GenAge entry for UCP2 (Homo sapiens)

Gene name (HAGRID: 235)

HGNC symbol: UCP2
Aliases: SLC25A8; BMIQ4
Common name: uncoupling protein 2 (mitochondrial, proton carrier)

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 non-mammalian animal model

Description

Mitochondrial uncoupling proteins create proton leaks across the inner mitochondrial membrane to uncouple oxidative phosphorylation from ATP synthesis resulting in energy being dissipated as heat. Like similar proteins, UCP2 appears thus to be involved in thermogenesis.

In the fruit fly, overexpression of human UCP2 in adult neurons decreases oxidative damage and extends lifespan [1496]. Transgenic mice overexpressing UCP2 in hypocretin neurons have an elevated hypothalamic temperature which results in reduction of the core body temperature. These animals had increased energy efficiency and an extended lifespan [1932]. UCP2-null mice have a significantly shorter lifespan as a result of an accelerated aging process [1505]. The mice reach sexual maturity earlier and progress into an aging phenotype earlier, demonstrated by a decrease in body weight, increased neutrophil numbers, and earlier emergence of spontaneous ulcerative dermatitis. This accelerated aging seems to be driven by increased levels of circulating IGF1, indicating potential crosstalk between UPC2 and the INS/IGF1 signalling pathway [4350]. In addition, UCP2-null mice have been shown to have increased glucose-stimulated INS secretion [1505]. In humans, UCP2 polymorphisms have been linked to obesity and are associated with longevity [1503].

Cytogenetic information

Cytogenetic band: 11q13
Location: 73,974,671 bp to 73,982,844 bp
Orientation: Minus strand

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

Protein information

Gene Ontology

Process:

GO:0000303; response to superoxide
GO:0001666; response to hypoxia
GO:0006810; transport
GO:0006839; mitochondrial transport
GO:0007565; female pregnancy
GO:0007568; aging
GO:0010942; positive regulation of cell death
GO:0015992; proton transport
GO:0032869; cellular response to insulin stimulus
GO:0034198; cellular response to amino acid starvation
GO:0043066; negative regulation of apoptotic process
GO:0051881; regulation of mitochondrial membrane potential
GO:0061179; negative regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0070542; response to fatty acid
GO:0071333; cellular response to glucose stimulus
GO:0097421; liver regeneration

Cellular component:

GO:0005743; mitochondrial inner membrane
GO:0016021; integral component of membrane

Function:

GO:0005515; protein binding

Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: YWHAZ
STRING interaction network

Retrieve sequences for UCP2

Promoter: Promoter
ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: ucp2
Mus musculus: Ucp2
Rattus norvegicus: Ucp2

In other databases

GenAge model organism genes

A homolog of this gene for Drosophila melanogaster is present as UCP2
A homolog of this gene for Mus musculus is present as Ucp2

LongevityMap

This gene is present as UCP2