Human Gene SOD1 (uc002ypa.3) Description and Page Index
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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1163657.518836.1, ERR279842.10182.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END## 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=188.8.131.52; 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";
Genetic Association Studies of Complex Diseases and Disorders
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.
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.
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.
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
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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.