Identification
NameNAD-dependent histone deacetylase SIR2
Synonyms
  • Regulatory protein SIR2
  • Silent information regulator 2
Gene NameSIR2
Enzyme ClassNot Available
Biological Properties
General FunctionTranscription
Specific FunctionNAD-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
Cellular LocationNucleus, nucleolus.
SMPDB Pathways
NAD metabolismPW002421 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG PathwaysNot Available
SMPDB Reactions
NAD + water + [histone]-N6-acetyl-L-lysine → 3''-O-acetyl-ADP-ribose + a [histone]-L-lysine + Niacinamide
KEGG Reactions
NAD + waterhydron + Niacinamide + Adenosine diphosphate ribose
Metabolites
YMDB IDNameView
YMDB00110NADShow
YMDB00274NiacinamideShow
YMDB00890waterShow
YMDB163063''-O-acetyl-ADP-riboseShow
GO Classification
Function
transition metal ion binding
zinc ion binding
catalytic activity
NAD binding
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
histone deacetylase activity
nucleotide binding
NAD-dependent histone deacetylase activity
NAD or NADH binding
hydrolase activity
binding
ion binding
cation binding
metal ion binding
Process
cellular process
gene silencing
chromatin silencing
macromolecule metabolic process
macromolecule modification
protein modification process
post-translational protein modification
protein amino acid deacetylation
regulation of transcription, DNA-dependent
biological regulation
metabolic process
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
Gene Properties
Chromosome LocationNot Available
Locus
Gene Sequence>1689 bp ATGACCATCCCACATATGAAATACGCCGTATCAAAGACTAGCGAAAATAAGGTTTCAAAT ACAGTAAGCCCCACACAAGATAAAGACGCGATCAGAAAACAACCCGATGACATTATAAAT AATGATGAACCTTCACATAAGAAGATAAAAGTAGCACAGCCGGATTCCTTGAGGGAAACC AACACAACAGATCCACTTGGGCACACTAAAGCTGCGCTCGGAGAAGTGGCATCGATGGAG CTCAAACCAACTAATGACATGGATCCCTTGGCAGTGTCAGCAGCTTCAGTAGTGTCAATG TCCAATGACGTTTTGAAACCAGAGACGCCCAAGGGGCCAATCATAATCAGTAAAAACCCA TCAAATGGTATTTTCTATGGTCCCTCCTTCACTAAACGAGAGTCTCTCAATGCTCGAATG TTTCTGAAATACTATGGTGCACACAAATTTTTAGACACTTACCTCCCCGAGGATTTGAAC TCGTTATACATTTACTATCTTATCAAGTTGCTAGGCTTTGAAGTTAAAGATCAAGCGCTT ATCGGCACCATCAACAGTATTGTCCATATCAACTCGCAAGAGCGTGTTCAAGATTTGGGA AGTGCAATATCTGTCACAAATGTTGAAGACCCATTGGCAAAAAAGCAAACAGTTCGTCTA ATCAAAGATTTGCAAAGAGCAATTAACAAAGTTCTATGTACAAGATTAAGATTATCCAAT TTTTTCACTATTGATCATTTTATTCAAAAATTACATACCGCTAGAAAAATTTTGGTCCTG ACTGGTGCAGGTGTTTCAACTTCATTAGGGATCCCGGACTTCAGATCTTCTGAGGGGTTC TATTCAAAGATCAAACATTTGGGGCTCGATGATCCCCAAGACGTTTTCAATTACAATATA TTTATGCACGACCCCTCTGTTTTCTATAATATTGCCAATATGGTTTTACCTCCAGAAAAA ATTTATTCTCCATTGCATAGTTTCATTAAGATGCTACAAATGAAAGGGAAATTATTGAGA AATTATACTCAAAACATTGATAATTTGGAATCTTATGCGGGAATAAGCACAGATAAACTG GTGCAGTGCCATGGCTCTTTTGCTACTGCCACCTGCGTTACCTGCCATTGGAACCTACCC GGTGAGAGGATATTTAATAAAATTAGAAACCTCGAACTTCCACTATGCCCGTACTGTTAC AAAAAAAGAAGAGAATATTTCCCAGAGGGATATAATAATAAAGTAGGTGTTGCTGCATCA CAGGGTTCAATGTCGGAAAGGCCTCCATATATCCTTAACTCATATGGCGTTCTCAAACCA GATATCACATTCTTTGGCGAAGCACTGCCAAATAAATTTCATAAGAGCATTCGCGAAGAT ATCTTAGAATGTGATTTGTTGATTTGCATTGGGACAAGTTTAAAAGTAGCGCCAGTGTCT GAAATCGTAAACATGGTTCCTTCCCACGTTCCCCAAGTCCTGATTAATCGTGATCCCGTC AAGCACGCAGAATTTGATTTATCTCTTTTGGGGTACTGTGATGACATTGCAGCTATGGTA GCCCAAAAATGTGGCTGGACGATTCCGCATAAGAAATGGAACGATTTGAAGAACAAGAAC TTTAAATGCCAAGAGAAGGATAAGGGCGTGTATGTCGTTACATCAGATGAACATCCCAAA ACCCTCTAA
Protein Properties
Pfam Domain Function
Protein Residues562
Protein Molecular Weight63261.30078
Protein Theoretical pI8.66
Signalling Regions
  • None
Transmembrane Regions
  • None
Protein Sequence>NAD-dependent histone deacetylase SIR2 MTIPHMKYAVSKTSENKVSNTVSPTQDKDAIRKQPDDIINNDEPSHKKIKVAQPDSLRET NTTDPLGHTKAALGEVASMELKPTNDMDPLAVSAASVVSMSNDVLKPETPKGPIIISKNP SNGIFYGPSFTKRESLNARMFLKYYGAHKFLDTYLPEDLNSLYIYYLIKLLGFEVKDQAL IGTINSIVHINSQERVQDLGSAISVTNVEDPLAKKQTVRLIKDLQRAINKVLCTRLRLSN FFTIDHFIQKLHTARKILVLTGAGVSTSLGIPDFRSSEGFYSKIKHLGLDDPQDVFNYNI FMHDPSVFYNIANMVLPPEKIYSPLHSFIKMLQMKGKLLRNYTQNIDNLESYAGISTDKL VQCHGSFATATCVTCHWNLPGERIFNKIRNLELPLCPYCYKKRREYFPEGYNNKVGVAAS QGSMSERPPYILNSYGVLKPDITFFGEALPNKFHKSIREDILECDLLICIGTSLKVAPVS EIVNMVPSHVPQVLINRDPVKHAEFDLSLLGYCDDIAAMVAQKCGWTIPHKKWNDLKNKN FKCQEKDKGVYVVTSDEHPKTL
References
External Links
ResourceLink
