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Available structures
PDBOrtholog search: PDBe RCSB
AliasesSESN2, HI95, SES2, SEST2, sestrin 2
External IDsOMIM: 607767 MGI: 2651874 HomoloGene: 12873 GeneCards: SESN2
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for SESN2
Genomic location for SESN2
Band1p35.3Start28,259,518 bp[1]
End28,282,491 bp[1]
RNA expression pattern
PBB GE SESN2 gnf1h00495 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 28.26 – 28.28 MbChr 4: 132.49 – 132.51 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Sestrin-2 also known as Hi95 is a protein that in humans is encoded by the SESN2 gene.[5][6][7]


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.[7][8] The Sestrins constitute a family of evolutionarily-conserved stress-inducible proteins that suppress oxidative stress and regulate adenosine monophosphate-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling. By virtue of these activities, the Sestrins serve as important regulators of metabolic homeostasis. Accordingly, inactivation of Sestrin genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction and muscle degeneration that resemble accelerated tissue aging.[7][9]


The NMDA receptor antagonist ketamine has been found to activate the mammalian target of rapamycin complex 1 (mTORC1) pathway in the medial prefrontal cortex (mPFC) of the brain as an essential downstream mechanism in the mediation of its rapid-acting antidepressant effects.[10] NV-5138 is a ligand and modulator of sestrin2, a leucine amino acid sensor and upstream regulatory pathway of mTORC1, and is under development for the treatment of depression.[10] The drug has been found to directly and selectively activate the mTORC1 pathway, including in the mPFC, and to produce rapid-acting antidepressant effects similar to those of ketamine.[10]

See also[edit]


  1. ^ a b c ENSG00000285069 GRCh38: Ensembl release 89: ENSG00000130766, ENSG00000285069 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028893 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Peeters H, Debeer P, Bairoch A, Wilquet V, Huysmans C, Parthoens E, Fryns JP, Gewillig M, Nakamura Y, Niikawa N, Van de Ven W, Devriendt K (Apr 2003). "PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse". Hum Genet. 112 (5–6): 573–80. doi:10.1007/s00439-003-0917-5. PMID 12607115.
  6. ^ Budanov AV, Shoshani T, Faerman A, Zelin E, Kamer I, Kalinski H, Gorodin S, Fishman A, Chajut A, Einat P, Skaliter R, Gudkov AV, Chumakov PM, Feinstein E (Aug 2002). "Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability". Oncogene. 21 (39): 6017–31. doi:10.1038/sj.onc.1205877. PMID 12203114.
  7. ^ a b c "Entrez Gene: SESN2 sestrin 2".
  8. ^ Lee JH, Bodmer R, Bier E, Karin M (June 2010). "Sestrins at the crossroad between stress and aging". Aging. 2 (6): 369–74. doi:10.18632/aging.100157. PMC 2919257. PMID 20606249.
  9. ^ Lee JH, Budanov AV, Karin M (Dec 2013). "Sestrins orchestrate cellular metabolism to attenuate aging". Cell Metab. 18 (6): 792–801. doi:10.1016/j.cmet.2013.08.018. PMC 3858445. PMID 24055102.
  10. ^ a b c Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res. 7. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.

Further reading[edit]