Nfe2l1
entrez
18023
canonical
uniprot
Q61985
canonical
ensembl
ENSMUSG00000038615
resolver
ensp
ENSMUSP00000080467
resolver
ensp
ENSMUSP00000127804
resolver
ensp
ENSMUSP00000128527
resolver
ensp
ENSMUSP00000131585
resolver
enst
ENSMUST00000169828
resolver
genesymbol
Nfe2l1
resolver
genesymbol_syn
Nrf1
resolver
uniprot
E9Q038
resolver
uniprot
F6YBZ6
resolver
uniprot
O70234
resolver
uniprot
Q3U5L0
resolver
uniprot
Q3UFI8
resolver
uniprot
Q3V3M1
resolver
uniprot
Q6GTN8
resolver
uniprot_entry
F6YBZ6_MOUSE
resolver
uniprot_entry
NF2L1_MOUSE
resolver
uniprot_entry
Q3U5L0_MOUSE
resolver
uniprot_entry
Q3UFI8_MOUSE
resolver
uniprot_entry
Q3V3M1_MOUSE
resolver
uniprot_entry
Q6GTN8_MOUSE
resolver
uniprot_sec
E9Q038
resolver
uniprot_sec
O70234
resolver
amino_acid_sequence
MLSLKKYLTEGLLQFTILLSLIGVRVDVDTYLTSQLPPLREIILGPSSAYTQTQFHNLRNTLDGYGIHPKSIDLDNYFTARRLLSQVRALDRFQVPTTEVNAWLVHRDPEGSVSGSQPNSGLALESSSGLQDVTGPDNGVRESETEQGFGEDLEDLGAVAPPVSGDLTKEDIDLIDILWRQDIDLGAGREVFDYSHRQKEQDVDKELQDGREREDTWSGEGAEALARDLLVDGETGESFPAQFPADVSSIPEAVPSESESPALQNSLLSPLLTGTESPFDLEQQWQDLMSIMEMQAMEVNTSASEILYNAPPGDPLSTNYSLAPNTPINQNVSLHQASLGGCSQDFSLFSPEVESLPVASSSTLLPLVPSNSTSLNSTFGSTNLAGLFFPSQLNGTANDTSGPELPDPLGGLLDEAMLDEISLMDLAIEEGFNPVQASQLEEEFDSDSGLSLDSSHSPSSLSSSEGSSSSSSSSSSSSASSSASSSFSEEGAVGYSSDSETLDLEEAEGAVGYQPEYSKFCRMSYQDPSQLSCLPYLEHVGHNHTYNMAPSALDSADLPPPSTLKKGSKEKQADFLDKQMSRDEHRARAMKIPFTNDKIINLPVEEFNELLSKYQLSEAQLSLIRDIRRRGKNKMAAQNCRKRKLDTILNLERDVEDLQRDKARLLREKVEFLRSLRQMKQKVQSLYQEVFGRLRDEHGRPYSPSQYALQYAGDGSVLLIPRTMADQQARRQERKPKDRRK
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:20385086, PubMed:21536885, PubMed:23816881, PubMed:29149604). Constitutes a precursor of the transcription factor NRF1. Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20385086, PubMed:21536885, PubMed:23816881, PubMed:29149604). 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 (PubMed:29149604). 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 (PubMed:29149604). 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:20385086, PubMed:21536885, PubMed:23816881). {ECO:0000269|PubMed:20385086, ECO:0000269|PubMed:21536885, ECO:0000269|PubMed:23816881, ECO:0000269|PubMed:29149604}.; 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:10601325, PubMed:11342101, PubMed:16872277, PubMed:21911472, PubMed:23144760, PubMed:23816881, PubMed:29149604). 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:12808106, PubMed:15738389, PubMed:16872277, PubMed:21911472, PubMed:23144760, PubMed:23816881). Activates or represses expression of target genes, depending on the context (PubMed:12808106, PubMed:15738389, PubMed:16872277, PubMed:21911472, PubMed:23144760, PubMed:23816881). 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 (PubMed:29149604). 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 (PubMed:29149604). 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 (PubMed:10601325, PubMed:11342101, PubMed:12968018, PubMed:15738389, PubMed:18826952). 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 (PubMed:12808106, PubMed:15738389, PubMed:18826952, PubMed:22586274, PubMed:9501099). 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:20385086, PubMed:21536885, PubMed:23816881). Also involved in regulating glucose flux (PubMed:25041126). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (By similarity). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts (PubMed:17510056). {ECO:0000250|UniProtKB:Q14494, ECO:0000269|PubMed:10601325, ECO:0000269|PubMed:11342101, ECO:0000269|PubMed:12808106, ECO:0000269|PubMed:12968018, ECO:0000269|PubMed:15738389, ECO:0000269|PubMed:16872277, ECO:0000269|PubMed:17510056, ECO:0000269|PubMed:18826952, ECO:0000269|PubMed:20385086, ECO:0000269|PubMed:21536885, ECO:0000269|PubMed:21911472, ECO:0000269|PubMed:22586274, ECO:0000269|PubMed:23144760, ECO:0000269|PubMed:23816881, ECO:0000269|PubMed:25041126, ECO:0000269|PubMed:29149604, ECO:0000269|PubMed:9501099}.; FUNCTION: [Isoform 2]: Transcription factor that binds the antioxidant response elements (ARE) consensus sequence on promoters and activates their expression. {ECO:0000269|PubMed:23144760, ECO:0000269|PubMed:9580677}.; FUNCTION: [Isoform 3]: Transcription factor that binds the extended kappa 3 site of the TNF promoter after Fc gamma RIII stimulation and participates in the induction of this cytokine (PubMed:9580677). {ECO:0000269|PubMed:9580677}.
