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nuclear factor erythroid 2-related factor 2; NF-E2-related factor 2; NFE2-related factor 2; nuclear factor, erythroid derived 2, like 2; HEBP1 (NFE2L2 NRF2)
Function:
- transcription activator
- binds to & regulates transcription through the antioxidant response elements (ARE) in promoter regions of target genes
- role in coordinated up-regulation of genes in response to oxidative stress
- role in transcriptional activation of beta-globin cluster genes by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region
- may bind to the ARE as a heterodimer with maf protein
- may bind DNA with an unknown protein
- interacts with KEAP1 (cytoplasmic inhibitor)
- interacts via its leucine-zipper domain with the coiled-coil domain of PMF1
- phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NRF2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus (putative)
- phosphorylation of NFE2L2 by member of the MAP kinase family appears to prevent degradation by the 26S proteasome
Structure:
- acidic activation domain in the N-terminus
- DNA-binding domain in the C-terminus
- belongs to the bZIP family, CNC subfamily
- contains 1 bZIP domain
Compartment:
- cytoplasm, nucleus
- cytosolic under unstressed conditions
- translocates into the nucleus upon induction by electrophilic agents
Alternative splicing: named isoforms=2
Expression:
- widely expressed
- highest expression in adult muscle, kidney, lung, liver & in fetal muscle
Interactions
molecular events
General
DNA-binding protein
phosphoprotein
transcription factor (TF)
Properties
SIZE: entity length = 605 aa
MW = 68 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Ser phosphorylation site {S40}
DNA-binding motif
SITE: 502-517
leucine zipper
SITE: 519-539
FOR-BINDING-VIA: leucine zipper
Database Correlations
OMIM 600492
UniProt Q16236
Pfam PF00170
Kegg hsa:4780
References
- UniProt :accession Q16236
- Nguyen T et al
Regulatory mechanisms controlling gene expression mediated
by the antioxidant response element.
Annu Rev Pharmacol Toxicol. 2003;43:233-60. Review.
PMID: 12359864
- Dhakshinamoorthy S & Jaiswal AK
c-Maf negatively regulates ARE-mediated detoxifying enzyme
genes expression and anti-oxidant induction.
Oncogene 21:5301, 2002
PMID: 12149651