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sirtuin 2; NAD-dependent deacetylase sirtuin 2; silent mating type information regulation 2 homolog 2 (SIRT2)
Function:
1) NAD-dependent deacetylase
2) deacetylates Lys-40 of alpha-tubulin
3) control of mitotic exit in cell cycle, via role in regulation of cytoskeleton
4) interacts with HDAC6, suggesting that SIRT2 belongs to a large complex that deacetylates cytoskeleton
5) role in tumor suppressor gene in human gliomas possibly through the regulation of microtubule network
6) phosphorylated at the G2/M transition of cell cycle
7) 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)
General
sirtuin (silent mating type information regulation 2 homolog)
Properties
SIZE: MW = 43 kD
entity length = 389 aa
COMPARTMENT: cytoplasm
MOTIF: histidine residue {H187}
Zn+2-binding site
SITE: 195-195
Zn+2-binding site
SITE: 200-200
Zn+2-binding site
SITE: 221-221
Zn+2-binding site
SITE: 224-224
Database Correlations
OMIM 604480
UniProt Q8IXJ6
Pfam PF02146
Entrez Gene 22933
References
- UniProt :accession Q8IXJ6