SESN2

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

SESN2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5DJ4, 5CUF
Identifiers
Aliases	SESN2, HI95, SES2, SEST2, sestrin 2
External IDs	OMIM: 607767; MGI: 2651874; HomoloGene: 12873; GeneCards: SESN2; OMA:SESN2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p35.3 Start 28,259,518 bp[1] End 28,282,491 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.3 Start 132,219,343 bp[2] End 132,237,812 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ovary gonad left ovary stromal cell of endometrium mucosa of transverse colon right lobe of liver duodenum blood islet of Langerhans human kidney Top expressed in granulocyte right kidney calvaria proximal tubule stroma of bone marrow yolk sac Rostral migratory stream spermatocyte lip internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding oxidoreductase activity, acting on peroxide as acceptor leucine binding sulfiredoxin activity oxidoreductase activity GDP-dissociation inhibitor activity Cellular component nucleus mitochondrion cytosol cytoplasm GATOR2 complex nucleotide-activated protein kinase complex Atg1/ULK1 kinase complex TORC2 complex Biological process mitochondrial DNA metabolic process mitochondrion organization protein kinase B signaling regulation of cAMP-dependent protein kinase activity response to insulin response to glucose glucose homeostasis glucose import regulation of response to reactive oxygen species triglyceride homeostasis fatty acid beta-oxidation negative regulation of TORC1 signaling positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress reactive oxygen species metabolic process positive regulation of macroautophagy cellular response to amino acid stimulus regulation of protein phosphorylation DNA damage response, signal transduction by p53 class mediator cellular response to leucine positive regulation of protein localization to nucleus cellular oxidant detoxification negative regulation of cell growth cellular response to oxidative stress negative regulation of translation in response to endoplasmic reticulum stress positive regulation of lipophagy cellular response to amino acid starvation cellular response to glucose starvation cellular response to leucine starvation regulation of gluconeogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 83667 230784 Ensembl ENSG00000130766 ENSG00000285069 ENSMUSG00000028893 UniProt P58004 P58043 RefSeq (mRNA) NM_031459 NM_144907 RefSeq (protein) NP_113647 NP_659156 Location (UCSC) Chr 1: 28.26 – 28.28 Mb Chr 4: 132.22 – 132.24 Mb PubMed search [3] [4]
Wikidata
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Function

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.^[9] 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][10]

Ligands

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.^[11] 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.^[11] 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.^[11]

See also

• SESN1