SIRT2 Human

Sirtuin 2 (SIRT2) is a member of the sirtuin family of proteins, which are homologs to the yeast Sir2 protein. Sirtuins are NAD±dependent deacetylases that play crucial roles in various cellular processes, including aging, transcription, and stress resistance .

The human SIRT2 gene is located on chromosome 19q13.2 and consists of 18 exons . The gene encodes a protein that belongs to class I of the sirtuin family. The SIRT2 protein has a catalytic domain that binds NAD+ and the acetyl-lysine substrate, as well as variable NH2 and COOH-terminal domains that regulate subcellular localization and catalytic activity .

SIRT2 is ubiquitously expressed in a wide range of tissues and organs, with particularly high expression in the brain, muscle, liver, testes, pancreas, kidney, and adipose tissue . Within the brain, SIRT2 is highly expressed in the cortex, striatum, hippocampus, and spinal cord . The protein is mainly localized in the cytosol but can migrate between the cytosol and nucleus to facilitate the deacetylation of both α-tubulin and histones .

SIRT2 has several important functions in the cell:

• Regulation of Microtubule Acetylation: SIRT2 deacetylates α-tubulin, which is crucial for microtubule stability and function .
• Control of Myelination: SIRT2 plays a role in the myelination process in the central and peripheral nervous systems .
• Gluconeogenesis: SIRT2 is involved in the regulation of gluconeogenesis, the metabolic pathway that generates glucose from non-carbohydrate substrates .
• Chromatin Compaction: During the G2/M transition, nuclear SIRT2 deacetylates H4K16, facilitating H4K20 methylation and subsequent chromatin compaction .
• DNA Damage Response: SIRT2 deacetylates H3K56 in response to DNA damage, playing a role in the DNA damage response .
• Regulation of Transcriptional Co-activator p300: SIRT2 negatively regulates the acetyltransferase activity of p300 via deacetylation of an automodification loop within its catalytic domain .

Human recombinant SIRT2 is typically expressed in Escherichia coli (E. coli) and purified for research purposes. It is used to study enzyme kinetics, screen inhibitors, and profile selectivity . Recombinant SIRT2 is characterized by a molecular weight of approximately 35.5 kDa and is available in various forms for experimental use .

SIRT2 has been implicated in various biological processes, including aging, metabolic homeostasis, and the regulation of microglial activation and brain inflammation . It is considered a potent therapeutic target for the treatment of type 2 diabetes and other metabolic disorders .