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FLASH GENE
Symbol RELA contributors: mct - updated : 09-04-2014
HGNC name v-rel reticuloendotheliosis viral oncogene homolog A (avian)
HGNC id 9955
Location 11q13.1      Physical location : 65.421.067 - 65.430.443
Synonym name
  • transcription factor p65
  • nuclear factor NF-kappa-B p65 subunit
  • v-rel avian reticuloendotheliosis viral oncogene homolog A
  • nuclear factor of kappa light polypeptide gene enhancer
  • in B-cells 3 (p65)
    Synonym symbol(s) NFKB3, p65, MGC131774
    DNA
    TYPE functioning gene
    STRUCTURE 9.38 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D11S4933 - D11S628 - D11S1957E - MAP3K11 - RELA - D11S546 - HTATIP - qter
    Text see MEN1
    Physical map
    TM7SF2 11q13 transmembrane 7 superfamily member 2 C11orf5 11q13 chromosome 11 open reading frame 5 FAU 11q12-q13.1 Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitously expressed (fox derived); ribosomal protein S30 MRPL49 11q13 mitochondrial ribosomal protein L49 HRD1 11q13 HRD1 protein LOC387778 11 similar to p33 ringo LOC387779 11 similar to Phosphoglycerate mutase 1 (Phosphoglycerate mutase isozyme B) (PGAM-B) (BPG-dependent PGAM 1) CAPN1 11q13 calpain 1, (mu/I) large subunit LOC387780 11 similar to solute carrier family 22 member 6; organic cationic transporter-like 1; solute carrier family 22 (organic anion transporter), member 6 POLA2 11q13.1 polymerase (DNA-directed), alpha (70kD) CDC42EP2 11q13 CDC42 effector protein (Rho GTPase binding) 2 DPF2 11q13 D4, zinc and double PHD fingers family 2 TIGD3 11q13.2 tigger transposable element derived 3 LOC283130 11q13.1 hypothetical protein LOC283130 FKSG44 11q13 hypothetical protein FKSG44 LOC387781 11 similar to UBIQUITIN-LIKE PROTEIN FUBI SCYL1 11q11-q12 SCY1-like 1 (S. cerevisiae) LTBP3 11q12 latent transforming growth factor beta binding protein 3 MTVR1 11q23 Mouse Mammary Turmor Virus Receptor homolog 1 SSSCA1 11q13.1 Sjogren's syndrome/scleroderma autoantigen 1 DKFZp762C186 11q13.1 tangerin KCNK7 11q13 potassium channel, subfamily K, member 7 MAP3K11 11q13.3 mitogen-activated protein kinase kinase kinase 11 RELA 11q13 v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) SIPA1 11q13.3 signal-induced proliferation-associated gene 1 LOC387782 11 LOC387782 HTATIP 11q13 HIV-1 Tat interactive protein, 60kDa AYP1 11q13.1 AYP1 protein LOC390211 11 similar to Keratin, type II cytoskeletal 8 (Cytokeratin 8) (K8) (CK 8) LOC91056 11q13.1 hypothetical protein BC004895 OVOL1 11q13 ovo-like 1(Drosophila) FLJ30934 11q13.1 hypothetical protein FLJ30934 CFL1 11q13 cofilin 1 (non-muscle) MUS81 11q13 MUS81 endonuclease homolog (yeast) EFEMP2 11q13 EGF-containing fibulin-like extracellular matrix protein 2 CTSW 11q13.1 cathepsin W (lymphopain) FIBP 11q13.1 fibroblast growth factor (acidic) intracellular binding protein DIPA 11q12.1 hepatitis delta antigen-interacting protein A FOSL1 11q13 FOS-like antigen 1 P5326 11q13.1 hypothetical protein p5326 DRAP1 11q13.3 DR1-associated protein 1 (negative cofactor 2 alpha) FLJ32880 11q13.1 hypothetical protein FLJ32880 SART1 11q12-q13 squamous cell carcinoma antigen recognised by T cells MGC11102 11q13.1 hypothetical protein MGC11102 BANF1 11q13.1 barrier to autointegration factor 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2586 59.8 548 - 2009 19339690
    11 - 2595 60 551 - 2009 19339690
    11 - 2388 - 482 - 2009 19339690
    12 - 2286 - 448 - 2009 19339690
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
     stomach   highly
    Lymphoid/Immunelymph node   highly
     spleen    
    Reproductivefemale systemovary   
     female systemuteruscervix  
     male systemprostate   
    Respiratorylung    
    Skin/Tegumentskin    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal fragment (AAs 21-186) can selectively modulate NFKB gene transcription by competing for RPS3 binding to RELA, fragment that preferentially localizes in the cytoplasm where it delays stimuli-induced RPS3 nuclear translocation, without affecting the nuclear translocation of RELA
  • a rel homology domain
  • a nuclear receptor interaction motif (LXXLL)
  • a TA1 and TA2 regions
  • HOMOLOGY
    Homologene
    FAMILY
  • NF-kappa B/REL family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • TRAF7 influences RELA nuclear distribution
  • basic FUNCTION
  • nuclear transcription factor of kappa light chain enhancer in B cells
  • regulates inducible transcription of a large number of genes in response to diverse stimuli
  • critical regulator of T-cell survival by affecting the balance of BCL2 family members
  • acetylated form of RELA coactivates transcriptional activation of NF-KappaB through binding to BRD4
  • RELA-mediated regulation of BECN1 could be important for T-cell activation and proliferation, highlighting a novel mechanism whereby RELA could promote cell survival
  • regulates BECN1 transcription, probably due to its ability to directly act on the BECN1 promoter
  • can positively regulate constitutive autophagy, possibly due to its ability to regulate BECN1 expression
  • represses CTNNB1-activated transcription of cyclin D1
  • transcription factor expressed in growth plate chondrocytes where it facilitates chondrogenesis
  • can function as an active transcriptional repressor through enhanced methylation of the BRMS1 metastasis suppressor gene promoter via direct recruitment of DNMT1 (DNA (cytosine-5)-methyltransferase 1) to chromatin in response to tumor necrosis factor (TNF)
  • direct role of RELA in antioxidant homeostasis, contributing to redox balance in renal cells
  • ACTN4 enhances RELA-dependant expression of FOS, MMP3 and MMP1 genes, but it does not affect TNC, ICAM1 and FN1 expression
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RNF25
  • interaction between IRAK1BP1 and RELA enhances RELA transactivation activity
  • interacting with NFKBIB (tight control of NFKBIB protein by RELA is necessary for the maintenance of cellular homeostasis)
  • interacting with PIAS3, to suppress NFKB transcription
  • bound to nucleosomes following deacetylation of H3K9 by SIRT6 (SIRT6-mediated deacetylation of H3K9 promotes RELA destabilization from target gene chromatin and termination of NF-KB
  • association of SIRT6 with RELA target promoters (SIRT6 levels might influence RELA-dependent transcription)
  • associates with alpha-actinin-4 (alpha-actinin-4 is important for the NF-kappaB nuclear translocation and its functions inside the nucleus
  • interacting with PDLIM2
  • interacting with IER3 (direct interaction with the C-terminal region of the subunit RELA harbouring the transactivation domain of the NF-kappaB transcription factor)
  • interacting with PSMD10
  • binds COMMD1, the rate-limiting component of the RELA ubiquitin ligase complex, in response to stress
  • direct contact between RELA and Mediator, through the MED17 subunit and the TA1 and TA2 regions of RELA
  • interaction between RELA and STAT5B in chondrocytes
  • reciprocal functional interaction between RELA and IGF1 in which the transcription factor modulates both IGF1 synthesis and action in growth plate chondrocytes
  • ability of RELA to directly recruit DNMT1 to chromatin, resulting in promoter-specific methylation and transcriptional repression of tumor metastasis suppressor gene BRMS1
  • NFKB is a strong inhibitor of collagen synthesis and of COL1A1 transcription in healthy and scleroderma fibroblasts, and RELA subunit of NFKB being responsible for the inhibitory action
  • ERG controls endothelial cell quiescence by repressing activity of nuclear factor RELA
  • NAA10 inhibits apoptosis through NAA10-RELA-dependent MCL1 transcriptional activation
  • PTK2B is a critical regulator of endothelial cell (EC) inflammation by virtue of engaging IKK to promote the release and the transcriptional capacity of RELA, and, additionally, by its ability to facilitate the nuclear translocation of the released RELA
  • KLF11 potently inhibits NFKB signaling pathway via physical interaction with RELA
  • PPARG acts as an E3 ubiquitin ligase, physically interacting with RELA to induce its ubiquitination and degradation
  • in the nucleus, ACTN4 functions as a selective transcriptional co-activator of RELA
  • ING4 acts as an E3 ubiquitin ligase to induce ubiquitination of RELA and degradation, which is critical to terminate NFKB activation
  • inhibition of FGF10 by inflammatory signaling involves the NFKB1-dependent interactions between RELA, SP3, and the FGF10 promoter
  • PHF20 induces canonical NFKB1 signalling by increasing the DNA-binding activity of NFKB1 subunit RELA
  • nuclear import of RELA mainly relies on the canonical KPNA2/KPNB1 pathway
  • RELA is a potent transcriptional activator of ADAMTS5 in chondrocytes during osteoarthritis development
  • BEX2 promotes proliferation of human glioblastoma cells via NFKB1 signaling pathway and BEX2 nuclear location is critical for RELA expression
  • CDK6 physically and functionally interacts with the NFKB1 subunit RELA in the nucleus and is found at promoters of many transcriptionally active NFKB1 target genes
  • ECSIT specifically interacted with RELA/NFKB1 proteins, which colocalized in the nucleus
  • KPNB1 transports nuclear factor RELA from the cytoplasm to the nucleus to increase pro-inflammatory genes expression
  • cell & other
    REGULATION
    activated by GH1, via STAT5B
    inhibited by LIMK1 or SSH1 depletion which inhibited RELA phosphorylation at Ser(536), a critical event conferring transcriptional competency to the bound NFKB
    Other degraded by both KAT2A and the IkappaB Kinase (IKK) complex
    RELA T505 phosphorylation is a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration
    PRMT5 dimethylates R30 of RELA
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia
    tumoral     --over  
    associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia
    tumoral fusion      
    C11orf95-RELA fusions drive oncogenic NFKB signalling in ependymoma
    tumoral fusion      
    ZMYND8-RELA in acute erythroid leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target therapeutic target for chronic lymphocytic leukemia (Hewamana 2008)
    ANIMAL & CELL MODELS
    RelA/p65(-/-) murine fibroblasts immortalize at considerably faster rates than RelA/p65(+/+) cells suggesting that RELA might function to maintain cellular senescence by regulating genomic stability and DNA repair