uniprot
proteins
mass_dalton
81575
uniprot
proteins
mutagenesis
MUTAGEN 350..354; /note="Missing: Abolishes interaction with FBXW7."; /evidence="ECO:0000269|PubMed:21953459"; MUTAGEN 448..451; /note="SGLS->AGLA: Abolishes ubiquitination and degradation by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:21911472"; MUTAGEN 496; /note="S->A: Does not affect phosphorylation by CK2."; /evidence="ECO:0000269|PubMed:23816881"; MUTAGEN 497; /note="S->A: Abolishes phosphorylation by CK2."; /evidence="ECO:0000269|PubMed:23816881"; MUTAGEN 499; /note="S->A: Does not affect phosphorylation by CK2."; /evidence="ECO:0000269|PubMed:23816881"; MUTAGEN 501; /note="T->A: Does not affect phosphorylation by CK2."; /evidence="ECO:0000269|PubMed:23816881
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. Ubiquitination is prerequisite for cleavage by aspartyl protease DDI2. {ECO:0000250|UniProtKB:Q14494}.; 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:17705787, PubMed:18990090). 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 (By similarity). {ECO:0000250|UniProtKB:Q14494, ECO:0000269|PubMed:17705787, ECO:0000269|PubMed:18990090}.; PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: Ubiquitinated by the SCF(FBXW7) complex and SYVN1/HRD1, leading to its degradation by the proteasome (PubMed:21911472, PubMed:21953459). 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 (By similarity). {ECO:0000250|UniProtKB:Q14494, ECO:0000269|PubMed:21911472, ECO:0000269|PubMed:21953459}.; PTM: [Transcription factor NRF1]: Phosphorylation by CK2 at Ser-497 inhibits transcription factor activity, possibly by affecting DNA-binding activity (PubMed:23816881, PubMed:9580677). Phosphorylation at Ser-568 is required for interaction with CEBPB (By similarity). {ECO:0000250|UniProtKB:Q14494, ECO:0000269|PubMed:23816881, ECO:0000269|PubMed:9580677}.; PTM: [Transcription factor NRF1]: Ubiquitinated by the SCF(BTRC) complex in the nucleus, leading to its degradation by the proteasome. {ECO:0000269|PubMed:21911472}.
uniprot
proteins
protein_family
BZIP family
uniprot
proteins
protein_family
CNC subfamily
uniprot
proteins
pubmed
10601325
uniprot
proteins
pubmed
11342101
uniprot
proteins
pubmed
12808106
uniprot
proteins
pubmed
12968018
uniprot
proteins
pubmed
15738389
uniprot
proteins
pubmed
16872277
uniprot
proteins
pubmed
17510056
uniprot
proteins
pubmed
17705787
uniprot
proteins
pubmed
18826952
uniprot
proteins
pubmed
18990090
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20385086
uniprot
proteins
pubmed
20629635
uniprot
proteins
pubmed
21536885
uniprot
proteins
pubmed
21554501
uniprot
proteins
pubmed
21911472
uniprot
proteins
pubmed
21953459
uniprot
proteins
pubmed
22586274
uniprot
proteins
pubmed
23144760
uniprot
proteins
pubmed
23816881
uniprot
proteins
pubmed
25041126
uniprot
proteins
pubmed
26268886
uniprot
proteins
pubmed
26947393
uniprot
proteins
pubmed
29149604
uniprot
proteins
pubmed
7759107
uniprot
proteins
pubmed
9087432
uniprot
proteins
pubmed
9501099
uniprot
proteins
pubmed
9580677
uniprot
proteins
sequence_length
741
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:16872277, ECO:0000269|PubMed:17705787, ECO:0000269|PubMed:18990090, ECO:0000269|PubMed:20629635, ECO:0000269|PubMed:21911472, ECO:0000269|PubMed:29149604}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q14494}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:16872277, ECO:0000269|PubMed:17705787, ECO:0000269|PubMed:18990090, ECO:0000269|PubMed:20629635, ECO:0000269|PubMed:21911472, ECO:0000269|PubMed:29149604}; Single-pass type III membrane protein {ECO:0000250|UniProtKB:Q14494}. Note=In normal conditions, probably has a single-pass type II membrane protein topology, with the DNA-binding domain facing the endoplasmic reticulum lumen (By similarity). 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 (By similarity). Retrotranslocated proteins are normally rapidly degraded by the proteasome and active species do not accumulate (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q14494}.; SUBCELLULAR LOCATION: [Transcription factor NRF1]: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:21911472, ECO:0000269|PubMed:23144760, ECO:0000269|PubMed:29149604}. Note=Translocates into the nucleus following cleavage of Endoplasmic reticulum membrane sensor NFE2L1 by aspartyl protease DDI2. {ECO:0000305|PubMed:29149604}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:23144760}. Nucleus {ECO:0000269|PubMed:23144760}.
uniprot
proteins
transmembrane_region
TRANSMEM 7..24; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins