NFE2L1
entrez
4779
canonical
uniprot
Q14494
canonical
ensembl
ENSG00000082641
resolver
ensp
ENSP00000350072
resolver
ensp
ENSP00000354855
resolver
ensp
ENSP00000355190
resolver
ensp
ENSP00000550129
resolver
ensp
ENSP00000550132
resolver
ensp
ENSP00000550133
resolver
ensp
ENSP00000607424
resolver
ensp
ENSP00000607425
resolver
enst
ENST00000361665
resolver
enst
ENST00000880070
resolver
genesymbol
NFE2L1
resolver
genesymbol_syn
HBZ17
resolver
genesymbol_syn
NRF1
resolver
genesymbol_syn
TCF11
resolver
hgnc
HGNC:7781
resolver
uniprot
D3DTU3
resolver
uniprot
D3DTU5
resolver
uniprot
J9JIE5
resolver
uniprot
Q12877
resolver
uniprot
Q96FN6
resolver
uniprot_entry
J9JIE5_HUMAN
resolver
uniprot_entry
NF2L1_HUMAN
resolver
uniprot_sec
D3DTU3
resolver
uniprot_sec
D3DTU5
resolver
uniprot_sec
Q12877
resolver
uniprot_sec
Q96FN6
resolver
amino_acid_sequence
MLSLKKYLTEGLLQFTILLSLIGVRVDVDTYLTSQLPPLREIILGPSSAYTQTQFHNLRNTLDGYGIHPKSIDLDNYFTARRLLSQVRALDRFQVPTTEVNAWLVHRDPEGSVSGSQPNSGLALESSSGLQDVTGPDNGVRESETEQGFGEDLEDLGAVAPPVSGDLTKEDIDLIDILWRQDIDLGAGREVFDYSHRQKEQDVEKELRDGGEQDTWAGEGAEALARNLLVDGETGESFPAQVPSGEDQTALSLEECLRLLEATCPFGENAEFPADISSITEAVPSESEPPALQNNLLSPLLTGTESPFDLEQQWQDLMSIMEMQAMEVNTSASEILYSAPPGDPLSTNYSLAPNTPINQNVSLHQASLGGCSQDFLLFSPEVESLPVASSSTLLPLAPSNSTSLNSTFGSTNLTGLFFPPQLNGTANDTAGPELPDPLGGLLDEAMLDEISLMDLAIEEGFNPVQASQLEEEFDSDSGLSLDSSHSPSSLSSSEGSSSSSSSSSSSSSSASSSASSSFSEEGAVGYSSDSETLDLEEAEGAVGYQPEYSKFCRMSYQDPAQLSCLPYLEHVGHNHTYNMAPSALDSADLPPPSALKKGSKEKQADFLDKQMSRDEHRARAMKIPFTNDKIINLPVEEFNELLSKYQLSEAQLSLIRDIRRRGKNKMAAQNCRKRKLDTILNLERDVEDLQRDKARLLREKVEFLRSLRQMKQKVQSLYQEVFGRLRDENGRPYSPSQYALQYAGDGSVLLIPRTMADQQARRQERKPKDRRK
uniprot
proteins
function
FUNCTION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20932482). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 (By similarity). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36 (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (PubMed:20932482). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}.; FUNCTION: [Transcription factor NRF1]: CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses (PubMed:8932385, PubMed:9421508). Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response (PubMed:8932385, PubMed:9421508). Activates or represses expression of target genes, depending on the context (PubMed:8932385, PubMed:9421508). Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess, such as CD36 (By similarity). In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (By similarity). Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1 and MT2 (By similarity). Plays an essential role during fetal liver hematopoiesis: probably has a protective function against oxidative stress and is involved in lipid homeostasis in the liver (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits (PubMed:20932482). Also involved in regulating glucose flux (By similarity). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (PubMed:15308669). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts. {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:8932385, ECO:0000269|PubMed:9421508}.
uniprot
proteins
mass_dalton
84704
uniprot
proteins
mutagenesis
MUTAGEN 101..106; /note="NAWLVH->AAAAAA: In m1; impaired protein cleavage."; /evidence="ECO:0000269|PubMed:24448410"; MUTAGEN 101..103; /note="NAW->AAA: In m2; impaired protein cleavage."; /evidence="ECO:0000269|PubMed:24448410"; MUTAGEN 103..104; /note="WL->AA: In m5; impaired protein cleavage."; /evidence="ECO:0000269|PubMed:24448410"; MUTAGEN 103; /note="W->A: In m3; impaired protein cleavage."; /evidence="ECO:0000269|PubMed:24448410"; MUTAGEN 104..106; /note="LVH->AAA: In m6; Slightly impaired protein cleavage."; /evidence="ECO:0000269|PubMed:24448410"; MUTAGEN 104; /note="L->A: In m4; Slightly impaired protein cleavage."; /evidence="ECO:0000269|PubMed:24448410"; MUTAGEN 599; /note="S->A: Impaired interaction with CEBPB."; /evidence="ECO:0000269|PubMed:15308669
uniprot
proteins
post_translational_modification
PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: Cleaved at Leu-104 by the aspartyl protease DDI2 following retrotranslocation, releasing the protein from the endoplasmic reticulum membrane and forming the transcription factor NRF1 that translocates into the nucleus (PubMed:24448410, PubMed:27528193, PubMed:27676297, PubMed:27676298). Ubiquitination is prerequisite for cleavage by aspartyl protease DDI2 (PubMed:27676298). {ECO:0000269|PubMed:24448410, ECO:0000269|PubMed:27528193, ECO:0000269|PubMed:27676297, ECO:0000269|PubMed:27676298}.; PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: N-glycosylated in normal conditions, when it has a single-pass type II membrane protein topology, with the DNA-binding domain facing the endoplasmic reticulum lumen (PubMed:20932482, PubMed:24448410, PubMed:24998528, PubMed:27528193). Deglycosylated during retrotranslocation to the cytosolic side of the membrane, to have a single-pass type III membrane protein topology with the major part of the protein facing the cytosol (PubMed:20932482, PubMed:24448410, PubMed:24998528). {ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410, ECO:0000269|PubMed:24998528, ECO:0000269|PubMed:27528193}.; PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: Ubiquitinated by the SCF(FBXW7) complex and SYVN1/HRD1, leading to its degradation by the proteasome (PubMed:20932482). Ubiquitinated during retrotranslocation to the cytosolic side of the membrane: ubiquitination does not lead to degradation and is required for processing by the aspartyl protease DDI2 and subsequent release from the endoplasmic reticulum membrane (PubMed:24998528, PubMed:27676298). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24998528, ECO:0000269|PubMed:27676298}.; PTM: [Transcription factor NRF1]: Phosphorylation by CK2 at Ser-528 inhibits transcription factor activity, possibly by affecting DNA-binding activity (By similarity). Phosphorylation at Ser-599 is required for interaction with CEBPB (PubMed:15308669). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669}.; PTM: [Transcription factor NRF1]: Ubiquitinated by the SCF(BTRC) complex in the nucleus, leading to its degradation by the proteasome. {ECO:0000250|UniProtKB:Q61985}.
uniprot
proteins
protein_family
BZIP family
uniprot
proteins
protein_family
CNC subfamily
uniprot
proteins
pubmed
15308669
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16687406
uniprot
proteins
pubmed
20932482
uniprot
proteins
pubmed
24448410
uniprot
proteins
pubmed
24998528
uniprot
proteins
pubmed
26947393
uniprot
proteins
pubmed
27528193
uniprot
proteins
pubmed
27676297
uniprot
proteins
pubmed
27676298
uniprot
proteins
pubmed
29983246
uniprot
proteins
pubmed
8001966
uniprot
proteins
pubmed
8036168
uniprot
proteins
pubmed
8248256
uniprot
proteins
pubmed
8932385
uniprot
proteins
pubmed
9421508
uniprot
proteins
sequence_length
772
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:16687406, ECO:0000269|PubMed:24448410, ECO:0000269|PubMed:24998528}; Single-pass type II membrane protein {ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:16687406, ECO:0000269|PubMed:24448410, ECO:0000269|PubMed:24998528}; Single-pass type III membrane protein {ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}. Note=In normal conditions, probably has a single-pass type II membrane protein topology, with the DNA-binding domain facing the endoplasmic reticulum lumen (PubMed:24448410). Following cellular stress, it is rapidly and efficiently retrotranslocated to the cytosolic side of the membrane, a process dependent on p97/VCP, to have a single-pass type III membrane protein topology with the major part of the protein facing the cytosol (PubMed:24448410). Retrotranslocated proteins are normally rapidly degraded by the proteasome and active species do not accumulate (PubMed:24448410). However, retrotranslocated protein NFE2L1 escapes degradation and is cleaved at Leu-104 by DDI2, releasing the protein from the endoplasmic reticulum membrane and forming the transcription factor NRF1 that translocates into the nucleus (PubMed:24448410). {ECO:0000269|PubMed:24448410}.; SUBCELLULAR LOCATION: [Transcription factor NRF1]: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:16687406, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24998528, ECO:0000269|PubMed:27528193}. Note=Translocates into the nucleus following cleavage of Endoplasmic reticulum membrane sensor NFE2L1 by aspartyl protease DDI2. {ECO:0000269|PubMed:24448410, ECO:0000269|PubMed:27528193}.
uniprot
proteins
transmembrane_region
TRANSMEM 7..24; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins