Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

SIR2 (P06700) - Overview - Molecular Target Synopsis


SIR2, NAD-dependent histone deacetylase SIR2
Enzyme Classification 3.5.1.-
UniProt P06700

Also Known as SIR2_YEAST, SIR2, MAR1

NAD-dependent deacetylase, which participates in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. Involved in transcriptional repression of the silent mating-type loci HML and HMR and telomeric silencing via its association with SIR3 and SIR4. Plays a central role in ribosomal DNA (rDNA) silencing via its association with the RENT complex, preventing hyperrecombination, and repressing transcription from foreign promoters, which contributes to extending life span. Probably represses transcription via the formation of heterochromatin structure, which involves the compaction of chromatin fiber into a more condensed form, although this complex in at least one case can still bind euchromatic levels of positive transcription regulators. Although it displays some NAD-dependent histone deacetylase activity on histone H3K9Ac and H3K14Ac and histone H4K16Ac in vitro, such activity is unclear in vivo and may not be essential. Homomultimer. Forms a complex with SIR3 and SIR4 (PubMed:9122169). Component of the RENT complex, at least composed of SIR2, CDC14 and NET1 (PubMed:10219244, PubMed:10219245). The RENT complex interacts with FOB1 (PubMed:12923057). Interacts with ESC8 (PubMed:12399377). Interacts with and ZDS2 (PubMed:10662670). Interacts with MCM10 (PubMed:16328881). Interacts with SLX5 (PubMed:18086879). Interacts with NSI1 (PubMed:22362748).

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Sub-cellular localization

UniProt: SIR2 is active in the following subcellular-locations: nucleolus, nucleus.
GO terms: SIR2 is active in the following subcellular-locations: chromatin silencing complex, nuclear chromatin, nuclear chromosome, nuclear heterochromatin, nuclear pericentric heterochromatin, nuclear telomeric heterochromatin, nucleolus, RENT complex, Set3 complex.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project SIR2 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures

For SIR2 there are:
2 structures (4 chains) solved
2 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

SIR2 has been screened with 93 compounds (212 bioactivities). (see details)