S. cerevisiae Gene SIR2 (YDL042C)
  Description: Conserved NAD+ dependent histone deacetylase of the Sirtuin family involved in regulation of lifespan plays roles in silencing at HML, HMR, telomeres, and the rDNA locus negatively regulates initiation of DNA replication
Transcript (Including UTRs)
   Position: sacCer3 chrIV:376,757-378,445 Size: 1,689 Total Exon Count: 1 Strand: -
Coding Region
   Position: sacCer3 chrIV:376,757-378,445 Size: 1,689 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsOther NamesMethods
Data last updated at UCSC: 2011-08-29

-  Sequence and Links to Tools and Databases
Genomic Sequence (chrIV:376,757-378,445)mRNAProtein (562 aa)
Gene SorterGenome BrowserOther Species FASTASGDUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=NAD-dependent histone deacetylase SIR2; EC=3.5.1.-; AltName: Full=Regulatory protein SIR2; AltName: Full=Silent information regulator 2;
FUNCTION: 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.
CATALYTIC ACTIVITY: NAD(+) + an acetylprotein = nicotinamide + O- acetyl-ADP-ribose + a protein.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
ENZYME REGULATION: Its activity is increased by calorie restriction, which slows the pace of aging and increases maximum lifespan. Activated by resveratrol (3,5,4'-trihydroxy-trans- stilbene), which is found in red wine.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=29.3 uM for NAD(+); KM=239 uM for a synthetic histone H3K9 acetyllysine peptide; KM=420 uM for a synthetic histone H3K14 acetyllysine peptide; KM=140 uM for a synthetic histone H4K5 acetyllysine peptide; KM=54 uM for a synthetic histone H4K8 acetyllysine peptide; KM=105 uM for a synthetic histone H4K12 acetyllysine peptide; KM=17 uM for a synthetic histone H4K16 acetyllysine peptide;
SUBUNIT: Homomultimer. Interacts with ESC8 and ZDS2. Component of the RENT complex, at least composed of SIR2, CDC14 and NET1. The RENT complex interacts with FOB1. Forms a complex with SIR3 and SIR4. Interacts with MCM10 and SLX5.
INTERACTION: Q00684:CDC14; NbExp=5; IntAct=EBI-17219, EBI-4192; P11978:SIR4; NbExp=7; IntAct=EBI-17219, EBI-17237;
SUBCELLULAR LOCATION: Nucleus, nucleolus. Note=Associated with nucleolar chromatin. Preferentially bound to the spacer regions of the rDNA repeats through its interaction with NET1.
MISCELLANEOUS: Its stability is directly linked to life span, which is extended when it is present in high dosage. Conversely, its absence shortens life span.
MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant (PubMed:19220062).
MISCELLANEOUS: Present with 3350 molecules/cell in log phase SD medium.
SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
SIMILARITY: Contains 1 deacetylase sirtuin-type domain.
CAUTION: Was originally (PubMed:10619427) thought to be an ADP- ribosyltransferase.
WEB RESOURCE: Name=Protein Spotlight; Note=In vino vita? - Issue 40 of November 2003; URL="http://web.expasy.org/spotlight/back_issues/sptlt040.shtml";

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007654 - NAD-dep_histone_deAcase_SIR2_N
IPR003000 - Sirtuin
IPR026591 - Sirtuin_cat_small_dom
IPR026590 - Ssirtuin_cat_dom

Pfam Domains:
PF04574 - Protein of unknown function (DUF592)
PF02146 - Sir2 family

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray

ModBase Predicted Comparative 3D Structure on P06700
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
HumanMouseRatZebrafishD. melanogasterC. elegans
No orthologNo orthologNo orthologNo orthologGenome BrowserGenome Browser
    Gene DetailsGene Details
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    Protein SequenceProtein Sequence

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0017136 NAD-dependent histone deacetylase activity
GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific)
GO:0046872 metal ion binding
GO:0046969 NAD-dependent histone deacetylase activity (H3-K9 specific)
GO:0046970 NAD-dependent histone deacetylase activity (H4-K16 specific)
GO:0070403 NAD+ binding
GO:0031491 nucleosome binding

Biological Process:
GO:0000183 chromatin silencing at rDNA
GO:0001300 chronological cell aging
GO:0001302 replicative cell aging
GO:0006281 DNA repair
GO:0006303 double-strand break repair via nonhomologous end joining
GO:0006325 chromatin organization
GO:0006333 chromatin assembly or disassembly
GO:0006348 chromatin silencing at telomere
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006974 cellular response to DNA damage stimulus
GO:0007062 sister chromatid cohesion
GO:0008156 negative regulation of DNA replication
GO:0016575 histone deacetylation
GO:0030466 chromatin silencing at silent mating-type cassette
GO:0034398 telomere tethering at nuclear periphery
GO:0045910 negative regulation of DNA recombination
GO:0061647 histone H3-K9 modification
GO:0070932 histone H3 deacetylation
GO:0070933 histone H4 deacetylation
GO:0097695 establishment of macromolecular complex localization to telomere
GO:1904524 negative regulation of DNA amplification
GO:1990619 histone H3-K9 deacetylation

Cellular Component:
GO:0000784 nuclear chromosome, telomeric region
GO:0005634 nucleus
GO:0005677 chromatin silencing complex
GO:0005720 nuclear heterochromatin
GO:0005724 nuclear telomeric heterochromatin
GO:0005730 nucleolus
GO:0030869 RENT complex

-  Descriptions from all associated GenBank mRNAs
  MN048126 - Synthetic construct clone CCSBy3022E03 Gateway entry clone sequence.

-  Other Names for This Gene
Protein: P06700 (aka SIR2_YEAST)

-  SGD Genes Methods, Credits, and Data Use Restrictions
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