NFE2L2 NFE2 like bZIP transcription factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NFE2L2provided by HGNC
Official Full Name: NFE2 like bZIP transcription factor 2provided by HGNC
Primary source: HGNC:HGNC:7782
See related: Ensembl:ENSG00000116044 MIM:600492; AllianceGenome:HGNC:7782
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NRF2; HEBP1; Nrf-2; IMDDHH
Summary: 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]
Expression: Ubiquitous expression in esophagus (RPKM 93.8), thyroid (RPKM 52.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q31.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (177230303..177264727, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (177712539..177746971, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (178095031..178129455, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Role of kidney function on Nrf2 mRNA levels in type 2 diabetes.
Title: Role of kidney function on Nrf2 mRNA levels in type 2 diabetes.
NRF2 regulates EGF stability through OTUD4 in lung adenocarcinoma.
Title: NRF2 regulates EGF stability through OTUD4 in lung adenocarcinoma.
Combined genetic polymorphisms of the GSTT1 and NRF2 genes increase susceptibility to cisplatin-induced ototoxicity: A preliminary study.
Title: Combined genetic polymorphisms of the GSTT1 and NRF2 genes increase susceptibility to cisplatin-induced ototoxicity: A preliminary study.
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.
Title: Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.
The crucial role of NRF2 in erythropoiesis and anemia: Mechanisms and therapeutic opportunities.
Title: The crucial role of NRF2 in erythropoiesis and anemia: Mechanisms and therapeutic opportunities.
Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.
Title: Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.
Amino acid deprivation induces TXNIP expression by NRF2 downregulation.
Title: Amino acid deprivation induces TXNIP expression by NRF2 downregulation.
Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer.
Title: Overexpression of Nrf2 reverses ferroptosis induced by Arenobufagin in gastric cancer.
NRF2 Shortage in Human Skin Fibroblasts Dysregulates Matrisome Gene Expression and Affects Collagen Fibrillogenesis.
Title: NRF2 Shortage in Human Skin Fibroblasts Dysregulates Matrisome Gene Expression and Affects Collagen Fibrillogenesis.
Identifying key antioxidative stress factors regulating Nrf2 in the genioglossus with human umbilical cord mesenchymal stem-cell therapy.
Title: Identifying key antioxidative stress factors regulating Nrf2 in the genioglossus with human umbilical cord mesenchymal stem-cell therapy.

Submit: New GeneRIF Correction See all GeneRIFs (1692)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Immunodeficiency, developmental delay, and hypohomocysteinemia MedGen: C4540293 OMIM: 617744 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 significantly upregulates Nrf2 in human astrocytes and is associated with increased levels of key antioxidant defensive enzymes Hemoxygenase (HO-1) and NAD(P)H dehydrogenase quinone1 (Nqo1)	PubMed
	env	Inhibition of NRF2 by siRNA results in increased NOX2, NFkappaB (p65/p50), TNF-alpha, and MMP-9 proteins in astrocytes exposed to HIV-1 gp120	PubMed
Tat	tat	HIV-1 Tat activates NFE2L2 (Nrf2) protein levels in SH-SY5Y cells	PubMed
	tat	HIV-1 Tat upregulates NFE2L2 (Nrf2) protein levels in SH-SY5Y cells	PubMed
	tat	HIV-1 Tat-induced reactive oxygen species production and down-regulation of glutathione levels in TZM-bl cells are reversed through tanshinone II A-induced upregulation of NRF2 expression	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-148447 (e-PCR)
- UniSTS:176399

D2S2070 (e-PCR)
- UniSTS:76816

DYS419 (e-PCR)
- UniSTS:26129

D2S1921 (e-PCR)
- UniSTS:153662

D2S2577 (e-PCR)
- UniSTS:82249

A003A39 (e-PCR)
- UniSTS:1648

RH76772 (e-PCR)
- UniSTS:92531

RH70788 (e-PCR)
- UniSTS:14980

D2S2715 (e-PCR)
- UniSTS:8854

Nfe2l2 (e-PCR), detects polymorphism
- UniSTS:507087

D2S1709E (e-PCR)
- UniSTS:150738

RH68866 (e-PCR)
- UniSTS:59884

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular condensate scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	TAS Traceable Author Statement more info	PubMed
enables transcription coregulator binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in PERK-mediated unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in PERK-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in aflatoxin catabolic process	IEA Inferred from Electronic Annotation more info
involved_in cell redox homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to angiotensin	IEA Inferred from Electronic Annotation more info
involved_in cellular response to copper ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to fluid shear stress	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to glucose starvation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to hydrogen peroxide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to hypoxia	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to laminar fluid shear stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to oxidative stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to oxidative stress	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to oxidative stress	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to tumor necrosis factor	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in endoplasmic reticulum unfolded protein response	ISS Inferred from Sequence or Structural Similarity more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in integrated stress response signaling	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of endothelial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hematopoietic stem cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of vascular associated smooth muscle cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ERAD pathway	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of blood vessel endothelial cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glucose import	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of glutathione biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of reactive oxygen species metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ubiquitin-dependent protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in proteasomal ubiquitin-independent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cellular response to oxidative stress	EXP Inferred from Experiment more info	PubMed
involved_in regulation of embryonic development	IEA Inferred from Electronic Annotation more info
involved_in regulation of innate immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of removal of superoxide radicals	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in response to ischemia	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
part_of RNA polymerase II transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
part_of mediator complex	EXP Inferred from Experiment more info	PubMed
is_active_in non-membrane-bounded organelle	EXP Inferred from Experiment more info	PubMed
is_active_in non-membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
part_of protein-DNA complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: nuclear factor erythroid 2-related factor 2

Names: nuclear factor erythroid-derived 2-like 2; nuclear factor, erythroid 2 like 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001145412.3 → NP_001138884.1 nuclear factor erythroid 2-related factor 2 isoform 2

See identical proteins and their annotated locations for NP_001138884.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 4 and 5 encode the same protein.

Source sequence(s)

AW471118, BC011558, DB133391, DC314553

Consensus CDS

CCDS46457.1

UniProtKB/TrEMBL

B4DNB0, B7ZA33

Related

ENSP00000380253.4, ENST00000397063.9

Conserved Domains (2) summary

cd14720
Location:478 → 545

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain

pfam06886
Location:25 → 58

TPX2; Targeting protein for Xklp2 (TPX2)
NM_001145413.3 → NP_001138885.1 nuclear factor erythroid 2-related factor 2 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents use of an alternate promoter and 5' UTR, uses a downstream start codon, and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (3) has a shorter N-terminus and is missing an internal segment, compared to isoform 1.

Source sequence(s)

AW471118, BC011558, DB133391, DC314553

Consensus CDS

CCDS46458.1

UniProtKB/TrEMBL

B4DNB0, B7ZA33

Related

ENSP00000411575.2, ENST00000446151.6

Conserved Domains (2) summary

cd14720
Location:471 → 538

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain

cd22249
Location:27 → 63

UDM1_RNF168_RNF169-like; UDM1 (ubiquitin-dependent DSB recruitment module 1) found in RING finger proteins RNF168, RNF169 and similar proteins
NM_001313900.1 → NP_001300829.1 nuclear factor erythroid 2-related factor 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 4 and 5 encode the same protein.

Source sequence(s)

AC079305, AK311688, AW471118

Consensus CDS

CCDS46457.1

UniProtKB/TrEMBL

B4DNB0, B7ZA33

Related

ENSP00000412191.2, ENST00000421929.6

Conserved Domains (2) summary

cd14720
Location:478 → 545

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain

pfam06886
Location:25 → 58

TPX2; Targeting protein for Xklp2 (TPX2)
NM_001313901.1 → NP_001300830.1 nuclear factor erythroid 2-related factor 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (5) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 4 and 5 encode the same protein.

Source sequence(s)

AC079305, AK311395, AW471118

Consensus CDS

CCDS46457.1

UniProtKB/TrEMBL

B4DNB0, B7ZA33

Related

ENSP00000400073.2, ENST00000448782.6

Conserved Domains (2) summary

cd14720
Location:478 → 545

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain

pfam06886
Location:25 → 58

TPX2; Targeting protein for Xklp2 (TPX2)
NM_001313902.2 → NP_001300831.1 nuclear factor erythroid 2-related factor 2 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an alternate in-frame exon in the 3' coding region compared to variant 1. The resulting isoform (4) is shorter compared to isoform 1.

Source sequence(s)

AC079305, BI910808

Consensus CDS

CCDS92903.1

UniProtKB/TrEMBL

A0A8V8TN14, A0A8V8TN85

Related

ENSP00000514280.1, ENST00000699300.1

Conserved Domains (2) summary

cd14720
Location:464 → 531

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain

pfam06886
Location:41 → 74

TPX2; Targeting protein for Xklp2 (TPX2)
NM_001313903.2 → NP_001300832.1 nuclear factor erythroid 2-related factor 2 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting isoform (5) is shorter compared to isoform 1.

Source sequence(s)

AC079305, BP228042

Consensus CDS

CCDS92904.1

UniProtKB/TrEMBL

A0A8V8TPA8, E2I973

Related

ENSP00000514217.1, ENST00000699223.1

Conserved Domains (1) summary

cd14720
Location:421 → 488

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain
NM_001313904.1 → NP_001300833.1 nuclear factor erythroid 2-related factor 2 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (8) represents use of an alternate promoter and 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (6) is shorter compared to isoform 1.

Source sequence(s)

AC079305, AV702059, AW471118

UniProtKB/TrEMBL

B7ZA33

Conserved Domains (1) summary

cd14720
Location:394 → 461

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain
NM_006164.5 → NP_006155.2 nuclear factor erythroid 2-related factor 2 isoform 1

See identical proteins and their annotated locations for NP_006155.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC011558, DA438735

Consensus CDS

CCDS42782.1

UniProtKB/Swiss-Prot

B2RBU2, B4E338, E9PGJ7, Q16236, Q53RW6, Q59HH2, Q96F71

UniProtKB/TrEMBL

E2I973

Related

ENSP00000380252.3, ENST00000397062.8

Conserved Domains (2) summary

cd14720
Location:494 → 561

bZIP_NFE2-like; Basic leucine zipper (bZIP) domain of Nuclear Factor, Erythroid-derived 2 (NFE2) and similar proteins: a DNA-binding and dimerization domain

pfam06886
Location:40 → 74

TPX2; Targeting protein for Xklp2 (TPX2)