Gene: SIRT6 - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | SIRT6 | ||||||||||||||||
NCBI Gene ID | : | 51548 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | NAD-dependent deacetylase sirtuin-6 | NAD-dependent protein deacetylase sirtuin-6 | regulatory protein SIR2 homolog 6 | SIR2-LIKE 6 | SIR2-like protein 6 | sir2-related protein type 6 | SIR2L6 | SIRT6 | sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae) | sirtuin (silent mating type information regulation 2, S. cerevisiae, homolog) 6 | SIRTUIN 6 | sirtuin 6 | sirtuin type 6 Source: GPSDB |
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Gene Homologs | : | AgaP_AGAP001458 (Anopheles gambiae) | NCU07624 (Neurospora crassa) | Os04g0271000 (Oryza sativa) | SIRT6 (Bos taurus) | SIRT6 (Canis lupus familiaris) | sirt6 (Danio rerio) | Sirt6 (Drosophila melanogaster) | SIRT6 (Gallus gallus) | SIRT6 (Homo sapiens) | SIRT6 (Macaca mulatta) | Sirt6 (Mus musculus) | SIRT6 (Pan troglodytes) | Sirt6 (Rattus norvegicus) | SRT1 (Arabidopsis thaliana) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_001356 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
---|---|---|---|---|---|
NAD-dependent protein deacetylase sirtuin-6 | Homo sapiens | Q8N6T7 (UniProtKB/Swiss-Prot) | SIR6_HUMAN (UniProtKB/Swiss-Prot) | NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate. | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
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1 | OB_009764 | Homo sapiens |
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In yeast, sirtuins regulate epigenetic gene silencing. SIRT6, a chromatin-associated protein, also appears to be involved in DNA repair. SIRT6-null mice are small, with low levels of IGF1, display evidence of genomic instability, and exhibit signs of premature ageing after 2-3 weeks [1590]. As such, it is possible that SIRT6 plays a role in human ageing. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
# | Observation Stable ID | Homology Group Genes | #EGHG | Description | Source | Homology Source |
---|---|---|---|---|---|---|
1 | OB_008240 | 3 | The HomoloGene homology group 6924 contains 3 genes with experimental evidence for ageing relevance (SIRT6 - Homo sapiens | Sirt6 - Drosophila melanogaster | Sirt6 - Mus musculus) and 11 other genes. | AgeFactDB Homology Analysis | HomoloGene homology group 6924 |
Sequences
SIR6_HUMAN | Q8N6T7 | NAD-dependent protein deacetylase sirtuin-6 (Homo sapiens) from UniProtKB/Swiss-Prot Length: 355 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 SIR6_HUMAN 1 MSVNYAAGLSPYADKGKCGLPEIFDPPEELERKVWELARLVWQSSSVVFHTGAGISTASGIPDFRGPHGVWTMEERGLAPKFDTTFESARPTQTHMALVQLERVGLLRFLVSQNVDGLHVRSGFPRDKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTVAKARGLRACRGELRDTILDWEDSLPDRDLALADEASRNADLSITLGTSLQIRPSGNLPLATKRRGGRLVIVNLQPTKHDRHADLRIHGYVDEVMTRLMKHLGLEIPAWDGPRVLERALPPLPRPPTPKLEPKEESPTRINGSIPAGPKQEPCAQHNGSEPASPKRERPTSPAPHRPPKRVKAKAVPS 355
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- Liszt G, Ford E, Kurtev M, Guarente L:
Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase.
J Biol Chem. 2005; 280: 21313-20.
PubMed (ID: 15795229), doi:10.1074/jbc.M413296200
MeSH Terms: ADP Ribose Transferases/chemistry; ADP Ribose Transferases/physiology; Cell Nucleus/enzymology; Sirtuins/metabolism - Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R:
The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha.
Cell. 2010; 140: 280-93.
PubMed (ID: 20141841), PubMed Central (ID: PMC2821045), doi:10.1016/j.cell.2009.12.041
MeSH Terms: Glucose/metabolism; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Sirtuins/metabolism - Kaidi A, Weinert BT, Choudhary C, Jackson SP:
Human SIRT6 promotes DNA end resection through CtIP deacetylation.
Science. 2010; 329: 1348-53.
PubMed (ID: 20829486), PubMed Central (ID: PMC3276839), doi:10.1126/science.1192049
MeSH Terms: Carrier Proteins/metabolism; DNA Breaks, Double-Stranded; DNA Repair; DNA/metabolism; Nuclear Proteins/metabolism; Sirtuins/metabolism - Schwer B, Schumacher B, Lombard DB, Xiao C, Kurtev MV, Gao J, Schneider JI, Chai H, Bronson RT, Tsai LH, Deng CX, Alt FW:
Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity.
Proc Natl Acad Sci USA. 2010; 107: 21790-4.
PubMed (ID: 21098266), doi:10.1073/pnas.1016306107
MeSH Terms: Growth/physiology; Neurons/physiology; Obesity/physiopathology; Sirtuins/metabolism - Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, Seluanov A, Gorbunova V:
SIRT6 promotes DNA repair under stress by activating PARP1.
Science. 2011; 332: 1443-6.
PubMed (ID: 21680843), doi:10.1126/science.1202723
MeSH Terms: DNA Breaks, Double-Stranded; DNA Repair; Oxidative Stress; Poly(ADP-ribose) Polymerases/metabolism; Sirtuins/metabolism - Kawahara TL, Rapicavoli NA, Wu AR, Qu K, Quake SR, Chang HY:
Dynamic chromatin localization of Sirt6 shapes stress- and aging-related transcriptional networks.
PLoS Genet. 2011; 7: e1002153.
PubMed (ID: 21738489), PubMed Central (ID: PMC3128103), doi:10.1371/journal.pgen.1002153
MeSH Terms: Aging/genetics; Chromatin/metabolism; Gene Regulatory Networks/genetics; Sirtuins/metabolism; Stress, Physiological/genetics - Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY:
The sirtuin SIRT6 regulates lifespan in male mice.
Nature. 2012; 483: 218-21.
PubMed (ID: 22367546), doi:10.1038/nature10815
MeSH Terms: Longevity/physiology; Sex Characteristics; Sirtuins/metabolism - Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW:
Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.
Cell. 2006; 124: 315-29.
PubMed (ID: 16439206), doi:10.1016/j.cell.2005.11.044
MeSH Terms: Aging/metabolism; Genetic Diseases, Inborn/genetics; Genomic Instability; Sirtuins/genetics; Sirtuins/physiology - Sauve AA, Wolberger C, Schramm VL, Boeke JD:
The biochemistry of sirtuins.
Annu Rev Biochem. 2006; 75: 435-65.
PubMed (ID: 16756498), doi:10.1146/annurev.biochem.74.082803.133500
MeSH Terms: Protein Isoforms/chemistry; Protein Isoforms/genetics; Protein Isoforms/metabolism; Sirtuins/chemistry; Sirtuins/genetics; Sirtuins/metabolism - Longo VD, Kennedy BK:
Sirtuins in aging and age-related disease.
Cell. 2006; 126: 257-68.
PubMed (ID: 16873059), doi:10.1016/j.cell.2006.07.002
MeSH Terms: Aging/physiology; Diabetes Mellitus/metabolism; Neoplasms/metabolism; Neurodegenerative Diseases/metabolism; Sirtuins/physiology - Kanfi Y, Shalman R, Peshti V, Pilosof SN, Gozlan YM, Pearson KJ, Lerrer B, Moazed D, Marine JC, de Cabo R, Cohen HY:
Regulation of SIRT6 protein levels by nutrient availability.
FEBS Lett. 2008; 582: 543-8.
PubMed (ID: 18242175), PubMed Central (ID: PMC3263697), doi:10.1016/j.febslet.2008.01.019
MeSH Terms: Sirtuins/metabolism - Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H, Damian M, Cheung P, Kusumoto R, Kawahara TL, Barrett JC, Chang HY, Bohr VA, Ried T, Gozani O, Chua KF:
SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin.
Nature. 2008; 452: 492-6.
PubMed (ID: 18337721), PubMed Central (ID: PMC2646112), doi:10.1038/nature06736
MeSH Terms: Chromatin/metabolism; Histone Deacetylases/metabolism; Sirtuins/metabolism; Telomere/metabolism - Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF:
SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span.
Cell. 2009; 136: 62-74.
PubMed (ID: 19135889), PubMed Central (ID: PMC2757125), doi:10.1016/j.cell.2008.10.052
MeSH Terms: Gene Expression Regulation, Developmental; NF-kappa B/metabolism; Sirtuins/metabolism; Transcription Factor RelA/metabolism - Kanfi Y, Peshti V, Gil R, Naiman S, Nahum L, Levin E, Kronfeld-Schor N, Cohen HY:
SIRT6 protects against pathological damage caused by diet-induced obesity.
Aging Cell. 2010; 9: 162-73.
PubMed (ID: 20047575), doi:10.1111/j.1474-9726.2009.00544.x
MeSH Terms: Animal Feed/adverse effects; Fats/adverse effects; Obesity/metabolism; Obesity/pathology; Sirtuins/metabolism - Tennen RI, Berber E, Chua KF:
Functional dissection of SIRT6: identification of domains that regulate histone deacetylase activity and chromatin localization.
Mech Ageing Dev. 2010; 131: 185-92.
PubMed (ID: 20117128), PubMed Central (ID: PMC2846990), doi:10.1016/j.mad.2010.01.006
MeSH Terms: Chromatin/metabolism; Histone Deacetylases/metabolism; Sirtuins/metabolism
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot