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UniProtKB - Q14494 (NF2L1_HUMAN)

Entry version 200 (25 May 2022)
Sequence version 1 (01 Nov 1996)
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Protein

Endoplasmic reticulum membrane sensor NFE2L1

Gene

NFE2L1

Organism
Homo sapiens (Human)
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: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).

By similarity2 Publications

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.

By similarity4 Publications

Caution

According to a report, processing following retrotranslocation is dependent on the proteasome (PubMed:24998528). However, it was later shown that processing takes place in a proteasome-independent manner (PubMed:27676297, PubMed:27676298).3 Publications
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 (PubMed:24448410). According to other reports, it is integrated into the endoplasmic reticulum membrane via multiple membrane-spanning alpha-helices.By similarity1 Publication
Was initially thought to activate erythroid-specific, globin gene expression (PubMed:8036168). Knockout experiments in mouse however demonstrated that it is not the case.By similarity1 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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q14494

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q14494

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q14494

<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 1
Short name:
NF-E2-related factor 12 Publications
Short name:
NFE2-related factor 12 Publications
Nuclear factor, erythroid derived 2, like 1
Protein NRF1, p120 form1 Publication
Transcription factor 111 Publication
Short name:
TCF-111 Publication
Cleaved into the following chain:
Transcription factor NRF1Curated
Alternative name(s):
Protein NRF1, p110 form1 Publication
<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:NFE2L1
Synonyms:HBZ17, NRF12 Publications, TCF111 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>OrganismiHomo sapiens (Human)
<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 identifieri9606 [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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<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
  • UP000005640 <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 17

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:7781, NFE2L1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		163260, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q14494

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000082641

<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

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

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

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>Mutagenesisi101 – 106NAWLVH → AAAAAA in m1; impaired protein cleavage. 1 Publication6
Mutagenesisi101 – 103NAW → AAA in m2; impaired protein cleavage. 1 Publication3
Mutagenesisi103 – 104WL → AA in m5; impaired protein cleavage. 1 Publication2
Mutagenesisi103W → A in m3; impaired protein cleavage. 1 Publication1
Mutagenesisi104 – 106LVH → AAA in m6; Slightly impaired protein cleavage. 1 Publication3
Mutagenesisi104L → A in m4; Slightly impaired protein cleavage. 1 Publication1
Mutagenesisi599S → A: Impaired interaction with CEBPB. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		4779

Open Targets

More...OpenTargetsi		ENSG00000082641

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA31587

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q14494, Tbio

Chemistry databases

Drug and drug target database

More...DrugBanki		DB04147, Dodecyldimethylamine N-oxide

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		NFE2L1

Domain mapping of disease mutations (DMDM)

More...DMDMi		3183180

<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_00000764471 – 772Endoplasmic reticulum membrane sensor NFE2L1Add BLAST772
ChainiPRO_0000443103104 – 772Transcription factor NRF11 PublicationAdd BLAST669

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>Glycosylationi348N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi360N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi412N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi423N-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 residuei528Phosphoserine; by CK2By similarity1
Modified residuei599Phosphoserine; by PKA1 Publication1

<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 (PubMed:24448410, PubMed:27676297, PubMed:27676298, PubMed:27528193). Ubiquitination is prerequisite for cleavage by aspartyl protease DDI2 (PubMed:27676298).4 Publications
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:24998528, PubMed:24448410, 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:24998528, PubMed:24448410).4 Publications
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).By similarity3 Publications
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).By similarity1 Publication
Ubiquitinated by the SCF(BTRC) complex in the nucleus, leading to its degradation by the proteasome.By similarity

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 DDI21 Publication2

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q14494

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q14494

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q14494

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q14494

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

More...PaxDbi		Q14494

PeptideAtlas

More...PeptideAtlasi		Q14494

PRoteomics IDEntifications database

More...PRIDEi		Q14494

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		60003 [Q14494-1]
60004 [Q14494-2]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q14494, 5 sites, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q14494

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

More...PhosphoSitePlusi		Q14494

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000082641, Expressed in deltoid and 257 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q14494, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q14494, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000082641, Group enriched (heart muscle, skeletal muscle, tongue)

<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.

1 Publication

Interacts (via CPD region) with FBXW7; leading to its ubiquitination and degradation (By similarity).

Interacts with SYVN1/HRD1; leading to its ubiquitination and degradation (By similarity).

Interacts (when ubiquitinated) with DDI2; leading to its cleavage (PubMed:27528193).

By similarity1 Publication

Interacts (via the bZIP domain) with small MAF protein (MAFF, MAFG or MAFK); required for binding to antioxidant response elements (AREs) on DNA (PubMed:8932385, PubMed:9421508).

Interacts (via Destruction motif) with BTRC; leading to its ubiquitination and degradation (By similarity).

Interacts with CEBPB; the heterodimer represses expression of DSPP during odontoblast differentiation (PubMed:15308669).

Interacts with MOTS-c, a peptide produced by the mitochondrially encoded 12S rRNA MT-RNR1 (PubMed:29983246).

By similarity4 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110851, 35 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-6569, bZIP transcription factor complex, ATF4-NFE2L1
CPX-6790, bZIP transcription factor complex, ATF7-NFE2L1
CPX-7015, bZIP transcription factor complex, BATF-NFE2L1

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q14494

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		Q14494

Protein interaction database and analysis system

More...IntActi		Q14494, 29 interactors

Molecular INTeraction database

More...MINTi		Q14494

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000354855

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q14494, 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

AlphaFold Protein Structure Database

More...AlphaFoldDBi		Q14494

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

More...SMRi		Q14494

Database of comparative protein structure models

More...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>Domaini654 – 717bZIPPROSITE-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>Regioni108 – 148DisorderedSequence analysisAdd BLAST41
Regioni191 – 199Cholesterol recognition/amino acid consensus (CRAC) regionBy similarity9
Regioni379 – 383CPDBy similarity5
Regioni470 – 532DisorderedSequence analysisAdd BLAST63
Regioni582 – 613DisorderedSequence analysisAdd BLAST32
Regioni656 – 675Basic motifPROSITE-ProRule annotationAdd BLAST20
Regioni682 – 696Leucine-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>Motifi476 – 480Destruction motifBy similarity5

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 type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi112 – 141Polar residuesSequence analysisAdd BLAST30
Compositional biasi470 – 526Polar residuesSequence analysisAdd BLAST57
Compositional biasi598 – 613Basic and acidic residuesSequence analysisAdd BLAST16

<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. Has much lower affinity for epicholesterol.By similarity

<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

More...GeneTreei		ENSGT00950000182892

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_024173_1_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q14494

Identification of Orthologs from Complete Genome Data

More...OMAi		LQAMDVN

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q14494

TreeFam database of animal gene trees

More...TreeFami		TF326681

Family and domain databases

Integrated resource of protein families, domains and functional sites

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

The PANTHER Classification System

More...PANTHERi		PTHR24411:SF31, PTHR24411:SF31, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF03131, bZIP_Maf, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00338, BRLZ, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF47454, SSF47454, 1 hit

PROSITE; a protein domain and family database

More...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 (2+)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 2 <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.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 15 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q14494-1) [UniParc]FASTAAdd to basket
Also known as: TCF111 Publication

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><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.

« Hide
        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
QDVEKELRDG GEQDTWAGEG AEALARNLLV DGETGESFPA QVPSGEDQTA 
       260        270        280        290        300
LSLEECLRLL EATCPFGENA EFPADISSIT EAVPSESEPP ALQNNLLSPL 
       310        320        330        340        350
LTGTESPFDL EQQWQDLMSI MEMQAMEVNT SASEILYSAP PGDPLSTNYS 
       360        370        380        390        400
LAPNTPINQN VSLHQASLGG CSQDFLLFSP EVESLPVASS STLLPLAPSN 
       410        420        430        440        450
STSLNSTFGS TNLTGLFFPP QLNGTANDTA GPELPDPLGG LLDEAMLDEI 
       460        470        480        490        500
SLMDLAIEEG FNPVQASQLE EEFDSDSGLS LDSSHSPSSL SSSEGSSSSS 
       510        520        530        540        550
SSSSSSSSSA SSSASSSFSE EGAVGYSSDS ETLDLEEAEG AVGYQPEYSK 
       560        570        580        590        600
FCRMSYQDPA QLSCLPYLEH VGHNHTYNMA PSALDSADLP PPSALKKGSK 
       610        620        630        640        650
EKQADFLDKQ MSRDEHRARA MKIPFTNDKI INLPVEEFNE LLSKYQLSEA 
       660        670        680        690        700
QLSLIRDIRR RGKNKMAAQN CRKRKLDTIL NLERDVEDLQ RDKARLLREK 
       710        720        730        740        750
VEFLRSLRQM KQKVQSLYQE VFGRLRDENG RPYSPSQYAL QYAGDGSVLL 
       760        770 
IPRTMADQQA RRQERKPKDR RK
Length:772
Mass (Da):84,704
Last modified:November 1, 1996 - v1
<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:iC868807C6046BEF5
GO
Isoform 2 (identifier: Q14494-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     242-271: Missing.

Show »
Length:742
Mass (Da):81,499
Checksum:iB99AAEF1C5F598E6
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 15 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J9JIE5J9JIE5_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
761Annotation 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>
F5H1B7F5H1B7_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
616Annotation 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>
J3QKY3J3QKY3_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
573Annotation 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>
B4DYE1B4DYE1_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
584Annotation 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>
J3QQQ1J3QQQ1_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
161Annotation 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>
J3KRF3J3KRF3_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
133Annotation 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>
J3QRG7J3QRG7_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
111Annotation 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>
J3KSR3J3KSR3_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
62Annotation 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>
J3QQY8J3QQY8_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
99Annotation 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>
J3QLQ1J3QLQ1_HUMAN
Endoplasmic reticulum membrane sens...
NFE2L1
82Annotation 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>
There are more potential isoformsShow all

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_04844063D → H. Corresponds to variant dbSNP:rs2229367Ensembl.1

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_000579242 – 271Missing in isoform 2. 2 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
L24123 mRNA No translation available.
X77366 mRNA Translation: CAA54555.1
CH471109 Genomic DNA Translation: EAW94762.1
CH471109 Genomic DNA Translation: EAW94763.1
CH471109 Genomic DNA Translation: EAW94764.1
CH471109 Genomic DNA Translation: EAW94765.1
CH471109 Genomic DNA Translation: EAW94766.1
CH471109 Genomic DNA Translation: EAW94767.1
BC010623 mRNA Translation: AAH10623.1
U08853 mRNA Translation: AAA20466.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS11524.1 [Q14494-1]
CCDS82150.1 [Q14494-2]

Protein sequence database of the Protein Information Resource

More...PIRi		A49672
A55004

NCBI Reference Sequences

More...RefSeqi		NP_001317191.1, NM_001330262.1 [Q14494-2]
NP_003195.1, NM_003204.2 [Q14494-1]
XP_005257467.1, XM_005257410.3 [Q14494-1]
XP_005257469.1, XM_005257412.3 [Q14494-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000357480.9; ENSP00000350072.5; ENSG00000082641.16 [Q14494-2]
ENST00000362042.8; ENSP00000354855.3; ENSG00000082641.16
ENST00000585291.5; ENSP00000461960.1; ENSG00000082641.16 [Q14494-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		4779

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:4779

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000362042.8; ENSP00000354855.3; NM_003204.3; NP_003195.1

UCSC genome browser

More...UCSCi		uc002imz.5, human [Q14494-1]

Keywords - Coding sequence diversityi

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
L24123 mRNA No translation available.
X77366 mRNA Translation: CAA54555.1
CH471109 Genomic DNA Translation: EAW94762.1
CH471109 Genomic DNA Translation: EAW94763.1
CH471109 Genomic DNA Translation: EAW94764.1
CH471109 Genomic DNA Translation: EAW94765.1
CH471109 Genomic DNA Translation: EAW94766.1
CH471109 Genomic DNA Translation: EAW94767.1
BC010623 mRNA Translation: AAH10623.1
U08853 mRNA Translation: AAA20466.1
CCDSiCCDS11524.1 [Q14494-1]
CCDS82150.1 [Q14494-2]
PIRiA49672
A55004
RefSeqiNP_001317191.1, NM_001330262.1 [Q14494-2]
NP_003195.1, NM_003204.2 [Q14494-1]
XP_005257467.1, XM_005257410.3 [Q14494-1]
XP_005257469.1, XM_005257412.3 [Q14494-2]

3D structure databases

AlphaFoldDBiQ14494
SMRiQ14494
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi110851, 35 interactors
ComplexPortaliCPX-6569, bZIP transcription factor complex, ATF4-NFE2L1
CPX-6790, bZIP transcription factor complex, ATF7-NFE2L1
CPX-7015, bZIP transcription factor complex, BATF-NFE2L1
CORUMiQ14494
ELMiQ14494
IntActiQ14494, 29 interactors
MINTiQ14494
STRINGi9606.ENSP00000354855

Chemistry databases

DrugBankiDB04147, Dodecyldimethylamine N-oxide

PTM databases

GlyGeniQ14494, 5 sites, 1 O-linked glycan (1 site)
iPTMnetiQ14494
PhosphoSitePlusiQ14494

Genetic variation databases

BioMutaiNFE2L1
DMDMi3183180

Proteomic databases

EPDiQ14494
jPOSTiQ14494
MassIVEiQ14494
MaxQBiQ14494
PaxDbiQ14494
PeptideAtlasiQ14494
PRIDEiQ14494
ProteomicsDBi60003 [Q14494-1]
60004 [Q14494-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		30234, 248 antibodies from 32 providers

The DNASU plasmid repository

More...DNASUi		4779

Genome annotation databases

EnsembliENST00000357480.9; ENSP00000350072.5; ENSG00000082641.16 [Q14494-2]
ENST00000362042.8; ENSP00000354855.3; ENSG00000082641.16
ENST00000585291.5; ENSP00000461960.1; ENSG00000082641.16 [Q14494-2]
GeneIDi4779
KEGGihsa:4779
MANE-SelectiENST00000362042.8; ENSP00000354855.3; NM_003204.3; NP_003195.1
UCSCiuc002imz.5, human [Q14494-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		4779
DisGeNETi4779

GeneCards: human genes, protein and diseases

More...GeneCardsi		NFE2L1
HGNCiHGNC:7781, NFE2L1
HPAiENSG00000082641, Group enriched (heart muscle, skeletal muscle, tongue)
MIMi163260, gene
neXtProtiNX_Q14494
OpenTargetsiENSG00000082641
PharmGKBiPA31587
VEuPathDBiHostDB:ENSG00000082641

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3863, Eukaryota
GeneTreeiENSGT00950000182892
HOGENOMiCLU_024173_1_0_1
InParanoidiQ14494
OMAiLQAMDVN
PhylomeDBiQ14494
TreeFamiTF326681

Enzyme and pathway databases

PathwayCommonsiQ14494
SignaLinkiQ14494
SIGNORiQ14494

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		4779, 44 hits in 1095 CRISPR screens

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

More...ChiTaRSi		NFE2L1, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		NFE2L1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		4779
PharosiQ14494, Tbio

Protein Ontology

More...PROi		PR:Q14494
RNActiQ14494, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000082641, Expressed in deltoid and 257 other tissues
ExpressionAtlasiQ14494, baseline and differential
GenevisibleiQ14494, HS

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

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_HUMAN
<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: Q14494
Secondary accession number(s): D3DTU3
, D3DTU5, Q12877, Q96FN6
<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: July 15, 1998
Last sequence update: November 1, 1996
Last modified: May 25, 2022
This is version 200 of the entry and version 1 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
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
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