InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RELA

Summary

InnateDB Protein

IDBP-295136.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RELA

Protein Name

v-rel reticuloendotheliosis viral oncogene homolog A (avian)

Synonyms

NFKB3; p65;

Species

Homo sapiens

Ensembl Protein

ENSP00000384273

InnateDB Gene

IDBG-57543 (RELA)

Protein Structure

UniProt Annotation

Function

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. {ECO:0000269PubMed:10928981, ECO:0000269PubMed:12748188, ECO:0000269PubMed:17000776, ECO:0000269PubMed:17620405, ECO:0000269PubMed:19058135, ECO:0000269PubMed:19103749, ECO:0000269PubMed:20547752}.

Subcellular Localization

Nucleus. Cytoplasm. Note=Colocalized with DDX1 in the nucleus upon TNF-alpha induction (By similarity). Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). Colocalizes with GFI1 in the nucleus after LPS stimulation. {ECO:0000250}.

Disease Associations

Note=A chromosomal aberration involving C11orf95 is found in more than two-thirds of supratentorial ependymomas. Translocation with C11orf95 produces a C11orf95-RELA fusion protein. C11orf95-RELA translocations are potent oncogenes that probably transform neural stem cells by driving an aberrant NF- kappa-B transcription program (PubMed:24553141). {ECO:0000269PubMed:24553141}.

Tissue Specificity

Comments

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

Protein Structure and Domains

PDB ID

InterPro

IPR000451 NF-kappa-B/Rel/Dorsal
IPR002909 IPT domain
IPR008967 p53-like transcription factor, DNA-binding
IPR011539 Rel homology domain
IPR014756 Immunoglobulin E-set

PFAM

PF01833
PF00554

PRINTS

PR00057

PIRSF

SMART

SM00429

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt