SOD2

Superoxide dismutase 2, mitochondrial
PDB rendering based on 1ap5.
Available structures PDB 1AP5, 1AP6, 1EM1, 1JA8, 1LUV, 1LUW, 1MSD, 1N0J, 1N0N, 1PL4, 1PM9, 1QNM, 1SZX, 1VAR, 1XDC, 1XIL, 1ZSP, 1ZTE, 1ZUQ, 2ADP, 2ADQ, 2GDS, 2P4K, 2QKA, 2QKC, 3C3S, 3C3T
Identifiers
Symbols	SOD2; IPOB; MNSOD; MVCD6
External IDs	OMIM: 147460 MGI: 98352 HomoloGene: 530 GeneCards: SOD2 Gene
EC number	1.15.1.1
Gene Ontology Molecular function • DNA binding • superoxide dismutase activity • superoxide dismutase activity • protein binding • oxidoreductase activity • oxygen binding • manganese ion binding • manganese ion binding • identical protein binding • metal ion binding Cellular component • soluble fraction • cytoplasm • mitochondrion • mitochondrial inner membrane • mitochondrial matrix • mitochondrial nucleoid Biological process • response to superoxide • age-dependent response to reactive oxygen species • response to hypoxia • release of cytochrome c from mitochondria • liver development • detection of oxygen • vasodilation by acetylcholine involved in regulation of systemic arterial blood pressure • regulation of transcription from RNA polymerase II promoter • glutathione metabolic process • superoxide metabolic process • superoxide metabolic process • anti-apoptosis • mitochondrion organization • heart development • aging • locomotory behavior • regulation of blood pressure • negative regulation of cell proliferation • post-embryonic development • response to manganese ion • response to zinc ion • response to selenium ion • response to gamma radiation • response to activity • removal of superoxide radicals • respiratory electron transport chain • hemopoiesis • response to nutrient levels • oxygen homeostasis • response to lipopolysaccharide • response to L-ascorbic acid • response to silicon dioxide • response to drug • response to hydrogen peroxide • superoxide anion generation • negative regulation of apoptosis • negative regulation of neuron apoptosis • positive regulation of nitric oxide biosynthetic process • negative regulation of fat cell differentiation • response to cadmium ion • negative regulation of fibroblast proliferation • neuron development • response to axon injury • erythrophore differentiation • hydrogen peroxide biosynthetic process • regulation of catalytic activity • protein homotetramerization • response to electrical stimulus • regulation of mitochondrial membrane potential • iron ion homeostasis • response to hyperoxia • cellular response to ethanol Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6648	20656
Ensembl	ENSG00000112096	ENSMUSG00000006818
UniProt	P04179	Q3TJA2
RefSeq (mRNA)	NM_000636.2	NM_013671.3
RefSeq (protein)	NP_000627.2	NP_038699.2
Location (UCSC)	Chr 6: 160.1 – 160.18 Mb	Chr 17: 13.2 – 13.21 Mb
PubMed search	[1]	[2]

Superoxide dismutase 2, mitochondrial, also known as SOD2, is an enzyme which in humans is encoded by the SOD2 gene.

Function

This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial matrix protein that forms a homotetramer and binds one manganese ion per subunit. This protein transforms toxic superoxide, a byproduct of the mitochondrial electron transport chain, into hydrogen peroxide and diatomic oxygen. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[1]

Clinical significance

Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), sporadic motor neuron disease, and cancer. A common polymorphism associated with greater susceptibility to various patholiges is found in the mitochondrial leader targeting sequence (Val9Ala).^[2] Mice lacking Sod2 die shortly after birth, indicating that unchecked levels of superoxide are incompatible with mammalian life.^[3] However, mice 50% deficient in Sod2 have a normal lifespan and minimal phenotypic defects but do suffer increased DNA damage and increased incidence of cancer.^[4]

SOD2 and Exercise-Induced Cardioprotection

When animals are exercised at a relatively high work rate, many exercise training studies report that exercise training promotes an increase in myocardial MnSOD activity. This is significant because two recent studies reveal that increased MnSOD activity is essential to achieve optimal training-induced protection against both ischemia/reperfusion(IR)-induced cardiac arrhythmias and infarction. Specifically, using an antisense oligonucleotide against MnSOD to prevent ExTr-induced increases in myocardial MnSOD activity, Yamashita et al. demonstrated that an increase in myocardial MnSOD activity is required to provide training-induced protection against IR-induced myocardial infarction. Similarly, Hamilton et al. [10], using a MnSOD gene silencing approach, reported that prevention of the ExTr-induced increase in myocardial MnSOD resulted in a loss of training-induced protection against IR-mediated arrhythmias. In contrast to these findings, training-induced increases in cardiac MnSOD are not required to achieve training-induced cardioprotection against myocardial stunning. (Power et al. 2007)

References

1. ^ "Entrez Gene: SOD2 superoxide dismutase 2, mitochondrial". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6648. 
2. ^ Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558. 
3. ^ Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (December 1995). "Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase". Nat. Genet. 11 (4): 376–81. doi:10.1038/ng1295-376. PMID 7493016. 
4. ^ Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, Alderson NL, Baynes JW, Epstein CJ, Huang TT, Nelson J, Strong R, Richardson A (December 2003). "Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging". Physiol. Genomics 16 (1): 29–37. doi:10.1152/physiolgenomics.00122.2003. PMID 14679299. 

Further reading

• Zelko IN, Mariani TJ, Folz RJ (2003). "Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression.". Free Radic. Biol. Med. 33 (3): 337–49. doi:10.1016/S0891-5849(02)00905-X. PMID 12126755. 
• Faraci FM, Didion SP (2005). "Vascular protection: superoxide dismutase isoforms in the vessel wall.". Arterioscler. Thromb. Vasc. Biol. 24 (8): 1367–73. doi:10.1161/01.ATV.0000133604.20182.cf. PMID 15166009.