Splice acceptor variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002531	hsa-miR-373-3p	Microarray, Microarray;Other	15685193
MIRT002616	hsa-miR-124-3p	Luciferase reporter assay, Microarray, Microarray;Other	15685193
MIRT025722	hsa-miR-7-5p	Sequencing, PAR-CLIP	20371350
MIRT025722	hsa-miR-7-5p	Microarray	17612493
MIRT025722	hsa-miR-7-5p	Microarray	19073608
MIRT025722	hsa-miR-7-5p	qRT-PCR, Western blot	25232110
MIRT025722	hsa-miR-7-5p	ChIP-seq, Immunofluorescence, Immunohistochemistry, In situ hybridization, Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	26261179
MIRT025722	hsa-miR-7-5p	qRT-PCR, Western blot	25814668
MIRT027888	hsa-miR-96-5p	Sequencing	20371350
MIRT043112	hsa-miR-324-5p	CLASH	23622248
MIRT044156	hsa-miR-30e-5p	CLASH	23622248
MIRT044799	hsa-miR-320a	CLASH	23622248
MIRT383563	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT559974	hsa-miR-1261	PAR-CLIP	20371350
MIRT559975	hsa-miR-3161	PAR-CLIP	20371350
MIRT559976	hsa-miR-599	PAR-CLIP	20371350
MIRT559977	hsa-miR-6077	PAR-CLIP	20371350
MIRT559978	hsa-miR-3134	PAR-CLIP	20371350
MIRT559979	hsa-miR-8082	PAR-CLIP	20371350
MIRT559980	hsa-miR-4534	PAR-CLIP	20371350
MIRT642954	hsa-miR-1303	HITS-CLIP	23824327
MIRT642955	hsa-miR-6720-5p	HITS-CLIP	23824327
MIRT642956	hsa-miR-6866-5p	HITS-CLIP	23824327
MIRT642957	hsa-miR-6512-3p	HITS-CLIP	23824327
MIRT642958	hsa-miR-877-5p	HITS-CLIP	23824327
MIRT642959	hsa-miR-6849-3p	HITS-CLIP	23824327
MIRT642960	hsa-miR-6859-5p	HITS-CLIP	23824327
MIRT642961	hsa-miR-3916	HITS-CLIP	23824327
MIRT642962	hsa-miR-3125	HITS-CLIP	23824327
MIRT735051	hsa-miR-186-5p	Luciferase reporter assay	28213656
MIRT740420	hsa-miR-3154	PAR-CLIP	26701625
MIRT740528	hsa-miR-3160-3p	PAR-CLIP	26701625
MIRT740539	hsa-miR-3162-3p	PAR-CLIP	26701625
MIRT742956	hsa-miR-3919	PAR-CLIP	26701625
MIRT743856	hsa-miR-4300	PAR-CLIP	26701625
MIRT744441	hsa-miR-4436a	PAR-CLIP	26701625
MIRT748986	hsa-miR-4797-5p	PAR-CLIP	26701625
MIRT749328	hsa-miR-5000-3p	PAR-CLIP	26701625
MIRT751085	hsa-miR-5591-5p	PAR-CLIP	26701625
MIRT751582	hsa-miR-591	PAR-CLIP	26701625
MIRT752733	hsa-miR-642b-5p	PAR-CLIP	26701625
MIRT753928	hsa-miR-6726-5p	PAR-CLIP	26701625
MIRT755292	hsa-miR-6770-5p	PAR-CLIP	26701625
MIRT758366	hsa-miR-6883-3p	PAR-CLIP	26701625
MIRT759393	hsa-miR-7515	PAR-CLIP	26701625
MIRT760482	hsa-miR-920	PAR-CLIP	26701625

Transcription factors

Transcription factor	Regulation	Reference
APEX1	Activation	17045925
AR	Repression	18386814
ATF2	Activation	21350211
BCL3	Unknown	7896265
EP300	Unknown	21146504
ETV3	Repression	18025162
FHL2	Unknown	18752053
GATA3	Unknown	19686049
HDAC9	Repression	15964798
HOXA9	Repression	18068911
HSF1	Unknown	18689673
NFKBIA	Activation	9500973
NFKBIA	Repression	11278471;18606063;20173029
NFKBIA	Unknown	15713458;17148610
NR1H4	Activation	21364590
NR1I2	Repression	22248096
PARP1	Unknown	16026317
PGR	Repression	8626413
RUNX1	Unknown	19686049
SP1	Activation	20538607;11964305;9151857
SP1	Unknown	8450395
SP3	Activation	20538607
SP4	Activation	20538607
TNFAIP3	Repression	19124729
TNFAIP3	Unknown	24039598
TP53	Unknown	15988033
TRIM22	Unknown	21651891
USF1	Unknown	19686049

