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Protein

Nuclear factor erythroid 2-related factor 2

Gene

Nfe2l2

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

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:Nrf2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi620360. Nfe2l2.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Nucleus PROSITE-ProRule annotation1 Publication

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

GO - Cellular componenti

  • centrosome Source: Ensembl
  • chromatin Source: Ensembl
  • cytoplasm Source: RGD
  • cytosol Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • plasma membrane Source: Ensembl
  • protein-DNA complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi40 – 401S → A: Fails to dissociate from KEAP1 after PKC activation. 1 Publication

Chemistry

ChEMBLiCHEMBL1075141.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 604604Nuclear factor erythroid 2-related factor 2PRO_0000076451Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei40 – 401Phosphoserine; by PKC1 Publication
Modified residuei214 – 2141PhosphoserineBy similarity
Modified residuei595 – 5951N6-acetyllysine; by CREBBPBy similarity
Modified residuei598 – 5981N6-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.1 Publication
Acetylation at Lys-595 and Lys-598 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

PaxDbiO54968.

PTM databases

iPTMnetiO54968.
PhosphoSiteiO54968.

Expressioni

Gene expression databases

ExpressionAtlasiO54968. baseline and differential.

Interactioni

Subunit structurei

Heterodimer. Forms a ternary complex with PGAM5 and KEAP1. Interacts via its leucine-zipper domain with the coiled-coil domain of PMF1. Interacts with EEF1D at heat shock promoter elements (HSE). 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.1 Publication

GO - Molecular functioni

  • transcription cofactor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi249784. 2 interactions.
STRINGi10116.ENSRNOP00000002114.

Structurei

3D structure databases

ProteinModelPortaliO54968.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini496 – 55964bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni498 – 51720Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni521 – 5288Leucine-zipperPROSITE-ProRule annotation
Regioni590 – 5956Mediates interaction with CHD6 and is necessary to activate transcription

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.
InParanoidiO54968.
KOiK05638.
PhylomeDBiO54968.

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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O54968-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMDLELPPPG LQSQQDMDLI DILWRQDIDL GVSREVFDFS QRQKDYELEK
60 70 80 90 100
QKKLEKERQE QLQKEQEKAF FAQLQLDEET GEFLPIQPAQ HIQTDTSGSV
110 120 130 140 150
SYSQVAHIPK QDALYFEDCM QLLAETFPFV DDHEVSSPTF QSLALDIPSH
160 170 180 190 200
VESSVFTTPD QAQSLDSSLE TAMTDLSSIQ QDMEQVWQEL FSIPELQCLN
210 220 230 240 250
TENKQQAETT TVPSPEATLT EMDSNYHFYS SIPSLEKEVD SCSPHFLHGF
260 270 280 290 300
EDSFSSILST DDASQLNSLD SNPTLNTDFG DEFYSAFLAE PSGGGSMPSS
310 320 330 340 350
AAISQSLSEL LGGPIEGCDL SLCKAFNQKH TEGTVEFNDS DSGISLNTSP
360 370 380 390 400
SRASPEHSVE SSIYGDPPPG FSDSEMEELD SAPGSVKQNG PKAQPTHSSG
410 420 430 440 450
DTVQPLSPAQ GHSAAVHESQ CENTTKKEVP VSPGHQKVPF TKDKHSSRLE
460 470 480 490 500
AHLTRDELRA KALHIPFPVE KIINLPVDDF NEMMSKEQFN EAQLALIRDI
510 520 530 540 550
RRRGKNKVAA QNCRKRKLEN IVELEQDLGH LKDEREKLLR EKGENDRNLH
560 570 580 590 600
LLKRKLSTLY LEVFSMLRDE DGKPYSPSEY SLQQTRDGNV FLVPKSKKPD

TKKN
Length:604
Mass (Da):67,703
Last modified:May 1, 2007 - v2
Checksum:iA07478F07F0C90B2
GO
Isoform 2 (identifier: O54968-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-141: Missing.

Show »
Length:597
Mass (Da):66,956
Checksum:iE568F5FB4F754272
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei135 – 1417Missing in isoform 2. 1 PublicationVSP_025046

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF037350 mRNA. Translation: AAB92256.1.
BC061724 mRNA. Translation: AAH61724.1.
RefSeqiNP_113977.1. NM_031789.2. [O54968-2]
XP_006234458.1. XM_006234396.2. [O54968-1]
UniGeneiRn.10867.

Genome annotation databases

EnsembliENSRNOT00000002114; ENSRNOP00000002114; ENSRNOG00000001548. [O54968-2]
GeneIDi83619.
KEGGirno:83619.
UCSCiRGD:620360. rat. [O54968-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF037350 mRNA. Translation: AAB92256.1.
BC061724 mRNA. Translation: AAH61724.1.
RefSeqiNP_113977.1. NM_031789.2. [O54968-2]
XP_006234458.1. XM_006234396.2. [O54968-1]
UniGeneiRn.10867.

3D structure databases

ProteinModelPortaliO54968.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249784. 2 interactions.
STRINGi10116.ENSRNOP00000002114.

Chemistry

ChEMBLiCHEMBL1075141.

PTM databases

iPTMnetiO54968.
PhosphoSiteiO54968.

Proteomic databases

PaxDbiO54968.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000002114; ENSRNOP00000002114; ENSRNOG00000001548. [O54968-2]
GeneIDi83619.
KEGGirno:83619.
UCSCiRGD:620360. rat. [O54968-1]

Organism-specific databases

CTDi4780.
RGDi620360. Nfe2l2.

Phylogenomic databases

eggNOGiENOG410KDJ5. Eukaryota.
ENOG41100FB. LUCA.
GeneTreeiENSGT00830000128250.
HOGENOMiHOG000234410.
HOVERGENiHBG052609.
InParanoidiO54968.
KOiK05638.
PhylomeDBiO54968.

Miscellaneous databases

PROiO54968.

Gene expression databases

ExpressionAtlasiO54968. baseline and differential.

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...

Publicationsi

« Hide 'large scale' publications
  1. Sakai M., Ito M., Sasaki K., Nishi S.
    Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Strain: Wistar.
    Tissue: Liver.
  2. "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] (ISOFORM 1).
    Tissue: Prostate.
  3. "Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription."
    Huang H.-C., Nguyen T., Pickett C.B.
    J. Biol. Chem. 277:42769-42774(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-40, MUTAGENESIS OF SER-40.
  4. "The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation."
    Nioi P., Nguyen T., Sherratt P.J., Pickett C.B.
    Mol. Cell. Biol. 25:10895-10906(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CHD6 AND MAFK, SUBCELLULAR LOCATION, REGION.

Entry informationi

Entry nameiNF2L2_RAT
AccessioniPrimary (citable) accession number: O54968
Secondary accession number(s): Q6P7C8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 2007
Last modified: July 6, 2016
This is version 122 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

Complete proteome, Reference proteome

Documents

  1. 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.