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NFE2L2 Gene(Protein Coding)

Nuclear Factor, Erythroid 2 Like 2

GCID:
GC02M177227
GIFtS:
67
Genes Participants
UDN Logo

Aliases for NFE2L2 Gene

Aliases for NFE2L2 Gene

  • Nuclear Factor, Erythroid 2 Like 2 2 3 5
  • Nuclear Factor, Erythroid 2-Like 2 2 3
  • NF-E2-Related Factor 2 2 4
  • HEBP1 3 4
  • NRF2 3 4
  • Nuclear Factor (Erythroid-Derived 2)-Like 2 2
  • Nuclear Factor, Erythroid Derived 2, Like 2 4
  • Nuclear Factor Erythroid-Derived 2-Like 2 3
  • NFE2-Related Factor 2 4

External Ids for NFE2L2 Gene

Previous GeneCards Identifiers for NFE2L2 Gene

  • GC02M176157
  • GC02M176766
  • GC02M178059
  • GC02M178297
  • GC02M177920
  • GC02M177803
  • GC02M169966
  • GC02M178092

Summaries for NFE2L2 Gene

Entrez Gene Summary for NFE2L2 Gene

  • This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

GeneCards Summary for NFE2L2 Gene

NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) is a Protein Coding gene. Diseases associated with NFE2L2 include Parkinson Disease 4 and Lung Squamous Cell Carcinoma. Among its related pathways are Keap1-Nrf2 Pathway and Oxidative Stress. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and protein domain specific binding. An important paralog of this gene is NFE2.

UniProtKB/Swiss-Prot for NFE2L2 Gene

  • Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.

Gene Wiki entry for NFE2L2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NFE2L2 Gene

Genomics for NFE2L2 Gene

Products:

  1. Regulatory Element

Regulatory Elements for NFE2L2 Gene

Enhancers for NFE2L2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around NFE2L2 on UCSC Golden Path with GeneCards custom track

Promoters for NFE2L2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NFE2L2 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the NFE2L2 gene promoter:

Genomic Location for NFE2L2 Gene

Chromosome:
2
Start:
177,227,595 bp from pter
End:
177,392,697 bp from pter
Size:
165,103 bases
Orientation:
Minus strand

Genomic View for NFE2L2 Gene

Genes around NFE2L2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NFE2L2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NFE2L2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for NFE2L2 Gene

Proteins for NFE2L2 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for NFE2L2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q16236-NF2L2_HUMAN
    Recommended name:
    Nuclear factor erythroid 2-related factor 2
    Protein Accession:
    Q16236
    Secondary Accessions:
    • B2RBU2
    • B4E338
    • E9PGJ7
    • Q53RW6
    • Q59HH2
    • Q96F71

    Protein attributes for NFE2L2 Gene

    Size:
    605 amino acids
    Molecular mass:
    67827 Da
    Quaternary structure:
    • Heterodimer. Forms a ternary complex with PGAM5 and KEAP1. May bind DNA with an unknown protein. Interacts via its leucine-zipper domain with the coiled-coil domain of PMF1. Interacts with EEF1D at heat shock promoter elements (HSE). Interacts (via the bZIP domain) with MAFK; required for binding to antioxidant response (ARE) elements on DNA. Interacts with CHD6; involved in activation of the transcription.
    SequenceCaution:
    • Sequence=AAB32188.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAD92023.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NFE2L2 Gene

    Alternative splice isoforms for NFE2L2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NFE2L2 Gene

Proteomics data for NFE2L2 Gene at MOPED

Protein Expression for NFE2L2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for NFE2L2 Gene

  • Acetylation at Lys-596 and Lys-599 increases nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence.
  • Phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus.
  • Ubiquitinated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and subject to proteasomal degradation. Ubiquitination is inhibited by sulforaphane.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NFE2L2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for NFE2L2 Gene

Domains & Families for NFE2L2 Gene

Gene Families for NFE2L2 Gene

HGNC:

Protein Domains for NFE2L2 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NFE2L2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q16236

UniProtKB/Swiss-Prot:

NF2L2_HUMAN :
  • Acidic activation domain in the N-terminus, and DNA binding domain in the C-terminus.
  • Belongs to the bZIP family. CNC subfamily.
Domain:
  • Acidic activation domain in the N-terminus, and DNA binding domain in the C-terminus.
  • Contains 1 bZIP (basic-leucine zipper) domain.
Family:
  • Belongs to the bZIP family. CNC subfamily.
genes like me logo Genes that share domains with NFE2L2: view

Function for NFE2L2 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for NFE2L2 Gene

GENATLAS Biochemistry:
nuclear factor,erythroid derived 2-like 2,Capncollar (CNC) family of transcription factor,NF-E2-like
UniProtKB/Swiss-Prot Function:
Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.
UniProtKB/Swiss-Prot Induction:
Down-regulated by ENC1 via a proteasomal ubiquitin-independent protein catabolic process.

Gene Ontology (GO) - Molecular Function for NFE2L2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16888629
genes like me logo Genes that share ontologies with NFE2L2: view

Phenotypes for NFE2L2 Gene

MGI mutant phenotypes for NFE2L2:
inferred from 6 alleles
GenomeRNAi human phenotypes for NFE2L2:
genes like me logo Genes that share phenotypes with NFE2L2: view

Animal Models for NFE2L2 Gene

MGI Knock Outs for NFE2L2:

Animal Model Products

CRISPR Products

miRNA for NFE2L2 Gene

miRTarBase miRNAs that target NFE2L2
Targeted motifs for NFE2L2 Gene
HOMER Transcription Factor Regulatory Elements motif NFE2L2
  • Consensus sequence: HTGCTGAGTCAT Submotif: canonical Cell Type: Lymphoblast GEO ID: GSE37589

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for NFE2L2 Gene

Localization for NFE2L2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NFE2L2 Gene

Cytoplasm, cytosol. Nucleus. Note=Cytosolic under unstressed conditions, translocates into the nucleus upon induction by electrophilic agents.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NFE2L2 Gene COMPARTMENTS Subcellular localization image for NFE2L2 gene
Compartment Confidence
cytoskeleton 5
cytosol 5
nucleus 5
plasma membrane 5
endoplasmic reticulum 2
extracellular 2
mitochondrion 2
peroxisome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for NFE2L2 Gene

Pathways & Interactions for NFE2L2 Gene

genes like me logo Genes that share pathways with NFE2L2: view

Pathways by source for NFE2L2 Gene

1 KEGG pathway for NFE2L2 Gene
1 R&D Systems pathway for NFE2L2 Gene

SIGNOR curated interactions for NFE2L2 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NFE2L2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006954 inflammatory response IEA --
GO:0010499 proteasomal ubiquitin-independent protein catabolic process IDA 19424503
GO:0010628 positive regulation of gene expression IGI 22492997
GO:0016567 protein ubiquitination IDA 15983046
GO:0030968 endoplasmic reticulum unfolded protein response ISS --
genes like me logo Genes that share ontologies with NFE2L2: view

Drugs & Compounds for NFE2L2 Gene

Products:

  1. Drug

(46) Drugs for NFE2L2 Gene - From: ApexBio, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dimethyl fumarate Approved, Investigational Pharma 73
Curcumin Pharma Tyrosinase inhibitor, Antitumor, anti-inflammatory and antioxidant 126
Andrographolide Pharma NF-κB signaling Inhibitor, Inhibits NFkappaB; blocks androgen receptor (AR) expression 6

(51) Additional Compounds for NFE2L2 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
CDDO Im
443104-02-7
DMF
624-49-7
MMF
2756-87-8

(5) Tocris Compounds for NFE2L2 Gene

Compound Action Cas Number
Andrographolide Inhibits NFkappaB; blocks androgen receptor (AR) expression 5508-58-7
CDDO Im Nrf2 signaling activator 443104-02-7
Curcumin Antitumor, anti-inflammatory and antioxidant 458-37-7
DMF Nrf2 pathway activator; neuroprotective 624-49-7
MMF Activator of Nrf2 pathway; primary metabolite of DMF (Cat. No. 4512) 2756-87-8

(2) ApexBio Compounds for NFE2L2 Gene

Compound Action Cas Number
Curcumin Tyrosinase inhibitor 458-37-7
Dimethyl Fumarate 624-49-7
genes like me logo Genes that share compounds with NFE2L2: view

Transcripts for NFE2L2 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for NFE2L2 Gene

(8) REFSEQ mRNAs :
(15) Additional mRNA sequences :
(629) Selected AceView cDNA sequences:
(14) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NFE2L2 Gene

Nuclear factor (erythroid-derived 2)-like 2:
Representative Sequences:

CRISPR Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NFE2L2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12 ^ 13a · 13b · 13c · 13d · 13e · 13f ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^ 18 ^
SP1: - - - - - -
SP2: - - - - - - - -
SP3: - - - - - - - -
SP4:
SP5:
SP6: - -
SP7: - -
SP8:
SP9:
SP10: - - - - - - - -
SP11: -
SP12: -
SP13:

ExUns: 19 ^ 20 ^ 21a · 21b ^ 22a · 22b
SP1:
SP2:
SP3:
SP4:
SP5: -
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for NFE2L2 Gene

GeneLoc Exon Structure for
NFE2L2
ECgene alternative splicing isoforms for
NFE2L2

Expression for NFE2L2 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for NFE2L2 Gene

mRNA expression in normal human tissues for NFE2L2 Gene
mRNA expression by BioGPS for NFE2L2 GenemRNA expression by GTEx for NFE2L2 Gene

Protein differential expression in normal tissues from HIPED for NFE2L2 Gene

This gene is overexpressed in Liver (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for NFE2L2 Gene



SOURCE GeneReport for Unigene cluster for NFE2L2 Gene Hs.744006

mRNA Expression by UniProt/SwissProt for NFE2L2 Gene

Q16236-NF2L2_HUMAN
Tissue specificity: Widely expressed. Highest expression in adult muscle, kidney, lung, liver and in fetal muscle.
genes like me logo Genes that share expression patterns with NFE2L2: view

Protein tissue co-expression partners for NFE2L2 Gene

- Elite partner

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for NFE2L2 Gene

Orthologs for NFE2L2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NFE2L2 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
 Mammalia NFE2L2 35
  • 90.45 (n)
  • 89.07 (a)
NFE2L2 36
  • 89 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia NFE2L2 35
  • 89.32 (n)
  • 88.81 (a)
NFE2L2 36
  • 87 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Nfe2l2 35
  • 83.36 (n)
  • 82.52 (a)
Nfe2l2 16
Nfe2l2 36
  • 82 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia NFE2L2 35
  • 99.94 (n)
  • 99.83 (a)
NFE2L2 36
  • 100 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Nfe2l2 35
  • 83.75 (n)
  • 83.19 (a)
oppossum
(Monodelphis domestica)
 Mammalia NFE2L2 36
  • 77 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia NFE2L2 36
  • 54 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves NFE2L2 35
  • 72.44 (n)
  • 67.42 (a)
NFE2L2 36
  • 65 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia NFE2L2 36
  • 60 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia nfe2l2 35
  • 62.45 (n)
  • 54.77 (a)
Str.11814 35
zebrafish
(Danio rerio)
 Actinopterygii -- 35
nfe2l2a 35
  • 55.74 (n)
  • 51.91 (a)
nfe2l2a 36
  • 44 (a)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta cnc 37
  • 50 (a)
cnc 36
  • 11 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 36
  • 14 (a)
 OneToMany
Species with no ortholog for NFE2L2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NFE2L2 Gene

ENSEMBL:
Gene Tree for NFE2L2 (if available)
TreeFam:
Gene Tree for NFE2L2 (if available)

Paralogs for NFE2L2 Gene

Paralogs for NFE2L2 Gene

(2) SIMAP similar genes for NFE2L2 Gene using alignment to 10 proteins:

Pseudogenes.org Pseudogenes for NFE2L2 Gene

genes like me logo Genes that share paralogs with NFE2L2: view

Variants for NFE2L2 Gene

Sequence variations from dbSNP and Humsavar for NFE2L2 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs5031039 - 177,234,022(-) GTGGA(C/T)CTGCC reference, missense
rs35248500 - 177,234,189(-) GCGAC(A/G)GAAAG reference, missense
rs34154613 - 177,231,801(-) TGACA(A/G)TGAAC reference, missense
rs1806649 -- 177,253,424(+) CTAAG(C/T)AGAGG intron-variant
rs2886160 -- 177,252,662(+) GTATT(G/T)TTAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NFE2L2 Gene

Variant ID Type Subtype PubMed ID
nsv834465 CNV Loss 17160897

Variation tolerance for NFE2L2 Gene

Residual Variation Intolerance Score: 58.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.66; 31.81% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NFE2L2 Gene

Human Gene Mutation Database (HGMD)
NFE2L2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NFE2L2 Gene

Disorders for NFE2L2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for NFE2L2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
parkinson disease 4
  • parkinson disease 4 autosomal dominant lewy body
lung squamous cell carcinoma
  • epidermoid cell carcinoma of the lung
lung papillary adenocarcinoma
  • papillary adenocarcinoma of the lung
vascular disease
  • vascular tissue disease
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for NFE2L2

Genetic Association Database (GAD)
NFE2L2
Human Genome Epidemiology (HuGE) Navigator
NFE2L2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NFE2L2
genes like me logo Genes that share disorders with NFE2L2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NFE2L2 Gene

Publications for NFE2L2 Gene

  1. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF- E2/AP1 repeat of the beta-globin locus control region. (PMID: 7937919) Moi P. … Kan Y.W. (Proc. Natl. Acad. Sci. U.S.A. 1994) 2 3 4 23 67
  2. Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture. (PMID: 19558496) Wagner A.E. … Rimbach G. (Exp. Dermatol. 2010) 3 23
  3. Transcriptional regulation of human carboxylesterase 1A1 by nuclear factor-erythroid 2 related factor 2 (Nrf2). (PMID: 19715681) Maruichi T. … Yokoi T. (Biochem. Pharmacol. 2010) 3 23
  4. Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway. (PMID: 19889935) Burdette D. … Waris G. (J. Gen. Virol. 2010) 3 23
  5. An internal ribosomal entry site mediates redox-sensitive translation of Nrf2. (PMID: 19934254) Li W. … Kong A.N. (Nucleic Acids Res. 2010) 3 23

Products for NFE2L2 Gene

Sources for NFE2L2 Gene

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