InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-57547

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-295136

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-584460

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-592201

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-588733

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-587752

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-593001

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-595401

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-585959

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-596478

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-587948

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-586996

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-596871

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-596247

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-597339

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-584984

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-599944

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

IDBP-809547

v-rel avian reticuloendotheliosis viral oncogene homolog A

IDBP-809554

v-rel avian reticuloendotheliosis viral oncogene homolog A

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 11980335

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.

PMID 21209118

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.

PMID 21216972

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)

PMID 21419662

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)

PMID 23271966

A RELA isoform, p43, lacks the transactivation domain but is still able to potentiate anti-viral innate immunity.

PMID 23994473

During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.

PMID 25520509

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.

PMID 26055519

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.

PMID 26642243

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.

PMID 26296289

MIR223 regulates macrophage function by modulating cytokine production and NF-κB activation through inhibition of RELA phosphorylation and nuclear translocation.

PMID 26394554

Enterovirus 71 2C protein binds to RELA and IKBKB to inhibit NF-kB activation and evade innate immune defenses.

InnateDB Annotation from Orthologs

Summary

PMID 21209118

[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.

PMID 21216972

[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.

PMID 21419662

[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.

PMID 24023826

[Mus musculus] Tnfaip3 is regulated by both Nf-κB and p38-dependent Cebpb in response to LPS in macrophages.

PMID 24656046

[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 .

PMID 25783839

[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

ENSMUSG00000024927

View Gene Order

ENSBTAG00000013895

Not yet available

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

REACT_118563

RIP-mediated NFkB activation via ZBP1 pathway

REACT_118764

ZBP1(DAI) mediated induction of type I IFNs pathway

REACT_24969

TRAF6 mediated NF-kB activation pathway

REACT_25359

RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway

REACT_21281

TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway

REACT_6809

MyD88-independent cascade pathway

REACT_6783

Toll Like Receptor 3 (TLR3) Cascade pathway

REACT_6788

MyD88:Mal cascade initiated on plasma membrane pathway

REACT_8005

Toll Like Receptor TLR1:TLR2 Cascade pathway

REACT_8006

Toll Like Receptor TLR6:TLR2 Cascade pathway

REACT_25024

TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway

REACT_25222

MyD88 dependent cascade initiated on endosome pathway

REACT_9047

Toll Like Receptor 9 (TLR9) Cascade pathway

REACT_27215

MyD88 cascade initiated on plasma membrane pathway

REACT_9027

Toll Like Receptor 10 (TLR10) Cascade pathway

REACT_6894

Toll Like Receptor 4 (TLR4) Cascade pathway

REACT_9061

Toll Like Receptor 5 (TLR5) Cascade pathway

REACT_12555

Downstream TCR signaling pathway

REACT_23950

Interleukin-1 processing pathway

REACT_118656

Activation of NF-kappaB in B cells pathway

REACT_13443

Regulated proteolysis of p75NTR pathway

REACT_13696

NF-kB is activated and signals survival pathway

REACT_27161

Transcriptional regulation of white adipocyte differentiation pathway

REACT_120956

Cellular responses to stress pathway

REACT_111045

Developmental Biology pathway

REACT_163994

FCERI mediated NF-kB activation pathway

REACT_11061

Signalling by NGF pathway

REACT_9020

Toll Like Receptor 7/8 (TLR7/8) Cascade pathway

REACT_12526

TCR signaling pathway

REACT_75790

Cytokine Signaling in Immune system pathway

REACT_6802

Innate Immune System pathway

REACT_7980

Toll Like Receptor 2 (TLR2) Cascade pathway

REACT_6966

Toll-Like Receptors Cascades pathway

REACT_163936

Fc epsilon receptor (FCERI) signaling pathway

REACT_13776

p75 NTR receptor-mediated signalling pathway

REACT_13537

p75NTR signals via NF-kB pathway

REACT_111102

Signal Transduction pathway

REACT_75774

Adaptive Immune System pathway

REACT_163773

DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway

REACT_6900

Immune System pathway

REACT_169274

Cellular Senescence pathway

REACT_22232

Signaling by Interleukins pathway

REACT_6890

Activated TLR4 signalling pathway

REACT_169168

Senescence-Associated Secretory Phenotype (SASP) pathway

REACT_25281

TRIF-mediated TLR3/TLR4 signaling pathway

REACT_118823

Cytosolic sensors of pathogen-associated DNA pathway

REACT_118773

Signaling by the B Cell Receptor (BCR) pathway

REACT_118638

Downstream signaling events of B Cell Receptor (BCR) pathway

KEGG

hsa05221

Acute myeloid leukemia pathway

hsa05120

Epithelial cell signaling in Helicobacter pylori infection pathway

hsa04210

Apoptosis pathway

hsa04010

MAPK signaling pathway pathway

hsa05222

Small cell lung cancer pathway

hsa04662

B cell receptor signaling pathway pathway

hsa05215

Prostate cancer pathway

hsa04660

T cell receptor signaling pathway pathway

hsa04620

Toll-like receptor signaling pathway pathway

hsa05220

Chronic myeloid leukemia pathway

hsa04920

Adipocytokine signaling pathway pathway

hsa05212

Pancreatic cancer pathway

hsa04722

Neurotrophin signaling pathway pathway

hsa04062

Chemokine signaling pathway pathway

hsa05200

Pathways in cancer pathway

hsa04622

RIG-I-like receptor signaling pathway pathway

hsa04621

NOD-like receptor signaling pathway pathway

hsa04623

Cytosolic DNA-sensing pathway pathway

hsa05140

Leishmaniasis pathway

hsa05146

Amoebiasis pathway

hsa05142

Chagas disease (American trypanosomiasis) pathway

hsa04380

Osteoclast differentiation pathway

hsa05131

Shigellosis pathway

hsa05145

Toxoplasmosis pathway

hsa05160

Hepatitis C pathway

INOH

INOH website

CD4 T cell receptor signaling pathway

INOH website

IL-1 signaling pathway pathway

INOH website

Toll-like receptor signaling pathway pathway

INOH website

B cell receptor signaling pathway

INOH website

TNFR1 signaling pathway pathway

PID NCI

cd40_pathway

CD40/CD40L signaling

nfkappabatypicalpathway

Atypical NF-kappaB pathway

ceramide_pathway

Ceramide signaling pathway

lysophospholipid_pathway

LPA receptor mediated events

il1pathway

IL1-mediated signaling events

tnfpathway

TNF receptor signaling pathway

il12_2pathway

IL12-mediated signaling events

hdac_classi_pathway

Signaling events mediated by HDAC Class I

reg_gr_pathway

Glucocorticoid receptor regulatory network

p73pathway

p73 transcription factor network

bcr_5pathway

BCR signaling pathway

angiopoietinreceptor_pathway

Angiopoietin receptor Tie2-mediated signaling

il23pathway

IL23-mediated signaling events

nfkappabcanonicalpathway

Canonical NF-kappaB pathway

fcer1pathway

Fc-epsilon receptor I signaling in mast cells

il2_pi3kpathway

IL2 signaling events mediated by PI3K

hivnefpathway

HIV-1 Nef: Negative effector of Fas and TNF-alpha

avb3_opn_pathway

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