Endoplasmic reticulum membrane sensor NFE2L1 - Q61985 (NF2L1_MOUSE)

 

Protein Feature View of PDB entries mapped to a UniProtKB sequence  

 
Function
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:20385086, PubMed:21536885, PubMed:23816881, PubMed:29149604). Constitutes a precursor of the transcription factor NRF1. Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20385086, PubMed:21536885, PubMed:23816881, PubMed:29149604). 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 (PubMed:29149604). 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 (PubMed:29149604). 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:20385086, PubMed:21536885, PubMed:23816881). UniProt
Pathway Maps
Maps:       
Reactions:
      ESCHER  BiGG
Subunit Structure
Interacts with KEAP1 (By similarity). Endoplasmic reticulum membrane sensor NFE2L1: Interacts (via CPD region) with FBXW7; leading to its ubiquitination and degradation (PubMed:21953459). Endoplasmic reticulum membrane sensor NFE2L1: Interacts with SYVN1/HRD1; leading to its ubiquitination and degradation (PubMed:21911472). Endoplasmic reticulum membrane sensor NFE2L1: Interacts (when ubiquitinated) with DDI2; leading to its cleavage (By similarity). Transcription factor NRF1: Interacts (via the bZIP domain) with small MAF protein (MAFF, MAFG or MAFK); required for binding to antioxidant response elements (AREs) on DNA (PubMed:11342101, PubMed:23144760). Transcription factor NRF1: Interacts (via Destruction motif) with BTRC; leading to its ubiquitination and degradation (PubMed:21911472). Transcription factor NRF1: Interacts with CEBPB; the heterodimer represses expression of DSPP during odontoblast differentiation. UniProt
Domain
The cholesterol recognition/amino acid consensus (CRAC) region directly binds cholesterol, as well as campesterol and 27-hydroxycholesterol (PubMed:29149604). Has much lower affinity for epicholesterol (PubMed:29149604). UniProt
Legend
The Protein Feature View requires a browser that supports SVG (Scalable Vector Graphics). Mouse over tracks and labels for more information.
Data origin/color codes
The vertical color bar on the left side indicates data provenance.
Data in green originates from UniProtKB  
Variation data (sourced from UniProt) shows non-genetic variation from the ExPASy   and dbSNP   websites.
Data in yellow originates from Pfam  , by interacting with the HMMER3 web site  
Data in purple originates from Phosphosite  .
Data in orange originates from the SCOP   (version 1.75) and SCOPe   (version 2.04) classifications.
Data in grey has been calculated using BioJava  . Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN  
  • Red: potentially disorderd region
  • Blue: probably ordered region.
Hydropathy has been calculated using a sliding window of 15 residues and summing up scores from standard hydrophobicity tables.
  • Red: hydrophobic
  • Blue: hydrophilic.
Data in lilac represent the genomic exon structure projected onto the UniProt sequence.
Data in blue originates from PDB
  • Secstruc: Secondary structure projected from representative PDB entries onto the UniProt sequence.
Sequence Mismatches It is now possible to see information about expression tags, cloning artifacts, and many other details related to sequence mismatches.
Icons represent a number of different sequence modifications that can be observed in PDB files. For example the 'T' icon T represents expression tags that have been added to the sequence. The 'E' icon E represents an engineered mutation. However, besides these two, there are many other icons. For more information about the meaning and exact position of a sequence modification, move the cursor over the icon.
Validation Track

For more details on the Validation Track (Structure Summary Page only) see the dedicated help page.

Data in red indicates combined ranges of Homology Models from the SWISS-MODEL Repository  
The PDB to UniProt mapping is based on the data provided by the EBI SIFTS project. See also Velankar et al., Nucleic Acids Research 33, D262-265 (2005).
Organism icons generated by flaticon.com under CC BY. The authors are: Freepik, Icons8, OCHA, Scott de Jonge.

For more details on the Protein Feature view see the dedicated help page.