Description: Homo sapiens superoxide dismutase 1, soluble (SOD1), mRNA. RefSeq Summary (NM_000454): The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. The other isozyme is a mitochondrial protein. Mutations in this gene have been implicated as causes of familial amyotrophic lateral sclerosis. Rare transcript variants have been reported for this gene. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr21:33,031,935-33,041,243 Size: 9,309 Total Exon Count: 5 Strand: + Coding Region Position: hg19 chr21:33,032,083-33,040,891 Size: 8,809 Coding Exon Count: 5
ID:SODC_HUMAN DESCRIPTION: RecName: Full=Superoxide dismutase [Cu-Zn]; EC=1.15.1.1; AltName: Full=Superoxide dismutase 1; Short=hSod1; FUNCTION: Destroys radicals which are normally produced within the cells and which are toxic to biological systems. CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2). COFACTOR: Binds 1 copper ion per subunit. COFACTOR: Binds 1 zinc ion per subunit. SUBUNIT: Homodimer; non-disulfide linked. Homodimerization may take place via the ditryptophan cross-link at Trp-33. The pathogenic variants ALS1 Arg-38, Arg-47, Arg-86 and Ala-94 interact with RNF19A, whereas wild-type protein does not. The pathogenic variants ALS1 Arg-86 and Ala-94 interact with MARCH5, whereas wild-type protein does not. INTERACTION: P26339:Chga (xeno); NbExp=5; IntAct=EBI-990792, EBI-990900; P16014:Chgb (xeno); NbExp=6; IntAct=EBI-990792, EBI-990820; SUBCELLULAR LOCATION: Cytoplasm. Note=The pathogenic variants ALS1 Arg-86 and Ala-94 gradually aggregates and accumulates in mitochondria. PTM: Unlike wild-type protein, the pathogenic variants ALS1 Arg- 38, Arg-47, Arg-86 and Ala-94 are polyubiquitinated by RNF19A leading to their proteasomal degradation. The pathogenic variants ALS1 Arg-86 and Ala-94 are ubiquitinated by MARCH5 leading to their proteasomal degradation. PTM: The ditryptophan cross-link at Trp-33 is responsible for the non-disulfide-linked homodimerization. Such modification might only occur in extreme conditions and additional experimental evidence is required. DISEASE: Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:105400]. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms. MISCELLANEOUS: The protein (both wild-type and ALS1 variants) has a tendency to form fibrillar aggregates in the absence of the intramolecular disulfide bond or of bound zinc ions. These aggregates may have cytotoxic effects. Zinc binding promotes dimerization and stabilizes the native form. SIMILARITY: Belongs to the Cu-Zn superoxide dismutase family. WEB RESOURCE: Name=Alsod; Note=ALS genetic mutations db; URL="http://alsod.iop.kcl.ac.uk/Als/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SOD1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/sod1/"; WEB RESOURCE: Name=Wikipedia; Note=Superoxide dismutase entry; URL="http://en.wikipedia.org/wiki/Superoxide_dismutase";
ALS/amyotrophic lateral sclerosis Mancuso, M. et al. 2002, A screening for superoxide dismutase-1 D90A mutation in Italian patients with sporadic amyotrophic lateral sclerosis., Amyotrophic lateral sclerosis and other motor neuron disorders. 2002 Dec;3(4):215-8.
[PubMed 12710511]
Our results confirm that recessive D90A mutation is present in Italy and it is associated with the phenotype already described A screening for that mutation, easily made by RFLP, should be made in sporadic ALS patients, especially where clinical investigation indicates its presence.
amyotrophic lateral sclerosis cause novel protein interactions Kunst CB et al. 1997, Mutations in SOD1 associated with amyotrophic lateral sclerosis cause novel protein interactions., Nature genetics. 1997 Jan;15(1):91-4.
[PubMed 8988176]
familial amyotrophic lateral sclerosis Morita M et al. 1996, A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan., Neuroscience letters. 1996 Feb;205(2):79-82.
[PubMed 8907321]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P00441
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000187 activation of MAPK activity GO:0000302 response to reactive oxygen species GO:0000303 response to superoxide GO:0001541 ovarian follicle development GO:0001819 positive regulation of cytokine production GO:0001890 placenta development GO:0001895 retina homeostasis GO:0001975 response to amphetamine GO:0002262 myeloid cell homeostasis GO:0002576 platelet degranulation GO:0006749 glutathione metabolic process GO:0006801 superoxide metabolic process GO:0006879 cellular iron ion homeostasis GO:0006979 response to oxidative stress GO:0007283 spermatogenesis GO:0007566 embryo implantation GO:0007568 aging GO:0007569 cell aging GO:0007605 sensory perception of sound GO:0007626 locomotory behavior GO:0008089 anterograde axonal transport GO:0008090 retrograde axonal transport GO:0008217 regulation of blood pressure GO:0009408 response to heat GO:0010033 response to organic substance GO:0019226 transmission of nerve impulse GO:0019430 removal of superoxide radicals GO:0031667 response to nutrient levels GO:0032287 peripheral nervous system myelin maintenance GO:0032930 positive regulation of superoxide anion generation GO:0033081 regulation of T cell differentiation in thymus GO:0034465 response to carbon monoxide GO:0034599 cellular response to oxidative stress GO:0035722 interleukin-12-mediated signaling pathway GO:0035865 cellular response to potassium ion GO:0040014 regulation of multicellular organism growth GO:0042493 response to drug GO:0042542 response to hydrogen peroxide GO:0042554 superoxide anion generation GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043085 positive regulation of catalytic activity GO:0043087 regulation of GTPase activity GO:0043524 negative regulation of neuron apoptotic process GO:0045471 response to ethanol GO:0045541 negative regulation of cholesterol biosynthetic process GO:0045859 regulation of protein kinase activity GO:0046620 regulation of organ growth GO:0046677 response to antibiotic GO:0046688 response to copper ion GO:0046716 muscle cell cellular homeostasis GO:0048538 thymus development GO:0048678 response to axon injury GO:0050665 hydrogen peroxide biosynthetic process GO:0051881 regulation of mitochondrial membrane potential GO:0055114 oxidation-reduction process GO:0060047 heart contraction GO:0060052 neurofilament cytoskeleton organization GO:0060087 relaxation of vascular smooth muscle GO:0060088 auditory receptor cell stereocilium organization GO:0071276 cellular response to cadmium ion GO:0071318 cellular response to ATP GO:0072593 reactive oxygen species metabolic process GO:0097332 response to antipsychotic drug GO:1902177 positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
