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FLASH GENE
Symbol RELA contributors: mct - updated : 09-04-2016
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
    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)
  • like other acidic TADs, the p65 TAD contains two subdomains (p65TA1 and p65TA2) that interact with different regulatory factors depending on the target gene
  • 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
  • redundant functions of GSK3A and GSK3B through phosphorylation of RELA at Thr-254 play a crucial role in early stages of chondrocyte differentiation
  • 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
  • RELA p65-dependent transcriptional activation of EIF4H increased the EIF4H protein content augmenting the rate of global protein synthesis
  • 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
  • RELA and STAT1 cooperate to control NOS2 gene transcription in response to proinflammatory cytokines by a coactivator exchange mechanism
  • 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
  • PPIA provided stability for RELA and promoted RELA nuclear translocation, resulting in increased nuclear accumulation and enhanced NFKB1 activity
  • 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
  • through its acidic transactivation domain (TAD), RELA has the capacity to form interactions with several different transcriptional regulatory proteins, including GTF2B, GTF2H1, EP300 and TAF9B
  • 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