UniProt entry for mouse Sirt2
Cloning and characterization of two mouse genes with homology to the yeast Sir2 gene.
Microtubule deacetylases, SirT2 and HDAC6, in the nervous system.
SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction.
Proteolipid protein is required for transport of sirtuin 2 into CNS myelin.
SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation.
SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma.
The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates.
Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling.
SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity.
Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of α-tubulin.
Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome.
A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection.
Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis.
SIRT2 regulates tumour hypoxia response by promoting HIF-1α hydroxylation.
Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein.
Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy.
Acetylation of PAX7 controls muscle stem cell self-renewal and differentiation potential in mice.
Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
Combined Automated Annotation using Multiple IEA Methods
Falcon deep research report on mouse Sirt2 (Q8VDQ8)
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Mouse Sirt2 is a class I sirtuin functioning as an NAD+-dependent lysine
deacylase (class III HDAC) that is predominantly cytoplasmic and
microtubule-associated, deacetylating alpha-tubulin at K40, and capable of
removing diverse lysine acyl groups including long-chain fatty-acyl
(e.g. myristoyl) modifications.
"The target gene/protein is **Mus musculus Sirt2** (UniProt **Q8VDQ8**), a **class I sirtuin** that functions as an **NAD+-dependent lysine deacylase** (class III HDAC family) with prominent **cytosolic localization** and stimulus-dependent **nuclear shuttling**. This matches the UniProt description and is consistently supported by 2023–2024 literature describing SIRT2/Sirt2 as predominantly cytoplasmic, microtubule-associated (α-tubulin K40 substrate), and capable of removing diverse lysine acyl groups including long-chain fatty acyl (e.g., myristoyl) modifications."
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SIRT2 catalyzes NAD+-dependent lysine deacylation, consuming NAD+ and
producing nicotinamide plus 2'-O-acyl-ADP-ribose along with the deacylated
protein product.
"Sirtuins are **NAD+-dependent protein deacylases** that couple cellular redox/energy state (NAD+ availability) to removal of acyl modifications from lysine residues. For SIRT2, mechanistic descriptions include consumption of NAD+ and production of **nicotinamide** plus **2′-O-acyl-ADP-ribose**, along with the **deacylated protein** product."
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SIRT2 has broad acyl substrate scope; deacetylation and defatty-acylation
(demyristoylation) are distinct, pharmacologically separable activities,
supporting the demyristoylase/depalmitoylase annotations as genuine but
mechanistically separable from core deacetylation.
"Modern understanding emphasizes that SIRT2 (and SIRT1–3 more broadly) can remove multiple lysine acyl modifications, and that **deacetylation and defatty-acylation can be pharmacologically separable activities**."
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The canonical SIRT2 substrate/function is alpha-tubulin K40 deacetylation;
SIRT2 co-localizes with microtubules primarily in the cytoplasm, providing
the core cytoskeletal anchor for annotation.
"SIRT2 is explicitly described as deacetylating **tubulin at lysine 40** and co-localizing with microtubules primarily in the cytoplasm."
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SIRT2 is predominantly cytoplasmic and shuttles to the nucleus only under
specific conditions (stress, cell cycle states, infection, ischemic injury);
mouse isoforms SIRT2.1/2.2 are predominantly cytoplasmic but can accumulate
in the nucleus.
"SIRT2 is repeatedly described as **predominantly cytoplasmic**, with ability to shuttle to the nucleus under specific conditions (e.g., stress, cell cycle states, infection, ischemic injury)."
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SIRT2 deacetylates p65/NF-kB and NLRP3 and binds/deacetylates FOXO1,
placing it within inflammasome/NF-kB and FOXO1-autophagy regulatory circuits.
"**Inflammation/innate immunity:** SIRT2 deacetylates **NF-κB** and **NLRP3**, positioning it at the interface of acetylation control and inflammasome/NF-κB signaling."
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In mouse liver fractionation (Schmidt et al. 2024), Sirt2 isoforms were
detected in nuclear and cytosolic fractions but purified mitochondria and
peroxisomes lacked detectable Sirt2 antigen, arguing against a genuine
resident mitochondrial pool despite many mitochondrial hyperacetylation
changes in Sirt2-/- liver.
"In wild-type mouse liver fractionation, Sirt2 isoforms were detected in nuclear/cytosolic fractions; purified mitochondria and peroxisomes lacked detectable Sirt2 antigen (N=3). Nevertheless, many of the “putative target” hyperacetylated sites in male Sirt2−/− liver mapped to mitochondria (44%)."
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Schmidt et al. 2024 provides direct mouse-genetics evidence that whole-body
Sirt2 regulates hepatic glucose metabolism and the acetylome in a
sex-specific manner, with mechanistic links to deacetylation/stabilization
of HNF4alpha and PEPCK1 in gluconeogenesis.
"Schmidt et al. 2024 provides direct mouse genetics evidence that whole-body Sirt2 impacts hepatic glucose metabolism and acetylome regulation in a **sex-specific** manner."