sirtuin 2; NAD-dependent deacetylase sirtuin 2; silent mating type information regulation 2 homolog 2 (SIRT2)
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Function
- NAD-dependent deacetylase
- deacetylates Lys-40 of alpha-tubulin
- control of mitotic exit in cell cycle, via role in regulation of cytoskeleton
- interacts with HDAC6, suggesting that SIRT2 belongs to a large complex that deacetylates cytoskeleton
- role in tumor suppressor gene in human gliomas possibly through the regulation of microtubule network
- phosphorylated at the G2/M transition of cell cycle
- despite some ability to deacetylate histones in vitro, but unlikely to do so in vivo
NAD+ + acetylprotein
<-->
nicotinamide + O-acetyl-ADP-ribose + protein
Cofactor: binds 1 Zn+2 per subunit
Inhibition:
- inhibited by Sirtinol, A3 & M15 small molecules
- inhibited by nicotinamide
Structure
belongs to the sirtuin family
Compartment
cytoplasm, colocalizes with microtubules
Alternative splicing
named isoforms=4
Expression
- widely expressed
- expressed in heart, brain & skeletal muscle > placenta, lung
- peaks during mitosis
- after mitosis, after mitosis probably degraded by 26S proteasome
Pathology
- down-regulated in many gliomas
- sirtuin-2 inhibitors rescue alpha-synuclein-mediated toxicity in fruit fly model of Parkinson's disease (see investigational treatment of Parkinson's disease)