SOD1

SECTIONS

1 - Function
2 - Involvement in disease
3 - Post-translational modifications
4 - Sequence similarities
5 - Cellular localization
6 - Alternative names
7 - Database links
8 - Target type
9 - Primary research area
10 - Molecular weight

Function

Destroys radicals which are normally produced within the cells and which are toxic to biological systems.

Involvement in disease

Amyotrophic lateral sclerosis 1

ALS1

A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. 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 the cases.

None

The disease is caused by variants affecting the gene represented in this entry.

Spastic tetraplegia and axial hypotonia, progressive

STAHP

An autosomal recessive, neurologic disorder characterized by loss of motor abilities in the first year of life, after which severe, progressive spastic tetraparesis develops. Affected individuals have severe axial hypotonia, hyperekplexia, hypertonia, and myokymia, reflecting upper motor neuron involvement. Cognitive development may be affected.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

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.

Palmitoylation helps nuclear targeting and decreases catalytic activity.

Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity.