Tbio NFE2L1 Endoplasmic reticulum membrane sensor NFE2L1

Protein Summary

Description

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 (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20932482). 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 (By similarity). 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 (By similarity). 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 (PubMed:20932482). 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 (PubMed:8932385, PubMed:9421508). 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 (PubMed:8932385, PubMed:9421508). Activates or represses expression of target genes, depending on the context (PubMed:8932385, PubMed:9421508). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (PubMed:20932482). Also involved in regulating glucose flux (By similarity). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (PubMed:15308669). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts. This gene encodes a protein that is involved in globin gene expression in erythrocytes. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene, NFE2L1, and for "nuclear respiratory factor 1" which has an official symbol of NRF1. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q14494
• D3DTU3
• D3DTU5
• Q12877
• Q96FN6

Gene Name

• NFE2L1

Ensembl ID

• ENST00000357480
• ENSP00000350072
• ENSG00000082641
• ENST00000362042
• ENSP00000354855
• ENST00000585291
• ENSP00000461960

Symbol

• HBZ17
• NRF1
• TCF11
• NRF1
• TCF11
• LCR-F1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
kinase perturbation	0.96
transcription factor binding site profile	0.94
molecular function	0.88
transcription factor	0.85

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Endoplasmic Reticulum Membrane Sensor Nfe2l1

Protein / Nucleic Acid Binding / Endoplasmic Reticulum Membrane Sensor Nfe2l1

Protein / Hydrolase / Endoplasmic Reticulum Membrane Sensor Nfe2l1

Protein / Cytoskeletal Protein / Actin Family Cytoskeletal Protein / Non-motor Actin Binding Protein / Endoplasmic Reticulum Membrane Sensor Nfe2l1

DTO Classes

Protein / Enzyme / Hydrolase / Nuclear Factor Erythroid 2-related Factor 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 83.5   (req: < 5)

Gene RIFs: 55   (req: <= 3)

Antibodies: 217   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 83.5   (req: >= 5)

Gene RIFs: 55   (req: > 3)

Antibodies: 217   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 30

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0