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 ... See more...

Aliases for RELA Gene

Aliases for RELA Gene

  • RELA Proto-Oncogene, NF-KB Subunit 2 3 5
  • Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells 3 2 3 4
  • V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A 2 3
  • Nuclear Factor NF-Kappa-B P65 Subunit 3 4
  • Transcription Factor P65 3 4
  • NFKB3 3 4
  • V-Rel Reticuloendotheliosis Viral Oncogene Homolog A 3
  • NF-Kappa-B Transcription Factor P65 3
  • NF-Kappa-B P65delta3 3
  • CMCU 3
  • P65 3

External Ids for RELA Gene

Previous HGNC Symbols for RELA Gene

  • NFKB3

Previous GeneCards Identifiers for RELA Gene

  • GC11M067936
  • GC11M067102
  • GC11M065671
  • GC11M065196
  • GC11M065172
  • GC11M065178
  • GC11M065421
  • GC11M061748

Summaries for RELA Gene

Entrez Gene Summary for RELA Gene

  • 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]

GeneCards Summary for RELA Gene

RELA (RELA Proto-Oncogene, NF-KB Subunit) is a Protein Coding gene. Diseases associated with RELA include Mucocutaneous Ulceration, Chronic and Rela Fusion-Positive Ependymoma. Among its related pathways are Cellular Senescence (REACTOME) and Activated TLR4 signalling. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and identical protein binding. An important paralog of this gene is REL.

UniProtKB/Swiss-Prot Summary for RELA Gene

  • 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.

Gene Wiki entry for RELA Gene

Additional gene information for RELA Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RELA Gene

Genomics for RELA Gene

GeneHancer (GH) Regulatory Elements for RELA Gene

Promoters and enhancers for RELA Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RELA on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RELA gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • HEN1
  • p300
  • Sp1
  • STAT3

Genomic Locations for RELA Gene

Genomic Locations for RELA Gene
chr11:65,653,596-65,663,090
(GRCh38/hg38)
Size:
9,495 bases
Orientation:
Minus strand
chr11:65,421,067-65,430,565
(GRCh37/hg19)
Size:
9,499 bases
Orientation:
Minus strand

Genomic View for RELA Gene

Genes around RELA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RELA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RELA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RELA Gene

Proteins for RELA Gene

  • Protein details for RELA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q04206-TF65_HUMAN
    Recommended name:
    Transcription factor p65
    Protein Accession:
    Q04206
    Secondary Accessions:
    • Q6GTV1
    • Q6SLK1

    Protein attributes for RELA Gene

    Size:
    551 amino acids
    Molecular mass:
    60219 Da
    Quaternary structure:
    • Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-c-Rel complex. Homodimer; component of the NF-kappa-B p65-p65 complex. Component of the NF-kappa-B p65-p52 complex. May interact with ETHE1. Binds TLE5 and TLE1. Interacts with TP53BP2. Binds to and is phosphorylated by the activated form of either RPS6KA4 or RPS6KA5. Interacts with ING4 and this interaction may be indirect. Interacts with CARM1, USP48 and UNC5CL. Interacts with IRAK1BP1 (By similarity). Interacts with NFKBID (By similarity). Interacts with NFKBIA (PubMed:1493333). Interacts with GSK3B. Interacts with NFKBIB (By similarity). Interacts with NFKBIE. Interacts with NFKBIZ. Interacts with EHMT1 (via ANK repeats) (By similarity). Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14. Interacts with HDAC3; HDAC3 mediates the deacetylation of RELA. Interacts with HDAC1; the interaction requires non-phosphorylated RELA. Interacts with CBP; the interaction requires phosphorylated RELA. Interacts (phosphorylated at 'Thr-254') with PIN1; the interaction inhibits p65 binding to NFKBIA. Interacts with SOCS1. Interacts with UXT. Interacts with MTDH and PHF11. Interacts with ARRB2. Interacts with NFKBIA (when phosphorylated), the interaction is direct; phosphorylated NFKBIA is part of a SCF(BTRC)-like complex lacking CUL1. Interacts with RNF25. Interacts (via C-terminus) with DDX1. Interacts with UFL1 and COMMD1. Interacts with BRMS1; this promotes deacetylation of 'Lys-310'. Interacts with NOTCH2 (By similarity). Directly interacts with MEN1; this interaction represses NFKB-mediated transactivation. Interacts with AKIP1, which promotes the phosphorylation and nuclear retention of RELA. Interacts (via the RHD) with GFI1; the interaction, after bacterial lipopolysaccharide (LPS) stimulation, inhibits the transcriptional activity by interfering with the DNA-binding activity to target gene promoter DNA. Interacts (when acetylated at Lys-310) with BRD4; leading to activation of the NF-kappa-B pathway. Interacts with MEFV. Interacts with CLOCK (By similarity). Interacts (via N-terminus) with CPEN1; this interaction induces proteolytic cleavage of p65/RELA subunit and inhibition of NF-kappa-B transcriptional activity (PubMed:18212740). Interacts with FOXP3. Interacts with CDK5RAP3; stimulates the interaction of RELA with HDAC1, HDAC2 and HDAC3 thereby inhibiting NF-kappa-B transcriptional activity (PubMed:17785205). Interacts with DHX9; this interaction is direct and activates NF-kappa-B-mediated transcription (PubMed:15355351). Interacts with LRRC25 (PubMed:29044191). Interacts with TBX21 (By similarity). Interacts with KAT2A (By similarity). Interacts with ZBTB7A; involved in the control by RELA of the accessibility of target gene promoters (PubMed:29813070).
    • (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein M2-1.
    • (Microbial infection) Interacts with molluscum contagiosum virus MC132.
    • (Microbial infection) Interacts with herpes virus 8 virus protein LANA1.

    Three dimensional structures from OCA and Proteopedia for RELA Gene

    Alternative splice isoforms for RELA Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RELA Gene

Post-translational modifications for RELA Gene

  • Ubiquitinated, 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 (PubMed:18212740).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

No data available for DME Specific Peptides for RELA Gene

Domains & Families for RELA Gene

Gene Families for RELA Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Suggested Antigen Peptide Sequences for RELA Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ57698, highly similar to Transcription factor p65 (B4E082_HUMAN)
  • RELA protein (Q96F54_HUMAN)
  • Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (TF65_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q04206

UniProtKB/Swiss-Prot:

TF65_HUMAN :
  • The transcriptional activation domain 3/TA3 does not participate to the direct transcriptional activity of RELA but is involved in the control by RELA of the accessibility of target gene promoters. Mediates interaction with ZBTB7A.
Domain:
  • The transcriptional activation domain 3/TA3 does not participate to the direct transcriptional activity of RELA but is involved in the control by RELA of the accessibility of target gene promoters. Mediates interaction with ZBTB7A.
  • The transcriptional activation domain 1/TA1 and the transcriptional activation domain 2/TA2 have direct transcriptional activation properties (By similarity). The 9aaTAD motif found within the transcriptional activation domain 2 is a conserved motif present in a large number of transcription factors that is required for their transcriptional transactivation activity (PubMed:17467953).
genes like me logo Genes that share domains with RELA: view

Function for RELA Gene

Molecular function for RELA Gene

UniProtKB/Swiss-Prot 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.
GENATLAS Biochemistry:
nuclear transcription factor of kappa light chain enhancer in B cells,3 (p65),NF-kappa B/REL family

Phenotypes From GWAS Catalog for RELA Gene

Gene Ontology (GO) - Molecular Function for RELA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IMP 18045535
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 17350185
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding IDA 1406630
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IDA,NAS 19274049
GO:0001225 RNA polymerase II transcription coactivator binding IPI 23811396
genes like me logo Genes that share ontologies with RELA: view
genes like me logo Genes that share phenotypes with RELA: view

Human Phenotype Ontology for RELA Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RELA Gene

MGI Knock Outs for RELA:

Animal Model Products

CRISPR Products

Transcription Factor Targets for RELA Gene

Selected GeneGlobe predicted Target genes for RELA
Targeted motifs for RELA Gene
HOMER Transcription Factor Regulatory Elements motif RELA
  • Consensus sequence: AGGGGATTTCCC Submotif: canonical Cell Type: GM12787 GEO ID: GSE19485

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RELA

Clone Products

  • Addgene plasmids for RELA

No data available for Enzyme Numbers (IUBMB) for RELA Gene

Localization for RELA Gene

Subcellular locations from UniProtKB/Swiss-Prot for RELA Gene

Nucleus. Cytoplasm. 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-alpha 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}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RELA gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for RELA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 26268439
GO:0005634 nucleus IEA,IMP 9425125
GO:0005654 nucleoplasm TAS,IBA --
GO:0005667 transcription factor complex IDA 12048232
GO:0005730 NOT nucleolus IDA 21343177
genes like me logo Genes that share ontologies with RELA: view

Pathways & Interactions for RELA Gene

PathCards logo

SuperPathways for RELA Gene

SuperPathway Contained pathways
1 Activated TLR4 signalling
2 Cytosolic sensors of pathogen-associated DNA
3 Toll-like Receptor Signaling Pathway
4 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
5 Immune response IL-23 signaling pathway
genes like me logo Genes that share pathways with RELA: view