SESN1: Sestrin 1, a Stress-Responsive Regulator of Metabolism and Aging
Comprehensive genomic and functional analysis of SESN1, a member of the sestrin family involved in antioxidant defense, mTORC1 regulation, and cellular homeostasis.
Gene Information Card
| Symbol | SESN1 |
|---|---|
| Full Name | Sestrin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 27244 ncbi.nlm.nih.gov/gene/27244 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | Q9Y6P5 |
| OMIM ID | 606103 |
| HGNC ID | 21595 |
| Aliases | PA26, SEST1 |
Description
SESN1 (Sestrin 1) is a protein-coding gene that belongs to the sestrin family. It is induced by p53 in response to DNA damage and oxidative stress. SESN1 functions as an antioxidant enzyme (peroxiredoxin reductase) and regulates AMPK-mTORC1 signaling, thereby controlling cell growth, metabolism, and aging. It is implicated in cellular protection against genotoxic and oxidative stress.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Dysregulation of SESN1 expression alters mTORC1 activity and antioxidant capacity, promoting tumorigenesis or resistance to therapy. | COSMIC; PMID: 21804562 |
| Metabolic syndrome | SESN1 deficiency impairs AMPK activation and lipid metabolism, contributing to insulin resistance and obesity. | PMID: 22958918 |
| Aging-related disorders | Reduced SESN1 levels are associated with accelerated cellular senescence and age-related pathologies. | PMID: 23954414 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.3 | Medium |
| Heart | 9.8 | Medium |
| Liver | 7.5 | Low |
| Brain | 6.2 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.4 | Embryonic kidney cells; high expression |
| HeLa | 11.2 | Cervical cancer cells; moderate expression |
| MCF7 | 8.9 | Breast cancer cells; moderate expression |
| HepG2 | 6.7 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.457C>T (p.Arg153Trp) | Missense | <0.01% | Unknown functional impact; reported in COSMIC |
| c.1120G>A (p.Gly374Ser) | Missense | <0.01% | Reported in cancer samples; potential loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense variants that disrupt the redox-active domain or impair interaction with AMPK/mTORC1 components may reduce antioxidant capacity and metabolic regulation.
Gain of Function (GOF)
Not well characterized; no clear gain-of-function mutations reported in literature or databases.
Dominant Negative (DN)
No dominant-negative mutations described for SESN1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• AMPK signaling pathway (Reactome: R-HSA-163285)
• mTORC1 signaling (Reactome: R-HSA-165159)
• p53-dependent G1 DNA damage response (Reactome: R-HSA-69541)
• Cellular response to stress (Reactome: R-HSA-2262752)
Protein Summary
Sestrin 1 (SESN1) is a 551-amino acid protein with a conserved sestrin domain. It functions as a peroxiredoxin reductase, reducing overoxidized peroxiredoxins to restore their antioxidant activity. SESN1 also interacts with AMPK and mTORC1 complexes to regulate energy metabolism and cell growth. Under stress conditions, it is transcriptionally activated by p53 and contributes to cellular homeostasis by suppressing reactive oxygen species and inhibiting mTORC1.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SESN1 Knockout HEK293 Cell Line | EDJ-KQ8724 | Human | 27244 | Details Get a Quote |
| SESN1 Knockout A-549 Cell Line | EDJ-KQ34962 | Human | 27244 | Details Get a Quote |
| SESN1 Knockout HCT 116 Cell Line | EDJ-KQ34963 | Human | 27244 | Details Get a Quote |
| SESN1 Knockout HeLa Cell Line | EDJ-KQ33696 | Human | 27244 | Details Get a Quote |
