LongevityMap Gene

Gene details

HGNC symbol: UCP2
Aliases: UCPH; BMIQ4; SLC25A8
Common name: uncoupling protein 2
Description: Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. This gene is expressed in many tissues, with the greatest expression in skeletal muscle. It is thought to play a role in nonshivering thermogenesis, obesity and diabetes. Chromosomal order is 5'-UCP3-UCP2-3'. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 11q13.4
UCSC Genome Browser: View 11q13.4 on the UCSC genome browser
OMIM: 601693
Ensembl: ENSG00000175567
UniProt/Swiss-Prot: A0A024R5N5_HUMAN
Entrez Gene: 7351
UniGene: 80658
1000 Genomes: 1000 Genomes

Homologs in model organisms

Danio rerio: ucp2
Mus musculus: Ucp2
Rattus norvegicus: Ucp2
Saccharomyces cerevisiae: DIC1

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

GenAge human genes

This gene is present as UCP2

GenDR gene manipulations

A homolog of this gene for Caenorhabditis elegans is present as ucp2

Studies (4)

Significant/Non-significant: 2/2

Study 1

Longevity Association

Non-significant

Population

Study Design

Promoter C/T SNP and 45 bp insertion/deletion (3'UTR) were examined in 1576 individuals aged >85

Conclusions

No association with reduced mortality risk was found

Indentifier

Reference

Study 2

Longevity Association: Significant
Population: Italian (Southern)
Study Design: A total of 598 subjects (293 men and 305 women, age range 64–105 years; mean ages 82.74 and 85.23 years, respectively) were analyzed for genetic variability in Uncoupling Proteins (UCPs). The set was divided into two age classes. The separation threshold for these two classes was 88 years for men and 91 years for women.
Conclusions: The genetic variability of UCP2, UCP3 and UCP4 affects the individual’s chances of surviving up to a very old age. Using the minor allele for each SNP as reference and after adjusting for BMI and sex, the dominant model for the rs660339 (UCP2) and the rs1800849 (UCP3) resulted to be significantly associated with the longevity phenotype (p = 0.001 in both cases), while the recessive model was the most likely for SNPs rs15763 (UCP3), rs9472817 (UCP4) and rs2235800 (UCP5) (p < 0.05). After adjusting for multiple testing, all the previous associations remained statistically significant, except those for rs2235800 of the UCP5 gene (p= 0.058).
Indentifier

Study 3

Longevity Association: Significant
Population: Italian
Study Design: 722 unrelated subjects (401 women and 321 men, mean age, 62.83±25.30 years; 514 subjects aged <85y, mean age = 49 ± 16 year, and 208 individuals aged from 86 y to 104 y, mean age=96 ± 4) were analyzed to assess the impact of specific IRS-2, IGF1R and UCP2 gene variants with longevity
Conclusions: A IGF1R/Asp-IRS2/Val-UCP2 allele combination was associated with an increased probability to reach extreme old age (OD = 3.185 95% CI, 1.63–6.19; p < 0.0006)
Indentifier

Study 4

Longevity Association: Non-significant
Population: Danish
Study Design: 38 genes (311 SNPs) belonging to pro-antioxidant pathways were investigated for the association with physical and cognitive performances in a Cohort of 1089 Danish nonagenarians. For each gene analyzed in the pro-antioxidant pathway, the influence on longitudinal survival was tested.
Conclusions: No gene found associated with a functional phenotype showed a corresponding association with survival in the whole cohort. NDUFS1, TXNRD1, SOD2 and UCP3 were found significantly associated with lifespan in the female cohort. No association with survival was reported in males for genes belonging to the pro-oxidant pathway here analyzed.
Indentifier