SESN2

Gene Information

Official Symbol: SESN2
Official Name: sestrin 2
Aliases and Previous Symbols: N/A
Entrez ID: 83667
UniProt: P58004
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: 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 (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190). 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 (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821). {ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:19113821, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24947615, ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190, ECO:0000269|PubMed:26612684}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
TRAIL 5ng/ml R00 exp35	-2.99
UM0125461 0.74μM R02 exp84	-2.66
TRAIL 50ng/ml R00 exp36	-2.38
MLN-4924 0.2μM R00 exp21	-2.17
PU-H71 1μM R08 exp515	-2.05
Rotenone 20μM R00 exp34	-2.04
3-Bromopyruvate 7μM R04 exp175	-1.97
LY2090314 0.003μM R08 exp500 no dilution day6	-1.74
L-74142 5μM R03 exp131	1.85

Gene	Correlation
NPRL3	0.656
SZT2	0.653
ITFG2	0.611
KPTN	0.606
DEPDC5	0.598
NPRL2	0.591
C12orf66	0.564
TSC2	0.463
TSC1	0.438
CCDC130	0.422
PDS5B	0.403

Global Fraction of Cell Lines Where Essential: 1/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	1/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 18603
Expression level (log2 read counts): 4.14

Expression Distribution

negative regulation of translation in response to endoplasmic reticulum stress
sulfiredoxin activity
positive regulation of lipophagy
regulation of lipophagy
positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress
oxidoreductase activity, acting on peroxide as acceptor
negative regulation of translation in response to stress
regulation of translation in response to endoplasmic reticulum stress
leucine binding
Atg1/ULK1 kinase complex
glucose import
mitochondrial DNA metabolic process
cellular response to leucine starvation
cellular response to leucine
regulation of transcription from RNA polymerase II promoter in response to oxidative stress
GDP-dissociation inhibitor activity
TORC2 complex
response to leucine
GATOR2 complex
nucleotide-activated protein kinase complex
regulation of translation in response to stress
regulation of cAMP-dependent protein kinase activity
negative regulation of TORC1 signaling
mitochondrial genome maintenance
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
positive regulation of transcription from RNA polymerase II promoter in response to stress
glucose transmembrane transport
regulation of response to reactive oxygen species
triglyceride homeostasis
acylglycerol homeostasis
hexose transmembrane transport
monosaccharide transmembrane transport
protein kinase B signaling
regulation of TORC1 signaling
carbohydrate transmembrane transport
cellular response to glucose starvation
cellular response to amino acid starvation
regulation of gluconeogenesis
response to amino acid starvation
negative regulation of TOR signaling