Gene Report

Basic Information

Approved Symbol	SOD2
Approved Name	superoxide dismutase 2, mitochondrial
Location	6q25
Position	chr6:160100148-160114353 (-)
External Links	Entrez Gene: 6648 Ensembl: ENSG00000112096 UCSC: uc003qsg.3 HGNC ID: 11180
No. of Studies (Positive/Negative)	1(0/1)
Type	Literature-origin

Positive relationships between SOD2 and MDD (count: 0)

Positive relationships between SOD2 and other components at different levels (count: 0)

Positive relationship network of SOD2 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between SOD2 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
MnSOD	Pae CU, 2006	Patients and nomal controls		The combined analysis (MDD plus BD) also failed to find any ...... The combined analysis (MDD plus BD) also failed to find any association between the Ala-9Val MnSOD polymorphism and mood disorders. Subgroup analyses according to the clinical variables such as the family history, age at onset, psychotic features and suicide history failed to identify any association with the Ala-9Val MnSOD polymorphism. More...

Negative relationships between SOD2 and other components at different levels (count: 0)

SOD2 related SNPs in MK4MDD (count: 0)

SOD2 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Superoxide dismutase [Mn], mitochondrial	P04179	0(0/0)	Gene mapped

SOD2 related GO terms (count: 56)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0042554	superoxide anion generation	biological process	IEA
GO:0004784	superoxide dismutase activity	molecular function	IDA[19265433]; IMP[12551919]
GO:0042802	identical protein binding	molecular function	IEA
GO:0043066	negative regulation of apoptotic process	biological process	IMP[12551919]
GO:0050665	hydrogen peroxide biosynthetic process	biological process	IEA
GO:0001315	age-dependent response to reactive oxygen species	biological process	IMP[14980699]
GO:0071361	cellular response to ethanol	biological process	IEA
GO:0033591	response to L-ascorbic acid	biological process	IEA
GO:0051602	response to electrical stimulus	biological process	IEA
GO:0042493	response to drug	biological process	IEA
GO:0042645	mitochondrial nucleoid	cellular component	IEA
GO:0003677	DNA binding	molecular function	IEA
GO:0055072	iron ion homeostasis	biological process	IEA
GO:0019825	oxygen binding	molecular function	IEA
GO:0032364	oxygen homeostasis	biological process	IMP[16179351]
GO:0006357	regulation of transcription from RNA polymerase II promoter	biological process	IMP[9393747]
GO:0008217	regulation of blood pressure	biological process	ISS
GO:0006801	superoxide metabolic process	biological process	IDA[14980699]; IMP[12551919]
GO:0030097	hemopoiesis	biological process	IEA
GO:0001666	response to hypoxia	biological process	IEA
GO:0010269	response to selenium ion	biological process	IEA
GO:0032496	response to lipopolysaccharide	biological process	IEA
GO:0045599	negative regulation of fat cell differentiation	biological process	IEA
GO:0003069	vasodilation by acetylcholine involved in regulation of systemic arterial blood pressure	biological process	ISS
GO:0007626	locomotory behavior	biological process	IEA
GO:0014823	response to activity	biological process	IEA
GO:0034021	response to silicon dioxide	biological process	IEA
GO:0022904	respiratory electron transport chain	biological process	IEA
GO:0046686	response to cadmium ion	biological process	IEA
GO:0048773	erythrophore differentiation	biological process	IEA
GO:0005743	mitochondrial inner membrane	cellular component	IEA
GO:0001836	release of cytochrome c from mitochondria	biological process	ISS
GO:0045429	positive regulation of nitric oxide biosynthetic process	biological process	IEA
GO:0051881	regulation of mitochondrial membrane potential	biological process	IEA
GO:0050790	regulation of catalytic activity	biological process	IEA
GO:0010332	response to gamma radiation	biological process	IEA
GO:0010043	response to zinc ion	biological process	IEA
GO:0003032	detection of oxygen	biological process	IEA
GO:0051289	protein homotetramerization	biological process	IPI[19265433]
GO:0005739	mitochondrion	cellular component	IDA[12551919]
GO:0006749	glutathione metabolic process	biological process	IEA
GO:0048678	response to axon injury	biological process	IEA
GO:0010042	response to manganese ion	biological process	IEA
GO:0030145	manganese ion binding	molecular function	IDA[19265433]; TAS[10511315]
GO:0043524	negative regulation of neuron apoptotic process	biological process	IGI[17251466]
GO:0001889	liver development	biological process	IEA
GO:0005759	mitochondrial matrix	cellular component	TAS[10511315]
GO:0019430	removal of superoxide radicals	biological process	IMP[16179351]
GO:0008285	negative regulation of cell proliferation	biological process	IMP[16179351]
GO:0055093	response to hyperoxia	biological process	IEA
GO:0048147	negative regulation of fibroblast proliferation	biological process	IEA
GO:0007507	heart development	biological process	IEA
GO:0009791	post-embryonic development	biological process	IEA
GO:0048666	neuron development	biological process	IEA
GO:0042542	response to hydrogen peroxide	biological process	IEA
GO:0000303	response to superoxide	biological process	IMP[16179351]

SOD2 related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05016	huntingtons disease	Huntington's disease	Huntington disease (HD) is an autosomal-dominant neurodegene...... Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NR2B/NR1 NMDAR activity, and destabilizing mitochondrial Ca2+ handling. As a result, stimulation of glutamate receptors leads to supranormal Ca2+ responses in HD MSN and mitochondrial Ca2+ overload. The mHtt translocates to the nucleus, where it forms intranuclear inclusions, though they are not primarily responsible for toxicity. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction. More...
hsa04146	peroxisome	Peroxisome	Peroxisomes are essential organelles that play a key role in...... Peroxisomes are essential organelles that play a key role in redox signalling and lipid homeostasis. They contribute to many crucial metabolic processes such as fatty acid oxidation, biosynthesis of ether lipids and free radical detoxification. The biogenesis of peroxisomes starts with the early peroxins PEX3, PEX16 and PEX19 and proceeds via several steps. The import of membrane proteins into peroxisomes needs PEX19 for recognition, targeting and insertion via docking at PEX3. Matrix proteins in the cytosol are recognized by peroxisomal targeting signals (PTS) and transported to the docking complex at the peroxisomal membrane. Peroxisomes' deficiencies lead to severe and often fatal inherited peroxisomal disorders (PD). PDs are usually classified in two groups. The first group is disorders of peroxisome biogenesis which include Zellweger syndrome, and the second group is single peroxisomal enzyme deficiencies. More...

SOD2 related BioCarta pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
LONGEVITY_PATHWAY	longevity pathway	The IGF-1 Receptor and Longevity	A demonstrated means to increase lifespan in a wide range of...... A demonstrated means to increase lifespan in a wide range of organisms is through the restriction of caloric intake. Reducing the consumption of calories increases the lifespan of many different organisms, including mice. Although caloric restriction has not been demonstrated experimentally to increase human lifespan, short-term changes in physiological measures like insulin responsiveness have been observed. Caloric restriction not only increases lifespan, but decreases age-related deterioration of systems and physiological responses, reducing age related diseases like cancer and neurodegenerative disease. Caloric restriction in animals reduces the levels of plasma glucose and insulin and reduces inflammatory responses and may reduce oxidative stress through reduced oxidative metabolism, further contributing to the health benefits of reduced calorie intake. The reduction in inflammation may be related to reduces plasma glucose and in humans could reduce an inflammation connection to cancer, heart disease, and Alzheimers disease. Genetic analysis has indicated several genes that influence lifespan, particularly those that alter pituitary development, reduce growth hormone secretion, reduce food intake, and reduce apoptosis (p66 Shc). All of these appear to converge on an IGF-1 receptor pathway and to reproduce many of the effects of caloric restriction. Although dwarf mice with defective growth hormone or IGF-1 signaling also have significantly increased lifespan, humans with defects in growth hormone signaling tend to develop diseases that shorten their lifespan. One of the downstream targets of IGF-1 signaling is to repress stress resistance proteins including antioxidant enzymes like superoxide dismutase, and heat shock proteins, so a reduction in IGF signaling may extend lifespan by increasing the expression of stress resistance genes. The link between caloric restriction and IGF signaling may be that a reduction in food intake reduces the expression of IGF-1, increasing the expression of stress resistance proteins. In addition to the IGF-1R mutation, p66 Shc mutation also increases lifespan without significant aberration of other systems. Shc is a target of IGF-1R phosphorylation, and a major inducer of cellular responses to oxidative stress. Shc increases levels of intracellular reactive oxygen species, repressing the forkhead factor FKHRL1. Alhtough FKHRL1 is also involved in apoptosis, in the absence of Shc, FKHRL1 mediates increased resistance to oxidative stress. Exploration of the genes that induce longevity in animals models may enlighten the role of these genes in human disease and lifespan. More...
EPONFKB_PATHWAY	eponfkb pathway	Erythropoietin mediated neuroprotection through NF-kB	Erythropoietin (Epo) is most commonly known as the cytokine ...... Erythropoietin (Epo) is most commonly known as the cytokine secreted by the kidneys that stimulates red blood cell production and is used as a drug for the treatment of anemias. Epo is also secreted in the brain in response to hypoxia, such as ischemic stroke. Epo production in the brain is stimulated by the hypoxia-inducible transcription factor HIF-1. Administration of Epo to the brain in rodents before hypoxic stress or other neuronal stresses is neuroprotective, preventing neuronal apoptosis. The erythropoietin receptor (EpoR) is known to associate with JAK kinases that phosphorylate and activate the STAT family of transcription factors. The neuroprotection by Epo involves cross-talk between Epo receptor and anti-apoptotic pathways through activation of NF-kB by the JAK2 kinase. Epo stimulates JAK2 phosphorylation of I-kB, releasing NF-kB to translocate into the nucleus and activate transcription of neuroprotective genes. Neuroprotective genes activated by NF-kB include the anti-oxidant enzyme manganese superoxide dismutase and calbindin-D(28k). The erythropoietin receptor is also essential for proper brain development in mice. The absence of EpoR causes high levels of neuronal apoptosis in the developing mouse brain, further confirming the important role of Epo as a neuroprotective agent. More...

SOD2 related Reactome pathways (count: 0)

SOD2 related interactors from protein-protein interaction data in HPRD (count: 7)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
SOD2	HDHD2	No	yeast 2-hybrid	16169070
SOD2	KIAA1549	No	yeast 2-hybrid	16169070
SOD2	RAB4A	No	in vitro;in vivo	123234
SOD2	NOL12	No	yeast 2-hybrid	16169070
SOD2	SOD2	Yes	in vitro	10852710 , 1394426 , 14638684 , 2738919
SOD2	RPS3A	No	yeast 2-hybrid	16169070
SOD2	C7orf20	No	yeast 2-hybrid	16169070

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways