Gene: RELA - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | RELA | ||||||||||||||||
NCBI Gene ID | : | 5970 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | NF-kappa-B p65delta3 | NFKB, p65 SUBUNIT | NFKB3 | NUCLEAR FACTOR KAPPA-B, SUBUNIT 3 | nuclear factor NF-kappa-B p65 subunit | NUCLEAR FACTOR OF KAPPA LIGHT CHAIN GENE ENHANCER IN B CELLS 3 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 | p65 | RELA | TRANSCRIPTION FACTOR NFKB3 | transcription factor p65 | V-REL AVIAN RETICULOENDOTHELIOSIS VIRAL ONCOGENE HOMOLOG A | v-rel reticuloendotheliosis viral oncogene homolog A (avian) Source: GPSDB |
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Gene Homologs | : | dl (Drosophila melanogaster) | REL1 (Anopheles gambiae) | RELA (Bos taurus) | RELA (Canis lupus familiaris) | rela (Danio rerio) | RELA (Gallus gallus) | RELA (Homo sapiens) | RELA (Macaca mulatta) | Rela (Mus musculus) | Rela (Rattus norvegicus) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_001416 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
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Transcription factor p65 | Homo sapiens | Q04206 (UniProtKB/Swiss-Prot) | TF65_HUMAN (UniProtKB/Swiss-Prot) | NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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. | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
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1 | OB_009752 | Homo sapiens |
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Also known as NFKB3, RELA is a component of the NF-kappa-B complex, involved in oxidative pathways and a myriad of other processes. Its role in ageing is unclear, but the NF-kappa-B complex appears to be important in age-related changes in inflammation and maybe in other age-related processes too [0260]. In addition, age-related changes in NF-kappa-B have been reported in numerous tissues [0261]. Mice without RELA die at embryonic stages [0712]. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
# | Observation Stable ID | Homology Group Genes | #EGHG | Description | Source | Homology Source | |||||||||||||||||||||||||||||||||
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1 | OB_008165 |
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1 | The HomoloGene homology group 32064 contains 1 gene with experimental evidence for ageing relevance (RELA - Homo sapiens) and 9 other genes. | AgeFactDB Homology Analysis | HomoloGene homology group 32064 |
Sequences
TF65_HUMAN | Q04206 | Transcription factor p65 (Homo sapiens) from UniProtKB/Swiss-Prot Length: 551 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 550 TF65_HUMAN 1 MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS 551
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- Wu H, Lozano G:
NF-kappa B activation of p53. A potential mechanism for suppressing cell growth in response to stress.
J Biol Chem. 1994; 269: 20067-74.
PubMed (ID: 8051093)
MeSH Terms: NF-kappa B/metabolism; Transcriptional Activation; Tumor Suppressor Protein p53/genetics - Kim HJ, Kim KW, Yu BP, Chung HY:
The effect of age on cyclooxygenase-2 gene expression: NF-kappaB activation and IkappaBalpha degradation.
Free Radic Biol Med. 2000; 28: 683-92.
PubMed (ID: 10754263)
MeSH Terms: Aging/genetics; Aging/metabolism; DNA-Binding Proteins/metabolism; I-kappa B Proteins; Isoenzymes/genetics; NF-kappa B/metabolism; Prostaglandin-Endoperoxide Synthases/genetics - Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR:
Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation.
Nature. 2000; 406: 86-90.
PubMed (ID: 10894547), doi:10.1038/35017574
MeSH Terms: Calcium-Calmodulin-Dependent Protein Kinases/physiology; NF-kappa B/metabolism - Lavrovsky Y, Chatterjee B, Clark RA, Roy AK:
Role of redox-regulated transcription factors in inflammation, aging and age-related diseases.
Exp Gerontol. 2000; 35: 521-32.
PubMed (ID: 10978675)
MeSH Terms: Aging; Inflammation/etiology; Transcription Factors/physiology - Helenius M, Kyrylenko S, Vehviläinen P, Salminen A:
Characterization of aging-associated up-regulation of constitutive nuclear factor-kappa B binding activity.
Antioxid Redox Signal. 2001; 3: 147-56.
PubMed (ID: 11291593), doi:10.1089/152308601750100669
MeSH Terms: Aging/metabolism; Calcium-Binding Proteins; Liver/metabolism; NF-kappa B/metabolism - Zhang J, Johnston G, Stebler B, Keller ET:
Hydrogen peroxide activates NFkappaB and the interleukin-6 promoter through NFkappaB-inducing kinase.
Antioxid Redox Signal. 2001; 3: 493-504.
PubMed (ID: 11491660), doi:10.1089/15230860152409121
MeSH Terms: Hydrogen Peroxide/pharmacology; I-kappa B Proteins; Interleukin-6/genetics; NF-kappa B/metabolism; Oxidants/pharmacology; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases/physiology - Digicaylioglu M, Lipton SA:
Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades.
Nature. 2001; 412: 641-7.
PubMed (ID: 11493922), doi:10.1038/35088074
MeSH Terms: Apoptosis; Erythropoietin/physiology; NF-kappa B/metabolism; Neurons/metabolism; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins - Chen Lf , Fischle W, Verdin E, Greene WC:
Duration of nuclear NF-kappaB action regulated by reversible acetylation.
Science. 2001; 293: 1653-7.
PubMed (ID: 11533489), doi:10.1126/science.1062374
MeSH Terms: Cell Nucleus/metabolism; I-kappa B Proteins; NF-kappa B/metabolism - Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, Karin M, Lin A:
Inhibition of JNK activation through NF-kappaB target genes.
Nature. 2001; 414: 313-7.
PubMed (ID: 11713531), doi:10.1038/35104568
MeSH Terms: Mitogen-Activated Protein Kinases/metabolism; NF-kappa B/physiology; Tumor Necrosis Factor-alpha/physiology - Zhong H, May MJ, Jimi E, Ghosh S:
The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1.
Mol Cell. 2002; 9: 625-36.
PubMed (ID: 11931769)
MeSH Terms: Histone Deacetylases/metabolism; NF-kappa B/metabolism; Nuclear Proteins/metabolism; Saccharomyces cerevisiae Proteins; Trans-Activators/metabolism; Transcription, Genetic - Medicherla R, Leers-Sucheta S, Luo Y, Azhar S:
Age-dependent modulation of NF-kappaB expression in rat adrenal gland.
Mech Ageing Dev. 2002; 123: 1211-27.
PubMed (ID: 12020944)
MeSH Terms: Adrenal Glands/metabolism; Aging; Gene Expression; I-kappa B Proteins; Lipopolysaccharides/pharmacology; NF-kappa B/genetics - Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D:
Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.
Nature. 1995; 376: 167-70.
PubMed (ID: 7603567), doi:10.1038/376167a0
MeSH Terms: Liver Diseases/embryology; NF-kappa B/deficiency; Transcription Factors - Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG:
Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein.
Cell. 2002; 110: 55-67.
PubMed (ID: 12150997)
MeSH Terms: Adaptor Proteins, Signal Transducing; Amyloid beta-Protein Precursor/physiology; Antigens, CD; Interleukin-1/physiology; MAP Kinase Kinase Kinase 1; Membrane Glycoproteins/genetics; NF-kappa B/physiology; Nuclear Proteins/physiology; Proto-Oncogene Proteins; Repressor Proteins/physiology - Giardina C, Hubbard AK:
Growing old with nuclear factor-kappaB.
Cell Stress Chaperones. 2002; 7: 207-12.
PubMed (ID: 12380689), PubMed Central (ID: PMC514819)
MeSH Terms: Aging/physiology; NF-kappa B/physiology - Tong L, Toliver-Kinsky T, Edwards M, Rassin DK, Werrbach-Perez K, Perez-Polo JR:
Attenuated transcriptional responses to oxidative stress in the aged rat brain.
J Neurosci Res. 2002; 70: 318-26.
PubMed (ID: 12391591), doi:10.1002/jnr.10428
MeSH Terms: Aging/metabolism; Brain Diseases/metabolism; Brain/metabolism; DNA-(Apurinic or Apyrimidinic Site) Lyase; DNA-Binding Proteins/metabolism; Down-Regulation/genetics; Oxidative Stress/physiology; Transcription Factor AP-1/metabolism; Transcription Factors/metabolism - Toliver-Kinsky T, Rassin D, Perez-Polo JR:
NF-kappaB activity decreases in basal forebrain of young and aged rats after hyperoxia.
Neurobiol Aging. 2002; 23: 899-905.
PubMed (ID: 12392794)
MeSH Terms: Aging/metabolism; Hyperoxia/metabolism; NF-kappa B/metabolism; Prosencephalon/metabolism - Hoffmann A, Levchenko A, Scott ML, Baltimore D:
The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation.
Science. 2002; 298: 1241-5.
PubMed (ID: 12424381), doi:10.1126/science.1071914
MeSH Terms: DNA-Binding Proteins/metabolism; Gene Expression Regulation; I-kappa B Proteins/metabolism; NF-kappa B/metabolism; Proto-Oncogene Proteins/metabolism; Signal Transduction - Kim HJ, Jung KJ, Yu BP, Cho CG, Choi JS, Chung HY:
Modulation of redox-sensitive transcription factors by calorie restriction during aging.
Mech Ageing Dev. 2002; 123: 1589-95.
PubMed (ID: 12470896)
MeSH Terms: Aging/metabolism; Caloric Restriction; Transcription Factors/metabolism - Wu D, Marko M, Claycombe K, Paulson KE, Meydani SN:
Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity.
J Biol Chem. 2003; 278: 10983-92.
PubMed (ID: 12529332), doi:10.1074/jbc.M207470200
MeSH Terms: Aging/metabolism; Ceramides/pharmacology; Gene Expression Regulation, Enzymologic/drug effects; Isoenzymes/genetics; Macrophages, Peritoneal/drug effects; NF-kappa B/metabolism; Prostaglandin-Endoperoxide Synthases/genetics; Up-Regulation/drug effects - Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW:
Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase.
EMBO J. 2004; 23: 2369-80.
PubMed (ID: 15152190), PubMed Central (ID: PMC423286), doi:10.1038/sj.emboj.7600244
MeSH Terms: Cell Survival/physiology; Histone Deacetylases/physiology; NF-kappa B/physiology; Sirtuins/physiology; Transcription, Genetic/physiology - Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L:
SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling.
J Biol Chem. 2005; 280: 40364-74.
PubMed (ID: 16183991), doi:10.1074/jbc.M509329200
MeSH Terms: Amyloid beta-Peptides/chemistry; Microglia/metabolism; NF-kappa B/metabolism; Sirtuins/physiology - Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschöp MH:
Sirt1 protects against high-fat diet-induced metabolic damage.
Proc Natl Acad Sci USA. 2008; 105: 9793-8.
PubMed (ID: 18599449), PubMed Central (ID: PMC2474520), doi:10.1073/pnas.0802917105
MeSH Terms: Dietary Fats/adverse effects; Metabolism; Nuclear Respiratory Factor 1/genetics; Sirtuins/physiology; Superoxide Dismutase/genetics - Helenius M, Hänninen M, Lehtinen SK, Salminen A:
Aging-induced up-regulation of nuclear binding activities of oxidative stress responsive NF-kB transcription factor in mouse cardiac muscle.
J Mol Cell Cardiol. 1996; 28: 487-98.
PubMed (ID: 9011632), doi:10.1006/jmcc.1996.0045
MeSH Terms: Aging/metabolism; I-kappa B Proteins; Myocardium/metabolism; NF-kappa B/metabolism - Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF:
SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span.
Cell. 2009; 136: 62-74.
PubMed (ID: 19135889), PubMed Central (ID: PMC2757125), doi:10.1016/j.cell.2008.10.052
MeSH Terms: Gene Expression Regulation, Developmental; NF-kappa B/metabolism; Sirtuins/metabolism; Transcription Factor RelA/metabolism - Kawahara TL, Rapicavoli NA, Wu AR, Qu K, Quake SR, Chang HY:
Dynamic chromatin localization of Sirt6 shapes stress- and aging-related transcriptional networks.
PLoS Genet. 2011; 7: e1002153.
PubMed (ID: 21738489), PubMed Central (ID: PMC3128103), doi:10.1371/journal.pgen.1002153
MeSH Terms: Aging/genetics; Chromatin/metabolism; Gene Regulatory Networks/genetics; Sirtuins/metabolism; Stress, Physiological/genetics - Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC, Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD:
NF-κB inhibition delays DNA damage-induced senescence and aging in mice.
J Clin Invest. 2012; 122: 2601-12.
PubMed (ID: 22706308), PubMed Central (ID: PMC3386805), doi:10.1172/JCI45785
MeSH Terms: Aging/drug effects; Cell Aging; DNA Damage; I-kappa B Kinase/antagonists & inhibitors; Transcription Factor RelA/metabolism - Korhonen P, Helenius M, Salminen A:
Age-related changes in the regulation of transcription factor NF-kappa B in rat brain.
Neurosci Lett. 1997; 225: 61-4.
PubMed (ID: 9143018)
MeSH Terms: Aging/metabolism; Brain/metabolism; Cell Nucleus/metabolism; Gene Expression Regulation/physiology; NF-kappa B/genetics; Nerve Tissue Proteins/genetics - Zhong H, Voll RE, Ghosh S:
Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
Mol Cell. 1998; 1: 661-71.
PubMed (ID: 9660950)
MeSH Terms: Cyclic AMP-Dependent Protein Kinases/metabolism; NF-kappa B/metabolism; Saccharomyces cerevisiae Proteins; Trans-Activators/metabolism; Transcriptional Activation/physiology - Dumont A, Hehner SP, Hofmann TG, Ueffing M, Dröge W, Schmitz ML:
Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-kappaB.
Oncogene. 1999; 18: 747-57.
PubMed (ID: 9989825), doi:10.1038/sj.onc.1202325
MeSH Terms: Antigens, CD95/metabolism; Apoptosis; Hydrogen Peroxide/pharmacology; I-kappa B Proteins; NF-kappa B/metabolism - Helenius M, Mäkeläinen L, Salminen A:
Attenuation of NF-kappaB signaling response to UVB light during cellular senescence.
Exp Cell Res. 1999; 248: 194-202.
PubMed (ID: 10094826), doi:10.1006/excr.1999.4393
MeSH Terms: Cell Aging/physiology; NF-kappa B/metabolism; Signal Transduction - Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB:
NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase.
Nature. 1999; 401: 82-5.
PubMed (ID: 10485710), doi:10.1038/43466
MeSH Terms: NF-kappa B/metabolism; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; Tumor Necrosis Factor-alpha/metabolism - Romashkova JA, Makarov SS:
NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling.
Nature. 1999; 401: 86-90.
PubMed (ID: 10485711), doi:10.1038/43474
MeSH Terms: Apoptosis; NF-kappa B/metabolism; Platelet-Derived Growth Factor/metabolism; Proto-Oncogene Proteins/metabolism; Signal Transduction
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot