NF2L1_HUMAN
ID NF2L1_HUMAN Reviewed; 772 AA.
AC Q14494; D3DTU3; D3DTU5; Q12877; Q96FN6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Endoplasmic reticulum membrane sensor NFE2L1 {ECO:0000305};
DE AltName: Full=Locus control region-factor 1 {ECO:0000303|PubMed:8036168};
DE Short=LCR-F1 {ECO:0000303|PubMed:8036168};
DE AltName: Full=Nuclear factor erythroid 2-related factor 1;
DE Short=NF-E2-related factor 1 {ECO:0000303|PubMed:16687406, ECO:0000303|PubMed:8248256};
DE Short=NFE2-related factor 1 {ECO:0000303|PubMed:16687406, ECO:0000303|PubMed:8248256};
DE AltName: Full=Nuclear factor, erythroid derived 2, like 1;
DE AltName: Full=Protein NRF1, p120 form {ECO:0000303|PubMed:24448410};
DE AltName: Full=Transcription factor 11 {ECO:0000303|PubMed:8001966};
DE Short=TCF-11 {ECO:0000303|PubMed:8001966};
DE Contains:
DE RecName: Full=Transcription factor NRF1 {ECO:0000305};
DE AltName: Full=Protein NRF1, p110 form {ECO:0000303|PubMed:24448410};
GN Name=NFE2L1;
GN Synonyms=HBZ17, NRF1 {ECO:0000303|PubMed:16687406,
GN ECO:0000303|PubMed:8248256}, TCF11 {ECO:0000303|PubMed:8001966};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=8248256; DOI=10.1073/pnas.90.23.11371;
RA Chan J.Y., Han X.-L., Kan Y.W.;
RT "Cloning of Nrf1, an NF-E2-related transcription factor, by genetic
RT selection in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:11371-11375(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8001966; DOI=10.1006/geno.1994.1428;
RA Luna L., Johnsen O., Skartlien A.H., Pedeutour F., Turc-Carel C., Prydz H.,
RA Kolstoe A.-B.;
RT "Molecular cloning of a putative novel human bZIP transcription factor on
RT chromosome 17q22.";
RL Genomics 22:553-562(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 326-772.
RX PubMed=8036168; DOI=10.1093/nar/22.12.2383;
RA Caterina J.J., Donze D., Sun C.W., Ciavatta D.J., Townes T.M.;
RT "Cloning and functional characterization of LCR-F1: a bZIP transcription
RT factor that activates erythroid-specific, human globin gene expression.";
RL Nucleic Acids Res. 22:2383-2391(1994).
RN [6]
RP FUNCTION, DNA-BINDING, AND INTERACTION WITH MAFF; MAFG AND MAFK.
RX PubMed=8932385; DOI=10.1093/nar/24.21.4289;
RA Johnsen O., Skammelsrud N., Luna L., Nishizawa M., Prydz H., Kolstoe A.B.;
RT "Small Maf proteins interact with the human transcription factor
RT TCF11/Nrf1/LCR-F1.";
RL Nucleic Acids Res. 24:4289-4297(1996).
RN [7]
RP FUNCTION, DNA-BINDING, AND INTERACTION WITH MAFG.
RX PubMed=9421508; DOI=10.1093/nar/26.2.512;
RA Johnsen O., Murphy P., Prydz H., Kolsto A.B.;
RT "Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-
RT site selection and regulation of transcription.";
RL Nucleic Acids Res. 26:512-520(1998).
RN [8]
RP FUNCTION, INTERACTION WITH CEBPB, AND PHOSPHORYLATION AT SER-599.
RX PubMed=15308669; DOI=10.1074/jbc.m405031200;
RA Narayanan K., Ramachandran A., Peterson M.C., Hao J., Kolstoe A.B.,
RA Friedman A.D., George A.;
RT "The CCAAT enhancer-binding protein (C/EBP)beta and Nrf1 interact to
RT regulate dentin sialophosphoprotein (DSPP) gene expression during
RT odontoblast differentiation.";
RL J. Biol. Chem. 279:45423-45432(2004).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KEAP1.
RX PubMed=16687406; DOI=10.1074/jbc.m602802200;
RA Wang W., Chan J.Y.;
RT "Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal
RT transmembrane domain. Inhibition of nuclear translocation and transacting
RT function.";
RL J. Biol. Chem. 281:19676-19687(2006).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=20932482; DOI=10.1016/j.molcel.2010.09.012;
RA Steffen J., Seeger M., Koch A., Krueger E.;
RT "Proteasomal degradation is transcriptionally controlled by TCF11 via an
RT ERAD-dependent feedback loop.";
RL Mol. Cell 40:147-158(2010).
RN [11]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, GLYCOSYLATION, AND
RP UBIQUITINATION.
RX PubMed=24998528; DOI=10.1016/j.cub.2014.06.004;
RA Sha Z., Goldberg A.L.;
RT "Proteasome-mediated processing of Nrf1 is essential for coordinate
RT induction of all proteasome subunits and p97.";
RL Curr. Biol. 24:1573-1583(2014).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION, PROTEOLYTIC
RP PROCESSING, AND MUTAGENESIS OF 101-ASN--HIS-106; 101-ASN--TRP-103; TRP-103;
RP 104-LEU--HIS-106 AND LEU-104.
RX PubMed=24448410; DOI=10.7554/elife.01856;
RA Radhakrishnan S.K., den Besten W., Deshaies R.J.;
RT "p97-dependent retrotranslocation and proteolytic processing govern
RT formation of active Nrf1 upon proteasome inhibition.";
RL Elife 3:E01856-E01856(2014).
RN [13]
RP PROTEOLYTIC PROCESSING.
RX PubMed=27676297; DOI=10.1016/j.cub.2016.08.008;
RA Vangala J.R., Sotzny F., Krueger E., Deshaies R.J., Radhakrishnan S.K.;
RT "Nrf1 can be processed and activated in a proteasome-independent manner.";
RL Curr. Biol. 26:R834-R835(2016).
RN [14]
RP PROTEOLYTIC PROCESSING, AND UBIQUITINATION.
RX PubMed=27676298; DOI=10.1016/j.cub.2016.08.030;
RA Sha Z., Goldberg A.L.;
RT "Reply to Vangala et al.: Complete inhibition of the proteasome reduces new
RT proteasome production by causing Nrf1 aggregation.";
RL Curr. Biol. 26:R836-R837(2016).
RN [15]
RP PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=27528193; DOI=10.7554/elife.18357;
RA Koizumi S., Irie T., Hirayama S., Sakurai Y., Yashiroda H., Naguro I.,
RA Ichijo H., Hamazaki J., Murata S.;
RT "The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome
RT dysfunction.";
RL Elife 5:0-0(2016).
RN [16]
RP REVIEW.
RX PubMed=26947393; DOI=10.1016/j.gene.2016.03.002;
RA Kim H.M., Han J.W., Chan J.Y.;
RT "Nuclear factor erythroid-2 like 1 (NFE2L1): structure, function and
RT regulation.";
RL Gene 584:17-25(2016).
RN [17]
RP INTERACTION WITH MOTS-C.
RX PubMed=29983246; DOI=10.1016/j.cmet.2018.06.008;
RA Kim K.H., Son J.M., Benayoun B.A., Lee C.;
RT "The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to
RT Regulate Nuclear Gene Expression in Response to Metabolic Stress.";
RL Cell Metab. 28:516-524(2018).
CC -!- FUNCTION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic
CC reticulum membrane sensor that translocates into the nucleus in
CC response to various stresses to act as a transcription factor
CC (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the
CC transcription factor NRF1 (By similarity). Able to detect various
CC cellular stresses, such as cholesterol excess, oxidative stress or
CC proteasome inhibition (PubMed:20932482). In response to stress, it is
CC released from the endoplasmic reticulum membrane following cleavage by
CC the protease DDI2 and translocates into the nucleus to form the
CC transcription factor NRF1 (By similarity). Acts as a key sensor of
CC cholesterol excess: in excess cholesterol conditions, the endoplasmic
CC reticulum membrane form of the protein directly binds cholesterol via
CC its CRAC motif, preventing cleavage and release of the transcription
CC factor NRF1, thereby allowing expression of genes promoting cholesterol
CC removal, such as CD36 (By similarity). Involved in proteasome
CC homeostasis: in response to proteasome inhibition, it is released from
CC the endoplasmic reticulum membrane, translocates to the nucleus and
CC activates expression of genes encoding proteasome subunits
CC (PubMed:20932482). {ECO:0000250|UniProtKB:Q61985,
CC ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}.
CC -!- FUNCTION: [Transcription factor NRF1]: CNC-type bZIP family
CC transcription factor that translocates to the nucleus and regulates
CC expression of target genes in response to various stresses
CC (PubMed:8932385, PubMed:9421508). Heterodimerizes with small-Maf
CC proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the
CC antioxidant response elements (AREs), which regulate expression of
CC genes involved in oxidative stress response (PubMed:8932385,
CC PubMed:9421508). Activates or represses expression of target genes,
CC depending on the context (PubMed:8932385, PubMed:9421508). Plays a key
CC role in cholesterol homeostasis by acting as a sensor of cholesterol
CC excess: in low cholesterol conditions, translocates into the nucleus
CC and represses expression of genes involved in defense against
CC cholesterol excess, such as CD36 (By similarity). In excess cholesterol
CC conditions, the endoplasmic reticulum membrane form of the protein
CC directly binds cholesterol via its CRAC motif, preventing cleavage and
CC release of the transcription factor NRF1, thereby allowing expression
CC of genes promoting cholesterol removal (By similarity). Critical for
CC redox balance in response to oxidative stress: acts by binding the AREs
CC motifs on promoters and mediating activation of oxidative stress
CC response genes, such as GCLC, GCLM, GSS, MT1 and MT2 (By similarity).
CC Plays an essential role during fetal liver hematopoiesis: probably has
CC a protective function against oxidative stress and is involved in lipid
CC homeostasis in the liver (By similarity). Involved in proteasome
CC homeostasis: in response to proteasome inhibition, mediates the
CC 'bounce-back' of proteasome subunits by translocating into the nucleus
CC and activating expression of genes encoding proteasome subunits
CC (PubMed:20932482). Also involved in regulating glucose flux (By
CC similarity). Together with CEBPB; represses expression of DSPP during
CC odontoblast differentiation (PubMed:15308669). In response to ascorbic
CC acid induction, activates expression of SP7/Osterix in osteoblasts.
CC {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669,
CC ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:8932385,
CC ECO:0000269|PubMed:9421508}.
CC -!- SUBUNIT: Interacts with KEAP1. {ECO:0000269|PubMed:16687406}.
CC -!- SUBUNIT: [Endoplasmic reticulum membrane sensor NFE2L1]: Interacts (via
CC CPD region) with FBXW7; leading to its ubiquitination and degradation
CC (By similarity). Interacts with SYVN1/HRD1; leading to its
CC ubiquitination and degradation (By similarity). Interacts (when
CC ubiquitinated) with DDI2; leading to its cleavage (PubMed:27528193).
CC {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:27528193}.
CC -!- SUBUNIT: [Transcription factor NRF1]: Interacts (via the bZIP domain)
CC with small MAF protein (MAFF, MAFG or MAFK); required for binding to
CC antioxidant response elements (AREs) on DNA (PubMed:8932385,
CC PubMed:9421508). Interacts (via Destruction motif) with BTRC; leading
CC to its ubiquitination and degradation (By similarity). Interacts with
CC CEBPB; the heterodimer represses expression of DSPP during odontoblast
CC differentiation (PubMed:15308669). Interacts with MOTS-c, a peptide
CC produced by the mitochondrially encoded 12S rRNA MT-RNR1
CC (PubMed:29983246). {ECO:0000250|UniProtKB:Q61985,
CC ECO:0000269|PubMed:15308669, ECO:0000269|PubMed:29983246,
CC ECO:0000269|PubMed:8932385, ECO:0000269|PubMed:9421508}.
CC -!- INTERACTION:
CC Q14494; Q9NS37: CREBZF; NbExp=3; IntAct=EBI-2804436, EBI-632965;
CC Q14494; Q14145: KEAP1; NbExp=6; IntAct=EBI-2804436, EBI-751001;
CC Q14494; Q9ULX9: MAFF; NbExp=2; IntAct=EBI-2804436, EBI-721128;
CC Q14494; O15525: MAFG; NbExp=4; IntAct=EBI-2804436, EBI-713514;
CC Q14494; Q14494: NFE2L1; NbExp=2; IntAct=EBI-2804436, EBI-2804436;
CC Q14494-2; O15525: MAFG; NbExp=3; IntAct=EBI-11745778, EBI-713514;
CC -!- SUBCELLULAR LOCATION: [Endoplasmic reticulum membrane sensor NFE2L1]:
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:16687406,
CC ECO:0000269|PubMed:24448410, ECO:0000269|PubMed:24998528}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:20932482,
CC ECO:0000269|PubMed:24448410}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16687406, ECO:0000269|PubMed:24448410,
CC ECO:0000269|PubMed:24998528}; Single-pass type III membrane protein
CC {ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}. Note=In
CC normal conditions, probably has a single-pass type II membrane protein
CC topology, with the DNA-binding domain facing the endoplasmic reticulum
CC lumen (PubMed:24448410). Following cellular stress, it is rapidly and
CC efficiently retrotranslocated to the cytosolic side of the membrane, a
CC process dependent on p97/VCP, to have a single-pass type III membrane
CC protein topology with the major part of the protein facing the cytosol
CC (PubMed:24448410). Retrotranslocated proteins are normally rapidly
CC degraded by the proteasome and active species do not accumulate
CC (PubMed:24448410). However, retrotranslocated protein NFE2L1 escapes
CC degradation and is cleaved at Leu-104 by DDI2, releasing the protein
CC from the endoplasmic reticulum membrane and forming the transcription
CC factor NRF1 that translocates into the nucleus (PubMed:24448410).
CC {ECO:0000269|PubMed:24448410}.
CC -!- SUBCELLULAR LOCATION: [Transcription factor NRF1]: Nucleus
CC {ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:16687406,
CC ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24998528,
CC ECO:0000269|PubMed:27528193}. Note=Translocates into the nucleus
CC following cleavage of Endoplasmic reticulum membrane sensor NFE2L1 by
CC aspartyl protease DDI2. {ECO:0000269|PubMed:24448410,
CC ECO:0000269|PubMed:27528193}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=TCF11 {ECO:0000303|PubMed:8001966};
CC IsoId=Q14494-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14494-2; Sequence=VSP_000579;
CC -!- DOMAIN: The cholesterol recognition/amino acid consensus (CRAC) region
CC directly binds cholesterol, as well as campesterol and 27-
CC hydroxycholesterol. Has much lower affinity for epicholesterol.
CC {ECO:0000250|UniProtKB:Q61985}.
CC -!- PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: Cleaved at Leu-104
CC by the aspartyl protease DDI2 following retrotranslocation, releasing
CC the protein from the endoplasmic reticulum membrane and forming the
CC transcription factor NRF1 that translocates into the nucleus
CC (PubMed:24448410, PubMed:27676297, PubMed:27676298, PubMed:27528193).
CC Ubiquitination is prerequisite for cleavage by aspartyl protease DDI2
CC (PubMed:27676298). {ECO:0000269|PubMed:24448410,
CC ECO:0000269|PubMed:27528193, ECO:0000269|PubMed:27676297,
CC ECO:0000269|PubMed:27676298}.
CC -!- PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: N-glycosylated in
CC normal conditions, when it has a single-pass type II membrane protein
CC topology, with the DNA-binding domain facing the endoplasmic reticulum
CC lumen (PubMed:20932482, PubMed:24998528, PubMed:24448410,
CC PubMed:27528193). Deglycosylated during retrotranslocation to the
CC cytosolic side of the membrane, to have a single-pass type III membrane
CC protein topology with the major part of the protein facing the cytosol
CC (PubMed:20932482, PubMed:24998528, PubMed:24448410).
CC {ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410,
CC ECO:0000269|PubMed:24998528, ECO:0000269|PubMed:27528193}.
CC -!- PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: Ubiquitinated by
CC the SCF(FBXW7) complex and SYVN1/HRD1, leading to its degradation by
CC the proteasome (PubMed:20932482). Ubiquitinated during
CC retrotranslocation to the cytosolic side of the membrane:
CC ubiquitination does not lead to degradation and is required for
CC processing by the aspartyl protease DDI2 and subsequent release from
CC the endoplasmic reticulum membrane (PubMed:24998528, PubMed:27676298).
CC {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482,
CC ECO:0000269|PubMed:24998528, ECO:0000269|PubMed:27676298}.
CC -!- PTM: [Transcription factor NRF1]: Phosphorylation by CK2 at Ser-528
CC inhibits transcription factor activity, possibly by affecting DNA-
CC binding activity (By similarity). Phosphorylation at Ser-599 is
CC required for interaction with CEBPB (PubMed:15308669).
CC {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669}.
CC -!- PTM: [Transcription factor NRF1]: Ubiquitinated by the SCF(BTRC)
CC complex in the nucleus, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q61985}.
CC -!- SIMILARITY: Belongs to the bZIP family. CNC subfamily. {ECO:0000305}.
CC -!- CAUTION: [Endoplasmic reticulum membrane sensor NFE2L1]: According to a
CC report, processing following retrotranslocation is dependent on the
CC proteasome (PubMed:24998528). However, it was later shown that
CC processing takes place in a proteasome-independent manner
CC (PubMed:27676297, PubMed:27676298). {ECO:0000269|PubMed:24998528,
CC ECO:0000269|PubMed:27676297, ECO:0000269|PubMed:27676298}.
CC -!- CAUTION: [Endoplasmic reticulum membrane sensor NFE2L1]: Its topology
CC is subject to discussion. According to some groups, it has a single-
CC pass type II membrane protein in normal conditions and is
CC retrotranslocated into a single-pass type III membrane protein in
CC response to stress (PubMed:24448410). According to other reports, it is
CC integrated into the endoplasmic reticulum membrane via multiple
CC membrane-spanning alpha-helices. {ECO:0000250|UniProtKB:Q61985,
CC ECO:0000269|PubMed:24448410}.
CC -!- CAUTION: [Transcription factor NRF1]: Was initially thought to activate
CC erythroid-specific, globin gene expression (PubMed:8036168). Knockout
CC experiments in mouse however demonstrated that it is not the case.
CC {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:8036168}.
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DR EMBL; L24123; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; X77366; CAA54555.1; -; mRNA.
DR EMBL; CH471109; EAW94762.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94763.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94764.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94765.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94766.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94767.1; -; Genomic_DNA.
DR EMBL; BC010623; AAH10623.1; -; mRNA.
DR EMBL; U08853; AAA20466.1; -; mRNA.
DR CCDS; CCDS11524.1; -. [Q14494-1]
DR CCDS; CCDS82150.1; -. [Q14494-2]
DR PIR; A49672; A49672.
DR PIR; A55004; A55004.
DR RefSeq; NP_001317191.1; NM_001330262.1. [Q14494-2]
DR RefSeq; NP_003195.1; NM_003204.2. [Q14494-1]
DR RefSeq; XP_005257467.1; XM_005257410.3. [Q14494-1]
DR RefSeq; XP_005257469.1; XM_005257412.3. [Q14494-2]
DR AlphaFoldDB; Q14494; -.
DR SMR; Q14494; -.
DR BioGRID; 110851; 35.
DR ComplexPortal; CPX-2473; bZIP transcription factor complex, BACH2-NFE2L1.
DR ComplexPortal; CPX-6569; bZIP transcription factor complex, ATF4-NFE2L1.
DR ComplexPortal; CPX-6790; bZIP transcription factor complex, ATF7-NFE2L1.
DR ComplexPortal; CPX-7015; bZIP transcription factor complex, BATF-NFE2L1.
DR CORUM; Q14494; -.
DR ELM; Q14494; -.
DR IntAct; Q14494; 29.
DR MINT; Q14494; -.
DR STRING; 9606.ENSP00000354855; -.
DR DrugBank; DB04147; Dodecyldimethylamine N-oxide.
DR GlyGen; Q14494; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q14494; -.
DR PhosphoSitePlus; Q14494; -.
DR BioMuta; NFE2L1; -.
DR DMDM; 3183180; -.
DR EPD; Q14494; -.
DR jPOST; Q14494; -.
DR MassIVE; Q14494; -.
DR MaxQB; Q14494; -.
DR PaxDb; Q14494; -.
DR PeptideAtlas; Q14494; -.
DR PRIDE; Q14494; -.
DR ProteomicsDB; 60003; -. [Q14494-1]
DR ProteomicsDB; 60004; -. [Q14494-2]
DR Antibodypedia; 30234; 252 antibodies from 32 providers.
DR DNASU; 4779; -.
DR Ensembl; ENST00000357480.9; ENSP00000350072.5; ENSG00000082641.16. [Q14494-2]
DR Ensembl; ENST00000362042.8; ENSP00000354855.3; ENSG00000082641.16. [Q14494-1]
DR Ensembl; ENST00000585291.5; ENSP00000461960.1; ENSG00000082641.16. [Q14494-2]
DR GeneID; 4779; -.
DR KEGG; hsa:4779; -.
DR MANE-Select; ENST00000362042.8; ENSP00000354855.3; NM_003204.3; NP_003195.1.
DR UCSC; uc002imz.5; human. [Q14494-1]
DR CTD; 4779; -.
DR DisGeNET; 4779; -.
DR GeneCards; NFE2L1; -.
DR HGNC; HGNC:7781; NFE2L1.
DR HPA; ENSG00000082641; Group enriched (heart muscle, skeletal muscle, tongue).
DR MIM; 163260; gene.
DR neXtProt; NX_Q14494; -.
DR OpenTargets; ENSG00000082641; -.
DR PharmGKB; PA31587; -.
DR VEuPathDB; HostDB:ENSG00000082641; -.
DR eggNOG; KOG3863; Eukaryota.
DR GeneTree; ENSGT00950000182892; -.
DR HOGENOM; CLU_024173_1_0_1; -.
DR InParanoid; Q14494; -.
DR OMA; LQAMDVN; -.
DR PhylomeDB; Q14494; -.
DR TreeFam; TF326681; -.
DR PathwayCommons; Q14494; -.
DR SignaLink; Q14494; -.
DR SIGNOR; Q14494; -.
DR BioGRID-ORCS; 4779; 44 hits in 1095 CRISPR screens.
DR ChiTaRS; NFE2L1; human.
DR GeneWiki; NFE2L1; -.
DR GenomeRNAi; 4779; -.
DR Pharos; Q14494; Tbio.
DR PRO; PR:Q14494; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14494; protein.
DR Bgee; ENSG00000082641; Expressed in gluteal muscle and 212 other tissues.
DR ExpressionAtlas; Q14494; baseline and differential.
DR Genevisible; Q14494; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006783; P:heme biosynthetic process; TAS:ProtInc.
DR GO; GO:0140467; P:integrated stress response signaling; IC:ComplexPortal.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0097201; P:negative regulation of transcription from RNA polymerase II promoter in response to stress; ISS:UniProtKB.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; ISS:UniProtKB.
DR GO; GO:1901329; P:regulation of odontoblast differentiation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR029847; NFE2L1.
DR InterPro; IPR008917; TF_DNA-bd_sf.
DR PANTHER; PTHR24411:SF31; PTHR24411:SF31; 1.
