• Gene id: 4780

Gene Summary

• Gene Symbol: NFE2L2   Gene   UCSC   Ensembl
• Aliases: HEBP1, IMDDHH, NRF2
• Gene name: nuclear factor, erythroid 2 like 2
• Alternate names: nuclear factor erythroid 2-related factor 2, nuclear factor erythroid-derived 2-like 2,
• Gene location: 2q31.2 (177265130: 177230302)     Exons: 6     NC_000002.12
• Gene summary(Entrez): 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 gene
• OMIM: 600492

Protein Summary

• Protein general information: Q16236  
  • Name: Nuclear factor erythroid 2 related factor 2 (NF E2 related factor 2) (NFE2 related factor 2) (HEBP1) (Nuclear factor, erythroid derived 2, like 2)
  • Length: 605  
  • Mass: 67,827
• Sequence:

  MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQEQLQKEQEKAFFAQLQ
  LDEETGEFLPIQPAQHIQSETSGSANYSQVAHIPKSDALYFDDCMQLLAQTFPFVDDNEVSSATFQSLVPDIPGH
  IESPVFIATNQAQSPETSVAQVAPVDLDGMQQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSPEAKLTEVDN
  YHFYSSIPSMEKEVGNCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDATVNTDFGDEFYSAFIAEPSISNSMP
  SPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPESTAEFNDSDSGISLNTSPSVASPEHSVESSSYGDTLLGLSD
  SEVEELDSAPGSVKQNGPKTPVHSSGDMVQPLSPSQGQSTHVHDAQCENTPEKELPVSPGHRKTPFTKDKHSSRL
  EAHLTRDELRAKALHIPFPVEKIINLPVVDFNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVEL
  EQDLDHLKDEKEKLLKEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKP
  DVKKN

• Structural information:
  • Protein Domains: bZIP. (497-560)
  • Interpro: IPR004827  IPR004826  IPR029845  IPR008917  
  • Prosite: PS50217 PS00036
  • PDB: 2FLU 2LZ1 3ZGC 4IFL
  • PDBsum: 2FLU 2LZ1 3ZGC 4IFL
  • DIP: 29971
  • STRING: ENSP00000380252
• Other Databases: GeneCards:  NFE2L2  Malacards:  NFE2L2

