SIRT3: Sirtuin 3 - Mitochondrial Deacetylase and Metabolic Regulator
A key mitochondrial sirtuin involved in energy metabolism, aging, and disease.
Gene Information Card
| Symbol | SIRT3 |
|---|---|
| Full Name | sirtuin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 23410 ncbi.nlm.nih.gov/gene/23410 |
| Ensembl ID | ENSG00000142082 |
| UniProt ID | Q9NTG7 |
| OMIM ID | 604481 |
| HGNC ID | 14931 |
| Aliases | SIR2L3, SIR2-LIKE 3 |
Description
SIRT3 is a member of the sirtuin family of NAD+-dependent deacetylases. It is primarily localized to the mitochondria and regulates key metabolic processes by deacetylating mitochondrial proteins, thereby modulating energy homeostasis, oxidative stress response, and apoptosis. SIRT3 is implicated in aging, metabolic disorders, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Metabolic syndrome | SIRT3 deficiency impairs mitochondrial function and fatty acid oxidation, contributing to insulin resistance and obesity. | PMID: 21258371 |
| Hearing loss (age-related) | SIRT3 deacetylates and activates mitochondrial antioxidant enzymes; loss of SIRT3 increases oxidative damage in cochlear cells. | PMID: 20581867 |
| Breast cancer | SIRT3 acts as a tumor suppressor by regulating mitochondrial metabolism and reducing reactive oxygen species; loss of SIRT3 promotes tumorigenesis. | PMID: 23563491 |
| Cardiovascular disease | SIRT3 protects against cardiac hypertrophy and ischemia-reperfusion injury by deacetylating mitochondrial proteins involved in energy production and stress resistance. | PMID: 21258371 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 18.3 | High |
| Kidney | 15.1 | High |
| Brain | 8.2 | Low |
| Skeletal muscle | 20.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.7 | Embryonic kidney cells |
| HepG2 | 11.2 | Hepatocellular carcinoma |
| MCF7 | 9.8 | Breast cancer |
| K562 | 6.5 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.585G>A (p.Met195Ile) | Missense | 0.01% (gnomAD) | Reduced deacetylase activity; associated with metabolic syndrome risk. |
| c.740C>T (p.Pro247Leu) | Missense | 0.005% (gnomAD) | Impaired mitochondrial localization; linked to hearing loss. |
| c.1A>G (p.Met1Val) | Start loss | 0.002% (gnomAD) | Loss of protein expression; potential tumor suppressor inactivation. |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Met195Ile) reduce enzymatic activity, impairing mitochondrial deacetylation and metabolic regulation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SIRT3.
Dominant Negative (DN)
No dominant-negative mutations described for SIRT3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005739 - mitochondrion | • GO:0017136 - NAD-dependent histone deacetylase activity |
| • GO:0006476 - protein deacetylation | • GO:0006915 - apoptotic process |
| • GO:0006119 - oxidative phosphorylation |
Pathways
• NAD+ metabolism
• Mitochondrial fatty acid beta-oxidation
• TCA cycle regulation
• Reactive oxygen species (ROS) detoxification
Protein Summary
SIRT3 is a 399-amino acid mitochondrial NAD+-dependent deacetylase. It is synthesized as a precursor and processed to a mature form upon mitochondrial import. The protein contains a conserved sirtuin catalytic domain and deacetylates a wide range of mitochondrial substrates, including acetyl-CoA synthetase 2 (ACSS2), isocitrate dehydrogenase 2 (IDH2), and superoxide dismutase 2 (SOD2). Through these actions, SIRT3 regulates energy metabolism, redox balance, and cell survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIRT3 Knockout HEK293 Cell Line | EDC90414 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout A-549 Cell Line | EDJ-KQ45951 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout HCT 116 Cell Line | EDJ-KQ45952 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout HeLa Cell Line | EDJ-KQ45953 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout HeLa S3 Cell Line | EDJ-KZ460 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout HT-29 Cell Line | EDJ-KZ461 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout U-87MG ATCC Cell Line | EDJ-KZ462 | Human | 23410 | Details Get a Quote |
| SIRT3 Knockout HAP1 Cell Line | EDC08314 | Human | 23410 | Details Get a Quote |
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