Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVZLIJ)

• DTT Name: NAD-dependent deacetylase sirtuin-3 (SIRT3)
• Synonyms: hSIRT3; SIR2L3; SIR2-like protein 3; Regulatory protein SIR2 homolog 3
• Gene Name: SIRT3
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Sirtuin family. Class I subfamily
• UniProt ID: SIR3_HUMAN
• TTD ID: T91959
• EC Number: EC 3.5.1.-
• Sequence:
  MAFWGWRAAAALRLWGRVVERVEAGGGVGPFQACGCRLVLGGRDDVSAGLRGSHGARGEP
  LDPARPLQRPPRPEVPRAFRRQPRAAAPSFFFSSIKGGRRSISFSVGASSVVGSGGSSDK
  GKLSLQDVAELIRARACQRVVVMVGAGISTPSGIPDFRSPGSGLYSNLQQYDLPYPEAIF
  ELPFFFHNPKPFFTLAKELYPGNYKPNVTHYFLRLLHDKGLLLRLYTQNIDGLERVSGIP
  ASKLVEAHGTFASATCTVCQRPFPGEDIRADVMADRVPRCPVCTGVVKPDIVFFGEPLPQ
  RFLLHVVDFPMADLLLILGTSLEVEPFASLTEAVRSSVPRLLINRDLVGPLAWHPRSRDV
  AQLGDVVHGVESLVELLGWTEEMRDLVQRETGKLDGPDK
• Function: NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090, PubMed:19535340). 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). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16788062, PubMed:18680753, PubMed:24121500, PubMed:24252090, PubMed:19535340). 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).
• KEGG Pathway: Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway:
  FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017)
  Regulation of FOXO transcriptional activity by acetylation (R-HSA-9617629)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)

References

• [1] The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes. Hum Mol Genet. 2017 Nov 1;26(21):4105-4117.