| Protein Name | Sirtuin 2 |
|---|---|
| Gene | [SIRT2](/genes/sirt2) |
| UniProt ID | [Q8IXJ6](https://www.uniprot.org/uniprot/Q8IXJ6) |
| Molecular Weight | 43 kDa |
| Subcellular Localization | Cytoplasm, Nucleus, Myelin Sheath |
| Protein Family | Sirtuin family (class I) |
| Gene Location | 19q13.2 |
SIRT2 (Sirtuin 2) is a NAD+-dependent deacetylase that belongs to the sirtuin family of proteins, which are conserved from yeast to humans and regulate cellular metabolism, aging, and stress responses[1][2]. SIRT2 is uniquely localized primarily in the cytoplasm, where it deacetylates various substrates including tubulin, p53, and FOXO transcription factors. The enzyme has attracted considerable interest for its roles in neurodegeneration, aging, and cancer[3].
Sirtuins are NAD+-dependent deacetylases that have been evolutionarily conserved from yeast to humans. The seven mammalian sirtuins (SIRT1-7) are located in different cellular compartments and perform diverse functions. SIRT2 is predominantly cytoplasmic but can shuttle to the nucleus under certain conditions, where it participates in epigenetic regulation and stress response pathways.
SIRT2 contains characteristic sirtuin features:
SIRT2 exists in multiple oligomeric states and can form tetramers in cells, which may regulate its activity[4]. The enzyme requires NAD+ as a cofactor for its deacetylase activity, linking its function to cellular metabolic status. Upon deacetylation, nicotinamide and O-acetyl-ADP-ribose are produced as byproducts.
SIRT2's best-characterized function is deacetylating α-tubulin:
As a metabolic sensor, SIRT2 regulates:
SIRT2 participates in stress responses:
SIRT2 is implicated in AD pathogenesis[5]:
SIRT2 has complex roles in PD[6]:
SIRT2 is a therapeutic target:
SIRT2: structure and function (2018). Journal of Molecular Biology. 2018. ↩︎
Sirtuins in aging and disease (2020). Nature Reviews Drug Discovery. 2020. ↩︎
SIRT2 in neurodegeneration (2021). Cell Death & Disease. 2021. ↩︎
SIRT2 structure and oligomerization (2019). Journal of Biological Chemistry. 2019. ↩︎
SIRT2 and Alzheimer's disease (2022). Neurobiology of Aging. 2022. ↩︎
SIRT2 in Parkinson's disease (2023). Movement Disorders. 2023. ↩︎