Nfe2l2
entrez
18024
canonical
uniprot
Q60795
canonical
ensembl
ENSMUSG00000015839
resolver
ensp
ENSMUSP00000099733
resolver
enst
ENSMUST00000102672
resolver
genesymbol
Nfe2l2
resolver
genesymbol_syn
Nrf2
resolver
uniprot
Q3UQK0
resolver
uniprot_entry
NF2L2_MOUSE
resolver
uniprot_sec
Q3UQK0
resolver
amino_acid_sequence
MMDLELPPPGLQSQQDMDLIDILWRQDIDLGVSREVFDFSQRQKDYELEKQKKLEKERQEQLQKEQEKAFFAQFQLDEETGEFLPIQPAQHIQTDTSGSASYSQVAHIPKQDALYFEDCMQLLAETFPFVDDHESLALDIPSHAESSVFTAPHQAQSLNSSLEAAMTDLSSIEQDMEQVWQELFSIPELQCLNTENKQLADTTAVPSPEATLTEMDSNYHFYSSISSLEKEVGNCGPHFLHGFEDSFSSILSTDDASQLTSLDSNPTLNTDFGDEFYSAFIAEPSDGGSMPSSAAISQSLSELLDGTIEGCDLSLCKAFNPKHAEGTMEFNDSDSGISLNTSPSRASPEHSVESSIYGDPPPGFSDSEMEELDSAPGSVKQNGPKAQPAHSPGDTVQPLSPAQGHSAPMRESQCENTTKKEVPVSPGHQKAPFTKDKHSSRLEAHLTRDELRAKALHIPFPVEKIINLPVDDFNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVELEQDLGHLKDEREKLLREKGENDRNLHLLKRRLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKPDTKKN
uniprot
proteins
function
FUNCTION: Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:12032331, PubMed:14517290, PubMed:14517554, PubMed:31398338, PubMed:9240432, PubMed:9887101). In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex (PubMed:14517290, PubMed:15282312, PubMed:15367669, PubMed:15581590). In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes (PubMed:12032331). The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes (PubMed:20173742, PubMed:20421418). The NFE2L2/NRF2 pathway is also activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival following endoplasmic reticulum stress (PubMed:14517290, PubMed:14978030). May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region (By similarity). Also plays an important role in the regulation of the innate immune response. It is a critical regulator of the innate immune response and survival during sepsis by maintaining redox homeostasis and restraint of the dysregulation of pro-inflammatory signaling pathways like MyD88-dependent and -independent and TNF signaling (PubMed:16585964). Suppresses macrophage inflammatory response by blocking pro-inflammatory cytokine transcription and the induction of IL6 (PubMed:27211851). Binds to the proximity of pro-inflammatory genes in macrophages and inhibits RNA Pol II recruitment. The inhibition is independent of the Nrf2-binding motif and reactive oxygen species level (PubMed:27211851). Represses antiviral cytosolic DNA sensing by suppressing the expression of the adapter protein STING1 and decreasing responsiveness to STING1 agonists while increasing susceptibility to infection with DNA viruses (By similarity). {ECO:0000250|UniProtKB:Q16236, ECO:0000269|PubMed:12032331, ECO:0000269|PubMed:14517290, ECO:0000269|PubMed:14517554, ECO:0000269|PubMed:14978030, ECO:0000269|PubMed:15282312, ECO:0000269|PubMed:15367669, ECO:0000269|PubMed:15581590, ECO:0000269|PubMed:16585964, ECO:0000269|PubMed:20173742, ECO:0000269|PubMed:20421418, ECO:0000269|PubMed:27211851, ECO:0000269|PubMed:31398338, ECO:0000269|PubMed:9240432, ECO:0000269|PubMed:9887101}.
uniprot
proteins
mass_dalton
66901
uniprot
proteins
mutagenesis
MUTAGEN 18..23; /note="DLIDIL->ALIDIA: Does not affect ubiquitination and degradation by the BCR(KEAP1) complex in the cytoplasm."; /evidence="ECO:0000269|PubMed:16790436"; MUTAGEN 19..23; /note="LIDIL->AIDIA: Abolished ubiquitination and degradation by the BCR(KEAP1) complex in the cytoplasm; when associated with A-30."; /evidence="ECO:0000269|PubMed:15581590"; MUTAGEN 29..31; /note="DLG->AGE: Abolished ubiquitination and degradation by the BCR(KEAP1) complex in the cytoplasm."; /evidence="ECO:0000269|PubMed:16790436"; MUTAGEN 30; /note="L->A: Abolished ubiquitination and degradation by the BCR(KEAP1) complex in the cytoplasm; when associated with 19-A--A-23."; /evidence="ECO:0000269|PubMed:15581590"; MUTAGEN 79..82; /note="Missing: Abolished interaction with KEAP1."; /evidence="ECO:0000269|PubMed:15282312, ECO:0000269|PubMed:16581765, ECO:0000269|PubMed:16790436
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated in the cytoplasm by the BCR(KEAP1) E3 ubiquitin ligase complex leading to its degradation (PubMed:15282312, PubMed:15367669, PubMed:15581590, PubMed:16790436, PubMed:20421418). In response to oxidative stress, electrophile metabolites, such as sulforaphane, modify KEAP1, leading to inhibit activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and activity (PubMed:15367669). In response to autophagy, the BCR(KEAP1) complex is inactivated (PubMed:20421418). {ECO:0000269|PubMed:15282312, ECO:0000269|PubMed:15367669, ECO:0000269|PubMed:15581590, ECO:0000269|PubMed:16790436, ECO:0000269|PubMed:20421418}.; PTM: Phosphorylated by EIF2AK3/PERK following unfolded protein response (UPR), promoting dissociation from its cytoplasmic inhibitor KEAP1, followed by its translocation into the nucleus (PubMed:14517290). Phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus (By similarity). {ECO:0000250|UniProtKB:O54968, ECO:0000269|PubMed:14517290}.; PTM: Acetylation at Lys-588 and Lys-591 increases nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence. {ECO:0000250|UniProtKB:Q16236}.; PTM: Glycation impairs transcription factor activity by preventing heterodimerization with small Maf proteins (PubMed:31398338). Deglycation by FN3K restores activity (PubMed:31398338). {ECO:0000269|PubMed:31398338}.
uniprot
proteins
protein_family
BZIP family
uniprot
proteins
protein_family
CNC subfamily
uniprot
proteins
pubmed
11248092
uniprot
proteins
pubmed
11583586
uniprot
proteins
pubmed
12032331
uniprot
proteins
pubmed
12968018
uniprot
proteins
pubmed
14517290
uniprot
proteins
pubmed
14517554
uniprot
proteins
pubmed
14978030
uniprot
proteins
pubmed
15282312
uniprot
proteins
pubmed
15367669
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15581590
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16507366
uniprot
proteins
pubmed
16581765
uniprot
proteins
pubmed
16585964
uniprot
proteins
pubmed
16790436
uniprot
proteins
pubmed
17920186
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20173742
uniprot
proteins
pubmed
20421418
uniprot
proteins
pubmed
20498371
uniprot
proteins
pubmed
27211851
uniprot
proteins
pubmed
28842501
uniprot
proteins
pubmed
31398338
uniprot
proteins
pubmed
7726861
uniprot
proteins
pubmed
8943040
uniprot
proteins
pubmed
9240432
uniprot
proteins
pubmed
9887101
uniprot
proteins
sequence_length
597
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:14517290, ECO:0000269|PubMed:15367669, ECO:0000269|PubMed:9887101}. Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:12032331, ECO:0000269|PubMed:14517290, ECO:0000269|PubMed:14517554, ECO:0000269|PubMed:9887101}. Note=Cytosolic under unstressed conditions: ubiquitinated and degraded by the BCR(KEAP1) E3 ubiquitin ligase complex (PubMed:14517290, PubMed:15367669). Translocates into the nucleus upon induction by electrophilic agents that inactivate the BCR(KEAP1) E3 ubiquitin ligase complex (PubMed:14517290, PubMed:14517554). {ECO:0000269|PubMed:14517290, ECO:0000269|PubMed:14517554, ECO:0000269|PubMed:15367669}.
uniprot
proteins