Molecule Information

General Information of the Molecule (ID: Mol00162)

• Name: NAD-dependent protein deacetylase sirtuin-3 (SIRT3) ,Homo sapiens
• Synonyms: hSIRT3; Regulatory protein SIR2 homolog 3; SIR2-like protein 3; SIR2L3
• Molecule Type: Protein
• Gene Name: SIRT3
• Gene ID: 23410
• Location: chr11:215030-236931[-]
• Sequence:
  MAFWGWRAAAALRLWGRVVERVEAGGGVGPFQACGCRLVLGGRDDVSAGLRGSHGARGEP
  LDPARPLQRPPRPEVPRAFRRQPRAAAPSFFFSSIKGGRRSISFSVGASSVVGSGGSSDK
  GKLSLQDVAELIRARACQRVVVMVGAGISTPSGIPDFRSPGSGLYSNLQQYDLPYPEAIF
  ELPFFFHNPKPFFTLAKELYPGNYKPNVTHYFLRLLHDKGLLLRLYTQNIDGLERVSGIP
  ASKLVEAHGTFASATCTVCQRPFPGEDIRADVMADRVPRCPVCTGVVKPDIVFFGEPLPQ
  RFLLHVVDFPMADLLLILGTSLEVEPFASLTEAVRSSVPRLLINRDLVGPLAWHPRSRDV
  AQLGDVVHGVESLVELLGWTEEMRDLVQRETGKLDGPDK
• Function: NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5PO. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels. In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription. 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.
• 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

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Pazopanib HCl

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Synovial sarcoma [1]

• Resistant Disease: Synovial sarcoma [ICD-11: 2B5A.0]
• Resistant Drug: Pazopanib HCl
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 1273/99 cells; Sarcoma; Homo sapiens (Human); CVCL_N588
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: YaFuSS cells; Sarcoma; Homo sapiens (Human); CVCL_L809
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: EV isolation, immunoblotting, and nanoparticle tracking analysis
• Mechanism Description: Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma by down-regulating TRIP6, LMNA, and SIRT3 expression.

References

• Ref 1: Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma. Biochem Biophys Res Commun. 2018 Jan 1;495(1):1322-1327. doi: 10.1016/j.bbrc.2017.11.164. Epub 2017 Nov 27.