Homo sapiens Protein: RELA
InnateDB Protein IDBP-57547.7
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 ENSP00000311508
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
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]
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:0019901 protein kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0033613 activating transcription factor binding
GO:0042301 phosphate ion binding
GO:0042802 identical protein 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
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
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:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006954 inflammatory response
GO:0006968 cellular defense response
GO:0008284 positive regulation of cell proliferation
GO:0010033 response to organic substance
GO:0010224 response to UV-B
GO:0016032 viral process
GO:0019221 cytokine-mediated signaling pathway
GO:0031293 membrane protein intracellular domain proteolysis
GO:0032481 positive regulation of type I interferon production
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:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
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: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: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: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
Protein Structure and Domains
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
Post-translational Modifications
SwissProt Q04206
PhosphoSite PhosphoSite-Q04206
UniProt Splice Variant
Entrez Gene 5970
UniGene Hs.502875
RefSeq NP_001138610
OMIM 164014
HPRD 01241
EMBL AP001362 AY455868 BC033522 L19067 M62399 Z22948 Z22949 Z22950 Z22951 Z22953
GenPept AAA20946 AAA36408 AAH33522 AAR13863 CAA80524