Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

SIRT3 (Q9NTG7) - Overview - Molecular Target Synopsis

Protein


SIRT3, NAD-dependent protein deacetylase sirtuin-3, mitochondrial
Enzyme Classification 3.5.1.-
UniProt Q9NTG7

Also Known as SIR3_HUMAN, SIRT3, SIR2L3

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). Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (PubMed:29445193). Interacts with NDUFA9, ACSS1, IDH2 and GDH (PubMed:16788062, PubMed:18794531, PubMed:19535340, PubMed:18680753). Interacts with PCCA (PubMed:23438705).

5ZGC
CRYSTAL STRUCTURE OF SIRT3 IN COMPLEX WITH H4K16BHB PEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for SIRT3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: SIRT3 is active in the following subcellular-locations: mitochondrion matrix.
GO terms: SIRT3 is active in the following subcellular-locations: mitochondrial matrix, mitochondrion, nucleoplasm, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project SIRT3 has gain in 0 cell-lines, loss in 7 cell-lines and no signal in 998 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H522, PC_3, HCT_116

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1651, DMS 454, NCI-H522

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, A549, K562

(see details)

3D Structures


For SIRT3 there are:
31 structures (71 chains) solved
18 are solved in complex with at least one small molecule ligand
2 are solved with an approved drug

SIRT3 is solved in complex with the approved drug(s):

BBI/AMIODARONE (4O8Z_A, 5H4D_A, 5H4D_H).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


SIRT3 has been screened with 505 compounds (610 bioactivities), 37 compounds have bioactivities that show binding affinity of <= 500nM (39 bioactivities). (see details)