GenAge entry for SIRT3 (Homo sapiens)

Gene name (HAGRID: 275)

HGNC symbol: SIRT3
Aliases: SIR2L3
Common name: sirtuin 3

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence linking the gene product to a pathway or mechanism linked to ageing

Description

Sirtuin 3 (SIRT3) is a member of the sirtuins, a family of proteins which promote longevity in lower model organisms and have been associated with adaptations to nutrient stresses such as fasting and the process of dietary restriction [4336]. SIRT3 is localized in the mitochondria and regulates mitochondrial function. In normally functioning mitochondria SIRT3 binds ATP synthase but dissociates in response to membrane depolarisation. SIRT3 is then required for the recovery of membrane potential [4376].

In mice, knockout of Sirt3 resulted in a decreased oxygen consumption, increased oxidative stress in skeletal muscle and impaired insulin signalling [2192]. Young Sirt3-deficient mice (8 weeks) showed signs of cardiac hypertrophy and interstitial fibrosis even though they appeared to have normal activity. In contrast, Sirt3-expressing transgenic mice were protected by blocking the cardiac hypertrophic response. In cell cultures, these results were linked to decreased ROS levels due to activation of FOXO3, SOD2 and CAT [2193]. Overexpression of SIRT3 in human fibroblasts antagonizes high glucose-induced cellular senescence [3621]. SIRT3 has also been associated with stem cell regeneration [3312].

In humans, variability in the SIRT3 has been associated with survival at old ages [2194], and increased levels of SIRT1 and SIRT3 have been associated with frailty [3607].

Cytogenetic information

Cytogenetic band: 11p15.5
Location: 215,030 bp to 236,362 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0006471; protein ADP-ribosylation
GO:0006476; protein deacetylation
GO:0007005; mitochondrion organization
GO:0007568; aging
GO:0009060; aerobic respiration
GO:0032024; positive regulation of insulin secretion
GO:0034983; peptidyl-lysine deacetylation
GO:0070373; negative regulation of ERK1 and ERK2 cascade
GO:2000378; negative regulation of reactive oxygen species metabolic process

Cellular component:

GO:0005739; mitochondrion
GO:0005759; mitochondrial matrix

Function:

GO:0003950; NAD+ ADP-ribosyltransferase activity
GO:0005515; protein binding
GO:0008270; zinc ion binding
GO:0016787; hydrolase activity
GO:0019899; enzyme binding
GO:0070403; NAD+ binding

Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: PEX5, XRCC6, FOXO3, HSPA9, HSPD1, GRN
STRING interaction network

Retrieve sequences for SIRT3

ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: sirt3
Mus musculus: Sirt3
Rattus norvegicus: Sirt3

In other databases

LongevityMap

This gene is present as SIRT3

CellAge

This gene is present as SIRT3