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000785	chromatin	IEA	cellular component
GO:0000976	transcription regulatory region sequence-specific DNA binding	TAS	molecular function
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding	IEA	molecular function
GO:0001102	RNA polymerase II activating transcription factor binding	IPI	molecular function
GO:0001205	transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding	IEA	molecular function
GO:0001221	transcription cofactor binding	IEA	molecular function
GO:0003677	DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IDA	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005813	centrosome	IDA	cellular component
GO:0005829	cytosol	IDA	cellular component
GO:0005886	plasma membrane	IDA	cellular component
GO:0006366	transcription from RNA polymerase II promoter	IEA	biological process
GO:0006954	inflammatory response	IEA	biological process
GO:0010499	proteasomal ubiquitin-independent protein catabolic process	IDA	biological process
GO:0010628	positive regulation of gene expression	IGI	biological process
GO:0016567	protein ubiquitination	IDA	biological process
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0030194	positive regulation of blood coagulation	IEA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	ISS	biological process
GO:0032993	protein-DNA complex	ISS	cellular component
GO:0034599	cellular response to oxidative stress	NAS	biological process
GO:0034599	cellular response to oxidative stress	TAS	biological process
GO:0035690	cellular response to drug	IEA	biological process
GO:0036003	positive regulation of transcription from RNA polymerase II promoter in response to stress	IMP	biological process
GO:0036091	positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress	IEA	biological process
GO:0036499	PERK-mediated unfolded protein response	ISS	biological process
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0042149	cellular response to glucose starvation	IEA	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	IDA	biological process
GO:0044212	transcription regulatory region DNA binding	TAS	molecular function
GO:0045454	cell redox homeostasis	IEA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IDA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IMP	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IC	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IMP	biological process
GO:0045995	regulation of embryonic development	IEA	biological process
GO:0046326	positive regulation of glucose import	IEA	biological process
GO:0070301	cellular response to hydrogen peroxide	IMP	biological process
GO:0071356	cellular response to tumor necrosis factor	IMP	biological process
GO:0071498	cellular response to fluid shear stress	IDA	biological process
GO:0071499	cellular response to laminar fluid shear stress	IMP	biological process
GO:1902037	negative regulation of hematopoietic stem cell differentiation	IEA	biological process
GO:1902176	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	IMP	biological process
GO:1903071	positive regulation of ER-associated ubiquitin-dependent protein catabolic process	TAS	biological process
GO:1903206	negative regulation of hydrogen peroxide-induced cell death	IGI	biological process
GO:1903788	positive regulation of glutathione biosynthetic process	IEA	biological process
GO:2000121	regulation of removal of superoxide radicals	IEA	biological process
GO:2000352	negative regulation of endothelial cell apoptotic process	IMP	biological process
GO:2000379	positive regulation of reactive oxygen species metabolic process	IEA	biological process
GO:0000785	chromatin	IEA	cellular component
GO:0000976	transcription regulatory region sequence-specific DNA binding	IEA	molecular function
GO:0000976	transcription regulatory region sequence-specific DNA binding	TAS	molecular function
GO:0000980	RNA polymerase II distal enhancer sequence-specific DNA binding	IEA	molecular function
GO:0001102	RNA polymerase II activating transcription factor binding	IPI	molecular function
GO:0001205	transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding	IEA	molecular function
GO:0001221	transcription cofactor binding	IEA	molecular function
GO:0003677	DNA binding	IEA	molecular function
GO:0003677	DNA binding	IEA	molecular function
GO:0003677	DNA binding	IEA	molecular function
GO:0003677	DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IEA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IEA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	TAS	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005813	centrosome	IDA	cellular component
GO:0005829	cytosol	IEA	cellular component
GO:0005829	cytosol	IEA	cellular component
GO:0005829	cytosol	IDA	cellular component
GO:0005886	plasma membrane	IDA	cellular component
GO:0006351	transcription, DNA-templated	IEA	biological process
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0006366	transcription from RNA polymerase II promoter	IEA	biological process
GO:0006366	transcription from RNA polymerase II promoter	TAS	biological process
GO:0006954	inflammatory response	IEA	biological process
GO:0010499	proteasomal ubiquitin-independent protein catabolic process	IDA	biological process
GO:0010628	positive regulation of gene expression	IEA	biological process
GO:0010628	positive regulation of gene expression	IGI	biological process
GO:0016567	protein ubiquitination	IDA	biological process
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0030194	positive regulation of blood coagulation	IEA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	IEA	biological process
GO:0030968	endoplasmic reticulum unfolded protein response	ISS	biological process
GO:0032993	protein-DNA complex	IEA	cellular component
GO:0032993	protein-DNA complex	ISS	cellular component
GO:0034599	cellular response to oxidative stress	IEA	biological process
GO:0034599	cellular response to oxidative stress	IEA	biological process
GO:0034599	cellular response to oxidative stress	NAS	biological process
GO:0034599	cellular response to oxidative stress	TAS	biological process
GO:0034976	response to endoplasmic reticulum stress	IEA	biological process
GO:0035690	cellular response to drug	IEA	biological process
GO:0036003	positive regulation of transcription from RNA polymerase II promoter in response to stress	IMP	biological process
GO:0036091	positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress	IEA	biological process
GO:0036499	PERK-mediated unfolded protein response	IEA	biological process
GO:0036499	PERK-mediated unfolded protein response	ISS	biological process
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0042149	cellular response to glucose starvation	IEA	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	IDA	biological process
GO:0043565	sequence-specific DNA binding	IEA	molecular function
GO:0043565	sequence-specific DNA binding	IEA	molecular function
GO:0044212	transcription regulatory region DNA binding	TAS	molecular function
GO:0045454	cell redox homeostasis	IEA	biological process
GO:0045893	positive regulation of transcription, DNA-templated	IEA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IEA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IDA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IMP	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IC	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IMP	biological process
GO:0045995	regulation of embryonic development	IEA	biological process
GO:0046326	positive regulation of glucose import	IEA	biological process
GO:0060548	negative regulation of cell death	IEA	biological process
GO:0070301	cellular response to hydrogen peroxide	IMP	biological process
GO:0071356	cellular response to tumor necrosis factor	IMP	biological process
GO:0071498	cellular response to fluid shear stress	IDA	biological process
GO:0071499	cellular response to laminar fluid shear stress	IMP	biological process
GO:1902037	negative regulation of hematopoietic stem cell differentiation	IEA	biological process
GO:1902176	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	IMP	biological process
GO:1903071	positive regulation of ER-associated ubiquitin-dependent protein catabolic process	TAS	biological process
GO:1903206	negative regulation of hydrogen peroxide-induced cell death	IGI	biological process
GO:1903788	positive regulation of glutathione biosynthetic process	IEA	biological process
GO:2000121	regulation of removal of superoxide radicals	IEA	biological process
GO:2000352	negative regulation of endothelial cell apoptotic process	IMP	biological process
GO:2000379	positive regulation of reactive oxygen species metabolic process	IEA	biological process
GO:0000976	transcription regulatory region sequence-specific DNA binding	TAS	molecular function
GO:0001102	RNA polymerase II activating transcription factor binding	IPI	molecular function
GO:0003677	DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	TAS	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005813	centrosome	IDA	cellular component
GO:0005829	cytosol	IDA	cellular component
GO:0005886	plasma membrane	IDA	cellular component
GO:0006366	transcription from RNA polymerase II promoter	TAS	biological process
GO:0010499	proteasomal ubiquitin-independent protein catabolic process	IDA	biological process
GO:0010628	positive regulation of gene expression	IGI	biological process
GO:0016567	protein ubiquitination	IDA	biological process
GO:0019904	protein domain specific binding	IPI	molecular function
GO:0030968	endoplasmic reticulum unfolded protein response	ISS	biological process
GO:0032993	protein-DNA complex	ISS	cellular component
GO:0034599	cellular response to oxidative stress	NAS	biological process
GO:0034599	cellular response to oxidative stress	TAS	biological process
GO:0036003	positive regulation of transcription from RNA polymerase II promoter in response to stress	IMP	biological process
GO:0036499	PERK-mediated unfolded protein response	ISS	biological process
GO:0036499	PERK-mediated unfolded protein response	TAS	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	IDA	biological process
GO:0044212	transcription regulatory region DNA binding	TAS	molecular function
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IDA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IMP	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IC	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IMP	biological process
GO:0070301	cellular response to hydrogen peroxide	IMP	biological process
GO:0071356	cellular response to tumor necrosis factor	IMP	biological process
GO:0071498	cellular response to fluid shear stress	IDA	biological process
GO:0071499	cellular response to laminar fluid shear stress	IMP	biological process
GO:1902176	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	IMP	biological process
GO:1903071	positive regulation of ER-associated ubiquitin-dependent protein catabolic process	TAS	biological process
GO:1903206	negative regulation of hydrogen peroxide-induced cell death	IGI	biological process
GO:2000352	negative regulation of endothelial cell apoptotic process	IMP	biological process

KEGG pathways

Pathway id	Pathway name
hsa04120	Ubiquitin mediated proteolysis
hsa02010	ABC transporters
hsa04010	MAPK signaling pathway
hsa05200	Pathways in cancer
hsa05225	Hepatocellular carcinoma
hsa05418	Fluid shear stress and atherosclerosis

Diseases

Associated diseases	References
Cancer	GAD: 18444152
Cancer (Adenoma)	GAD: 18074351
Cancer (colorectal)	GAD: 18444152
Cancer (Squamous cell)	GAD: 20421815
Cancer (breast)	GAD: 17726138
Atherosclerosis	GAD: 19948975
Ulcerative colitis	GAD: 18613373
Systemic lupus erythematosus (SLE)	GAD: 20507872
Asthma	GAD: 20805158
Parkinson disease	GAD: 20196834
Alzheimer's disease	GAD: 20064547
Asthenozoospermia	MIK: 22648520
Leukocytospermia	MIK: 26227162
Male factor infertility	MIK: 22648520
Oligoasthenozoospermia	MIK: 22648520
Low sperm motility	MIK: 23089668
Spermatogenesis defects	MIK: 22648520
Asthenozoospermia	MIK: 23089668
Defective spermatogenesis	MIK: 22648520
Pulmonary disease	GAD: 19671143
Pulmonary embolism	GAD: 21107315
Chronic obstructive pulmonary disease (COPD)	GAD: 19671143
Vitiligo	GAD: 21085187
Male infertility	MIK: 26823733
Asthenozoospermia	MIK: 23089668
Oligoasthenozoospermia	MIK: 26823733
Cryptorchidism	MIK: 28606200
Leukocytospermia	MIK: 26227162
Low sperm motility	MIK: 23089668
Plays a role in preventing oxidative disruption of spermatogenesis	MIK: 20692336
Spermatogenic defects	MIK: 22648520
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
23089668	Asthenozoospermia, oligoasthenozoospermia			120 (55 asthenozoospermic and oligoasthenozoospermic patients, 65 controls)	Male infertility	NRF2 CAT GSTM1 SOD2
26227162	Leukocytospermia, idiopathic male infertility			85 (38 non-LCS patients, 47 LCS patients)	Male infertility	TLR-2/4 COX-2 and Nrf-2
22648520	Defective spermatogenesis	Nrf2 SNPs (-617 G > T and -653 T > C)		631 (196 idiopathic asthenozoospermic patients, 140 idiopathic oligoasthenozoospermic patients, 295 controls)	Male infertility	NRF2 GSTM1 SOD2
20692336	Plays a role in preventing oxidative disruption of spermatogenesis				Male infertility
26823733	Asthenozoospermia, Oligoasthenozoospermia, Male infertility			135 (45 healthy control, 45 asthenozoospermic patients and 45 oligoasthenozoospermic patients)	Male infertility
17327269	Teratozoospermia			13 (5 controls, 8 cases)	Male infertility	GSE6967 analyzed by GEO2R (cutoff 1.5 fold)
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq