GenAge entry for NFE2L2 (Homo sapiens)

Gene name (HAGRID: 283)

HGNC symbol
NFE2L2 
Aliases
NRF2 
Common name
nuclear factor, erythroid 2-like 2 

Potential relevance to the human ageing process

Main reason for selection
Entry selected based on evidence directly linking the gene product to ageing in a cellular model system
Description

Also known as NFE2L2, NF-E2-related factor 2 (NRF2) is a transcription factor that is activated by oxidative stress and electrophiles and has a role in inducing a number of antioxidative and carcinogen-detoxifying enzymes. Nrf2-deficient mice develop more tumors in response to carcinogens, and caloric restriction is ineffective in suppressing them in knockout mice. In contrast, caloric restriction remains effective in extending lifespan and increasing insulin sensitivity [2210]. In Nrf2-null mice fed a high-fat diet, the levels of hepatic triglycerides and cholesterol in liver were similar to wild type, while the levels of hepatic free fatty acid and malondialdehyde equivalents were higher, suggesting that Nrf2 inhibits lipid accumulation and oxidative stress in the mouse liver [2211].

In human fibroblasts, NRF2 shows a declined function in replicative senescence and its silencing leads to premature senescence. NRF2 activation results in the enhanced survival of cells following oxidative stress, whereas continuous treatment leads to lifespan extension of human fibroblasts [2212]. NRF2 has been also linked to several human age-related diseases, including atherosclerosis [2213], neurodegenerative diseases [2214], and cancer [2215]. It has been shown that progerin, an alternatively spliced product of LMNA involved in Hutchinson-Gilford progeria syndrome, sequesters NRF2, resulting in impaired NRF2 activity and increased oxidative stress. Suppressed NRF2 activity or increased oxidative stress is sufficient to recapitulate some of the accelerated aging effects seen in Hutchinson-Gilford progeria syndrome patients. Thus, NRF2 may play a role in accelerated human aging [4358].

Cytogenetic information

Cytogenetic band
2q31
Location
177,230,303 bp to 177,264,131 bp
Orientation
Minus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0006366; transcription from RNA polymerase II promoter
GO:0006954; inflammatory response
GO:0007568; aging
GO:0010499; proteasomal ubiquitin-independent protein catabolic process
GO:0010628; positive regulation of gene expression
GO:0010667; negative regulation of cardiac muscle cell apoptotic process
GO:0010976; positive regulation of neuron projection development
GO:0016567; protein ubiquitination
GO:0030194; positive regulation of blood coagulation
GO:0030968; endoplasmic reticulum unfolded protein response
GO:0034599; cellular response to oxidative stress
And 27 more GO terms
Cellular component: GO:0000785; chromatin
GO:0005634; nucleus
GO:0005737; cytoplasm
GO:0005813; centrosome
GO:0005829; cytosol
GO:0005886; plasma membrane
GO:0032993; protein-DNA complex
Function: GO:0000976; transcription regulatory region sequence-specific DNA binding
GO:0000980; RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0001102; RNA polymerase II activating transcription factor binding
GO:0001205; transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0001221; transcription cofactor binding
GO:0003677; DNA binding
GO:0003700; transcription factor activity, sequence-specific DNA binding
GO:0005515; protein binding
GO:0019904; protein domain specific binding
GO:0044212; transcription regulatory region DNA binding
Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
HDAC3, AKT1, MYC, NCOR1, PRKCD, BRCA1, CREBBP, GSK3B, PRKCA, HDAC1, MAPK8, JUN, MAPK9, HDAC2, SUMO1, NCOR2, CDKN1A, SQSTM1
STRING interaction network
Protein-Protein network diagram for NFE2L2

Retrieve sequences for NFE2L2

ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
nfe2l2a
Drosophila melanogaster
cnc
Mus musculus
Nfe2l2
Rattus norvegicus
Nfe2l2

In other databases

CellAge
  • This gene is present as NFE2L2

Selected references

External links

EPD
ORF Accession
NM_001145413
CDS Accession
NP_001138885
OMIM
600492
HPRD
02732
Ensembl
NFE2L2
UniProt/Swiss-Prot
NF2L2_HUMAN
GeneCards
NFE2L2
Entrez Gene
4780
UniGene
731566
GenAtlas
NFE2L2
Internet
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