Protein / target
NAD-dependent protein deacetylase sirtuin-3, mitochondrial
Protein at a glance
Biological role
NAD-dependent protein lysine deacetylase
Strongest disease association
Intracranial Aneurysm
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
NAD-dependent protein deacetylase.
View complete UniProt function annotationHide complete annotation
NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:19535340, PubMed:23283301, PubMed:24121500, PubMed:24252090). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090, PubMed:38146092). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA, MRPL12 and the ATP synthase subunit ATP5PO (PubMed:16788062, PubMed:18680753, PubMed:19535340, PubMed:24121500, PubMed:24252090, PubMed:38146092). Contributes to the regulation of the cellular energy metabolism (PubMed:24252090). Important for regulating tissue-specific ATP levels (PubMed:18794531). In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription (PubMed:23283301). Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation (By similarity). Regulates hepatic lipogenesis (By similarity). Uses NAD(+) substrate imported by SLC25A47, triggering downstream activation of PRKAA1/AMPK-alpha signaling cascade that ultimately downregulates sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance (By similarity). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups, such as benzoyl and lactoyl, leading to protein debenzoylation and delactylation, respectively (PubMed:39524354, PubMed:36896611, PubMed:37720100). Catalyzes debenzoylation of PPIF and ACLY (PubMed:37720100). Mediates delactylation of CCNE2 and 'Lys-16' of histone H4 (H4K16la) (PubMed:36896611, PubMed:37720100)
Subcellular location
Domains and Gene Ontology detail (25)Hide
Domains & features
Gene Ontology
- Cmitochondrial matrix
- Cmitochondrion
- Cnucleoplasm
- Cnucleus
- Cprotein-containing complex
- Fenzyme binding
- Fhistone deacetylase activity, NAD-dependent
- FNAD+ binding
- FNAD-dependent protein lysine deacetylase activity
- FNAD-dependent protein lysine delactylase activity
- Fprotein lysine deacetylase activity
- Fsequence-specific DNA binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Lipid & lipoprotein metabolism
- ·NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, Pu…
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene SIRT3
Gene-level evidence surfaced through the gene SIRT3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Tractability
Small molecules — Emerging
Protein degraders — Emerging
View underlying tractability evidence (6)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Related family literature
Papers about “Sirtuins” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.
via Sirtuins
via Sirtuins
Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.