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GenAge entry for SOD2 (Homo sapiens)


Gene name (HAGRID: 0129)

HGNC symbolSOD2
Aliases
Common namesuperoxide dismutase 2, mitochondrial

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

SOD2 is an antioxidant, the mitochondrial form of SOD and an important defence against oxidative damage. Evidence from invertebrates suggests it may play a role in ageing. Overexpression of SOD2 in flies significantly extends lifespan [1239]. Mice without SOD2 are not viable [0658]. Reducing the activity of SOD2 in mice increases the levels of oxidative damage to DNA but does not affect lifespan [0655]. SOD2 overexpression in mice slightly increases lifespan [1939]. Polymorphisms in the human SOD2 gene have been associated with type 2 diabetes [0661] and cardiomyopathy [1693]. Although it is possible that SOD2 plays a role in human ageing, further studies are needed to investigate this hypothesis.

Cytogenetic information

Cytogenetic band6q25.3
Location160,073,582 bp to 160,084,614 bp
OrientationMinus strand
Display region using the UCSC Genome Browser

Protein information

Functionredox and oxidative regulation
Cellular locationmitochondria
Expressionubiquitous
Gene Ontology

GO:0001315; age-dependent response to reactive oxygen species; Process
GO:0001836; release of cytochrome c from mitochondria; Process
GO:0006302; double-strand break repair; Process
GO:0006357; regulation of transcription from RNA polymerase II promoter; Process
GO:0006801; superoxide metabolic process; Process
GO:0042542; response to hydrogen peroxide; Process
GO:0043066; negative regulation of apoptosis; Process
GO:0055114; oxidation reduction; Process

GO:0004784; superoxide dismutase activity; Function
GO:0016491; oxidoreductase activity; Function
GO:0030145; manganese ion binding; Function
GO:0046872; metal ion binding; Function

GO:0005743; mitochondrial inner membrane; Cellular component
GO:0005759; mitochondrial matrix; Cellular component

Protein-protein interactions

No interactions in records.

Retrieve sequences for SOD2

PromoterPromoter
ORFORF
CDSCDS

Homologues in model organisms

P. troglodytesSOD2 (superoxide dismutase 2, mitochondrial)
C. lupus familiarisSOD2 (superoxide dismutase 2, mitochondrial)
B. taurusSOD2 (superoxide dismutase 2, mitochondrial)
M. musculusSod2 (superoxide dismutase 2, mitochondrial)
R. norvegicusSod2 (superoxide dismutase 2, mitochondrial)
G. gallusSOD2 (superoxide dismutase 2, mitochondrial)
D. reriosod2 (superoxide dismutase 2, mitochondrial)
D. melanogasterSod2 (Superoxide dismutase 2 (Mn))
A. gambiaeSOD1 (superoxide dismutase (AGAP010517-PA))
C. eleganssod-2 (SOD (superoxide dismutase))
S. pombeSPAC1486.01 (manganese superoxide dismutase (AF069292))
S. cerevisiaeSOD2 (Mitochondrial superoxide dismutase, protects cells against oxygen toxicity; phosphorylated)
K. lactisKLLA0E03509g (mRNA gene KLLA0E03509g)
M. griseaMGG_00212 (hypothetical protein)
N. crassaNCU09560.1 (hypothetical protein)
A. thalianaMSD1 (MSD1 (MANGANESE SUPEROXIDE DISMUTASE 1); manganese superoxide dismutase)
O. sativaOs05g0323900 (hypothetical protein)
HomoloGene (530)

Selected references

[1897] Pfluger et al. (2008), Sirt1 protects against high-fat diet-induced metabolic damage, PubMed
[1919] Taguchi et al. (2007), Brain IRS2 signaling coordinates life span and nutrient homeostasis, PubMed
[1849] Bonawitz et al. (2007), Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression, PubMed
[1939] Hu et al. (2007), Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase, PubMed
[1793] Esposito et al. (2006), Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice, PubMed
[1637] Ehrenbrink et al. (2006), Antioxidant enzymes activities and protein damage in rat brain of both sexes, PubMed
[1636] Sinitsyna et al. (2006), Age-associated changes in oxidative damage and the activity of antioxidant enzymes in rats with inherited overgeneration of free radicals, PubMed
[1635] Alvarez-Garcia et al. (2006), Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age, PubMed
[1634] Son et al. (2006), SMP30 deficiency causes increased oxidative stress in brain, PubMed
[1630] Martinez-Romero et al. (2006), Aging affects but does not eliminate the enzymatic antioxidative response to hypoxia/reoxygenation in cerebral cortex, PubMed
[1632] Kakarla et al. (2005), Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: influence of exercise training on antioxidant defense system, PubMed
[1631] Siqueira et al. (2005), Total antioxidant capacity is impaired in different structures from aged rat brain, PubMed
[1583] Greer and Brunet (2005), FOXO transcription factors at the interface between longevity and tumor suppression, PubMed
[1694] Silva et al. (2005), SOD2 overexpression: enhanced mitochondrial tolerance but absence of effect on UCP activity, PubMed
[1628] Marzani et al. (2005), Human muscle aging: ROS-mediated alterations in rectus abdominis and vastus lateralis muscles, PubMed
[1514] Yamamoto et al. (2005), Regulation of oxidative stress by the anti-aging hormone Klotho, PubMed
[1561] Tirosh et al. (2005), Long-lived alphaMUPA transgenic mice show reduced SOD2 expression, enhanced apoptosis and reduced susceptibility to the carcinogen dimethylhydrazine, PubMed
[1538] Wolf et al. (2005), Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence, PubMed
[1781] Bayne et al. (2005), Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in transgenic Drosophila, PubMed
[1544] Taufer et al. (2005), Is the Val16Ala manganese superoxide dismutase polymorphism associated with the aging process?, PubMed
[1287] Landis and Tower (2005), Superoxide dismutase evolution and life span regulation, PubMed
[1350] Stessman et al. (2005), Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study, PubMed
[1142] Fabrizio et al. (2004), Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae, PubMed
[1119] Martin and Friedman (2004), Ticking fast or ticking slow, through shc must you go?, PubMed
[1940] Sun et al. (2004), Effects of simultaneous over-expression of Cu/ZnSOD and MnSOD on Drosophila melanogaster life span, PubMed
[1823] Hussain et al. (2004), p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis, PubMed
[1172] Liang and Patel (2004), Mitochondrial oxidative stress and increased seizure susceptibility in Sod2(-/+) mice, PubMed
[0655] Van Remmen et al. (2003), Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging, PubMed
[0560] Liu et al. (2003), Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics, PubMed
[0040] Orr et al. (2003), Effects of overexpression of copper-zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster, PubMed
[0661] Nomiyama et al. (2003), The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients, PubMed
[0656] Kirby et al. (2002), RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress, PubMed
[0152] Kops et al. (2002), Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress, PubMed
[1239] Sun et al. (2002), Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster, PubMed
[1499] Sreekumar et al. (2002), Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle, PubMed
[0053] Van Remmen et al. (2001), Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial function and apoptosis, PubMed
[0911] Hall et al. (2001), Aging lowers steady-state antioxidant enzyme and stress protein expression in primary hepatocytes, PubMed
[0657] Kokoszka et al. (2001), Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis, PubMed
[0204] Melov et al. (2000), Extension of life-span with superoxide dismutase/catalase mimetics, PubMed
[1693] Hiroi et al. (1999), Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese, PubMed
[0659] Melov et al. (1999), Mitochondrial disease in superoxide dismutase 2 mutant mice, PubMed
[0052] Williams et al. (1998), Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice, PubMed
[0660] Melov et al. (1998), A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase, PubMed
[0882] Lebovitz et al. (1996), Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice, PubMed
[1245] Allen et al. (1995), Expression and regulation of superoxide dismutase activity in human skin fibroblasts from donors of different ages, PubMed
[0658] Li et al. (1995), Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase, PubMed

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External links

EPDHS_SOD2
ORF AccessionNM_000636
CDS AccessionNP_000627
OMIM147460
HPRD00938
EnsemblSOD2
Swiss-ProtSODM_HUMAN
GeneCardsSOD2
Entrez Gene6648
UniGene487046
GenAtlasSOD2
InternetSearch Google


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