Sestrin-2 - P58043 (SESN2_MOUSE)


Protein Feature View of PDB entries mapped to a UniProtKB sequence  

Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:18692468, PubMed:25259925). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Has an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (By similarity). However, this could not be confirmed (By similarity). UniProt
Catalytic Activity
[protein]-dithiol + a hydroperoxide = [protein]-disulfide + an alcohol + H2O UniProt
Pathway Maps
      ESCHER  BiGG
Subunit Structure
Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (By similarity). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). May interact with the TORC2 complex (PubMed:25377878). Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the degradation of KEAP1 (PubMed:25040165). May also associate with the complex composed of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to regulate TORC1 signaling (PubMed:18692468). May interact with PRDX1 (By similarity). UniProt
Composed of an N-terminal domain that has an alkylhydroperoxide reductase activity and a C-terminal domain that mediates interaction with GATOR2 through which it regulates TORC1 signaling. UniProt
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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.
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  • 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.
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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).
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