RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian))

2002-01-01   Fei Chen 

Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA

Identity

HGNC
LOCATION
11q13.1
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CMCU,NFKB3,p65
FUSION GENES

DNA/RNA

Description

The gene encoding human RelA has 10 exons spanning 8.1 kb. The shorter variants of RelA (p65d) can be generated by alternative splicing of intron 1, 6, or 7. The p65d1 lacks codons for amino acids 222 to 231 and p65d2 lacks codons for amino acids 13 to 25 of the conserved Rel homology domain. An additional alternative splicing form of p65, p65d3 has been identified in a non-small-cell lung carcinoma cell line that lacks codons for amino acids 187 to 293 of the Rel homology domain.

Proteins

Expression

wide.

Localisation

cytosol, nuclei after activation.

Function

regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, cell apoptosis, and initiation or acceleration of tumorigenesis. The p50/RelA complex is the most abundant NF-kB complex in all type tissues or cells. Interaction with: members of IkB family and Rel family; GR; HDAC3; CREB; p300; Sp1, Egr1; AES; TFIIB.

Implicated in

Entity name
cancer, autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, HTLV-1 infection, and AIDS.
Oncogenesis
Chromosomal rearrangement or point mutation of relA gene has been implicated infrequently in human lymphoid tumors. A t(11;14)(q14;q32?) chromosomal translocation was described in 4 cases of lymphoproliferative disorders (LPD), which possibly involved p65 gene rearrangement. Gene amplification or increased expression of relA has also been noted in some cases of squamous carcinomas of head and neck, and in adenocarcinomas of breast and stomach.

Bibliography

Pubmed IDLast YearTitleAuthors
87175281996The NF-kappa B and I kappa B proteins: new discoveries and insights.Baldwin AS Jr et al
82811531993Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing.Deloukas P et al
95971301998NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.Ghosh S et al
106024681999Aberrant rel/nfkb genes and activity in human cancer.Rayet B et al
5822931979A new characteristic karyotypic anomaly in lymphoproliferative disorders.Van Den Berghe H et al
96609501998Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.Zhong H et al

Other Information

Locus ID:

NCBI: 5970
MIM: 164014
HGNC: 9955
Ensembl: ENSG00000173039

Variants:

dbSNP: 5970
ClinVar: 5970
TCGA: ENSG00000173039
COSMIC: RELA

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000173039ENST00000308639Q04206
ENSG00000173039ENST00000406246Q04206
ENSG00000173039ENST00000525658E9PSE4
ENSG00000173039ENST00000525693Q2TAM5
ENSG00000173039ENST00000526257H0YCB4
ENSG00000173039ENST00000526283E9PKV4
ENSG00000173039ENST00000527749E9PI38
ENSG00000173039ENST00000527874E9PJR1
ENSG00000173039ENST00000527909E9PN69
ENSG00000173039ENST00000529389E9PNV4
ENSG00000173039ENST00000531238E9PNK5
ENSG00000173039ENST00000532879E9PMD5
ENSG00000173039ENST00000532999E9PKH5
ENSG00000173039ENST00000533187E9PRX2
ENSG00000173039ENST00000533546E9PM47
ENSG00000173039ENST00000534283E9PJZ9
ENSG00000173039ENST00000534558E9PQS6
ENSG00000173039ENST00000612991A0A087X0W8
ENSG00000173039ENST00000615805A0A087WVP0

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ApoptosisKEGGko04210
Toll-like receptor signaling pathwayKEGGko04620
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Adipocytokine signaling pathwayKEGGko04920
Epithelial cell signaling in Helicobacter pylori infectionKEGGko05120
Pancreatic cancerKEGGko05212
Prostate cancerKEGGko05215
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Small cell lung cancerKEGGko05222
MAPK signaling pathwayKEGGhsa04010
ApoptosisKEGGhsa04210
Toll-like receptor signaling pathwayKEGGhsa04620
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Adipocytokine signaling pathwayKEGGhsa04920
Epithelial cell signaling in Helicobacter pylori infectionKEGGhsa05120
ShigellosisKEGGhsa05131
Pathways in cancerKEGGhsa05200
Pancreatic cancerKEGGhsa05212
Prostate cancerKEGGhsa05215
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Small cell lung cancerKEGGhsa05222
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
RIG-I-like receptor signaling pathwayKEGGko04622
RIG-I-like receptor signaling pathwayKEGGhsa04622
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Cytosolic DNA-sensing pathwayKEGGko04623
Cytosolic DNA-sensing pathwayKEGGhsa04623
LeishmaniasisKEGGko05140
LeishmaniasisKEGGhsa05140
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
AmoebiasisKEGGko05146
AmoebiasisKEGGhsa05146
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
MeaslesKEGGko05162
MeaslesKEGGhsa05162
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Influenza AKEGGko05164
Influenza AKEGGhsa05164
PertussisKEGGko05133
PertussisKEGGhsa05133
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
LegionellosisKEGGko05134
LegionellosisKEGGhsa05134
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Cocaine addictionKEGGhsa05030
Cocaine addictionKEGGko05030
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
HIF-1 signaling pathwayKEGGhsa04066
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Inflammatory bowel disease (IBD)KEGGhsa05321
Inflammatory bowel disease (IBD)KEGGko05321
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Ras signaling pathwayKEGGhsa04014
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Toll-like receptor signalingKEGGhsa_M00686
Toll-like receptor signalingKEGGM00686
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
DiseaseREACTOMER-HSA-1643685
Diseases of Immune SystemREACTOMER-HSA-5260271
Diseases associated with the TLR signaling cascadeREACTOMER-HSA-5602358
IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)REACTOMER-HSA-5603027
IkBA variant leads to EDA-IDREACTOMER-HSA-5603029
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
TCR signalingREACTOMER-HSA-202403
Downstream TCR signalingREACTOMER-HSA-202424
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
Activation of NF-kappaB in B cellsREACTOMER-HSA-1169091
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
TAK1 activates NFkB by phosphorylation and activation of IKKs complexREACTOMER-HSA-445989
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathwaysREACTOMER-HSA-168928
TRAF6 mediated NF-kB activationREACTOMER-HSA-933542
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
ZBP1(DAI) mediated induction of type I IFNsREACTOMER-HSA-1606322
RIP-mediated NFkB activation via ZBP1REACTOMER-HSA-1810476
DEx/H-box helicases activate type I IFN and inflammatory cytokines productionREACTOMER-HSA-3134963
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated NF-kB activationREACTOMER-HSA-2871837
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CLEC7A (Dectin-1) signalingREACTOMER-HSA-5607764
Dectin-1 mediated noncanonical NF-kB signalingREACTOMER-HSA-5607761
CLEC7A/inflammasome pathwayREACTOMER-HSA-5660668
CD209 (DC-SIGN) signalingREACTOMER-HSA-5621575
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-1 processingREACTOMER-HSA-448706
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
p75 NTR receptor-mediated signallingREACTOMER-HSA-193704
p75NTR signals via NF-kBREACTOMER-HSA-193639
NF-kB is activated and signals survivalREACTOMER-HSA-209560
Regulated proteolysis of p75NTRREACTOMER-HSA-193692
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of white adipocyte differentiationREACTOMER-HSA-381340
Cellular responses to stressREACTOMER-HSA-2262752
Cellular SenescenceREACTOMER-HSA-2559583
Senescence-Associated Secretory Phenotype (SASP)REACTOMER-HSA-2559582
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841
Insulin resistanceKEGGhsa04931
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Longevity regulating pathwayKEGGhsa04211
Antifolate resistanceKEGGko01523
Antifolate resistanceKEGGhsa01523
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
IL-17 signaling pathwayKEGGko04657
Fluid shear stress and atherosclerosisKEGGko05418
IL-17 signaling pathwayKEGGhsa04657
Fluid shear stress and atherosclerosisKEGGhsa05418
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA131301952gefitinibChemicalClinicalAnnotationassociatedPD31664190
PA134992438CAMK1DGenePathwayassociated
PA164925725Toxic liver diseaseDiseaseClinicalAnnotationassociatedPD31664190
PA24684AKT1GenePathwayassociated
PA24685AKT2GenePathwayassociated
PA24686AKT3GenePathwayassociated
PA26048CAMK1GenePathwayassociated
PA26049CAMK1GGenePathwayassociated
PA283MAPK8GenePathwayassociated
PA30616MAPK1GenePathwayassociated
PA30622MAPK3GenePathwayassociated
PA33678PPP3CAGenePathwayassociated23922006
PA33679PPP3CBGenePathwayassociated23922006
PA33680PPP3CCGenePathwayassociated23922006
PA33681PPP3R1GenePathwayassociated23922006
PA33682PPP3R2GenePathwayassociated23922006
PA337STAT3GenePathwayassociated
PA33759PRKCAGenePathwayassociated
PA33761PRKCBGenePathwayassociated
PA33766PRKCGGenePathwayassociated
PA338STAT5AGenePathwayassociated
PA36183STAT1GenePathwayassociated
PA36184STAT2GenePathwayassociated
PA36185STAT4GenePathwayassociated
PA36186STAT5BGenePathwayassociated
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD31664190
PA444552HypertensionDiseaseLiterature, MultilinkAnnotationassociated24560520
PA90CAMK2AGenePathwayassociated
PA91CAMK2BGenePathwayassociated
PA92CAMK2DGenePathwayassociated
PA93CAMK2GGenePathwayassociated

References

Pubmed IDYearTitleCitations
154990232004Oscillations in NF-kappaB signaling control the dynamics of gene expression.437
202995482010Variation in transcription factor binding among humans.284
146905962003Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA.228
191037492009Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA.208
126900992003NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4.204
174787312007Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB.191
124198062003Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65.186
161357892005NF-kappaB RelA phosphorylation regulates RelA acetylation.176
182416762008NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK.161
211999552011Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein.161

Citation

Fei Chen

RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian))

Atlas Genet Cytogenet Oncol Haematol. 2002-01-01

Online version: http://atlasgeneticsoncology.org/gene/325/rela