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Q60795 (NF2L2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Nfe2l2
Synonyms:Nrf-2, Nrf2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6

Subunit structure

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. Ref.6 Ref.7

Subcellular location

Cytoplasmcytosol. Nucleus. Note: Cytosolic under unstressed conditions, translocates into the nucleus upon induction by electrophilic agents. Ref.6

Tissue specificity

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.

Post-translational modification

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.

Sequence similarities

Belongs to the bZIP family. CNC subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to laminar fluid shear stress

Inferred from electronic annotation. Source: Ensembl

cellular response to oxidative stress

Inferred from direct assay PubMed 20978343. Source: BHF-UCL

cellular response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum unfolded protein response

Inferred from direct assay PubMed 14517290. Source: MGI

negative regulation of endothelial cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

positive regulation of blood coagulation

Inferred from mutant phenotype PubMed 20978343. Source: BHF-UCL

positive regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype PubMed 20978343. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20978343. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter in response to stress

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 14517290PubMed 15870285. Source: MGI

proteasomal ubiquitin-independent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of embryonic development

Inferred from genetic interaction PubMed 15087497. Source: MGI

regulation of removal of superoxide radicals

Inferred from mutant phenotype PubMed 20978343. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12220541. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcentrosome

Inferred from electronic annotation. Source: Ensembl

chromatin

Inferred from direct assay PubMed 20978343. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 20978343. Source: BHF-UCL

cytosol

Inferred from direct assay PubMed 23043106. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 23043106. Source: BHF-UCL

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from direct assay PubMed 12220541PubMed 14517290PubMed 15870285. Source: MGI

protein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12220541PubMed 14517290. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Arrb1Q8BWG84EBI-642563,EBI-641778

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 597597Nuclear factor erythroid 2-related factor 2
PRO_0000076450

Regions

Domain489 – 55264bZIP
Region491 – 51020Basic motif By similarity
Region514 – 5218Leucine-zipper By similarity
Region583 – 5886Mediates interaction with CHD6 and is necessary to activate transcription By similarity

Amino acid modifications

Modified residue401Phosphoserine By similarity
Modified residue2071Phosphoserine By similarity
Modified residue5881N6-acetyllysine; by CREBBP By similarity
Modified residue5911N6-acetyllysine; by CREBBP By similarity

Secondary structure

......... 597
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q60795 [UniParc].

Last modified January 1, 1998. Version 2.
Checksum: 6128707C82CAE239

FASTA59766,901
        10         20         30         40         50         60 
MMDLELPPPG LQSQQDMDLI DILWRQDIDL GVSREVFDFS QRQKDYELEK QKKLEKERQE 

        70         80         90        100        110        120 
QLQKEQEKAF FAQFQLDEET GEFLPIQPAQ HIQTDTSGSA SYSQVAHIPK QDALYFEDCM 

       130        140        150        160        170        180 
QLLAETFPFV DDHESLALDI PSHAESSVFT APHQAQSLNS SLEAAMTDLS SIEQDMEQVW 

       190        200        210        220        230        240 
QELFSIPELQ CLNTENKQLA DTTAVPSPEA TLTEMDSNYH FYSSISSLEK EVGNCGPHFL 

       250        260        270        280        290        300 
HGFEDSFSSI LSTDDASQLT SLDSNPTLNT DFGDEFYSAF IAEPSDGGSM PSSAAISQSL 

       310        320        330        340        350        360 
SELLDGTIEG CDLSLCKAFN PKHAEGTMEF NDSDSGISLN TSPSRASPEH SVESSIYGDP 

       370        380        390        400        410        420 
PPGFSDSEME ELDSAPGSVK QNGPKAQPAH SPGDTVQPLS PAQGHSAPMR ESQCENTTKK 

       430        440        450        460        470        480 
EVPVSPGHQK APFTKDKHSS RLEAHLTRDE LRAKALHIPF PVEKIINLPV DDFNEMMSKE 

       490        500        510        520        530        540 
QFNEAQLALI RDIRRRGKNK VAAQNCRKRK LENIVELEQD LGHLKDEREK LLREKGENDR 

       550        560        570        580        590 
NLHLLKRRLS TLYLEVFSML RDEDGKPYSP SEYSLQQTRD GNVFLVPKSK KPDTKKN 

« Hide

References

« Hide 'large scale' references
[1]"NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development."
Chan K., Lu R., Chang J.C., Kan Y.W.
Proc. Natl. Acad. Sci. U.S.A. 93:13943-13948(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/SvJ.
Tissue: Lung.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Embryonic lung.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II.
Tissue: Mammary gland.
[5]"cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor."
Chui D.H.K., Tang W., Orkin S.H.
Biochem. Biophys. Res. Commun. 209:40-46(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-597.
Strain: C57BL/6J.
Tissue: Erythroblast.
[6]"Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain."
Itoh K., Wakabayashi N., Katoh Y., Ishii T., Igarashi K., Engel J.D., Yamamoto M.
Genes Dev. 13:76-86(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH KEAP1.
[7]"Cloning and characterization of the mouse polyamine-modulated factor-1 (mPMF-1) gene: an alternatively spliced homologue of the human transcription factor."
Wang Y., Devereux W., Woster P.M., Casero R.A. Jr.
Biochem. J. 359:387-392(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFE2L2.
[8]"Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer."
Padmanabhan B., Tong K.I., Ohta T., Nakamura Y., Scharlock M., Ohtsuji M., Kang M., Kobayashi A., Yokoyama S., Yamamoto M.
Mol. Cell 21:689-700(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 76-84 IN COMPLEX WITH KEAP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS16150.1.
PIRI49261.
RefSeqNP_035032.1. NM_010902.3.
UniGeneMm.1025.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X2RX-ray1.70B76-84[»]
2DYHX-ray1.90B22-36[»]
3WN7X-ray1.57B/M17-51[»]
ProteinModelPortalQ60795.
SMRQ60795. Positions 441-549.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201744. 24 interactions.
IntActQ60795. 1 interaction.
MINTMINT-1744109.

Chemistry

ChEMBLCHEMBL1075148.

PTM databases

PhosphoSiteQ60795.

Proteomic databases

PaxDbQ60795.
PRIDEQ60795.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000102672; ENSMUSP00000099733; ENSMUSG00000015839.
GeneID18024.
KEGGmmu:18024.
UCSCuc008keq.1. mouse.

Organism-specific databases

CTD4780.
MGIMGI:108420. Nfe2l2.

Phylogenomic databases

eggNOGNOG309753.
GeneTreeENSGT00550000074399.
HOGENOMHOG000234410.
HOVERGENHBG052609.
InParanoidQ60795.
KOK05638.
OMAALHIPFP.
OrthoDBEOG715Q3N.
PhylomeDBQ60795.
TreeFamTF326681.

Gene expression databases

BgeeQ60795.
CleanExMM_NFE2L2.
GenevestigatorQ60795.

Family and domain databases

Gene3D1.10.880.10. 1 hit.
InterProIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR008917. TF_DNA-bd.
[Graphical view]
PfamPF03131. bZIP_Maf. 1 hit.
[Graphical view]
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
SUPFAMSSF47454. SSF47454. 1 hit.
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNFE2L2. mouse.
EvolutionaryTraceQ60795.
NextBio293087.
PROQ60795.
SOURCESearch...

Entry information

Entry nameNF2L2_MOUSE
AccessionPrimary (citable) accession number: Q60795
Secondary accession number(s): Q3UQK0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot