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Entry version 170 (12 Aug 2020)
Sequence version 2 (29 May 2013)
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Protein

Endoplasmic reticulum membrane sensor NFE2L1

Gene

Nfe2l1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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).4 Publications
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:23144760, PubMed:16872277, PubMed:21911472, 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:23144760, PubMed:16872277, PubMed:21911472, PubMed:23816881). Activates or represses expression of target genes, depending on the context (PubMed:12808106, PubMed:15738389, PubMed:23144760, PubMed:16872277, PubMed:21911472, 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:9501099, PubMed:12808106, PubMed:15738389, PubMed:18826952, PubMed:22586274). 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).By similarity17 Publications
Transcription factor that binds the antioxidant response elements (ARE) consensus sequence on promoters and activates their expression.2 Publications
Transcription factor that binds the extended kappa 3 site of the TNF-alpha promoter after Fc gamma RIII stimulation and participates in the induction of this cytokine (PubMed:9580677).1 Publication

Caution

its topology is subject to discussion. According to some groups, it has a single-pass type II membrane protein in normal conditions and is retrotranslocated into a single-pass type III membrane protein in response to stress. According to other reports, it is integrated into the endoplasmic reticulum membrane via multiple membrane-spanning alpha-helices (PubMed:20629635, PubMed:26268886).2 Publications
Was initially thought to be either inactive as transcription factor or to repress transcriptional activation mediated by other isoforms (PubMed:9580677). The presence of the transmembrane region at the N-terminus may explain the inability to observe transcription factor activity.1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transcription, Transcription regulation
LigandLipid-binding

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Endoplasmic reticulum membrane sensor NFE2L1Curated
Alternative name(s):
Locus control region-factor 11 Publication
Short name:
LCR-F11 Publication
Nuclear factor erythroid 2-related factor 1Curated
Short name:
NF-E2-related factor 11 Publication
Short name:
NFE2-related factor 11 Publication
Nuclear factor, erythroid derived 2, like 1
Cleaved into the following chain:
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Nfe2l11 PublicationImported
Synonyms:Nrf11 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

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MGIi
MGI:99421, Nfe2l1

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei7 – 24Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST18

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Embryonic lethality: embryos progress normally to the late egg cylinder stage at approximately 6.5 days post coitus (dpc), but development is arrested before 7.5 dpc (PubMed:9087432, PubMed:9501099). Mutant embryos fail to form a primitive streak and lack detectable mesoderm (PubMed:9087432). Homozygous embryos suffer from anemia as a result of abnormal fetal liver erythropoiesis (PubMed:9501099). No defect in globin gene expression are detected; abnormal red cell production being the result of a defect in the fetal liver microenvironment specific for erythroid cells (PubMed:9501099). Mice lacking both Nfe2l1 and Nfe2l2 die early between embryonic days 9 and 10 and exhibit extensive apoptosis due to marked oxidative stress in cells that is indicated by elevated intracellular reactive oxygen species levels and cell death (PubMed:12968018). Conditional knockout mice lacking Nfe2l1 in the liver do not show any liver damage when they are maintained in an unstressed condition (PubMed:15738389). In oxidative stress condition, they develop hepatic cancer following steatosis, apoptosis, necrosis, inflammation, and fibrosis (PubMed:15738389). Hepatocyte-specific deletion causes liver damage resembling the human disease non-alcoholic steatohepatitis (PubMed:18826952). Liver of conditional knockout mice lacking Nfe2l1 show massive hepatic cholesterol accumulation and damage due to inability to mediate response to cholesterol excess (PubMed:29149604). Conditional knockout mice lacking Nfe2l1 in the brain show proteasome impairment and progressive degeneration in cortical neurons (PubMed:21554501, PubMed:21536885).8 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi350 – 354Missing : Abolishes interaction with FBXW7. 1 Publication5
Mutagenesisi448 – 451SGLS → AGLA: Abolishes ubiquitination and degradation by the SCF(BTRC) complex. 1 Publication4
Mutagenesisi496S → A: Does not affect phosphorylation by CK2. 1 Publication1
Mutagenesisi497S → A: Abolishes phosphorylation by CK2. 1 Publication1
Mutagenesisi499S → A: Does not affect phosphorylation by CK2. 1 Publication1
Mutagenesisi501T → A: Does not affect phosphorylation by CK2. 1 Publication1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000764481 – 741Endoplasmic reticulum membrane sensor NFE2L1Add BLAST741
ChainiPRO_0000443104104 – 741Transcription factor NRF1By similarityAdd BLAST638

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi319N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi331N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi394N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei497Phosphoserine; by CK21 Publication1
Modified residuei568PhosphoserineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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.By similarity
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).By similarity2 Publications
Ubiquitinated by the SCF(FBXW7) complex and SYVN1/HRD1, leading to its degradation by the proteasome (PubMed:21953459, PubMed:21911472). 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).By similarity2 Publications
Phosphorylation by CK2 at Ser-497 inhibits transcription factor activity, possibly by affecting DNA-binding activity (PubMed:9580677, PubMed:23816881). Phosphorylation at Ser-568 is required for interaction with CEBPB (By similarity).By similarity2 Publications
Ubiquitinated by the SCF(BTRC) complex in the nucleus, leading to its degradation by the proteasome.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei103 – 104Cleavage; by DDI2By similarity2

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q61985

PRoteomics IDEntifications database

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PRIDEi
Q61985

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...
GlyGeni
Q61985, 3 sites

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q61985

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q61985

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Isoform 1: Widely expressed including kidney, brown fat, white fat, large intestine, small intestine, stomach, lung, brain and liver (PubMed:23144760). Isoform 1: Expressed in mouse embryonic fibroblasts (MEF) (PubMed:23144760). Isoform 2: Widely expressed including kidney, brown fat, white fat, large intestine, small intestine, stomach, lung, brain and liver (PubMed:23144760). Isoform 2: levels in white fat, lung and liver are increased compared to isoform 1 (at protein level) (PubMed:23144760). Isoform 2: levels are elevated in brown fat and brain, but are reduced in liver compared to isoform 1 levels (PubMed:23144760). Isoform 2: Expressed in mouse embryonic fibroblasts (MEF) (PubMed:23144760).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000038615, Expressed in hindlimb stylopod muscle and 334 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q61985, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q61985, MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with KEAP1 (By similarity). Endoplasmic reticulum membrane sensor NFE2L1:

Interacts (via CPD region) with FBXW7; leading to its ubiquitination and degradation (PubMed:21953459). Endoplasmic reticulum membrane sensor NFE2L1:

Interacts with SYVN1/HRD1; leading to its ubiquitination and degradation (PubMed:21911472). Endoplasmic reticulum membrane sensor NFE2L1:

Interacts (when ubiquitinated) with DDI2; leading to its cleavage (By similarity). Transcription factor NRF1:

Interacts (via the bZIP domain) with small MAF protein (MAFF, MAFG or MAFK); required for binding to antioxidant response elements (AREs) on DNA (PubMed:11342101, PubMed:23144760). Transcription factor NRF1:

Interacts (via Destruction motif) with BTRC; leading to its ubiquitination and degradation (PubMed:21911472). Transcription factor NRF1:

Interacts with CEBPB; the heterodimer represses expression of DSPP during odontoblast differentiation (By similarity).

By similarity5 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000103286

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
Q61985, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q61985

Database of comparative protein structure models

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ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini623 – 686bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni191 – 199Cholesterol recognition/amino acid consensus (CRAC) region1 Publication9
Regioni350 – 354CPD1 Publication5
Regioni625 – 644Basic motifPROSITE-ProRule annotationAdd BLAST20
Regioni651 – 665Leucine-zipperPROSITE-ProRule annotationAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi447 – 451Destruction motif1 Publication5
Motifi730 – 737Nuclear localization signalSequence analysis8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi125 – 259Asp/Glu-rich (acidic)Add BLAST135
Compositional biasi414 – 447Asp/Glu-rich (acidic)Add BLAST34
Compositional biasi467 – 486Poly-SerAdd BLAST20

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The cholesterol recognition/amino acid consensus (CRAC) region directly binds cholesterol, as well as campesterol and 27-hydroxycholesterol (PubMed:29149604). Has much lower affinity for epicholesterol (PubMed:29149604).1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the bZIP family. CNC subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3863, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00950000182892

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_024173_1_0_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q61985

KEGG Orthology (KO)

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KOi
K09040

Identification of Orthologs from Complete Genome Data

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OMAi
HKHSGPS

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR004827, bZIP
IPR004826, bZIP_Maf
IPR029847, NFE2L1
IPR008917, TF_DNA-bd_sf

The PANTHER Classification System

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PANTHERi
PTHR24411:SF31, PTHR24411:SF31, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF03131, bZIP_Maf, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00338, BRLZ, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF47454, SSF47454, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50217, BZIP, 1 hit
PS00036, BZIP_BASIC, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q61985-1) [UniParc]FASTAAdd to basket
Also known as: Long1 Publication, Nrf1a1 Publication

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MLSLKKYLTE GLLQFTILLS LIGVRVDVDT YLTSQLPPLR EIILGPSSAY
60 70 80 90 100
TQTQFHNLRN TLDGYGIHPK SIDLDNYFTA RRLLSQVRAL DRFQVPTTEV
110 120 130 140 150
NAWLVHRDPE GSVSGSQPNS GLALESSSGL QDVTGPDNGV RESETEQGFG
160 170 180 190 200
EDLEDLGAVA PPVSGDLTKE DIDLIDILWR QDIDLGAGRE VFDYSHRQKE
210 220 230 240 250
QDVDKELQDG REREDTWSGE GAEALARDLL VDGETGESFP AQFPADVSSI
260 270 280 290 300
PEAVPSESES PALQNSLLSP LLTGTESPFD LEQQWQDLMS IMEMQAMEVN
310 320 330 340 350
TSASEILYNA PPGDPLSTNY SLAPNTPINQ NVSLHQASLG GCSQDFSLFS
360 370 380 390 400
PEVESLPVAS SSTLLPLVPS NSTSLNSTFG STNLAGLFFP SQLNGTANDT
410 420 430 440 450
SGPELPDPLG GLLDEAMLDE ISLMDLAIEE GFNPVQASQL EEEFDSDSGL
460 470 480 490 500
SLDSSHSPSS LSSSEGSSSS SSSSSSSSAS SSASSSFSEE GAVGYSSDSE
510 520 530 540 550
TLDLEEAEGA VGYQPEYSKF CRMSYQDPSQ LSCLPYLEHV GHNHTYNMAP
560 570 580 590 600
SALDSADLPP PSTLKKGSKE KQADFLDKQM SRDEHRARAM KIPFTNDKII
610 620 630 640 650
NLPVEEFNEL LSKYQLSEAQ LSLIRDIRRR GKNKMAAQNC RKRKLDTILN
660 670 680 690 700
LERDVEDLQR DKARLLREKV EFLRSLRQMK QKVQSLYQEV FGRLRDEHGR
710 720 730 740
PYSPSQYALQ YAGDGSVLLI PRTMADQQAR RQERKPKDRR K
Note: Produced by alternative promoter usage.
Length:741
Mass (Da):81,575
Last modified:May 29, 2013 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iDDB267F32CD2A92C
GO
Isoform 2 (identifier: Q61985-3) [UniParc]FASTAAdd to basket
Also known as: Nrf1b1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-158: Missing.
     159-170: VAPPVSGDLTKE → MGWESRLTAASA

Note: Produced by alternative promoter usage.Curated
Show »
Length:583
Mass (Da):64,269
Checksum:iFA621B98FA01E566
GO
Isoform 3 (identifier: Q61985-2) [UniParc]FASTAAdd to basket
Also known as: Short1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-158: Missing.
     159-291: Missing.
     447-583: Missing.

Note: Produced by alternative splicing of isoform 1.Curated
Show »
Length:313
Mass (Da):35,158
Checksum:iE204C4337A71E365
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2A6D2A2A6D2_MOUSE
Endoplasmic reticulum membrane sens...
Nfe2l1
742Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q3V3M1Q3V3M1_MOUSE
Endoplasmic reticulum membrane sens...
Nfe2l1
453Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A2A6D1A2A6D1_MOUSE
Endoplasmic reticulum membrane sens...
Nfe2l1
152Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A2A6D0A2A6D0_MOUSE
Endoplasmic reticulum membrane sens...
Nfe2l1
148Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti318T → S in CAA55362 (PubMed:7759107).Curated1
Sequence conflicti387L → P in CAA55362 (PubMed:7759107).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0005801 – 158Missing in isoform 2 and isoform 3. CuratedAdd BLAST158
Alternative sequenceiVSP_046523159 – 291Missing in isoform 3. CuratedAdd BLAST133
Alternative sequenceiVSP_046524159 – 170VAPPV…DLTKE → MGWESRLTAASA in isoform 2. CuratedAdd BLAST12
Alternative sequenceiVSP_000581447 – 583Missing in isoform 3. CuratedAdd BLAST137

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X78709 mRNA Translation: CAA55362.1
AF015881 Genomic DNA Translation: AAC40108.1
AL596384 Genomic DNA No translation available.

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS25304.1 [Q61985-1]
CCDS48894.1 [Q61985-3]

Protein sequence database of the Protein Information Resource

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PIRi
I48694

NCBI Reference Sequences

More...
RefSeqi
NP_001123922.1, NM_001130450.1 [Q61985-1]
NP_032712.2, NM_008686.3 [Q61985-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000081775; ENSMUSP00000080467; ENSMUSG00000038615 [Q61985-1]
ENSMUST00000107657; ENSMUSP00000103284; ENSMUSG00000038615 [Q61985-1]
ENSMUST00000107658; ENSMUSP00000103285; ENSMUSG00000038615 [Q61985-1]
ENSMUST00000167110; ENSMUSP00000127804; ENSMUSG00000038615 [Q61985-3]
ENSMUST00000167149; ENSMUSP00000128527; ENSMUSG00000038615 [Q61985-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
18023

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:18023

UCSC genome browser

More...
UCSCi
uc007lcq.2, mouse [Q61985-1]
uc011ydl.1, mouse [Q61985-3]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78709 mRNA Translation: CAA55362.1
AF015881 Genomic DNA Translation: AAC40108.1
AL596384 Genomic DNA No translation available.
CCDSiCCDS25304.1 [Q61985-1]
CCDS48894.1 [Q61985-3]
PIRiI48694
RefSeqiNP_001123922.1, NM_001130450.1 [Q61985-1]
NP_032712.2, NM_008686.3 [Q61985-1]

3D structure databases

SMRiQ61985
ModBaseiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000103286

PTM databases

GlyGeniQ61985, 3 sites
iPTMnetiQ61985
PhosphoSitePlusiQ61985

Proteomic databases

PaxDbiQ61985
PRIDEiQ61985

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
30234, 222 antibodies

Genome annotation databases

EnsembliENSMUST00000081775; ENSMUSP00000080467; ENSMUSG00000038615 [Q61985-1]
ENSMUST00000107657; ENSMUSP00000103284; ENSMUSG00000038615 [Q61985-1]
ENSMUST00000107658; ENSMUSP00000103285; ENSMUSG00000038615 [Q61985-1]
ENSMUST00000167110; ENSMUSP00000127804; ENSMUSG00000038615 [Q61985-3]
ENSMUST00000167149; ENSMUSP00000128527; ENSMUSG00000038615 [Q61985-1]
GeneIDi18023
KEGGimmu:18023
UCSCiuc007lcq.2, mouse [Q61985-1]
uc011ydl.1, mouse [Q61985-3]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4779
MGIiMGI:99421, Nfe2l1

Phylogenomic databases

eggNOGiKOG3863, Eukaryota
GeneTreeiENSGT00950000182892
HOGENOMiCLU_024173_1_0_1
InParanoidiQ61985
KOiK09040
OMAiHKHSGPS

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
18023, 1 hit in 18 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
Nfe2l1, mouse

Protein Ontology

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PROi
PR:Q61985
RNActiQ61985, protein

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000038615, Expressed in hindlimb stylopod muscle and 334 other tissues
ExpressionAtlasiQ61985, baseline and differential
GenevisibleiQ61985, MM

Family and domain databases

InterProiView protein in InterPro
IPR004827, bZIP
IPR004826, bZIP_Maf
IPR029847, NFE2L1
IPR008917, TF_DNA-bd_sf
PANTHERiPTHR24411:SF31, PTHR24411:SF31, 1 hit
PfamiView protein in Pfam
PF03131, bZIP_Maf, 1 hit
SMARTiView protein in SMART
SM00338, BRLZ, 1 hit
SUPFAMiSSF47454, SSF47454, 1 hit
PROSITEiView protein in PROSITE
PS50217, BZIP, 1 hit
PS00036, BZIP_BASIC, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiNF2L1_MOUSE
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q61985
Secondary accession number(s): E9Q038, O70234
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 29, 2013
Last modified: August 12, 2020
This is version 170 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families
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