GenAge entry for SIRT6 (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Gene name (HAGRID: 239)

HGNC symbol
SIRT6 
Aliases
 
Common name
sirtuin 6 

Potential relevance to the human ageing process

Main reason for selection
Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism
Description

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]. One of the roles of SIRT6 appears to be repression of L1 retrotransposons' activity, thus contributing to genome stability. This characteristic however declines over the course of ageing and in response to DNA damage [3634]. Overexpression of SIRT6 increases lifespan by 10-14.5% in mice males, but not in females [1966]. SIRT6 intraarticular injection is protective against chondrocyte degeneration [4347]. In mice overexpressing exogenous SIRT6 (MOSES mice) both lifespan and health span are increased. MOSES mice show improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity. MOSES mice fed on a high fat diet accumulate less fat and show improved glucose tolerance. These mice also show reduced levels of circulating IGF1 [4360].

In humans SIRT6 levels were reduced in the articular chondrocytes of osteoarthritis patients. In chondrocyte cell cultures SIRT6 overexpression supresses replicative senescence, thus inhibiting the inflammatory senescence associated secretory phenotype (SASP). The expression of NFKB1 dependent genes is significantly attenuated by SIRT6 overexpression [4347]. As such, it is possible that SIRT6 plays a role in human ageing and could ameliorate age-related pathologies.

Cytogenetic information

Cytogenetic band
19p13.3
Location
4,174,109 bp to 4,182,599 bp
Orientation
Minus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0003247; post-embryonic cardiac muscle cell growth involved in heart morphogenesis
GO:0006284; base-excision repair
GO:0006471; protein ADP-ribosylation
GO:0008285; negative regulation of cell proliferation
GO:0010569; regulation of double-strand break repair via homologous recombination
GO:0031648; protein destabilization
GO:0031667; response to nutrient levels
GO:0031940; positive regulation of chromatin silencing at telomere
GO:0032206; positive regulation of telomere maintenance
GO:0042593; glucose homeostasis
GO:0045820; negative regulation of glycolytic process
And 11 more GO terms
Cellular component: GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005724; nuclear telomeric heterochromatin
GO:0005730; nucleolus
GO:0005737; cytoplasm
Function: GO:0003682; chromatin binding
GO:0003714; transcription corepressor activity
GO:0003950; NAD+ ADP-ribosyltransferase activity
GO:0003956; NAD(P)+-protein-arginine ADP-ribosyltransferase activity
GO:0005515; protein binding
GO:0008270; zinc ion binding
GO:0017136; NAD-dependent histone deacetylase activity
GO:0034979; NAD-dependent protein deacetylase activity
GO:0046969; NAD-dependent histone deacetylase activity (H3-K9 specific)
GO:0070403; NAD+ binding
Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
LMNA, AKT1, EEF2, PRKDC, XRCC5, XRCC6, RELA, HDAC1, MAPK3, EEF1A1, HSPA8, HDAC2, MDM2, STUB1
STRING interaction network
Protein-Protein network diagram for SIRT6

Retrieve sequences for SIRT6

ORF
ORF
CDS
CDS

Homologs in model organisms

Caenorhabditis elegans
sir-2.4
Danio rerio
SIRT6
Drosophila melanogaster
Sirt6
Mus musculus
Sirt6
Rattus norvegicus
Sirt6

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Sirt6
LongevityMap
  • This gene is present as SIRT6
CellAge
  • This gene is present as SIRT6

Selected references

External links

EPD
ORF Accession
NM_016539
CDS Accession
NP_057623
OMIM
606211
HPRD
12093
Ensembl
SIRT6
UniProt/Swiss-Prot
SIRT6_HUMAN
GeneCards
SIRT6
Entrez Gene
51548
GenAtlas
SIRT6
Internet
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