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27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SIRT2
sirtuin 2
Chromosome 19 · 19q13.2
NCBI Gene: 22933Ensembl: ENSG00000068903.21HGNC: HGNC:10886UniProt: A0A0A0MRF5
309PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
NAD+ poly-ADP-ribosyltransferase activitychromatin bindinghistone deacetylase activityprotein bindingneoplasmhepatocellular carcinomaParkinson diseaseAlzheimer disease
✦AI Summary

SIRT2 is a cytoplasmic NAD+-dependent deacetylase that plays crucial roles in aging, metabolism, and cellular homeostasis through post-translational modification of key regulatory proteins. The enzyme functions by deacetylating specific lysine residues on target proteins, including STAT3 in cardiomyocytes 1, p66Shc in vascular tissues 2, MLH1 in colorectal cancer cells 3, septin4 in kidney podocytes 4, and LDHA in ovarian granulosa cells 5. SIRT2 expression and activity decline with aging across multiple tissues, contributing to age-related pathologies 21. The protein regulates diverse cellular processes including mitotic fidelity through BubR1 regulation 6, metabolic homeostasis via glycolysis modulation 57, and immune surveillance by controlling DNA repair mechanisms 3. Clinically, SIRT2 deficiency is associated with accelerated vascular aging, cardiac dysfunction, and altered tumor immunity, while its therapeutic targeting shows promise for treating osteoporosis 8, hypertensive nephropathy 4, and enhancing cancer immunotherapy 3. The enzyme's dependence on NAD+ availability links cellular energy status to epigenetic regulation and aging processes.

Sources cited
1
SIRT2 counteracts cardiac aging by deacetylating STAT3, which silences CDKN2B
PMID: 37783815
2
SIRT2 delays vascular aging by deacetylating p66Shc and reducing mitochondrial ROS production
PMID: 37377116
3
SIRT2 deacetylates MLH1 in colorectal cancer, affecting DNA repair and tumor immunity
PMID: 40668890
4
SIRT2 deacetylates septin4 at K174, mitigating hypertensive nephropathy
PMID: 36786216
5
SIRT2 regulates LDHA deacetylation and lactate production in ovarian granulosa cells
PMID: 39489197
6
SIRT2 acts as upstream regulator of BubR1, influencing genomic stability and aging
PMID: 39490401
7
Hepatocyte SIRT2 deficiency affects bone metabolism through extracellular vesicle communication
PMID: 37188819
8
SIRT2 loss attenuates GLO1 expression and activity in skeletal muscle
PMID: 39142179
Disease Associationsⓘ20
neoplasmOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
Parkinson diseaseOpen Targets
0.11Weak
Alzheimer diseaseOpen Targets
0.11Weak
infectionOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
melanomaOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Weak
gastric cancerOpen Targets
0.10Suggestive
SepsisOpen Targets
0.10Suggestive
subarachnoid hemorrhageOpen Targets
0.10Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.10Suggestive
colitisOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
Huntington diseaseOpen Targets
0.08Suggestive
type 2 diabetes mellitusOpen Targets
0.08Suggestive
dilated cardiomyopathyOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPARGC1AProtein interaction100%TP53Protein interaction100%RRP8Protein interaction100%HDAC1Protein interaction99%EP300Protein interaction97%KAT2BProtein interaction96%
Tissue Expression6 tissues
Brain
100%
Heart
63%
Ovary
55%
Liver
53%
Lung
46%
Bone Marrow
42%
Gene Interaction Network
Click a node to explore
SIRT2PPARGC1ATP53RRP8HDAC1EP300KAT2B
PROTEIN STRUCTURE
Preparing viewer…
PDB4RMH · 1.42 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.03LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.80 [0.63–1.03]
RankingsWhere SIRT2 stands among ~20K protein-coding genes
  • #1,114of 20,598
    Most Researched309 · top 10%
  • #10,217of 17,882
    Most Constrained (LOEUF)1.03
Genes detectedSIRT2
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
SIRT2 regulates extracellular vesicle-mediated liver-bone communication.
PMID: 37188819
Nat Metab · 2023
1.00
2
SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B.
PMID: 37783815
Nat Aging · 2023
0.90
3
Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice.
PMID: 37377116
Eur Heart J · 2023
0.80
4
GCLC desuccinylation regulated by oxidative stress protects human cancer cells from ferroptosis.
PMID: 40188196
Cell Death Differ · 2025
0.72
5
Targeting SIRT2 induces MLH1 deficiency and boosts antitumor immunity in preclinical colorectal cancer models.
PMID: 40668890
Sci Transl Med · 2025
0.70