Homo sapiens Gene: RELA
Summary
InnateDB Gene IDBG-57543.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol RELA
Gene Name v-rel reticuloendotheliosis viral oncogene homolog A (avian)
Synonyms NFKB3; p65;
Species Homo sapiens
Ensembl Gene ENSG00000173039
Encoded Proteins
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel reticuloendotheliosis viral oncogene homolog A (avian)
v-rel avian reticuloendotheliosis viral oncogene homolog A
v-rel avian reticuloendotheliosis viral oncogene homolog A
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
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.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Rela is a subunit of NFKB and is not essential for virus-stimulated Ifnb expression, instead, Rela sustains autocrine Ifnb signaling prior to infection. The absence of Rela causes significant delays in Ifnb induction and consequently defective secondary antiviral gene expression. Rela maintains autocrine Ifnb signaling in uninfected cells, facilitates inflammatory and adaptive immune responses following infection, and promotes infected cell survival during this process.
[Mus musculus] Rela is critical for pulmonary host defense 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.
[Mus musculus] 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.
[Mus musculus] Tnfaip3 is regulated by both Nf-κB and p38-dependent Cebpb in response to LPS in macrophages.
[Mus musculus] The noncanonical NFκB pathway regulates histone modifications at the Ifnb1 promoter resulting in attenuated recruitment of Rela and histone demethylase, Kdm4a, to the Ifnb1 promoter. This provides a mechanism for regulating the induction of type I interferons .
[Mus musculus] Lysophosphatidic acid plays an anti-inflammatory role in macrophages by diminishing lipopolysaccharide-induced phosphorylation of Mapk14 and Akt1, as well as Rela nuclear translocation.
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
Transcripts
ENST00000308639 ENSP00000311508
ENST00000406246 ENSP00000384273
ENST00000525693 ENSP00000432537
ENST00000531484
ENST00000526283 ENSP00000435290
ENST00000532999 ENSP00000433526
ENST00000526257 ENSP00000431304
ENST00000529389 ENSP00000437137
ENST00000525658 ENSP00000434008
ENST00000533546 ENSP00000433144
ENST00000526738
ENST00000527909 ENSP00000432922
ENST00000534558 ENSP00000434372
ENST00000527749 ENSP00000436545
ENST00000529330
ENST00000532879 ENSP00000431153
ENST00000531238 ENSP00000434745
ENST00000527074
ENST00000525301
ENST00000533187 ENSP00000434098
ENST00000527874 ENSP00000435531
ENST00000525858
ENST00000534305
ENST00000532776
ENST00000534283 ENSP00000433616
ENST00000612991 ENSP00000483705
ENST00000615805 ENSP00000479572
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 570 experimentally validated interaction(s) in this database.
They are also associated with 108 interaction(s) predicted by orthology.
Experimentally validated
Total 570 [view]
Protein-Protein 407 [view]
Protein-DNA 157 [view]
Protein-RNA 0
DNA-DNA 6 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 108 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0001077 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0001078 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription
GO:0001205 RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0003705 RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0032403 protein complex binding
GO:0033613 activating transcription factor binding
GO:0042301 phosphate ion binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
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:0002224 toll-like receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006117 acetaldehyde metabolic process
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
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 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:0033590 response to cobalamin
GO:0034097 response to cytokine
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 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:0045084 positive regulation of interleukin-12 biosynthetic process
GO:0045087 innate immune response (InnateDB)
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:0048011 neurotrophin TRK receptor signaling pathway
GO:0050727 regulation of inflammatory response
GO:0050852 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:0070301 cellular response to hydrogen peroxide
GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0070555 response to interleukin-1
GO:0071222 cellular response to lipopolysaccharide
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:0071375 cellular response to peptide hormone stimulus
GO:2000630 positive regulation of miRNA metabolic process
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0043234 protein complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
Notch pathway
EGFR1 pathway
KitReceptor pathway
TNFalpha pathway
TCR pathway
BCR pathway
IL1 pathway
IL2 pathway
IL4 pathway
RANKL pathway
Leptin pathway
TSH pathway
TSLP pathway
FSH pathway
TWEAK pathway
Prolactin pathway
IL11 pathway
Oncostatin_M pathway
REACTOME
RIP-mediated NFkB activation via ZBP1 pathway
Cellular responses to stress pathway
MyD88 dependent cascade initiated on endosome pathway
Developmental Biology pathway
FCERI mediated NF-kB activation pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
TCR signaling pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
NF-kB is activated and signals survival pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated NF-kB activation pathway
Fc epsilon receptor (FCERI) signaling pathway
p75 NTR receptor-mediated signalling pathway
p75NTR signals via NF-kB pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Signal Transduction pathway
Regulated proteolysis of p75NTR pathway
Interleukin-1 processing pathway
Activation of NF-kappaB in B cells pathway
Adaptive Immune System pathway
DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Cellular Senescence pathway
Signaling by Interleukins pathway
Downstream TCR signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
Transcriptional regulation of white adipocyte differentiation pathway
Senescence-Associated Secretory Phenotype (SASP) pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
Signaling by the B Cell Receptor (BCR) pathway
Downstream signaling events of B Cell Receptor (BCR) pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
KEGG
MAPK signaling pathway pathway
Chemokine signaling pathway pathway
Apoptosis 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
T cell receptor signaling pathway pathway
B cell receptor signaling pathway pathway
Neurotrophin signaling pathway pathway
Adipocytokine signaling pathway pathway
Epithelial cell signaling in Helicobacter pylori infection pathway
Shigellosis pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
Toxoplasmosis pathway
Amoebiasis pathway
Hepatitis C pathway
Pathways in cancer pathway
Pancreatic cancer pathway
Prostate cancer pathway
Chronic myeloid leukemia pathway
Acute myeloid leukemia pathway
Small cell lung cancer pathway
INOH
TNFR1 signaling pathway pathway
CD4 T cell receptor signaling pathway
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
B cell receptor signaling pathway
PID BIOCARTA
Atm signaling pathway [Biocarta view]
The 41bb-dependent immune response [Biocarta view]
The information processing pathway at the ifn beta enhancer [Biocarta view]
Toll-like receptor pathway [Biocarta view]
Chaperones modulate interferon signaling pathway [Biocarta view]
Mechanism of gene regulation by peroxisome proliferators via ppara [Biocarta view]
Corticosteroids and cardioprotection [Biocarta view]
Nf-kb signaling pathway [Biocarta view]
Role of egf receptor transactivation by gpcrs in cardiac hypertrophy [Biocarta view]
Human cytomegalovirus and map kinase pathways [Biocarta view]
Tnfr2 signaling pathway [Biocarta view]
Acetylation and deacetylation of rela in nucleus [Biocarta view]
Inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages [Biocarta view]
Keratinocyte differentiation [Biocarta view]
Bone remodeling [Biocarta view]
Double stranded rna induced gene expression [Biocarta view]
Trefoil factors initiate mucosal healing [Biocarta view]
Signal transduction through il1r [Biocarta view]
Fmlp induced chemokine gene expression in hmc-1 cells [Biocarta view]
Cd40l signaling pathway [Biocarta view]
Hiv-1 nef: negative effector of fas and tnf [Biocarta view]
Ceramide signaling pathway [Biocarta view]
T cell receptor signaling pathway [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
Erythropoietin mediated neuroprotection through nf-kb [Biocarta view]
Influence of ras and rho proteins on g1 to s transition [Biocarta view]
Akt signaling pathway [Biocarta view]
Cadmium induces dna synthesis and proliferation in macrophages [Biocarta view]
PID NCI
CD40/CD40L signaling
Atypical NF-kappaB pathway
Ceramide signaling pathway
LPA receptor mediated events
IL1-mediated signaling events
TNF receptor signaling pathway
IL12-mediated signaling events
Signaling events mediated by HDAC Class I
Glucocorticoid receptor regulatory network
p73 transcription factor network
BCR signaling pathway
Angiopoietin receptor Tie2-mediated signaling
IL23-mediated signaling events
Canonical NF-kappaB pathway
Fc-epsilon receptor I signaling in mast cells
IL2 signaling events mediated by PI3K
HIV-1 Nef: Negative effector of Fas and TNF-alpha
Osteopontin-mediated events
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene
RefSeq NM_001145138 NM_001243984 NM_001243985 NM_021975
HUGO
OMIM
CCDS CCDS31609 CCDS44651 CCDS73322
HPRD
IMGT
EMBL
GenPept
RNA Seq Atlas