SESN3: Sestrin 3 - A Stress-Responsive Regulator of Metabolism and Aging
Comprehensive genomic and functional analysis of SESN3, a member of the sestrin family involved in antioxidant defense, mTOR signaling, and metabolic homeostasis.
Gene Information Card
| Symbol | SESN3 |
|---|---|
| Full Name | Sestrin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q21 |
| NCBI Gene ID | 143686 ncbi.nlm.nih.gov/gene/143686 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q9Y3P9 |
| OMIM ID | 607767 |
| HGNC ID | 21595 |
| Aliases | SEST3, SESN3_HUMAN |
Description
SESN3 (Sestrin 3) is a member of the sestrin family of stress-responsive proteins. It functions as a sensor of amino acid availability and regulates the mTORC1 signaling pathway. SESN3 also exhibits oxidoreductase activity, protecting cells from oxidative stress and contributing to metabolic homeostasis, aging, and cellular senescence. The gene is located on chromosome 11q21 and is widely expressed in human tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | SESN3 regulates insulin sensitivity and glucose metabolism via AMPK and mTOR pathways; variants may alter risk. | PMID: 23472056 |
| Obesity | SESN3 expression in adipose tissue correlates with metabolic dysfunction; involved in lipid metabolism. | PMID: 25931412 |
| Aging and Longevity | SESN3 mediates stress resistance and lifespan extension through antioxidant and mTOR inhibition. | PMID: 23746838 |
| Cancer (multiple types) | Dysregulation of SESN3 affects cell proliferation and apoptosis; altered expression in breast, lung, and colorectal cancers. | PMID: 28431213 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 8.3 | Medium |
| Skeletal muscle | 6.7 | Low |
| Heart | 5.2 | Low |
| Brain | 4.1 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| MCF7 (breast) | 9.8 | Medium expression |
| A549 (lung) | 7.5 | Medium expression |
| HEK293 (embryonic kidney) | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.124G>A (p.Glu42Lys) | Missense | <0.01% | Unknown functional impact; rare population variant |
| c.457C>T (p.Arg153Trp) | Missense | <0.01% | Potential loss of function; reported in ClinVar |
| c.789_790insA (p.Gln264fs) | Frameshift | <0.01% | Predicted loss of function; rare |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in SESN3 are predicted to cause loss of function, impairing mTOR regulation and antioxidant defense.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SESN3.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SESN3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mTOR signaling pathway (Reactome: R-HSA-165159)
• AMPK signaling pathway (KEGG: hsa04152)
• p53 signaling pathway (KEGG: hsa04115)
• Autophagy (KEGG: hsa04140)
• FoxO signaling pathway (KEGG: hsa04068)
Protein Summary
Sestrin 3 (SESN3) is a 492-amino acid protein with a molecular weight of approximately 55 kDa. It contains a conserved sestrin domain and functions as a leucine sensor for the mTORC1 pathway. SESN3 also exhibits peroxiredoxin-like activity, reducing peroxides and protecting cells from oxidative damage. The protein is predominantly cytoplasmic and is induced under stress conditions such as DNA damage, hypoxia, and nutrient deprivation. SESN3 interacts with AMPK and TSC1/2 to inhibit mTORC1, linking stress signals to growth control.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SESN3 Knockout HEK293 Cell Line | EDJ-KQ10391 | Human | 143686 | Details Get a Quote |
| SESN3 Knockout A-549 Cell Line | EDJ-KQ37730 | Human | 143686 | Details Get a Quote |
| SESN3 Knockout HeLa Cell Line | EDJ-KQ37731 | Human | 143686 | Details Get a Quote |
| SESN3 Knockout HCT 116 Cell Line | EDJ-KQ75382 | Human | 143686 | Details Get a Quote |
