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Protein

NAD-dependent histone deacetylase SIR2

Gene

SIR2

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.6 Publications

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

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.1 Publication

Kineticsi

  1. KM=29.3 µM for NAD+1 Publication
  2. KM=239 µM for a synthetic histone H3K9 acetyllysine peptide1 Publication
  3. KM=420 µM for a synthetic histone H3K14 acetyllysine peptide1 Publication
  4. KM=140 µM for a synthetic histone H4K5 acetyllysine peptide1 Publication
  5. KM=54 µM for a synthetic histone H4K8 acetyllysine peptide1 Publication
  6. KM=105 µM for a synthetic histone H4K12 acetyllysine peptide1 Publication
  7. KM=17 µM for a synthetic histone H4K16 acetyllysine peptide1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei364Proton acceptorPROSITE-ProRule annotation1
    Metal bindingi372Zinc2 Publications1
    Metal bindingi375Zinc2 Publications1
    Metal bindingi396Zinc2 Publications1
    Metal bindingi399Zinc2 Publications1
    Binding sitei513NAD; via amide nitrogen1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi262 – 281NAD2 PublicationsAdd BLAST20
    Nucleotide bindingi344 – 347NADBy similarity4
    Nucleotide bindingi471 – 473NAD1 Publication3
    Nucleotide bindingi496 – 498NAD1 Publication3

    GO - Molecular functioni

    • NAD+ binding Source: InterPro
    • NAD-dependent histone deacetylase activity Source: SGD
    • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: SGD
    • NAD-dependent histone deacetylase activity (H3-K9 specific) Source: SGD
    • NAD-dependent histone deacetylase activity (H4-K16 specific) Source: SGD
    • zinc ion binding Source: InterPro

    GO - Biological processi

    • chromatin assembly or disassembly Source: SGD
    • chromatin organization Source: SGD
    • chromatin silencing at rDNA Source: SGD
    • chromatin silencing at silent mating-type cassette Source: SGD
    • chromatin silencing at telomere Source: SGD
    • chronological cell aging Source: SGD
    • DNA repair Source: UniProtKB-KW
    • negative regulation of DNA amplification Source: SGD
    • negative regulation of DNA recombination Source: SGD
    • negative regulation of DNA replication Source: SGD
    • replicative cell aging Source: SGD
    • telomere tethering at nuclear periphery Source: SGD
    • transcription, DNA-templated Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Chromatin regulator, Hydrolase, Repressor

    Keywords - Biological processi

    DNA damage, DNA repair, Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Enzyme and pathway databases

    BioCyciYEAST:MONOMER3O-4152.
    ReactomeiR-SCE-3371453. Regulation of HSF1-mediated heat shock response.
    R-SCE-427359. SIRT1 negatively regulates rRNA Expression.
    SABIO-RKP06700.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD-dependent histone deacetylase SIR2 (EC:3.5.1.-)
    Alternative name(s):
    Regulatory protein SIR2
    Silent information regulator 2
    Gene namesi
    Name:SIR2
    Synonyms:MAR1
    Ordered Locus Names:YDL042C
    ORF Names:D2714
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    Proteomesi
    • UP000002311 Componenti: Chromosome IV

    Organism-specific databases

    EuPathDBiFungiDB:YDL042C.
    SGDiS000002200. SIR2.

    Subcellular locationi

    GO - Cellular componenti

    • chromatin silencing complex Source: SGD
    • nuclear chromosome, telomeric region Source: SGD
    • nuclear heterochromatin Source: SGD
    • nuclear telomeric heterochromatin Source: SGD
    • nucleolus Source: SGD
    • RENT complex Source: SGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi139R → K: Defects in telomeric silencing. 1 Publication1
    Mutagenesisi270G → E: Defects in telomeric silencing. 1 Publication1
    Mutagenesisi296F → L: Defects in telomeric silencing. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL3275.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001102801 – 562NAD-dependent histone deacetylase SIR2Add BLAST562

    Proteomic databases

    MaxQBiP06700.
    PRIDEiP06700.

    PTM databases

    iPTMnetiP06700.

    Interactioni

    Subunit structurei

    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).9 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDC14Q006845EBI-17219,EBI-4192
    SIR4P119786EBI-17219,EBI-17237

    Protein-protein interaction databases

    BioGridi32017. 303 interactors.
    DIPiDIP-596N.
    IntActiP06700. 48 interactors.
    MINTiMINT-509141.

    Chemistry databases

    BindingDBiP06700.

    Structurei

    Secondary structure

    1562
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi102 – 105Combined sources4
    Beta strandi111 – 113Combined sources3
    Beta strandi124 – 126Combined sources3
    Helixi132 – 154Combined sources23
    Helixi163 – 170Combined sources8
    Beta strandi173 – 175Combined sources3
    Helixi178 – 187Combined sources10
    Beta strandi213 – 217Combined sources5
    Helixi244 – 253Combined sources10
    Beta strandi255 – 261Combined sources7
    Helixi263 – 269Combined sources7
    Beta strandi274 – 276Combined sources3
    Helixi280 – 283Combined sources4
    Helixi284 – 287Combined sources4
    Helixi292 – 296Combined sources5
    Helixi298 – 303Combined sources6
    Helixi306 – 311Combined sources6
    Helixi312 – 315Combined sources4
    Helixi324 – 334Combined sources11
    Beta strandi338 – 343Combined sources6
    Helixi349 – 352Combined sources4
    Turni357 – 359Combined sources3
    Beta strandi360 – 362Combined sources3
    Beta strandi365 – 372Combined sources8
    Turni373 – 375Combined sources3
    Beta strandi378 – 380Combined sources3
    Helixi381 – 384Combined sources4
    Helixi385 – 389Combined sources5
    Turni397 – 399Combined sources3
    Helixi400 – 406Combined sources7
    Turni417 – 420Combined sources4
    Turni433 – 436Combined sources4
    Beta strandi437 – 442Combined sources6
    Helixi451 – 460Combined sources10
    Turni461 – 463Combined sources3
    Beta strandi466 – 471Combined sources6
    Helixi479 – 481Combined sources3
    Helixi482 – 485Combined sources4
    Beta strandi492 – 498Combined sources7
    Beta strandi506 – 511Combined sources6
    Helixi513 – 524Combined sources12
    Helixi533 – 537Combined sources5
    Beta strandi541 – 547Combined sources7
    Beta strandi550 – 555Combined sources6

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HJHX-ray1.85A/B209-562[»]
    4IAOX-ray2.90A/B87-562[»]
    ProteinModelPortaliP06700.
    SMRiP06700.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP06700.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini245 – 529Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST285

    Sequence similaritiesi

    Belongs to the sirtuin family. Class I subfamily.Curated
    Contains 1 deacetylase sirtuin-type domain.PROSITE-ProRule annotation

    Phylogenomic databases

    GeneTreeiENSGT00850000132399.
    HOGENOMiHOG000191845.
    InParanoidiP06700.
    KOiK11121.
    OMAiVAQKCGW.
    OrthoDBiEOG092C1NXT.

    Family and domain databases

    Gene3Di3.30.1600.10. 3 hits.
    3.40.50.1220. 3 hits.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR007654. NAD-dep_histone_deAcase_SIR2_N.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view]
    PANTHERiPTHR11085. PTHR11085. 2 hits.
    PfamiPF04574. DUF592. 1 hit.
    PF02146. SIR2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52467. SSF52467. 2 hits.
    PROSITEiPS50305. SIRTUIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P06700-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTIPHMKYAV SKTSENKVSN TVSPTQDKDA IRKQPDDIIN NDEPSHKKIK
    60 70 80 90 100
    VAQPDSLRET NTTDPLGHTK AALGEVASME LKPTNDMDPL AVSAASVVSM
    110 120 130 140 150
    SNDVLKPETP KGPIIISKNP SNGIFYGPSF TKRESLNARM FLKYYGAHKF
    160 170 180 190 200
    LDTYLPEDLN SLYIYYLIKL LGFEVKDQAL IGTINSIVHI NSQERVQDLG
    210 220 230 240 250
    SAISVTNVED PLAKKQTVRL IKDLQRAINK VLCTRLRLSN FFTIDHFIQK
    260 270 280 290 300
    LHTARKILVL TGAGVSTSLG IPDFRSSEGF YSKIKHLGLD DPQDVFNYNI
    310 320 330 340 350
    FMHDPSVFYN IANMVLPPEK IYSPLHSFIK MLQMKGKLLR NYTQNIDNLE
    360 370 380 390 400
    SYAGISTDKL VQCHGSFATA TCVTCHWNLP GERIFNKIRN LELPLCPYCY
    410 420 430 440 450
    KKRREYFPEG YNNKVGVAAS QGSMSERPPY ILNSYGVLKP DITFFGEALP
    460 470 480 490 500
    NKFHKSIRED ILECDLLICI GTSLKVAPVS EIVNMVPSHV PQVLINRDPV
    510 520 530 540 550
    KHAEFDLSLL GYCDDIAAMV AQKCGWTIPH KKWNDLKNKN FKCQEKDKGV
    560
    YVVTSDEHPK TL
    Length:562
    Mass (Da):63,262
    Last modified:January 1, 1988 - v1
    Checksum:i52E6937533654586
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X01419 Genomic DNA. Translation: CAA25667.1.
    Z71781 Genomic DNA. Translation: CAA96447.1.
    Z74090 Genomic DNA. Translation: CAA98600.1.
    BK006938 Genomic DNA. Translation: DAA11814.1.
    PIRiS05891. RGBYS2.
    RefSeqiNP_010242.1. NM_001180101.1.

    Genome annotation databases

    EnsemblFungiiYDL042C; YDL042C; YDL042C.
    GeneIDi851520.
    KEGGisce:YDL042C.

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    In vino vita? - Issue 40 of November 2003

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X01419 Genomic DNA. Translation: CAA25667.1.
    Z71781 Genomic DNA. Translation: CAA96447.1.
    Z74090 Genomic DNA. Translation: CAA98600.1.
    BK006938 Genomic DNA. Translation: DAA11814.1.
    PIRiS05891. RGBYS2.
    RefSeqiNP_010242.1. NM_001180101.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HJHX-ray1.85A/B209-562[»]
    4IAOX-ray2.90A/B87-562[»]
    ProteinModelPortaliP06700.
    SMRiP06700.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi32017. 303 interactors.
    DIPiDIP-596N.
    IntActiP06700. 48 interactors.
    MINTiMINT-509141.

    Chemistry databases

    BindingDBiP06700.
    ChEMBLiCHEMBL3275.

    PTM databases

    iPTMnetiP06700.

    Proteomic databases

    MaxQBiP06700.
    PRIDEiP06700.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYDL042C; YDL042C; YDL042C.
    GeneIDi851520.
    KEGGisce:YDL042C.

    Organism-specific databases

    EuPathDBiFungiDB:YDL042C.
    SGDiS000002200. SIR2.

    Phylogenomic databases

    GeneTreeiENSGT00850000132399.
    HOGENOMiHOG000191845.
    InParanoidiP06700.
    KOiK11121.
    OMAiVAQKCGW.
    OrthoDBiEOG092C1NXT.

    Enzyme and pathway databases

    BioCyciYEAST:MONOMER3O-4152.
    ReactomeiR-SCE-3371453. Regulation of HSF1-mediated heat shock response.
    R-SCE-427359. SIRT1 negatively regulates rRNA Expression.
    SABIO-RKP06700.

    Miscellaneous databases

    EvolutionaryTraceiP06700.
    PROiP06700.

    Family and domain databases

    Gene3Di3.30.1600.10. 3 hits.
    3.40.50.1220. 3 hits.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR007654. NAD-dep_histone_deAcase_SIR2_N.
    IPR003000. Sirtuin.
    IPR026591. Sirtuin_cat_small_dom.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view]
    PANTHERiPTHR11085. PTHR11085. 2 hits.
    PfamiPF04574. DUF592. 1 hit.
    PF02146. SIR2. 1 hit.
    [Graphical view]
    SUPFAMiSSF52467. SSF52467. 2 hits.
    PROSITEiPS50305. SIRTUIN. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSIR2_YEAST
    AccessioniPrimary (citable) accession number: P06700
    Secondary accession number(s): D6VRV4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: January 1, 1988
    Last modified: November 2, 2016
    This is version 182 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    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.
    The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant.1 Publication
    Present with 3350 molecules/cell in log phase SD medium.1 Publication

    Caution

    Was originally thought to be an ADP-ribosyltransferase.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    3. SIMILARITY comments
      Index of protein domains and families
    4. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    5. Yeast chromosome IV
      Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.