Protein-coding gene in the species Homo sapiens
SESN2 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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5DJ4, 5CUF |
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Identifiers |
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Aliases | SESN2, HI95, SES2, SEST2, sestrin 2 |
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External IDs | OMIM: 607767; MGI: 2651874; HomoloGene: 12873; GeneCards: SESN2; OMA:SESN2 - orthologs |
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Gene location (Human) |
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![Chromosome 1 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Ideogram_human_chromosome_1.svg/300px-Ideogram_human_chromosome_1.svg.png) | Chr. | Chromosome 1 (human)[1] |
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| Band | 1p35.3 | Start | 28,259,518 bp[1] |
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End | 28,282,491 bp[1] |
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Gene location (Mouse) |
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![Chromosome 4 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/9/9c/Ideogram_house_mouse_chromosome_4.svg/260px-Ideogram_house_mouse_chromosome_4.svg.png) | Chr. | Chromosome 4 (mouse)[2] |
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| Band | 4|4 D2.3 | Start | 132,219,343 bp[2] |
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End | 132,237,812 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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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
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| Top expressed in | - granulocyte
- right kidney
- calvaria
- proximal tubule
- stroma of bone marrow
- yolk sac
- Rostral migratory stream
- spermatocyte
- lip
- internal carotid artery
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| More reference expression data |
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BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/3/31/PBB_GE_SESN2_gnf1h00495_at_fs.png/250px-PBB_GE_SESN2_gnf1h00495_at_fs.png) | More reference expression data |
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Gene ontology |
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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 |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | |
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ENSG00000130766 ENSG00000285069 |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 1: 28.26 – 28.28 Mb | Chr 4: 132.22 – 132.24 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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Sestrin-2 also known as Hi95 is a protein that in humans is encoded by the SESN2 gene.[5][6][7]
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
References
- ^ a b c ENSG00000285069 GRCh38: Ensembl release 89: ENSG00000130766, ENSG00000285069 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028893 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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. S2CID 22257894.
- ^ 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. S2CID 7991114.
- ^ a b c "Entrez Gene: SESN2 sestrin 2".
- ^ 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.
- ^ Gong L, Wang Z, Wang Z, Zhang Z (2021). "Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases". Front Endocrinol (Lausanne). 12: 751020. doi:10.3389/fendo.2021.751020. PMC 8595836. PMID 34803916.
- ^ 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.
- ^ a b c Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res. 7: 659. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.
Further reading
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Budanov AV, Sablina AA, Feinstein E, et al. (2004). "Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD". Science. 304 (5670): 596–600. Bibcode:2004Sci...304..596B. doi:10.1126/science.1095569. PMID 15105503. S2CID 27871118.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.