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Protein

Nuclear factor erythroid 2-related factor 2

Gene

Nfe2l2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 and the regulation of cellular redox conditions. 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

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi620360 Nfe2l2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40S → A: Fails to dissociate from KEAP1 after PKC activation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1075141

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000764511 – 604Nuclear factor erythroid 2-related factor 2Add BLAST604

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40Phosphoserine; by PKC1 Publication1
Modified residuei214PhosphoserineBy similarity1
Modified residuei595N6-acetyllysine; by CREBBPBy similarity1
Modified residuei598N6-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.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
PRIDEiO54968

PTM databases

iPTMnetiO54968
PhosphoSitePlusiO54968

Expressioni

Gene expression databases

BgeeiENSRNOG00000001548 Expressed in 10 organ(s), highest expression level in colon

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. Interacts with ESRRB; represses NFE2L2 transcriptional activity (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi249784, 2 interactors
STRINGi10116.ENSRNOP00000002114

Structurei

3D structure databases

ProteinModelPortaliO54968
SMRiO54968
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini496 – 559bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni498 – 517Basic motifPROSITE-ProRule annotationAdd BLAST20
Regioni521 – 528Leucine-zipperPROSITE-ProRule annotation8
Regioni590 – 595Mediates interaction with CHD6 and is necessary to activate transcription1 Publication6

Sequence similaritiesi

Belongs to the bZIP family. CNC subfamily.Curated

Phylogenomic databases

eggNOGiENOG410KDJ5 Eukaryota
ENOG41100FB LUCA
GeneTreeiENSGT00920000148991
HOGENOMiHOG000234410
HOVERGENiHBG052609
InParanoidiO54968
KOiK05638
OMAiALHIPFP
PhylomeDBiO54968

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR004826 bZIP_Maf
IPR029845 Nrf2
IPR008917 TF_DNA-bd_sf
PANTHERiPTHR24411:SF3 PTHR24411:SF3, 1 hit
PfamiView protein in Pfam
PF03131 bZIP_Maf, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
SUPFAMiSSF47454 SSF47454, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025046135 – 141Missing in isoform 2. 1 Publication7

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_006234396.3 [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

Similar proteinsi

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_006234396.3 [O54968-1]
UniGeneiRn.10867

3D structure databases

ProteinModelPortaliO54968
SMRiO54968
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249784, 2 interactors
STRINGi10116.ENSRNOP00000002114

Chemistry databases

ChEMBLiCHEMBL1075141

PTM databases

iPTMnetiO54968
PhosphoSitePlusiO54968

Proteomic databases

PaxDbiO54968
PRIDEiO54968

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
GeneTreeiENSGT00920000148991
HOGENOMiHOG000234410
HOVERGENiHBG052609
InParanoidiO54968
KOiK05638
OMAiALHIPFP
PhylomeDBiO54968

Miscellaneous databases

PROiPR:O54968

Gene expression databases

BgeeiENSRNOG00000001548 Expressed in 10 organ(s), highest expression level in colon

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR004826 bZIP_Maf
IPR029845 Nrf2
IPR008917 TF_DNA-bd_sf
PANTHERiPTHR24411:SF3 PTHR24411:SF3, 1 hit
PfamiView protein in Pfam
PF03131 bZIP_Maf, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
SUPFAMiSSF47454 SSF47454, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNF2L2_RAT
AccessioniPrimary (citable) accession number: O54968
Secondary accession number(s): Q6P7C8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 2007
Last modified: September 12, 2018
This is version 142 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health

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