DR Pfam; PF03131; bZIP_Maf; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; SSF47454; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cholesterol metabolism; DNA-binding;
KW Endoplasmic reticulum; Glycoprotein; Lipid metabolism; Lipid-binding;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Signal-anchor; Steroid metabolism; Sterol metabolism; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..772
FT /note="Endoplasmic reticulum membrane sensor NFE2L1"
FT /id="PRO_0000076447"
FT CHAIN 104..772
FT /note="Transcription factor NRF1"
FT /evidence="ECO:0000305|PubMed:24448410"
FT /id="PRO_0000443103"
FT TRANSMEM 7..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 654..717
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 108..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 191..199
FT /note="Cholesterol recognition/amino acid consensus (CRAC)
FT region"
FT /evidence="ECO:0000250|UniProtKB:Q61985"
FT REGION 379..383
FT /note="CPD"
FT /evidence="ECO:0000250|UniProtKB:Q61985"
FT REGION 470..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 582..613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 656..675
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 682..696
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 476..480
FT /note="Destruction motif"
FT /evidence="ECO:0000250|UniProtKB:Q61985"
FT COMPBIAS 112..141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..613
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 103..104
FT /note="Cleavage; by DDI2"
FT /evidence="ECO:0000269|PubMed:24448410"
FT MOD_RES 528
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q61985"
FT MOD_RES 599
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:15308669"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 242..271
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8248256"
FT /id="VSP_000579"
FT VARIANT 63
FT /note="D -> H (in dbSNP:rs2229367)"
FT /id="VAR_048440"
FT MUTAGEN 101..106
FT /note="NAWLVH->AAAAAA: In m1; impaired protein cleavage."
FT /evidence="ECO:0000269|PubMed:24448410"
FT MUTAGEN 101..103
FT /note="NAW->AAA: In m2; impaired protein cleavage."
FT /evidence="ECO:0000269|PubMed:24448410"
FT MUTAGEN 103..104
FT /note="WL->AA: In m5; impaired protein cleavage."
FT /evidence="ECO:0000269|PubMed:24448410"
FT MUTAGEN 103
FT /note="W->A: In m3; impaired protein cleavage."
FT /evidence="ECO:0000269|PubMed:24448410"
FT MUTAGEN 104..106
FT /note="LVH->AAA: In m6; Slightly impaired protein
FT cleavage."
FT /evidence="ECO:0000269|PubMed:24448410"
FT MUTAGEN 104
FT /note="L->A: In m4; Slightly impaired protein cleavage."
FT /evidence="ECO:0000269|PubMed:24448410"
FT MUTAGEN 599
FT /note="S->A: Impaired interaction with CEBPB."
FT /evidence="ECO:0000269|PubMed:15308669"
SQ SEQUENCE 772 AA; 84704 MW; C868807C6046BEF5 CRC64;
MLSLKKYLTE GLLQFTILLS LIGVRVDVDT YLTSQLPPLR EIILGPSSAY TQTQFHNLRN
TLDGYGIHPK SIDLDNYFTA RRLLSQVRAL DRFQVPTTEV NAWLVHRDPE GSVSGSQPNS
GLALESSSGL QDVTGPDNGV RESETEQGFG EDLEDLGAVA PPVSGDLTKE DIDLIDILWR
QDIDLGAGRE VFDYSHRQKE QDVEKELRDG GEQDTWAGEG AEALARNLLV DGETGESFPA
QVPSGEDQTA LSLEECLRLL EATCPFGENA EFPADISSIT EAVPSESEPP ALQNNLLSPL
LTGTESPFDL EQQWQDLMSI MEMQAMEVNT SASEILYSAP PGDPLSTNYS LAPNTPINQN
VSLHQASLGG CSQDFLLFSP EVESLPVASS STLLPLAPSN STSLNSTFGS TNLTGLFFPP
QLNGTANDTA GPELPDPLGG LLDEAMLDEI SLMDLAIEEG FNPVQASQLE EEFDSDSGLS
LDSSHSPSSL SSSEGSSSSS SSSSSSSSSA SSSASSSFSE EGAVGYSSDS ETLDLEEAEG
AVGYQPEYSK FCRMSYQDPA QLSCLPYLEH VGHNHTYNMA PSALDSADLP PPSALKKGSK
EKQADFLDKQ MSRDEHRARA MKIPFTNDKI INLPVEEFNE LLSKYQLSEA QLSLIRDIRR
RGKNKMAAQN CRKRKLDTIL NLERDVEDLQ RDKARLLREK VEFLRSLRQM KQKVQSLYQE
VFGRLRDENG RPYSPSQYAL QYAGDGSVLL IPRTMADQQA RRQERKPKDR RK
