RELA
Transcription factor p65
Also known as: NFKB3, p65, TF65_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q04206
- Gene
- RELA
- Ensembl
- ENSG00000173039
- Chromosome
- 11
- Canonical length
- 551 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, RAS pathway related proteins, Transcription factors
- Subcellular location
- Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
551 residues, UniProt reviewed canonical sequence.
>Q04206|RELA
1 MDELFPLIFP AEPAQASGPY VEIIEQPKQR GMRFRYKCEG RSAGSIPGER STDTTKTHPT
61 IKINGYTGPG TVRISLVTKD PPHRPHPHEL VGKDCRDGFY EAELCPDRCI HSFQNLGIQC
121 VKKRDLEQAI SQRIQTNNNP FQVPIEEQRG DYDLNAVRLC FQVTVRDPSG RPLRLPPVLS
181 HPIFDNRAPN TAELKICRVN RNSGSCLGGD EIFLLCDKVQ KEDIEVYFTG PGWEARGSFS
241 QADVHRQVAI VFRTPPYADP SLQAPVRVSM QLRRPSDREL SEPMEFQYLP DTDDRHRIEE
301 KRKRTYETFK SIMKKSPFSG PTDPRPPPRR IAVPSRSSAS VPKPAPQPYP FTSSLSTINY
361 DEFPTMVFPS GQISQASALA PAPPQVLPQA PAPAPAPAMV SALAQAPAPV PVLAPGPPQA
421 VAPPAPKPTQ AGEGTLSEAL LQLQFDDEDL GALLGNSTDP AVFTDLASVD NSEFQQLLNQ
481 GIPVAPHTTE PMLMEYPEAI TRLVTGAQRP PDPAPAPLGA PGLPNGLLSG DEDFSSIADM
541 DFSALLSQIS SLocalizationUniProt · AlphaFold · HPA
Whether an antibody against RELA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.49
- Highest tissue expression
- 89 nTPM
Expression across tissuesHPA
Tissue
- blood vessel: 89 nTPM
- skeletal muscle: 76 nTPM
- bone marrow: 75 nTPM
- lung: 71 nTPM
- adipose tissue: 69 nTPM
- skin: 67 nTPM
Single-cell type
- esophageal apical cells: 156 nCPM
- neutrophils: 71 nCPM
- urothelial cells: 70 nCPM
- epididymal basal cells: 70 nCPM
- esophageal suprabasal cells: 65 nCPM
- megakaryocytes: 62 nCPM
Immune cell
- MAIT T-cell: 26 nTPM
- NK-cell: 25 nTPM
- gdT-cell: 23 nTPM
- memory CD8 T-cell: 22 nTPM
- T-reg: 21 nTPM
- neutrophil: 21 nTPM
Brain region
- medulla oblongata: 50 nTPM
- white matter: 42 nTPM
- cerebral cortex: 42 nTPM
- thalamus: 41 nTPM
- pons: 40 nTPM
- midbrain: 38 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about RELA.
Disease | AllUniProt
Conditions RELA is implicated in, by any mechanism.
- Autoinflammatory disease, familial, Behcet-like 3 (AIFBL3) MIM:618287
Disease | GeneticClinVar
42 pathogenic / likely-pathogenic of 529 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Mucocutaneous ulceration, chronic
- RELA-related disorder
- Childhood-onset schizophrenia
- Mucocutaneous ulceration
Disease | ImmuneIEDB
Conditions an epitope on RELA was assayed in.
- type 1 diabetes mellitus T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.18
- gnomAD pLI
- 1
- gnomAD missense Z
- 2.45
- DepMap mean gene effect
- -0.41
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- animal organ morphogenesis
- antiviral innate immune response
- canonical NF-kappaB signal transduction
- cellular defense response
- cellular response to angiotensin
- cellular response to hepatocyte growth factor stimulus
- cellular response to hydrogen peroxide
- cellular response to interleukin-1
- cellular response to interleukin-6
- cellular response to lipopolysaccharide
- cellular response to lipoteichoic acid
- cellular response to nicotine
- cellular response to peptidoglycan
- cellular response to tumor necrosis factor
- chromatin organization
- cytokine-mediated signaling pathway
- defense response to tumor cell
- defense response to virus
- DNA-templated transcription
- hair follicle development
- inflammatory response
- innate immune response
- interleukin-1-mediated signaling pathway
- intracellular signal transduction
- liver development
- negative regulation of angiogenesis
- negative regulation of apoptotic process
- negative regulation of cytokine production involved in inflammatory response
- negative regulation of DNA-templated transcription
- negative regulation of extrinsic apoptotic signaling pathway
- negative regulation of miRNA transcription
- negative regulation of non-canonical NF-kappaB signal transduction
- negative regulation of protein catabolic process
- negative regulation of protein sumoylation
- negative regulation of transcription by RNA polymerase II
- neuropeptide signaling pathway
- non-canonical NF-kappaB signal transduction
- nucleotide-binding oligomerization domain containing 2 signaling pathway
- positive regulation of amyloid-beta formation
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of cell population proliferation
- positive regulation of DNA-templated transcription
- positive regulation of gene expression
- positive regulation of interleukin-1 beta production
- positive regulation of interleukin-12 production
- positive regulation of interleukin-6 production
- positive regulation of interleukin-8 production
- positive regulation of leukocyte adhesion to vascular endothelial cell
- positive regulation of miRNA metabolic process
- positive regulation of miRNA transcription
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of transcription by RNA polymerase II
- positive regulation of vascular endothelial growth factor production
- postsynapse to nucleus signaling pathway
- prolactin signaling pathway
- protein catabolic process
- regulation of inflammatory response
- regulation of transcription by RNA polymerase II
- response to cytokine
- response to interleukin-1
- response to muramyl dipeptide
- response to muscle stretch
- response to UV-B
- toll-like receptor 4 signaling pathway
- toll-like receptor TLR6:TLR2 signaling pathway
- tumor necrosis factor-mediated signaling pathway
- vascular endothelial growth factor signaling pathway
Molecular functions
- actinin binding
- ankyrin repeat binding
- chromatin binding
- chromatin DNA binding
- DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- general transcription initiation factor binding
- histone deacetylase binding
- identical protein binding
- NF-kappaB binding
- peptide binding
- phosphate ion binding
- protein homodimerization activity
- protein kinase binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II core promoter sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- transcription cis-regulatory region binding
- transcription coactivator binding
- ubiquitin protein ligase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- NF-kappa-B/Dorsal
- IPT domain
- p53-like transcription factor, DNA-binding domain superfamily
- Rel homology domain, DNA-binding domain
- Immunoglobulin-like fold
- Immunoglobulin E-set
- Rel homology domain, conserved site
- Rel homology dimerisation domain
- NFkappaB IPT domain
- Rel homology domain (RHD), DNA-binding domain superfamily
- Rel homology DNA-binding domain
- Rel homology dimerisation domain
- Transcription factor p65, RHD domain, N-terminal
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of RELA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads RELA as an antibody target. Whether an autoantibody or antibody against RELA could matter depends on whether native RELA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
RELA is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label RELA as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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