Molecule Information

General Information of the Molecule (ID: Mol04156)

• Name: Sirtuin 3 (SIRT3) ,Homo sapiens
• Synonyms: NAD-dependent protein delactylase sirtuin-3; Regulatory protein SIR2 homolog 3; SIR2-like protein 3
• Molecule Type: Protein
• Gene Name: SIRT3
• Gene ID: 23410
• Location: chr11:215030-236931[-]
• Sequence:
  MAFWGWRAAAALRLWGRVVERVEAGGGVGPFQACGCRLVLGGRDDVSAGLRGSHGARGEP
  LDPARPLQRPPRPEVPRAFRRQPRAAAPSFFFSSIKGGRRSISFSVGASSVVGSGGSSDK
  GKLSLQDVAELIRARACQRVVVMVGAGISTPSGIPDFRSPGSGLYSNLQQYDLPYPEAIF
  ELPFFFHNPKPFFTLAKELYPGNYKPNVTHYFLRLLHDKGLLLRLYTQNIDGLERVSGIP
  ASKLVEAHGTFASATCTVCQRPFPGEDIRADVMADRVPRCPVCTGVVKPDIVFFGEPLPQ
  RFLLHVVDFPMADLLLILGTSLEVEPFASLTEAVRSSVPRLLINRDLVGPLAWHPRSRDV
  AQLGDVVHGVESLVELLGWTEEMRDLVQRETGKLDGPDK
• 3D-structure: PDB ID: 8BBK; Classification: Hydrolase; Method: X-ray diffraction; Resolution: 3.27 Å
• Function: 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 mediating delactylation of proteins, such as CCNE2 and 'Lys-16' of histone H4 (H4K16la) (PubMed:36896611, PubMed:37720100). .
• Uniprot ID: SIR3_HUMAN
• Ensembl ID: ENSG00000142082
• HGNC ID: HGNC:14931

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

Resveratrol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Clear cell renal cell carcinoma [ICD-11: 2C90.Y] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
• Resistant Drug: Resveratrol
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Clear cell renal cell carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.47E-39; Fold-change: -9.88E-01; Z-score: -1.66E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• In Vitro Model: Hk-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• In Vitro Model: RPTEC cells; Kidney; Homo sapiens (Human); N.A.
• In Vitro Model: SIRT3-overexpressing 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: SIRT3-overexpressing Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: qRT-PCR and western blotting
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The expression of SIRT3 improves mitochondrial function and biogenesis. Furthermore, the anti-proliferative effects of SIRT3 and RSV are increased in ccRCC through metabolic reprogramming.

References

• Ref 1: Mitochondrial metabolic reprogramming by SIRT3 regulation ameliorates drug resistance in renal cell carcinoma. PLoS One. 2022 Jun 7;17(6):e0269432.