SESN1

The N-terminal domain may have an alkylhydroperoxide reductase activity.

The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.

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:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). 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). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the 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 (PubMed:15105503). However, this could not be confirmed (By similarity).

Belongs to the sestrin family.

Widely expressed.

• Nucleus
• Cytoplasm

PA26, SEST1, SESN1, Sestrin-1, p53-regulated protein PA26

• entrezGene:27244
• omim:606103
• swissprot:Q9Y6P5

Proteins

Neuroscience

56557Da