SIR2 / YDL042C Overview


Standard Name
SIR2 1
Systematic Name
YDL042C
SGD ID
SGD:S000002200
Aliases
MAR1 29
Feature Type
ORF , Verified
Description
Conserved NAD+ dependent histone deacetylase of the Sirtuin family; deacetylation targets are primarily nuclear proteins; required for telomere hypercluster formation in quiescent yeast cells; involved in regulation of lifespan; plays roles in silencing at HML, HMR, telomeres, and rDNA; negatively regulates initiation of DNA replication, suppressing early firing of multicopy rDNA origins; functions as regulator of autophagy like mammalian homolog SIRT1, and also of mitophagy 1 2 3 4 5 6 7 8 9
Name Description
Silent Information Regulator 1
Paralog
HST1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Summary
SIR2 is located on the left arm of chromosome IV between PRP11 SF3a splicing factor subunit and NAT1 N-terminal acetyltransferase NatA subunit; dubious ORF YDL041W overlaps 5' end of SIR2 on opposite strand; coding sequence is 1689 nucleotides long with 12 SNPs, 4 of which cause amino acid polymorphisms
Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Summary
Sir2p is 562 amino acids long, shorter-lived, low in abundance; glutathionylated on 3 cysteines, sumoylated on 3 lysines, phosphorylated on 8 residues
Length (a.a.)
562
Mol. Weight (Da)
63270.6
Isoelectric Point
8.66
Median Abundance (molecules/cell)
2711 +/- 557
Half-life (hr)
6.4

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results. Click "YeastMine" to view all alleles in YeastMine.


View all SIR2 alleles in SGD search | YeastMine

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
NAD-dependent histone deacetylase involved in chromatin assembly, organization and silencing; also involved in sister chromatid cohesion, double-strand break repair, and the tethering of telomeres at the nuclear periphery

View computational annotations

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.


Pathways


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Summary
Non-essential gene; null mutant has decreased growth in rich media but increased growth on non-fermentable carbon sources; null mutant has decreased replicative lifespan, abnormal chronological lifespan, decreased ionic stress and desiccation resistance but increased oxidative stress resistance in aging cells; null mutant has elevated mitotic and meiotic recombination, increased mutation frequency and increased chromosome instability; null mutant has increased thermotolerance and decreased sporulation efficiency in aging cells; null is pheromone-unresponsive; conditional mutant has defective silencing at telomeres, HML, HMR and rDNA loci; heterozygous null mutant is haploinsufficient; overexpression increases ionic stress resistance and both replicative and chronological lifespan

Classical Genetics

null
overexpression
reduction of function
conditional
unspecified
Disease Details

Disease

Disease Annotations consist of three mandatory components: a gene product, a term from the Disease Ontology (DO) controlled vocabulary and an evidence code. SGD provides manually curated DO Annotations derived from the literature. Click "Disease Details" to view all Disease information and evidence for this locus as well as diseases it shares with other genes.


Summary
Yeast SIR2 is homologous to human SIRT1, and has been used to study prostate cancer, Alzheimer's disease, Parkinson's disease, and diabetes mellitus
Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


Summary
Sir2p interacts physically with proteins involved in chromatic organization, SIR2 interacts genetically with genes involved in DNA repair; the sir2 null mutant is viable; the null mutant of paralog hst1 is viable; the sir2 hst1 double mutant displays a synthetic growth defect.

721 total interactions for 401 unique genes

Physical Interactions

  • Affinity Capture-MS: 67
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 63
  • Biochemical Activity: 14
  • Co-crystal Structure: 2
  • Co-localization: 13
  • Co-purification: 6
  • Protein-peptide: 2
  • Protein-RNA: 1
  • Proximity Label-MS: 3
  • Reconstituted Complex: 18
  • Two-hybrid: 32

Genetic Interactions

  • Dosage Lethality: 1
  • Dosage Rescue: 22
  • Negative Genetic: 5
  • Phenotypic Enhancement: 60
  • Phenotypic Suppression: 140
  • Positive Genetic: 1
  • Synthetic Growth Defect: 215
  • Synthetic Lethality: 7
  • Synthetic Rescue: 45
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Summary
SIR2 promoter is bound by Bur6p, Med4p, Swi5p, and Yap6p in response to heat; SIR2 transcription is regulated by Spt10p; Sir2p protein activity is regulated by Cdc28p
Regulators
6
Targets
145
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2008-03-06

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
382
Additional
479
Reviews
401

Resources