NAD-dependent protein deacetylase sirtuin-2

SIRT2 is a NAD-dependent protein deacetylase that removes acetyl groups from lysine residues on histones, alpha-tubulin, and numerous transcription factors (UniProt: Q8IXJ6). The enzyme regulates diverse cellular processes including cell cycle control, genomic stability, microtubule dynamics, autophagy, and metabolic homeostasis through deacetylation of substrates such as CDC20, FOXO1, HIF1A, and p53. It also possesses deacylase activity toward other acyl groups and catalyzes demyristoylation and depalmitoylation of membrane-associated proteins.

SIRT2 is widely expressed and implicated in cell cycle progression, antephase checkpoint control, histone modification, and the regulation of glucose homeostasis and pentose phosphate pathway metabolism. The protein plays roles in neuronal processes including neurite outgrowth and myelination, consistent with its expression in neuronal and glial cells. UniProt records no primary disease associations for SIRT2.

SIRT2 is tagged as downregulated in Alzheimer's disease. Proteomic analysis of post-mortem AD brain tissue versus age-matched controls revealed decreased SIRT2 abundance with a mean log2 fold-change of −0.59 (Chaparral AD proteomics). This reduction may impact NAD-dependent deacetylation of substrates involved in mitochondrial function, autophagy, and proteostasis—processes relevant to neurodegeneration.