Saccharomyces Genome Database SIR2
Uniprot IDP06700
Uniprot NameSIR2_YEAST
GenBank Gene IDX01419
Genebank Protein ID4470
General Reference
  • Shore, D., Squire, M., Nasmyth, K. A. (1984). "Characterization of two genes required for the position-effect control of yeast mating-type genes." EMBO J 3:2817-2823.6098447
  • Saren, A. M., Laamanen, P., Lejarcegui, J. B., Paulin, L. (1997). "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." Yeast 13:65-71.9046088
  • Jacq, C., Alt-Morbe, J., Andre, B., Arnold, W., Bahr, A., Ballesta, J. P., Bargues, M., Baron, L., Becker, A., Biteau, N., Blocker, H., Blugeon, C., Boskovic, J., Brandt, P., Bruckner, M., Buitrago, M. J., Coster, F., Delaveau, T., del Rey, F., Dujon, B., Eide, L. G., Garcia-Cantalejo, J. M., Goffeau, A., Gomez-Peris, A., Zaccaria, P., et, a. l. .. (1997). "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV." Nature 387:75-78.9169867
  • Gotta, M., Strahl-Bolsinger, S., Renauld, H., Laroche, T., Kennedy, B. K., Grunstein, M., Gasser, S. M. (1997). "Localization of Sir2p: the nucleolus as a compartment for silent information regulators." EMBO J 16:3243-3255.9214640
  • Tanny, J. C., Dowd, G. J., Huang, J., Hilz, H., Moazed, D. (1999). "An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing." Cell 99:735-745.10619427
  • Imai, S., Armstrong, C. M., Kaeberlein, M., Guarente, L. (2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase." Nature 403:795-800.10693811
  • Tsukamoto, Y., Kato, J., Ikeda, H. (1997). "Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae." Nature 388:900-903.9278054
  • Moazed, D., Kistler, A., Axelrod, A., Rine, J., Johnson, A. D. (1997). "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." Proc Natl Acad Sci U S A 94:2186-2191.9122169
  • Shou, W., Seol, J. H., Shevchenko, A., Baskerville, C., Moazed, D., Chen, Z. W., Jang, J., Shevchenko, A., Charbonneau, H., Deshaies, R. J. (1999). "Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex." Cell 97:233-244.10219244
  • Straight, A. F., Shou, W., Dowd, G. J., Turck, C. W., Deshaies, R. J., Johnson, A. D., Moazed, D. (1999). "Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity." Cell 97:245-256.10219245
  • Roy, N., Runge, K. W. (2000). "Two paralogs involved in transcriptional silencing that antagonistically control yeast life span." Curr Biol 10:111-114.10662670
  • Sekinger, E. A., Gross, D. S. (2001). "Silenced chromatin is permissive to activator binding and PIC recruitment." Cell 105:403-414.11348596
  • Cuperus, G., Shore, D. (2002). "Restoration of silencing in Saccharomyces cerevisiae by tethering of a novel Sir2-interacting protein, Esc8." Genetics 162:633-645.12399377
  • Garcia, S. N., Pillus, L. (2002). "A unique class of conditional sir2 mutants displays distinct silencing defects in Saccharomyces cerevisiae." Genetics 162:721-736.12399383
  • Huang, J., Moazed, D. (2003). "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." Genes Dev 17:2162-2176.12923057
  • Ghaemmaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., Weissman, J. S. (2003). "Global analysis of protein expression in yeast." Nature 425:737-741.14562106
  • 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. (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan." Nature 425:191-196.12939617
  • Gasser, S. M., Cockell, M. M. (2001). "The molecular biology of the SIR proteins." Gene 279:1-16.11722841
  • Douglas, N. L., Dozier, S. K., Donato, J. J. (2005). "Dual roles for Mcm10 in DNA replication initiation and silencing at the mating-type loci." Mol Biol Rep 32:197-204.16328881
  • Smolka, M. B., Albuquerque, C. P., Chen, S. H., Zhou, H. (2007). "Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Proc Natl Acad Sci U S A 104:10364-10369.17563356
  • Darst, R. P., Garcia, S. N., Koch, M. R., Pillus, L. (2008). "Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2." Mol Cell Biol 28:1361-1372.18086879
  • Albuquerque, C. P., Smolka, M. B., Payne, S. H., Bafna, V., Eng, J., Zhou, H. (2008). "A multidimensional chromatography technology for in-depth phosphoproteome analysis." Mol Cell Proteomics 7:1389-1396.18407956