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FLASH GENE
Symbol NFE2L1 contributors: mct/shn - updated : 07-03-2015
HGNC name nuclear factor (erythroid-derived 2)-like 1
HGNC id 7781
Location 17q21.32      Physical location : 46.125.685 - 46.138.906
Synonym name
  • NF-E2-related factor 1
  • NFE2-related factor 1
  • TCF-11
  • locus control region-factor 1
  • nuclear factor erythroid 2-related factor 1
  • nuclear factor, erythroid derived 2, like 1
  • transcription factor 11 (basic leucine zipper type)
  • transcription factor HBZ17; transcription factor LCR-F1
  • Synonym symbol(s) TCF11, BRF1, LCR-F1, HBZ17, FLJ00380, NRF-1, NRF1
    DNA
    TYPE functioning gene
    STRUCTURE 13.22 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - D17S1859 - D17S1785 - NFE2L1 - D17S958 - D17S1150 - qter
    Physical map
    NPEPPS 17q21.2-q21.32 aminopeptidase puromycin sensitive KPNB1 17q21.32 karyopherin (importin) beta 1 ProSAPiP2 17q21.32 ProSAPiP2 protein TBX21 17q21.3 T-box 21 OSBPL7 17q21.2 oxysterol binding protein-like 7 MRPL10 17q21.32 mitochondrial ribosomal protein L10 MGC16309 17q21.32 hypothetical gene MGC16309 Ses2 17q21.32 secernin 2 SP6 17q21.3-q22 Sp6 transcription factor LOC388398 17 LOC388398 SP2 17q21.3-q22 Sp2 transcription factor PNPO 17q21.32 pyridoxine-5'-phosphate oxidase MGC11242 17q21.32 hypothetical protein MGC11242 CDK5RAP3 17q21.2 CDK5 regulatory subunit associated protein 3 COPZ2 17q21.3 coatomer protein complex, subunit zeta 2 NFE2L1 17q21.3 nuclear factor (erythroid-derived 2)-like 1 CBX1 17q21.32 chromobox homolog 1 (HP1 beta homolog Drosophila ) SNX11 17q21.2 sorting nexin 11 SCAP1 17q21.32 src family associated phosphoprotein 1 HOXB1 17q21.3 homeo box B1 HOXB2 17q21.3 homeo box B2 HOXB3 17q21.3 homeo box B3 HOXB4 17q21.3 homeo box B4 HOXB5 17q21.3 homeo box B5 HOXB6 17q21.3 homeo box B6
    regionally located physically linked to BTR (PMID: 7557987)
    RNA
    TRANSCRIPTS type messenger
    text several mRNA isoforms generated by alternative splicing (Luna), at least six variants (PMID: 9826775)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 4891 84.7 772 - 2007 16806233
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestivemouthtongue  highly
    Endocrinethyroid   highly
    Nervousbrain   highly Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • NTD (N-terminal domain), AAs 1124, with a leucine-rich sequence, called NHB1 (N-terminal homology box 1, which tethers NFE2L1 to the ER (endoplasmic reticulum , and an NHB2 (N-terminal
  • homology box 2; AAs 82106), and region located between NHB1 and NHB2 includes the SAS and CRACs motifs (SAS, CRACs and NHB2 subdomains are transiently translocated into the ER lumen)
  • basic leucine zipper (bZIP) motif
  • two putative Cdc4 CPD motifs
  • two separate domain, N terminal acidic domain and a serine-rich stretch adjacent to the CNC bZIP domain required for transactivation
  • a nuclear export signal (NES) localised in the N-terminus responsible for the active nuclear export of the protein
  • a large C-terminal portion is dynamically retrotranslocated from
  • the ER lumen to the cytoplasmic and/or nucleoplasmic sides
    conjugated ubiquitinated
    HOMOLOGY
    interspecies ortholog to Nfe2l1, Mus musculus
    ortholog to Nfe2l1, Rattus nrvegicus
    ortholog to NFE2L1, Pan troglodytes
    ortholog to nfe2l1, Danio rerio
    intraspecies paralog to NEF2
    Homologene
    FAMILY
  • Cap'n'collar (CNC) family of transcription factor
  • BZIP family
  • CATEGORY immunity/defense , regulatory , transcription factor , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    intracellular,nuclear envelope
    text
  • NHB1 (N-terminal homology box 1) sequence is required to anchor it to the endoplasmic reticulum
  • an integral membrane protein which can be sorted from the ER to the nuclear envelope
  • tethered to ER (endoplasmic reticulum) and nuclear envelope membranes
  • basic FUNCTION
  • activating erythroid specific, globin gene expression
  • regulating expression of ferritin genes and heme synthesis
  • may be playing a distinct functional role in regulating antioxidant response element (ARE)-driven genes
  • playing an essential role during fetal liver hematopoiesis
  • a novel transcriptional inhibitor of the human ACCbeta gene promoter in the mammalian heart
  • a pivotal transcriptional modulator controlling gene expression of mitochondrial proteins
  • CNC (cap'n'collar) bZIP (basic-region leucine zipper) transcription factor that is tethered to ER (endoplasmic reticulum) and nuclear envelope membranes through its N-terminal signal peptide
  • can adopt several topologies within membranes that are determined by its NTD (N-terminal domain)
  • plays a critical role in regulating the expression of many antioxidant response element (ARE)-dependent genes
  • in response to proteasome inhibition, plays a central role in upregulating the proteasome system via an ERAD-dependent feedback loop
  • up-regulation of NFE2L1, together with other FBXW7 substrates, such as JUN, MYC, and cyclin E, promotes tumorigenesis
  • role of NFE2L1 in UVB-induced DNA damage repair, suggesting that NFE2L1 is a tumor suppressor in the skin
  • is a novel regulator of the LPIN1 and PPPARGC1B genes, providing new insights into the NFE2L1 function in hepatic lipid metabolism
  • may play a role in maintaining genomic integrity, and NFE2L1 dysregulation may induce tumorigenesis
  • plays an integral role in the maintenance of proteasome function in hepatocytes and in the prevention of liver steatosis development
  • promotes glial fate under direct SOX9 regulatory control
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , cell to cell transport
    text
  • circulation, intercellular transport
  • PATHWAY
    metabolism porphyrin/heme
    signaling
    a component
  • forming a transcription factor complex with several AP1 binding proteins
  • forms a ternary complex containing both KEAP1 and NFE2L2, in which the dimeric KEAP1 protein simultaneously binds both PGAM5 and NFE2L2 through their conserved E(S/T)GE motifs
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • p45 NF-E2, ECH and Fos
  • v-maf musculoaponeurotic fibrosarcoma oncogene homolog G (avian), MafG
  • c-Jun, Jun-B and Jun-D proteins
  • FBXW7 is a regulator of NFE2L1 expression, suggesting a novel function of FBXW7 in cellular stress response (FBXW7 regulates NFE2L1 via a CPD motif)
  • NFE2L1 binds to the antioxidant response elements (AREs) in regulatory regions of the LPIN1 and PPARGC1B genes
  • GSK3B interacts with NFE2L1 and phosphorylates the CDC4 phosphodegron domain (CPD) in NFE2L1 , and regulates NFE2L1 expression and cell survival function in response to stress activation
  • proteasome-mediated processing of NFE2L1 is essential for coordinate induction of all proteasome subunits and VCP
  • cell & other
    REGULATION
    inhibited by negatively controlled by its NTD (N-terminal domain) that lies between amino acids 1 and 124
    Other glycosylated through its Asn/Ser/Thr-rich domain, between AAs 296 and 403 (glycosylation not necessary to retain it in the ER)
    ubiquitinated and stabilized by proteasomal inhibition, and proteasome pathway plays a role in regulating its stability in the cell
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    NFE2L1 deficiency leads to the reduced expression of the transcriptional coactivator genes LPIN1 and PPARGC1B
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    NFE2L1-mediated proteasome homeostasis could be an attractive target for therapeutic intervention in cancer
    ANIMAL & CELL MODELS
  • disruption of the transcription factor Nrf-1 results in anemia and embryonic lethality in mice
  • mice with somatic inactivation of nrf1 in the liver develop hepatic cancer whose livers exhibit steatosis, apoptosis, necrosis, inflammation, and fibrosis