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Protein

Nuclear factor erythroid 2-related factor 2

Gene

Nfe2l2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

GO - Biological processi

  • aging Source: Ensembl
  • cell redox homeostasis Source: ParkinsonsUK-UCL
  • cellular response to drug Source: MGI
  • cellular response to fluid shear stress Source: UniProtKB
  • cellular response to glucose starvation Source: ParkinsonsUK-UCL
  • cellular response to hydrogen peroxide Source: MGI
  • cellular response to hypoxia Source: Ensembl
  • cellular response to laminar fluid shear stress Source: MGI
  • cellular response to oxidative stress Source: BHF-UCL
  • cellular response to tumor necrosis factor Source: MGI
  • endoplasmic reticulum unfolded protein response Source: MGI
  • inflammatory response Source: MGI
  • negative regulation of cardiac muscle cell apoptotic process Source: Ensembl
  • negative regulation of endothelial cell apoptotic process Source: MGI
  • negative regulation of hematopoietic stem cell differentiation Source: CACAO
  • negative regulation of hydrogen peroxide-induced cell death Source: MGI
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of vascular associated smooth muscle cell migration Source: Ensembl
  • PERK-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • positive regulation of angiogenesis Source: Ensembl
  • positive regulation of blood coagulation Source: BHF-UCL
  • positive regulation of blood vessel endothelial cell migration Source: Ensembl
  • positive regulation of gene expression Source: ParkinsonsUK-UCL
  • positive regulation of glucose import Source: CACAO
  • positive regulation of glutathione biosynthetic process Source: ParkinsonsUK-UCL
  • positive regulation of neuron projection development Source: Ensembl
  • positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter in response to stress Source: MGI
  • proteasomal ubiquitin-independent protein catabolic process Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of embryonic development Source: MGI
  • regulation of removal of superoxide radicals Source: BHF-UCL
  • regulation of transcription, DNA-templated Source: MGI
  • response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear factor erythroid 2-related factor 2
Short name:
NF-E2-related factor 2
Short name:
NFE2-related factor 2
Alternative name(s):
Nuclear factor, erythroid derived 2, like 2
Gene namesi
Name:Nfe2l2
Synonyms:Nrf-2, Nrf2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:108420. Nfe2l2.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Nucleus PROSITE-ProRule annotation1 Publication

  • Note: Cytosolic under unstressed conditions, translocates into the nucleus upon induction by electrophilic agents.

GO - Cellular componenti

  • centrosome Source: MGI
  • chromatin Source: BHF-UCL
  • cytoplasm Source: ParkinsonsUK-UCL
  • cytosol Source: BHF-UCL
  • nucleus Source: ParkinsonsUK-UCL
  • plasma membrane Source: MGI
  • protein-DNA complex Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075148.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000764501 – 597Nuclear factor erythroid 2-related factor 2Add BLAST597

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40Phosphoserine; by PKCBy similarity1
Modified residuei207PhosphoserineBy similarity1
Modified residuei588N6-acetyllysine; by CREBBPBy similarity1
Modified residuei591N6-acetyllysine; by CREBBPBy similarity1

Post-translational modificationi

Phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus.By similarity
Acetylation at Lys-588 and Lys-591 increases nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence.By similarity
Ubiquitinated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and subject to proteasomal degradation. Ubiquitination is inhibited by sulforaphane (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ60795.
PRIDEiQ60795.

PTM databases

iPTMnetiQ60795.
PhosphoSitePlusiQ60795.

Expressioni

Tissue specificityi

Widely expressed. Highest expression in liver, skeletal muscle, luminal cells of the stomach and intestine, lining of the bronchi and alveoli, and in renal tubules; followed by heart, spleen, testis and brain.

Gene expression databases

BgeeiENSMUSG00000015839.
CleanExiMM_NFE2L2.
GenevisibleiQ60795. MM.

Interactioni

Subunit structurei

Heterodimer. Forms a ternary complex with PGAM5 and KEAP1. Interacts with EEF1D at heat shock promoter elements (HSE). Interacts with KEAP1. Interacts via its leucine-zipper domain with the coiled-coil domain of PMF1. 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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Arrb1Q8BWG84EBI-642563,EBI-641778
Keap1Q9Z2X822EBI-642563,EBI-647110

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201744. 24 interactors.
DIPiDIP-49666N.
IntActiQ60795. 2 interactors.
MINTiMINT-1744109.
STRINGi10090.ENSMUSP00000099733.

Structurei

Secondary structure

1597
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi19 – 25Combined sources7
Helixi28 – 30Combined sources3
Helixi34 – 37Combined sources4
Turni78 – 80Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X2RX-ray1.70B76-84[»]
2DYHX-ray1.90B22-36[»]
3WN7X-ray1.57B/M17-51[»]
ProteinModelPortaliQ60795.
SMRiQ60795.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ60795.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini489 – 552bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni491 – 510Basic motifPROSITE-ProRule annotationAdd BLAST20
Regioni514 – 521Leucine-zipperPROSITE-ProRule annotation8
Regioni583 – 588Mediates interaction with CHD6 and is necessary to activate transcriptionBy similarity6

Sequence similaritiesi

Belongs to the bZIP family. CNC subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410KDJ5. Eukaryota.
ENOG41100FB. LUCA.
GeneTreeiENSGT00830000128250.
HOGENOMiHOG000234410.
HOVERGENiHBG052609.
InParanoidiQ60795.
KOiK05638.
OMAiALHIPFP.
OrthoDBiEOG091G02EB.
PhylomeDBiQ60795.
TreeFamiTF326681.

Family and domain databases

Gene3Di1.10.880.10. 1 hit.
InterProiIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR029845. Nrf2.
IPR008917. TF_DNA-bd.
[Graphical view]
PANTHERiPTHR24411:SF3. PTHR24411:SF3. 1 hit.
PfamiPF03131. bZIP_Maf. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
SUPFAMiSSF47454. SSF47454. 1 hit.
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60795-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMDLELPPPG LQSQQDMDLI DILWRQDIDL GVSREVFDFS QRQKDYELEK
60 70 80 90 100
QKKLEKERQE QLQKEQEKAF FAQFQLDEET GEFLPIQPAQ HIQTDTSGSA
110 120 130 140 150
SYSQVAHIPK QDALYFEDCM QLLAETFPFV DDHESLALDI PSHAESSVFT
160 170 180 190 200
APHQAQSLNS SLEAAMTDLS SIEQDMEQVW QELFSIPELQ CLNTENKQLA
210 220 230 240 250
DTTAVPSPEA TLTEMDSNYH FYSSISSLEK EVGNCGPHFL HGFEDSFSSI
260 270 280 290 300
LSTDDASQLT SLDSNPTLNT DFGDEFYSAF IAEPSDGGSM PSSAAISQSL
310 320 330 340 350
SELLDGTIEG CDLSLCKAFN PKHAEGTMEF NDSDSGISLN TSPSRASPEH
360 370 380 390 400
SVESSIYGDP PPGFSDSEME ELDSAPGSVK QNGPKAQPAH SPGDTVQPLS
410 420 430 440 450
PAQGHSAPMR ESQCENTTKK EVPVSPGHQK APFTKDKHSS RLEAHLTRDE
460 470 480 490 500
LRAKALHIPF PVEKIINLPV DDFNEMMSKE QFNEAQLALI RDIRRRGKNK
510 520 530 540 550
VAAQNCRKRK LENIVELEQD LGHLKDEREK LLREKGENDR NLHLLKRRLS
560 570 580 590
TLYLEVFSML RDEDGKPYSP SEYSLQQTRD GNVFLVPKSK KPDTKKN
Length:597
Mass (Da):66,901
Last modified:January 1, 1998 - v2
Checksum:i6128707C82CAE239
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70475, U70474 Genomic DNA. Translation: AAC52983.1.
AK142347 mRNA. Translation: BAE25040.1.
AL772404 Genomic DNA. Translation: CAM22493.1.
BC026943 mRNA. Translation: AAH26943.1.
U20532 mRNA. Translation: AAA68291.1.
CCDSiCCDS16150.1.
PIRiI49261.
RefSeqiNP_035032.1. NM_010902.4.
UniGeneiMm.1025.

Genome annotation databases

EnsembliENSMUST00000102672; ENSMUSP00000099733; ENSMUSG00000015839.
GeneIDi18024.
KEGGimmu:18024.
UCSCiuc008keq.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70475, U70474 Genomic DNA. Translation: AAC52983.1.
AK142347 mRNA. Translation: BAE25040.1.
AL772404 Genomic DNA. Translation: CAM22493.1.
BC026943 mRNA. Translation: AAH26943.1.
U20532 mRNA. Translation: AAA68291.1.
CCDSiCCDS16150.1.
PIRiI49261.
RefSeqiNP_035032.1. NM_010902.4.
UniGeneiMm.1025.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X2RX-ray1.70B76-84[»]
2DYHX-ray1.90B22-36[»]
3WN7X-ray1.57B/M17-51[»]
ProteinModelPortaliQ60795.
SMRiQ60795.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201744. 24 interactors.
DIPiDIP-49666N.
IntActiQ60795. 2 interactors.
MINTiMINT-1744109.
STRINGi10090.ENSMUSP00000099733.

Chemistry databases

ChEMBLiCHEMBL1075148.

PTM databases

iPTMnetiQ60795.
PhosphoSitePlusiQ60795.

Proteomic databases

PaxDbiQ60795.
PRIDEiQ60795.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000102672; ENSMUSP00000099733; ENSMUSG00000015839.
GeneIDi18024.
KEGGimmu:18024.
UCSCiuc008keq.1. mouse.

Organism-specific databases

CTDi4780.
MGIiMGI:108420. Nfe2l2.

Phylogenomic databases

eggNOGiENOG410KDJ5. Eukaryota.
ENOG41100FB. LUCA.
GeneTreeiENSGT00830000128250.
HOGENOMiHOG000234410.
HOVERGENiHBG052609.
InParanoidiQ60795.
KOiK05638.
OMAiALHIPFP.
OrthoDBiEOG091G02EB.
PhylomeDBiQ60795.
TreeFamiTF326681.

Miscellaneous databases

ChiTaRSiNfe2l2. mouse.
EvolutionaryTraceiQ60795.
PROiQ60795.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000015839.
CleanExiMM_NFE2L2.
GenevisibleiQ60795. MM.

Family and domain databases

Gene3Di1.10.880.10. 1 hit.
InterProiIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR029845. Nrf2.
IPR008917. TF_DNA-bd.
[Graphical view]
PANTHERiPTHR24411:SF3. PTHR24411:SF3. 1 hit.
PfamiPF03131. bZIP_Maf. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
SUPFAMiSSF47454. SSF47454. 1 hit.
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNF2L2_MOUSE
AccessioniPrimary (citable) accession number: Q60795
Secondary accession number(s): Q3UQK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.