SOD2

Superoxide dismutase 2, mitochondrial
PDB rendering based on 1ap5.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 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 • oxygen binding • manganese ion binding • identical protein binding Cellular component • 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 • heart development • 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 • 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 apoptotic process • negative regulation of neuron apoptotic process • 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	P09671
RefSeq (mRNA)	NM_000636	NM_013671
RefSeq (protein)	NP_000627	NP_038699
Location (UCSC)	Chr 6: 160.1 – 160.18 Mb	Chr 17: 13.01 – 13.02 Mb
PubMed search
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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] In Drosophila melanogaster, over-expression of Sod2 has been show to increase lifespan by 20%^[5]

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

Further reading

v t e PDB gallery 1ap5: TYR34->PHE MUTANT OF HUMAN MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE  1ap6: TYR34->PHE MUTANT OF HUMAN MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE  1em1: X-RAY CRYSTAL STRUCTURE FOR HUMAN MANGANESE SUPEROXIDE DISMUTASE, Q143A  1ja8: Kinetic Analysis of Product Inhibition in Human Manganese Superoxide Dismutase  1luv: CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL  1luw: CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL  1msd: COMPARISON OF THE CRYSTAL STRUCTURES OF GENETICALLY ENGINEERED HUMAN MANGANESE SUPEROXIDE DISMUTASE AND MANGANESE SUPEROXIDE DISMUTASE FROM THERMUS THERMOPHILUS. DIFFERENCES IN DIMER-DIMER INTERACTIONS.  1n0j: The Structure of Human Mitochondrial MN3+ Superoxide Dismutase Reveals a Novel Tetrameric Interface of Two 4-Helix Bundles  1n0n: Catalytic and Structural Effects of Amino-Acid Substitution at His30 in Human Manganese Superoxide Dismutase  1pl4: Crystal Structure of human MnSOD Y166F mutant  1pm9: CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT  1qnm: HUMAN MANGANESE SUPEROXIDE DISMUTASE MUTANT Q143N  1szx: Role Of Hydrogen Bonding In The Active Site Of Human Manganese Superoxide Dismutase  1var: MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE VARIANT WITH ILE 58 REPLACED BY THR  1xdc: Hydrogen Bonding in Human Manganese Superoxide Dismutase containing 3-Fluorotyrosine  1xil: HYDROGEN BONDING IN HUMAN MANGANESE SUPEROXIDE DISMUTASE CONTAINING 3-FLUOROTYROSINE  1zsp: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase  1zte: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Suerpoxide Dismutase  1zuq: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase  2adp: Nitrated Human Manganese Superoxide Dismutase  2adq: Human Manganese Superoxide Dismutase  2gds: Interrupting the Hydrogen Bonding Network at the Active Site of Human Manganese Superoxide Dismutase  2p4k: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase