P06700 (SIR2_YEAST) Reviewed, UniProtKB/Swiss-Prot
Last modified
December 14, 2011.
Version 135.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: NAD-dependent histone deacetylase SIR2 EC=3.5.1.- Alternative name(s): Regulatory protein SIR2 Silent information regulator 2 | ||||||||
| Gene names |
| ||||||||
| Organism | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | ||||||||
| Taxonomic identifier | 559292 [NCBI] | ||||||||
| Taxonomic lineage | Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces |
Protein attributes
| Sequence length | 562 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| 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 'Lys-9' and 'Lys-14' of histone H3 and 'Lys-16' of histone H4 in vitro, such activity is unclear in vivo and may not be essential. Ref.6 Ref.7 Ref.8 Ref.16 Ref.22 |
| 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. Ref.18 |
| Subunit structure | 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. Ref.9 Ref.12 Ref.14 Ref.16 Ref.20 Ref.22 |
| Subcellular location | Nucleus › nucleolus. Note: Associated with nucleolar chromatin. Preferentially bound to the spacer regions of the rDNA repeats through its interaction with NET1. Ref.5 |
| 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. Present with 3350 molecules/cell in log phase SD medium. Ref.17 |
| Sequence similarities | Belongs to the sirtuin family. Contains 1 deacetylase sirtuin-type domain. |
| Caution | Was originally (Ref.6) thought to be an ADP-ribosyltransferase. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CDC14 | Q00684 | 5 | EBI-17219,EBI-4192 | |
| SIR4 | P11978 | 7 | EBI-17219,EBI-17237 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 562 | 562 | NAD-dependent histone deacetylase SIR2 | PRO_0000110280 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 245 – 529 | 285 | Deacetylase sirtuin-type | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nucleotide binding | 262 – 281 | 20 | NAD By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nucleotide binding | 344 – 348 | 5 | NAD By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sites | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Active site | 364 | 1 | Proton acceptor By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metal binding | 372 | 1 | Zinc By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metal binding | 375 | 1 | Zinc By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metal binding | 396 | 1 | Zinc By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metal binding | 399 | 1 | Zinc By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 23 | 1 | Phosphoserine Ref.21 Ref.23 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 400 | 1 | Phosphotyrosine Ref.23 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 139 | 1 | R → K: Defects in telomeric silencing. Ref.15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 270 | 1 | G → E: Defects in telomeric silencing. Ref.15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 296 | 1 | F → L: Defects in telomeric silencing. Ref.15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 213 – 217 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 244 – 253 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 255 – 261 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 274 – 276 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 282 – 284 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 292 – 296 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 298 – 303 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 306 – 311 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 312 – 315 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 324 – 334 | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 338 – 343 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 349 – 352 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 357 – 359 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 360 – 362 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 370 – 372 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 373 – 375 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 385 – 389 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 397 – 399 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 400 – 406 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 438 – 442 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 451 – 460 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 461 – 463 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 466 – 469 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 479 – 481 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 482 – 485 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 492 – 498 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 506 – 510 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 513 – 523 | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 533 – 537 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 541 – 545 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 551 – 555 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Characterization of two genes required for the position-effect control of yeast mating-type genes." Shore D., Squire M., Nasmyth K.A. EMBO J. 3:2817-2823(1984) [PubMed: 6098447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [2] | "The sequence of a 36.7 kb segment on the left arm of chromosome IV from Saccharomyces cerevisiae reveals 20 non-overlapping open reading frames (ORFs) including SIT4, FAD1, NAM1, RNA11, SIR2, NAT1, PRP9, ACT2 and MPS1 and 11 new ORFs." Saren A.-M., Laamanen P., Lejarcegui J.B., Paulin L. Yeast 13:65-71(1997) [PubMed: 9046088] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c. |
| [3] | "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV." Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T. Zaccaria P.Nature 387:75-78(1997) [PubMed: 9169867] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c. |
| [4] | Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c. |
| [5] | "Localization of Sir2p: the nucleolus as a compartment for silent information regulators." Gotta M., Strahl-Bolsinger S., Renauld H., Laroche T., Kennedy B.K., Grunstein M., Gasser S.M. EMBO J. 16:3243-3255(1997) [PubMed: 9214640] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [6] | "An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing." Tanny J.C., Dowd G.J., Huang J., Hilz H., Moazed D. Cell 99:735-745(1999) [PubMed: 10619427] [Abstract] Cited for: PRELIMINARY FUNCTION. |
| [7] | "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase." Imai S., Armstrong C.M., Kaeberlein M., Guarente L. Nature 403:795-800(2000) [PubMed: 10693811] [Abstract] Cited for: FUNCTION. |
| [8] | "Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae." Tsukamoto Y., Kato J., Ikeda H. Nature 388:900-903(1997) [PubMed: 9278054] [Abstract] Cited for: FUNCTION. |
| [9] | "Silent information regulator protein complexes in Saccharomyces cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits its interaction with SIR3." Moazed D., Kistler A., Axelrod A., Rine J., Johnson A.D. Proc. Natl. Acad. Sci. U.S.A. 94:2186-2191(1997) [PubMed: 9122169] [Abstract] Cited for: INTERACTION WITH SIR3 AND SIR4. |
| [10] | "Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex." Shou W., Seol J.H., Shevchenko A., Baskerville C., Moazed D., Chen Z.W.S., Jang J., Shevchenko A., Charbonneau H., Deshaies R.J. Cell 97:233-244(1999) [PubMed: 10219244] [Abstract] Cited for: IDENTIFICATION IN A RENT COMPLEX WITH CDC14. |
| [11] | "Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity." Straight A.F., Shou W., Dowd G.J., Turck C.W., Deshaies R.J., Johnson A.D., Moazed D. Cell 97:245-256(1999) [PubMed: 10219245] [Abstract] Cited for: IDENTIFICATION IN A RENT COMPLEX WITH NET1. |
| [12] | "Two paralogs involved in transcriptional silencing that antagonistically control yeast life span." Roy N., Runge K.W. Curr. Biol. 10:111-114(2000) [PubMed: 10662670] [Abstract] Cited for: INTERACTION WITH ZDS2. |
| [13] | "Silenced chromatin is permissive to activator binding and PIC recruitment." Sekinger E.A., Gross D.S. Cell 105:403-414(2001) [PubMed: 11348596] [Abstract] Cited for: MECHANISM OF TRANSCRIPTION REPRESSION. |
| [14] | "Restoration of silencing in Saccharomyces cerevisiae by tethering of a novel Sir2-interacting protein, Esc8." Cuperus G., Shore D. Genetics 162:633-645(2002) [PubMed: 12399377] [Abstract] Cited for: INTERACTION WITH ESC8. |
| [15] | "A unique class of conditional sir2 mutants displays distinct silencing defects in Saccharomyces cerevisiae." Garcia S.N., Pillus L. Genetics 162:721-736(2002) [PubMed: 12399383] [Abstract] Cited for: MUTAGENESIS OF ARG-139; GLY-270 AND PHE-296. |
| [16] | "Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing." Huang J., Moazed D. Genes Dev. 17:2162-2176(2003) [PubMed: 12923057] [Abstract] Cited for: FUNCTION, INTERACTION WITH FOB1. |
| [17] | "Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. |
| [18] | "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan." Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., Zipkin R.E., Chung P., Kisielewski A., Zhang L.-L., Scherer B., Sinclair D.A. Nature 425:191-196(2003) [PubMed: 12939617] [Abstract] Cited for: ENZYME REGULATION. |
| [19] | "The molecular biology of the SIR proteins." Gasser S.M., Cockell M.M. Gene 279:1-16(2001) [PubMed: 11722841] [Abstract] Cited for: REVIEW. |
| [20] | "Dual roles for Mcm10 in DNA replication initiation and silencing at the mating-type loci." Douglas N.L., Dozier S.K., Donato J.J. Mol. Biol. Rep. 32:197-204(2005) [PubMed: 16328881] [Abstract] Cited for: INTERACTION WITH MCM10. |
| [21] | "Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed: 17563356] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23, MASS SPECTROMETRY. |
| [22] | "Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2." Darst R.P., Garcia S.N., Koch M.R., Pillus L. Mol. Cell. Biol. 28:1361-1372(2008) [PubMed: 18086879] [Abstract] Cited for: FUNCTION, INTERACTION WITH SLX5/HEX3. |
| [23] | "A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND TYR-400, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Web resources
| Protein Spotlight In vino vita? - Issue 40 of November 2003 |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | X01419 Genomic DNA. Translation: CAA25667.1. Z71781 Genomic DNA. Translation: CAA96447.1. Z74090 Genomic DNA. Translation: CAA98600.1. BK006938 Genomic DNA. Translation: DAA11814.1. | ||||||||||||
| PIR | RGBYS2. S05891. | ||||||||||||
| RefSeq | NP_010242.1. NM_001180101.1. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | P06700. | ||||||||||||
| SMR | P06700. Positions 211-555. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-596N. | ||||||||||||
| IntAct | P06700. 50 interactions. | ||||||||||||
| MINT | MINT-509141. | ||||||||||||
| STRING | P06700. | ||||||||||||
Proteomic databases | |||||||||||||
| PeptideAtlas | P06700. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| EnsemblFungi | YDL042C; YDL042C; YDL042C. | ||||||||||||
| GeneID | 851520. | ||||||||||||
| KEGG | sce:YDL042C. | ||||||||||||
| NMPDR | fig|4932.3.peg.982. | ||||||||||||
Organism-specific databases | |||||||||||||
| CYGD | YDL042c. | ||||||||||||
| SGD | S000002200. SIR2. | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | fuNOG07733. | ||||||||||||
| GeneTree | EFGT00050000002392. | ||||||||||||
| HOGENOM | HBG203103. | ||||||||||||
| OMA | PVKHAEF. | ||||||||||||
| OrthoDB | EOG4DZ53T. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P06700. | ||||||||||||
| Genevestigator | P06700. | ||||||||||||
| GermOnline | YDL042C. Saccharomyces cerevisiae. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR003000. NAD-dep_deAcase_sirtuin. IPR007654. NAD-dep_histone_deAcase_SIR2_N. [Graphical view] | ||||||||||||
| KO | K11121. | ||||||||||||
| PANTHER | PTHR11085. SIR2. 1 hit. | ||||||||||||
| Pfam | PF04574. DUF592. 1 hit. PF02146. SIR2. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS50305. SIRTUIN. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| NextBio | 968896. | ||||||||||||
Entry information
| Entry name | SIR2_YEAST | ||||||||
| Accession | Primary (citable) accession number: P06700 Secondary accession number(s): D6VRV4 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Fungal Protein Annotation Program | ||||||||
Relevant documents
| Yeast Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |
| Protein Spotlight Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries |

Clusters with