SESN2

This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. [provided by RefSeq, Jul 2008]

Sestrin 2

Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100).
In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100).
Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100).
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).
Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684).
Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503).
However, this could not be confirmed (PubMed:19113821).

Biological Process cellular oxidant detoxificationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cellular response to amino acid starvationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to amino acid stimulusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to glucose starvationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to leucineManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to leucine starvationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to oxidative stressISS:UniProtKB
Biological Process DNA damage response, signal transduction by p53 class mediatorManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process fatty acid beta-oxidationIEA:Ensembl
Biological Process glucose homeostasisIEA:Ensembl
Biological Process glucose importIEA:Ensembl
Biological Process mitochondrial DNA metabolic processIEA:Ensembl
Biological Process negative regulation of cell growthISS:UniProtKB
Biological Process negative regulation of TORC1 signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of translation in response to endoplasmic reticulum stressManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of lipophagyIEA:Ensembl
Biological Process positive regulation of macroautophagyManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of protein localization to nucleusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein kinase B signalingIEA:Ensembl
Biological Process reactive oxygen species metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of cAMP-dependent protein kinase activityIEA:Ensembl
Biological Process regulation of gluconeogenesisIEA:Ensembl
Biological Process regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of response to reactive oxygen speciesIEA:InterPro
Biological Process response to glucoseIEA:Ensembl
Biological Process response to insulinIEA:Ensembl
Biological Process triglyceride homeostasisIEA:Ensembl

Cytoplasm

Phosphorylated by ULK1 at multiple sites.
Ubiquitinated at Lys-175 by RNF167 via 'Lys-63'-linked polyubiquitination in response to leucine deprivation: ubiquitination promotes SESN2-interaction with the GATOR2 complex, leading to inhibit the TORC1 signaling pathway (PubMed:35114100).
Deubiquitinated at Lys-175 by STAMBPL1, promoting the TORC1 signaling pathway (PubMed:35114100).
Ubiquitinated by RNF186; ubiquitination mediates proteasomal degradation (PubMed:31586034).