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REL REL proto-oncogene, NF-kB subunit [ Homo sapiens (human) ]

Gene ID: 5966, updated on 2-Sep-2018

Summary

Official Symbol
RELprovided by HGNC
Official Full Name
REL proto-oncogene, NF-kB subunitprovided by HGNC
Primary source
HGNC:HGNC:9954
See related
Ensembl:ENSG00000162924 MIM:164910; Vega:OTTHUMG00000129418
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
C-Rel
Summary
This gene encodes a protein that belongs to the Rel homology domain/immunoglobulin-like fold, plexin, transcription factor (RHD/IPT) family. Members of this family regulate genes involved in apoptosis, inflammation, the immune response, and oncogenic processes. This proto-oncogene plays a role in the survival and proliferation of B lymphocytes. Mutation or amplification of this gene is associated with B-cell lymphomas, including Hodgkin's lymphoma. Single nucleotide polymorphisms in this gene are associated with susceptibility to ulcerative colitis and rheumatoid arthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]
Expression
Ubiquitous expression in bone marrow (RPKM 13.2), appendix (RPKM 8.6) and 25 other tissues See more
Orthologs

Genomic context

See REL in Genome Data Viewer
Location:
2p16.1
Exon count:
12
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (60881495..60928171)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (61108709..61171410)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 632, pseudogene Neighboring gene long intergenic non-protein coding RNA 1185 Neighboring gene ribosomal protein L21 pseudogene 33 Neighboring gene RNA, U4 small nuclear 51, pseudogene Neighboring gene ribosomal protein S12 pseudogene 3 Neighboring gene non-POU domain containing, octamer-binding pseudogene 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
NHGRI GWA Catalog
A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3).
NHGRI GWA Catalog
A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
NHGRI GWA Catalog
A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.
NHGRI GWA Catalog
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
NHGRI GWA Catalog
Genome-wide association identifies multiple ulcerative colitis susceptibility loci.
NHGRI GWA Catalog
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
NHGRI GWA Catalog
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
NHGRI GWA Catalog
Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog
REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat specifically associates with c-Rel promoter to downregulate c-Rel expression in T cells PubMed
tat HIV-1 Tat upregulates c-rel and RelA transcription factor binding to the CD28-responsive element in the IL-8 promoter, leading to super-induction of IL-8 PubMed
tat HIV-1 Tat interacts with the cooperative rel/AP1 complex, downregulating its transactivation activity and leading to a decrease in IL-2 gene transcription PubMed
tat The c-rel protein is a strong activator of HIV-1 gene expression suggesting a possible interaction with HIV-1 Tat, however results from co-expression experiments did not detect synergy with Tat activation PubMed
Vpr vpr Overexpression of REL is induced by HIV-1 Vpr in the transfected 293T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Activation of NF-kappaB in B cells, organism-specific biosystem (from REACTOME)
    Activation of NF-kappaB in B cells, organism-specific biosystemDAG and calcium activate protein kinase C beta (PKC-beta, Kochs et al. 1991) which phosphorylates CARMA1 and other proteins (Sommer et al. 2005). Phosphorylated CARMA1 recruits BCL10 and MALT1 to for...
  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Atypical NF-kappaB pathway, organism-specific biosystem (from Pathway Interaction Database)
    Atypical NF-kappaB pathway, organism-specific biosystem
    Atypical NF-kappaB pathway
  • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
    B Cell Receptor Signaling Pathway, organism-specific biosystemThe functional B-cell receptor is a multi-protein complex consisting of an antigen binding subunit and a signaling subunit. The antigen binding subunit is the membrane bound immunoglobulin and the si...
  • Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystemSecond messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RA...
  • IL-1 signaling pathway, organism-specific biosystem (from WikiPathways)
    IL-1 signaling pathway, organism-specific biosystemThe IL-1 family of cytokines currently consists of 11 members which are encoded by distinct genes and includes IL-1?, IL-1?, and the IL-1 Receptor antagonist (IL-1RA). The major role of IL-1 type cyt...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Interferon type I signaling pathways, organism-specific biosystem (from WikiPathways)
    Interferon type I signaling pathways, organism-specific biosystemThe type I IFNs (IFN? family, IFN?, IFN?, IFN? and IFN?) all bind to and signal via the type I IFN receptor complex. The type I receptor consists of two main IFNAR1, IFNAR2c receptor chains and other...
  • Leptin signaling pathway, organism-specific biosystem (from WikiPathways)
    Leptin signaling pathway, organism-specific biosystemLeptin is a peptide hormone mainly synthesised and secreted from adipocytes. It is also expressed in other tissues including placenta, stomach and skeletal muscle. Leptin mediates its effects by bind...
  • Photodynamic therapy-induced NF-kB survival signaling, organism-specific biosystem (from WikiPathways)
    Photodynamic therapy-induced NF-kB survival signaling, organism-specific biosystemPhotodynamic therapy may induce a pro-inflammatory and angiogenic response mediated by NF-?B.
  • Ras signaling pathway, organism-specific biosystem (from KEGG)
    Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
  • Regulation of Androgen receptor activity, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of Androgen receptor activity, organism-specific biosystem
    Regulation of Androgen receptor activity
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
  • TNF alpha Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TNF alpha Signaling Pathway, organism-specific biosystemTumor necrosis factor alpha (TNF?) is a proinflammatory cytokine involved in various biological processes including regulation of cell proliferation, differentiation, apoptosis and immune response. T...
  • Toll-like Receptor Signaling, organism-specific biosystem (from WikiPathways)
    Toll-like Receptor Signaling, organism-specific biosystemThis pathway is based on the figure 1 of "Genetic variation in TLR or NFkappaB pathways and the risk of breast cancer: a case-control study" (see bibliography). TLR and NFkB are important in inflamma...
  • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
    Transcriptional misregulation in cancer, organism-specific biosystem
    Transcriptional misregulation in cancer
  • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
    Transcriptional misregulation in cancer, conserved biosystem
    Transcriptional misregulation in cancer
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
I-kappaB kinase/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
I-kappaB kinase/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
 
NIK/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of interferon-beta production IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of neuron death IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
Inferred from Expression Pattern
more info
PubMed 
positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
response to cytokine IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nucleoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription factor complex IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
proto-oncogene c-Rel
Names
oncogene REL, avian reticuloendotheliosis
v-rel avian reticuloendotheliosis viral oncogene homolog

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001291746.1NP_001278675.1  proto-oncogene c-Rel isoform 2

    See identical proteins and their annotated locations for NP_001278675.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC010733, BC143885, BG036646, HY123671
    Consensus CDS
    CCDS74515.1
    UniProtKB/Swiss-Prot
    Q04864
    Related
    ENSP00000377989.3, OTTHUMP00000201246, ENST00000394479.3, OTTHUMT00000325344
    Conserved Domains (2) summary
    cd07933
    Location:8179
    RHD-n_c-Rel; N-terminal sub-domain of the Rel homology domain (RHD) of c-Rel
    pfam16179
    Location:187282
    RHD_dimer; Rel homology dimerisation domain
  2. NM_002908.3NP_002899.1  proto-oncogene c-Rel isoform 1

    See identical proteins and their annotated locations for NP_002899.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC010733, BG036646, HY123671, X75042
    Consensus CDS
    CCDS1864.1
    UniProtKB/Swiss-Prot
    Q04864
    Related
    ENSP00000295025.7, OTTHUMP00000159786, ENST00000295025.12, OTTHUMT00000251576
    Conserved Domains (2) summary
    cd07933
    Location:8179
    RHD-n_c-Rel; N-terminal sub-domain of the Rel homology domain (RHD) of c-Rel
    pfam16179
    Location:187282
    RHD_dimer; Rel homology dimerization domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    60881495..60928171
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017004627.2XP_016860116.1  proto-oncogene c-Rel isoform X1

  2. XM_011533010.3XP_011531312.1  proto-oncogene c-Rel isoform X2

    Conserved Domains (2) summary
    pfam16179
    Location:89184
    RHD_dimer; Rel homology dimerization domain
    cl08275
    Location:281
    RHD-n; N-terminal sub-domain of the Rel homology domain (RHD)
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