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	17350185
GO:0000785	Component	Chromatin	IDA	21343296, 26268439
GO:0000785	Component	Chromatin	IGI	23729669
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	17350185
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	7959007, 23811396, 24955228, 25411248
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IMP	18045535
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	1406630, 17350185, 21343177, 23729669
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS	21329555
GO:0000979	Function	RNA polymerase II core promoter sequence-specific DNA binding	IDA	21343296
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	3091258
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001225	Function	RNA polymerase II transcription coactivator binding	IPI	23811396
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA	17350185
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	1406630, 17350185, 23811396, 26435691
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	26268439
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	ISS	21329555
GO:0001889	Process	Liver development	IEA
GO:0001942	Process	Hair follicle development	IEA
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0003677	Function	DNA binding	IDA	15790681, 18073330, 23091055
GO:0003677	Function	DNA binding	IMP	18212740
GO:0003682	Function	Chromatin binding	IDA	19058135
GO:0003700	Function	DNA-binding transcription factor activity	IDA	12048232
GO:0003700	Function	DNA-binding transcription factor activity	IMP	9425125
GO:0005515	Function	Protein binding	IPI	1493333, 7651415, 8246997, 9865693, 10498867, 11387332, 11526476, 11591705, 11931769, 12628924, 12842894, 14600157, 14624448, 14685242, 15029197, 15125834, 15140884, 15152190, 15355351, 15601829, 15799966, 15917220, 16291753, 16452207, 16683270, 16951195, 17000776, 17003112, 1715778
GO:0005634	Component	Nucleus	IDA	3140380, 15790681, 17350185, 18045535, 18212740, 19058135, 21097510, 21343177, 21343296, 21474709, 21830064, 22065573, 25411248
GO:0005634	Component	Nucleus	IGI	25327529
GO:0005634	Component	Nucleus	IMP	9425125
GO:0005654	Component	Nucleoplasm	TAS
GO:0005667	Component	Transcription regulator complex	IDA	12048232
GO:0005730	Component	Nucleolus	IDA	21343177
GO:0005737	Component	Cytoplasm	IDA	3140380, 15790681, 21097510, 21343177, 21830064, 25411248, 27736973
GO:0005737	Component	Cytoplasm	IGI	23729669
GO:0005829	Component	Cytosol	IDA	21474709, 25327529
GO:0005829	Component	Cytosol	TAS
GO:0006117	Process	Acetaldehyde metabolic process	IEA
GO:0006325	Process	Chromatin organization	IEA
GO:0006351	Process	Transcription, DNA-templated	IEA
GO:0006355	Process	Regulation of transcription, DNA-templated	IMP	23178297
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006954	Process	Inflammatory response	IBA	21873635
GO:0006954	Process	Inflammatory response	IDA	12924514
GO:0006968	Process	Cellular defense response	NAS	8717528
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0007568	Process	Aging	IEA
GO:0008134	Function	Transcription factor binding	IPI	10849440
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	23091055
GO:0009887	Process	Animal organ morphogenesis	IEA
GO:0010033	Process	Response to organic substance	IDA	10747850
GO:0010224	Process	Response to UV-B	IDA	15616591
GO:0014040	Process	Positive regulation of Schwann cell differentiation	IEA
GO:0016032	Process	Viral process	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	IDA	15876188
GO:0019899	Function	Enzyme binding	IPI	23811396
GO:0019901	Function	Protein kinase binding	IPI	10521409, 15465828
GO:0031293	Process	Membrane protein intracellular domain proteolysis	TAS
GO:0031490	Function	Chromatin DNA binding	IDA	25411248
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	12748188
GO:0032481	Process	Positive regulation of type I interferon production	TAS
GO:0032495	Process	Response to muramyl dipeptide	IEA
GO:0032570	Process	Response to progesterone	IEA
GO:0032735	Process	Positive regulation of interleukin-12 production	IEA
GO:0032757	Process	Positive regulation of interleukin-8 production	IGI	21343296
GO:0032868	Process	Response to insulin	IEA
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IDA	21343177, 25411248
GO:0033234	Process	Negative regulation of protein sumoylation	IEA
GO:0033554	Process	Cellular response to stress	IBA	21873635
GO:0033590	Process	Response to cobalamin	IEA
GO:0033613	Function	Activating transcription factor binding	IPI	15489227
GO:0034097	Process	Response to cytokine	IBA	21873635
GO:0035525	Component	NF-kappaB p50/p65 complex	IDA	18045535
GO:0035729	Process	Cellular response to hepatocyte growth factor stimulus	IEA
GO:0035924	Process	Cellular response to vascular endothelial growth factor stimulus	IMP	23878390
GO:0035994	Process	Response to muscle stretch	IEA
GO:0038061	Process	NIK/NF-kappaB signaling	IBA	21873635
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042177	Process	Negative regulation of protein catabolic process	IEA
GO:0042277	Function	Peptide binding	IPI	18045535
GO:0042301	Function	Phosphate ion binding	IDA	10521409
GO:0042493	Process	Response to drug	IEA
GO:0042802	Function	Identical protein binding	IDA	9437432
GO:0042802	Function	Identical protein binding	IPI	8246997, 10498867
GO:0042803	Function	Protein homodimerization activity	IDA	18045535, 18212740
GO:0042805	Function	Actinin binding	IPI	25411248
GO:0042826	Function	Histone deacetylase binding	IPI	17785205
GO:0043066	Process	Negative regulation of apoptotic process	IDA	10747850, 23091055
GO:0043066	Process	Negative regulation of apoptotic process	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP	12761501
GO:0043200	Process	Response to amino acid	IEA
GO:0043278	Process	Response to morphine	IEA
GO:0043620	Process	Regulation of DNA-templated transcription in response to stress	IMP	26649771
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	17350185
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	17350185, 18073330
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	9425125
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	1406630, 17350185, 23091055, 23811396, 26435691
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IGI	21343296, 21518763
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	10660609, 21310825, 25762865
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS	21329555
GO:0046627	Process	Negative regulation of insulin receptor signaling pathway	IEA
GO:0047485	Function	Protein N-terminus binding	IPI	7739562
GO:0050727	Process	Regulation of inflammatory response	ISS
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0050862	Process	Positive regulation of T cell receptor signaling pathway	IMP	18045535
GO:0051059	Function	NF-kappaB binding	IPI	8441377
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	15790681
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IGI	18045535
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IMP	18045535
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	TAS
GO:0051591	Process	Response to cAMP	IEA
GO:0051607	Process	Defense response to virus	NAS	8717528
GO:0070301	Process	Cellular response to hydrogen peroxide	IDA	21830064
GO:0070431	Process	Nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA	12527755
GO:0070491	Function	Repressing transcription factor binding	IPI	10660609
GO:0070498	Process	Interleukin-1-mediated signaling pathway	IGI	25327529
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0070555	Process	Response to interleukin-1	IGI	15489227
GO:0071222	Process	Cellular response to lipopolysaccharide	IMP	25762865
GO:0071223	Process	Cellular response to lipoteichoic acid	IMP	26649771
GO:0071224	Process	Cellular response to peptidoglycan	IMP	24955228
GO:0071316	Process	Cellular response to nicotine	IMP	22357537
GO:0071347	Process	Cellular response to interleukin-1	IDA	18073330
GO:0071354	Process	Cellular response to interleukin-6	IMP	22357537
GO:0071356	Process	Cellular response to tumor necrosis factor	IDA	18073330, 23091055
GO:0071356	Process	Cellular response to tumor necrosis factor	IMP	18045535, 23878390
GO:0071532	Function	Ankyrin repeat binding	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099527	Process	Postsynapse to nucleus signaling pathway	IEA
GO:1901222	Process	Regulation of NIK/NF-kappaB signaling	IGI	21343177
GO:1901223	Process	Negative regulation of NIK/NF-kappaB signaling	IMP	18212740
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IDA	21343177
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IMP	23178297
GO:1901522	Process	Positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus	IMP	24955228
GO:1902004	Process	Positive regulation of amyloid-beta formation	ISS	21329555
GO:1902894	Process	Negative regulation of pri-miRNA transcription by RNA polymerase II	IMP	23878390
GO:1902895	Process	Positive regulation of pri-miRNA transcription by RNA polymerase II	IMP	23619365, 26268439
GO:1904385	Process	Cellular response to angiotensin	IMP	22357537
GO:1904996	Process	Positive regulation of leukocyte adhesion to vascular endothelial cell	IMP	25515214
GO:2000630	Process	Positive regulation of miRNA metabolic process	IMP	22357537
GO:2001237	Process	Negative regulation of extrinsic apoptotic signaling pathway	IMP	21310825

Other IDs

• MIM: 164014
• HGNC: 9955
• e!Ensembl: ENSG00000173039

Protein

• UniProt ID: Q04206
• Protein name: Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3)
• Protein 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).
• PDB: 1NFI, 2LSP, 2O61, 3GUT, 3QXY, 3RC0, 4KV1, 4KV4, 5U4K, 5URN, 6NV2, 6QHL, 6QHM, 6YOW, 6YOX, 6YOY, 6YP2, 6YP3, 6YP8, 6YPL, 6YPY, 6YQ2
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00554	RHD_DNA_bind	21 → 186	Rel homology DNA-binding domain	Domain
  PF16179	RHD_dimer	195 → 292	Rel homology dimerisation domain	Domain

• Sequence:

  MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPT
  IKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQC
  VKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLS
  HPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFS
  QADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEE
  KRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINY
  DEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQA
  VAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQ
  GIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADM
  DFSALLSQISS

• Sequence length: 551