NFE2L1 Endoplasmic reticulum membrane sensor NFE2L1: Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor. Constitutes a precursor of the transcription factor NRF1. Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition. In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1. Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36. Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits. Transcription factor NRF1: CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses. Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response. Activates or represses expression of target genes, depending on the context. Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess, such as CD36. In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal. Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1 and MT2. Plays an essential role during fetal liver hematopoiesis: probably has a protective function against oxidative stress and is involved in lipid homeostasis in the liver. Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits. Also involved in regulating glucose flux. Together with CEBPB; represses expression of DSPP during odontoblast differentiation. In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts. Belongs to the bZIP family. CNC subfamily. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Transcription factor
Chromosomal Location of mouse Ortholog: 11 D|11 60.12 cM
Cellular Component:  cytoplasm; cytosol; endoplasmic reticulum; endoplasmic reticulum membrane; integral component of membrane; membrane; nucleus; protein-containing complex
Molecular Function:  cholesterol binding; chromatin binding; DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; lipid binding; promoter-specific chromatin binding; protein binding; protein domain specific binding; protein-containing complex binding; RNA polymerase II distal enhancer sequence-specific DNA binding; transcription coactivator activity; transcription regulatory region sequence-specific DNA binding
Biological Process:  cellular homeostasis; cellular response to cholesterol; cellular response to cold; cellular response to oxidative stress; cholesterol homeostasis; cholesterol metabolic process; cysteine transport; erythrocyte differentiation; fructose 6-phosphate metabolic process; glial cell fate commitment; glucose 6-phosphate metabolic process; glutathione metabolic process; lipid metabolic process; positive regulation of transcription by RNA polymerase II; positive regulation of transcription, DNA-templated; protein polyubiquitination; regulation of fatty acid metabolic process; regulation of gene expression; regulation of glucose metabolic process; regulation of inflammatory response; regulation of lipid metabolic process; regulation of mitotic nuclear division; regulation of nucleus organization; regulation of proteasomal protein catabolic process; regulation of response to endoplasmic reticulum stress; regulation of transcription by RNA polymerase II; regulation of transcription from RNA polymerase II promoter in response to copper ion; regulation of transcription, DNA-templated; response to endoplasmic reticulum stress; spinal cord motor neuron differentiation; steroid metabolic process
Reference #:  Q61985 (UniProtKB)
Alt. Names/Synonyms: AA408798; AW212678; Endoplasmic reticulum membrane sensor NFE2L1; Lcr; LCR-; LCR-F1; Lcrf1; Locus control region-factor 1; NF-E2-related factor 1; NF2L1; NFE2-related factor 1; Nfe2l1; Nrf1; Nuclear factor erythroid 2-related factor 1; Nuclear factor, erythroid derived 2, like 1; nuclear factor, erythroid derived 2,-like 1; OTTMUSP00000001551; OTTMUSP00000001552; TCF-11; TCF11; Transcription factor NRF1
Gene Symbols: Nfe2l1
Molecular weight: 81,575 Da
Basal Isoelectric point: 4.58  Predict pI for various phosphorylation states
CST Pathways:  Adherens Junction Dynamics  |  Wnt/ß-Catenin Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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NFE2L1

Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  Pfam  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene