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Q60795

- NF2L2_MOUSE

UniProt

Q60795 - NF2L2_MOUSE

Protein

Nuclear factor erythroid 2-related factor 2

Gene

Nfe2l2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (01 Jan 1998)
      Previous versions | rss
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    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

    1. DNA binding Source: MGI
    2. protein binding Source: UniProtKB
    3. RNA polymerase II distal enhancer sequence-specific DNA binding Source: NTNU_SB
    4. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    5. sequence-specific DNA binding transcription factor activity Source: MGI

    GO - Biological processi

    1. cellular response to hydrogen peroxide Source: Ensembl
    2. cellular response to laminar fluid shear stress Source: Ensembl
    3. cellular response to oxidative stress Source: BHF-UCL
    4. cellular response to tumor necrosis factor Source: Ensembl
    5. endoplasmic reticulum unfolded protein response Source: MGI
    6. negative regulation of endothelial cell apoptotic process Source: Ensembl
    7. negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: Ensembl
    8. positive regulation of blood coagulation Source: BHF-UCL
    9. positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
    10. positive regulation of transcription, DNA-templated Source: MGI
    11. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    12. positive regulation of transcription from RNA polymerase II promoter in response to stress Source: Ensembl
    13. proteasomal ubiquitin-independent protein catabolic process Source: UniProtKB
    14. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    15. protein ubiquitination Source: UniProtKB
    16. regulation of embryonic development Source: MGI
    17. regulation of removal of superoxide radicals Source: BHF-UCL
    18. regulation of transcription, DNA-templated Source: MGI

    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
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:108420. Nfe2l2.

    Subcellular locationi

    Cytoplasmcytosol 1 Publication. Nucleus 1 PublicationPROSITE-ProRule annotation
    Note: Cytosolic under unstressed conditions, translocates into the nucleus upon induction by electrophilic agents.

    GO - Cellular componenti

    1. centrosome Source: Ensembl
    2. chromatin Source: BHF-UCL
    3. cytoplasm Source: BHF-UCL
    4. cytosol Source: BHF-UCL
    5. nucleus Source: BHF-UCL
    6. plasma membrane Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 597597Nuclear factor erythroid 2-related factor 2PRO_0000076450Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei40 – 401PhosphoserineBy similarity
    Modified residuei207 – 2071PhosphoserineBy similarity
    Modified residuei588 – 5881N6-acetyllysine; by CREBBPBy similarity
    Modified residuei591 – 5911N6-acetyllysine; by CREBBPBy similarity

    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

    PhosphoSiteiQ60795.

    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

    BgeeiQ60795.
    CleanExiMM_NFE2L2.
    GenevestigatoriQ60795.

    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

    Protein-protein interaction databases

    BioGridi201744. 24 interactions.
    IntActiQ60795. 1 interaction.
    MINTiMINT-1744109.

    Structurei

    Secondary structure

    1
    597
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi19 – 257
    Helixi28 – 303
    Helixi34 – 374
    Turni78 – 803

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1X2RX-ray1.70B76-84[»]
    2DYHX-ray1.90B22-36[»]
    3WN7X-ray1.57B/M17-51[»]
    ProteinModelPortaliQ60795.
    SMRiQ60795. Positions 441-549.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ60795.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini489 – 55264bZIPPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni491 – 51020Basic motifPROSITE-ProRule annotationAdd
    BLAST
    Regioni514 – 5218Leucine-zipperPROSITE-ProRule annotation
    Regioni583 – 5886Mediates interaction with CHD6 and is necessary to activate transcriptionBy similarity

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiNOG309753.
    GeneTreeiENSGT00550000074399.
    HOGENOMiHOG000234410.
    HOVERGENiHBG052609.
    InParanoidiQ60795.
    KOiK05638.
    OMAiALHIPFP.
    OrthoDBiEOG715Q3N.
    PhylomeDBiQ60795.
    TreeFamiTF326681.

    Family and domain databases

    Gene3Di1.10.880.10. 1 hit.
    InterProiIPR004827. bZIP.
    IPR004826. bZIP_Maf.
    IPR008917. TF_DNA-bd.
    [Graphical view]
    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

    MMDLELPPPG LQSQQDMDLI DILWRQDIDL GVSREVFDFS QRQKDYELEK    50
    QKKLEKERQE QLQKEQEKAF FAQFQLDEET GEFLPIQPAQ HIQTDTSGSA 100
    SYSQVAHIPK QDALYFEDCM QLLAETFPFV DDHESLALDI PSHAESSVFT 150
    APHQAQSLNS SLEAAMTDLS SIEQDMEQVW QELFSIPELQ CLNTENKQLA 200
    DTTAVPSPEA TLTEMDSNYH FYSSISSLEK EVGNCGPHFL HGFEDSFSSI 250
    LSTDDASQLT SLDSNPTLNT DFGDEFYSAF IAEPSDGGSM PSSAAISQSL 300
    SELLDGTIEG CDLSLCKAFN PKHAEGTMEF NDSDSGISLN TSPSRASPEH 350
    SVESSIYGDP PPGFSDSEME ELDSAPGSVK QNGPKAQPAH SPGDTVQPLS 400
    PAQGHSAPMR ESQCENTTKK EVPVSPGHQK APFTKDKHSS RLEAHLTRDE 450
    LRAKALHIPF PVEKIINLPV DDFNEMMSKE QFNEAQLALI RDIRRRGKNK 500
    VAAQNCRKRK LENIVELEQD LGHLKDEREK LLREKGENDR NLHLLKRRLS 550
    TLYLEVFSML RDEDGKPYSP SEYSLQQTRD GNVFLVPKSK KPDTKKN 597
    Length:597
    Mass (Da):66,901
    Last modified:January 1, 1998 - v2
    Checksum:i6128707C82CAE239
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_010902.3.
    UniGeneiMm.1025.

    Genome annotation databases

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

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS16150.1.
    PIRi I49261.
    RefSeqi NP_035032.1. NM_010902.3.
    UniGenei Mm.1025.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1X2R X-ray 1.70 B 76-84 [» ]
    2DYH X-ray 1.90 B 22-36 [» ]
    3WN7 X-ray 1.57 B/M 17-51 [» ]
    ProteinModelPortali Q60795.
    SMRi Q60795. Positions 441-549.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201744. 24 interactions.
    IntActi Q60795. 1 interaction.
    MINTi MINT-1744109.

    Chemistry

    ChEMBLi CHEMBL1075148.

    PTM databases

    PhosphoSitei Q60795.

    Proteomic databases

    PaxDbi Q60795.
    PRIDEi Q60795.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000102672 ; ENSMUSP00000099733 ; ENSMUSG00000015839 .
    GeneIDi 18024.
    KEGGi mmu:18024.
    UCSCi uc008keq.1. mouse.

    Organism-specific databases

    CTDi 4780.
    MGIi MGI:108420. Nfe2l2.

    Phylogenomic databases

    eggNOGi NOG309753.
    GeneTreei ENSGT00550000074399.
    HOGENOMi HOG000234410.
    HOVERGENi HBG052609.
    InParanoidi Q60795.
    KOi K05638.
    OMAi ALHIPFP.
    OrthoDBi EOG715Q3N.
    PhylomeDBi Q60795.
    TreeFami TF326681.

    Miscellaneous databases

    ChiTaRSi NFE2L2. mouse.
    EvolutionaryTracei Q60795.
    NextBioi 293087.
    PROi Q60795.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q60795.
    CleanExi MM_NFE2L2.
    Genevestigatori Q60795.

    Family and domain databases

    Gene3Di 1.10.880.10. 1 hit.
    InterProi IPR004827. bZIP.
    IPR004826. bZIP_Maf.
    IPR008917. TF_DNA-bd.
    [Graphical view ]
    Pfami PF03131. bZIP_Maf. 1 hit.
    [Graphical view ]
    SMARTi SM00338. BRLZ. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47454. SSF47454. 1 hit.
    PROSITEi PS50217. BZIP. 1 hit.
    PS00036. BZIP_BASIC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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.

    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: October 1, 2014
    This is version 126 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

    External Data

    Dasty 3