Homo sapiens Gene: RELA
InnateDB Gene IDBG-118586.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol RELA
Gene Name RELA proto-oncogene, NF-kB subunit
Synonyms NFKB3; p65;
Species Homo sapiens
Ensembl Gene ENSG00000173039
Encoded Proteins
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
RELA proto-oncogene, NF-kB subunit
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
RELA, NF-kappaB p65 subunit, is involved in the transcription regulation of many genes including those genes involved in apoptosis, response to stress and inflammation.
RELA is a subunit of NFKB and is not essential for virus-stimulated IFNB expression, instead, RELA sustains autocrine IFNB signalling prior to infection. The absence of RELA causes significant delays in IFNB induction and consequently defective secondary antiviral gene expression. RELA maintains autocrine IFNB signalling in uninfected cells, facilitates inflammatory and adaptive immune responses following infection, and promotes infected cell survival during this process.
RELA is critical for pulmonary host defence during Streptococcus pneumoniae pneumonia in alveolar macrophages. During pneumococcal pneumonia, only the earliest induction of cytokines depends on transcription regulated by RELA in myeloid cells, and this transcriptional activity contributes to effective immunity. (Demonstrated in murine model)
RELA is required for IL17A production in T cell in response to bacterial infection. RELA deficient T cells resulted in a diminished innate immune response to E. coli infection. (Demonstrated in murine model)
A RELA isoform, p43, lacks the transactivation domain but is still able to potentiate anti-viral innate immunity.
During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
Human papillomaviruses impair the acetylation of NFκB/RelA K310 in keratinocytes by augmenting the expression of interferon-related developmental regulator 1 (IFRD1) in an EGFR-dependent manner.
Haploinsufficiency of A20 (HA20) is caused by high-penetrance loss-of-function germline mutations in TNFAIP3 with increased degradation of NFKBIA, nuclear translocation of RELA, increased expression of NFκB mediated proinflammatory cytokines, and defective deubiquitinating activity.
MIR223 regulates macrophage function by modulating cytokine production and NF-κB activation through inhibition of RELA phosphorylation and nuclear translocation.
Enterovirus 71 2C protein binds to RELA and IKBKB to inhibit NF-kB activation and evade innate immune defenses.
Entrez Gene
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 11:65653596-65663094
Strand Reverse strand
Band q13.1
ENST00000308639 ENSP00000311508
ENST00000406246 ENSP00000384273
ENST00000525658 ENSP00000434008
ENST00000525693 ENSP00000432537
ENST00000526257 ENSP00000431304
ENST00000526283 ENSP00000435290
ENST00000527749 ENSP00000436545
ENST00000527874 ENSP00000435531
ENST00000527909 ENSP00000432922
ENST00000529389 ENSP00000437137
ENST00000531238 ENSP00000434745
ENST00000532879 ENSP00000431153
ENST00000532999 ENSP00000433526
ENST00000533187 ENSP00000434098
ENST00000533546 ENSP00000433144
ENST00000534283 ENSP00000433616
ENST00000534558 ENSP00000434372
ENST00000612991 ENSP00000483705
ENST00000615805 ENSP00000479572
Number of Interactions This gene and/or its encoded proteins are associated with 749 experimentally validated interaction(s) in this database.
They are also associated with 156 interaction(s) predicted by orthology.
Experimentally validated
Total 749 [view]
Protein-Protein 536 [view]
Protein-DNA 206 [view]
Protein-RNA 0
DNA-DNA 7 [view]
Predicted by orthology
Total 156 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0000983 transcription factor activity, RNA polymerase II core promoter sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding
GO:0001078 transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding
GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 DNA binding transcription factor activity
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0031490 chromatin DNA binding
GO:0031625 ubiquitin protein ligase binding
GO:0033613 activating transcription factor binding
GO:0042301 phosphate ion binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0042805 actinin binding
GO:0042826 histone deacetylase binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046982 protein heterodimerization activity
GO:0047485 protein N-terminus binding
GO:0051059 NF-kappaB binding
GO:0070491 repressing transcription factor binding
GO:0071532 ankyrin repeat binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001889 liver development
GO:0001942 hair follicle development
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0006117 acetaldehyde metabolic process
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006952 defense response
GO:0006954 inflammatory response
GO:0006968 cellular defense response
GO:0007568 aging
GO:0008284 positive regulation of cell proliferation
GO:0009612 response to mechanical stimulus
GO:0009617 response to bacterium
GO:0009887 animal organ morphogenesis
GO:0010033 response to organic substance
GO:0010035 response to inorganic substance
GO:0010224 response to UV-B
GO:0014040 positive regulation of Schwann cell differentiation
GO:0014070 response to organic cyclic compound
GO:0016032 viral process
GO:0019221 cytokine-mediated signaling pathway
GO:0031293 membrane protein intracellular domain proteolysis
GO:0032332 positive regulation of chondrocyte differentiation
GO:0032481 positive regulation of type I interferon production
GO:0032495 response to muramyl dipeptide
GO:0032496 response to lipopolysaccharide
GO:0032570 response to progesterone
GO:0032868 response to insulin
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0033234 negative regulation of protein sumoylation
GO:0033590 response to cobalamin
GO:0034097 response to cytokine
GO:0035729 cellular response to hepatocyte growth factor stimulus
GO:0035994 response to muscle stretch
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042177 negative regulation of protein catabolic process
GO:0042493 response to drug
GO:0042542 response to hydrogen peroxide
GO:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043200 response to amino acid
GO:0043278 response to morphine
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0045084 positive regulation of interleukin-12 biosynthetic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0050727 regulation of inflammatory response
GO:0050852 T cell receptor signaling pathway
GO:0050862 positive regulation of T cell receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051591 response to cAMP
GO:0051607 defense response to virus
GO:0061614 pri-miRNA transcription from RNA polymerase II promoter
GO:0070301 cellular response to hydrogen peroxide
GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0070498 interleukin-1-mediated signaling pathway
GO:0070555 response to interleukin-1
GO:0071222 cellular response to lipopolysaccharide
GO:0071223 cellular response to lipoteichoic acid
GO:0071224 cellular response to peptidoglycan
GO:0071316 cellular response to nicotine
GO:0071347 cellular response to interleukin-1
GO:0071354 cellular response to interleukin-6
GO:0071356 cellular response to tumor necrosis factor
GO:1901222 regulation of NIK/NF-kappaB signaling
GO:1901223 negative regulation of NIK/NF-kappaB signaling
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1904385 cellular response to angiotensin
GO:2000630 positive regulation of miRNA metabolic process
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Cellular Component
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0033256 I-kappaB/NF-kappaB complex
GO:0035525 NF-kappaB p50/p65 complex
GO:0071159 NF-kappaB complex
No orthologs found for this gene
RANKL pathway
IL1 pathway
TCR pathway
BCR pathway
TWEAK pathway
TSLP pathway
KitReceptor pathway
EGFR1 pathway
Leptin pathway
TNFalpha pathway
Notch pathway
IL4 pathway
TSH pathway
IL2 pathway
FSH pathway
Prolactin pathway
Diseases associated with the TLR signaling cascade pathway
DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Death Receptor Signalling pathway
Cellular responses to external stimuli pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
p75 NTR receptor-mediated signalling pathway
Post-translational protein modification pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Regulated proteolysis of p75NTR pathway
FCERI mediated NF-kB activation pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
IkBA variant leads to EDA-ID pathway
Toll-Like Receptors Cascades pathway
NF-kB is activated and signals survival pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Cellular responses to stress pathway
Signaling by the B Cell Receptor (BCR) pathway
Interleukin-1 family signaling pathway
p75NTR signals via NF-kB pathway
Signaling by Interleukins pathway
The NLRP3 inflammasome pathway
Chromatin modifying enzymes pathway
Inflammasomes pathway
CLEC7A/inflammasome pathway pathway
Signal Transduction pathway
Metabolism of proteins pathway
Activation of NF-kappaB in B cells pathway
Interleukin-1 processing pathway
Immune System pathway
Transcriptional regulation of white adipocyte differentiation pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
Downstream signaling events of B Cell Receptor (BCR) pathway
TCR signaling pathway
Dectin-1 mediated noncanonical NF-kB signaling pathway
CLEC7A (Dectin-1) signaling pathway
Interleukin-1 signaling pathway
TRIF(TICAM1)-mediated TLR4 signaling pathway
Downstream TCR signaling pathway
TRAF6 mediated NF-kB activation pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
Innate Immune System pathway
Cellular Senescence pathway
Cytosolic sensors of pathogen-associated DNA pathway
MyD88 cascade initiated on plasma membrane pathway
DDX58/IFIH1-mediated induction of interferon-alpha/beta pathway
SUMOylation pathway
SUMOylation of immune response proteins pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Developmental Biology pathway
MyD88-independent TLR4 cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Senescence-Associated Secretory Phenotype (SASP) pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
SUMO E3 ligases SUMOylate target proteins pathway
Cytokine Signaling in Immune system pathway
Adaptive Immune System pathway
Disease pathway
PKMTs methylate histone lysines pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
RIP-mediated NFkB activation via ZBP1 pathway
Diseases of Immune System pathway
Chromatin organization pathway
Fc epsilon receptor (FCERI) signaling pathway
C-type lectin receptors (CLRs) pathway
CD209 (DC-SIGN) signaling pathway
MAPK signaling pathway pathway
Ras signaling pathway pathway
cAMP signaling pathway pathway
Chemokine signaling pathway pathway
NF-kappa B signaling pathway pathway
HIF-1 signaling pathway pathway
Sphingolipid signaling pathway pathway
Mitophagy pathway
PI3K-Akt signaling pathway pathway
Apoptosis pathway
Longevity regulating pathway pathway
Cellular senescence pathway
Osteoclast differentiation pathway
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
C-type lectin receptor signaling pathway pathway
IL-17 signaling pathway pathway
Th1 and Th2 cell differentiation pathway
Th17 cell differentiation pathway
T cell receptor signaling pathway pathway
B cell receptor signaling pathway pathway
TNF signaling pathway pathway
Neurotrophin signaling pathway pathway
Prolactin signaling pathway pathway
Adipocytokine signaling pathway pathway
Relaxin signaling pathway pathway
Insulin resistance pathway
Non-alcoholic fatty liver disease (NAFLD) pathway
AGE-RAGE signaling pathway in diabetic complications pathway
Cocaine addiction pathway
Epithelial cell signaling in Helicobacter pylori infection pathway
Shigellosis pathway
Salmonella infection pathway
Pertussis pathway
Legionellosis pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
Toxoplasmosis pathway
Amoebiasis pathway
Tuberculosis pathway
Hepatitis C pathway
Hepatitis B pathway
Measles pathway
Influenza A pathway
Human papillomavirus infection pathway
HTLV-I infection pathway
Kaposi's sarcoma-associated herpesvirus infection pathway
Herpes simplex infection pathway
Epstein-Barr virus infection pathway
Pathways in cancer pathway
Transcriptional misregulation in cancer pathway
Viral carcinogenesis pathway
Pancreatic cancer pathway
Prostate cancer pathway
Chronic myeloid leukemia pathway
Acute myeloid leukemia pathway
Small cell lung cancer pathway
Inflammatory bowel disease (IBD) pathway
Fluid shear stress and atherosclerosis pathway
TNF.owl pathway
B cell receptor signaling.owl pathway
IL-1 NFkB.owl pathway
TLR NFkB.owl pathway
HIV-1 Nef: Negative effector of Fas and TNF-alpha
p73 transcription factor network
Fc-epsilon receptor I signaling in mast cells
IL1-mediated signaling events
LPA receptor mediated events
CD40/CD40L signaling
IL23-mediated signaling events
Signaling events mediated by HDAC Class I
BCR signaling pathway
IL2 signaling events mediated by PI3K
IL12-mediated signaling events
Angiopoietin receptor Tie2-mediated signaling
Canonical NF-kappaB pathway
Ceramide signaling pathway
Glucocorticoid receptor regulatory network
Atypical NF-kappaB pathway
TNF receptor signaling pathway
Osteopontin-mediated events
UniProt Splice Variant
Entrez Gene
RefSeq NM_001145138 NM_001243984 NM_001243985 NM_021975 XM_011545206 XM_011545207
CCDS CCDS31609 CCDS44651 CCDS73322
RNA Seq Atlas