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UniProtKB/Swiss-Prot P00441: Variant p.Gly86Arg

Superoxide dismutase [Cu-Zn]
Gene: SOD1
Variant information

Variant position:  86
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Glycine (G) to Arginine (R) at position 86 (G86R, p.Gly86Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In ALS1; ubiquitinated by RNF19A; interferes with zinc-binding; ubiquitinated by MARCH5; leading to the degradation of mitochondrial SOD1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  86
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  154
The length of the canonical sequence.

Location on the sequence:   NPLSRKHGGPKDEERHVGDL  G NVTADKDGVADVSIEDSVIS
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 2 – 154 Superoxide dismutase [Cu-Zn]
Metal binding 72 – 72 Zinc; via pros nitrogen
Metal binding 81 – 81 Zinc; via pros nitrogen
Metal binding 84 – 84 Zinc; structural
Modified residue 92 – 92 N6-succinyllysine
Modified residue 99 – 99 Phosphoserine
Modified residue 103 – 103 Phosphoserine
Modified residue 106 – 106 Phosphoserine
Disulfide bond 58 – 147
Mutagenesis 81 – 81 H -> A. Loss of zinc binding and enhanced tendency to form aggregates; when associated with A-84.
Mutagenesis 81 – 81 H -> S. Destabilization of dimer and loss of zinc binding; when associated with S-84.
Mutagenesis 84 – 84 D -> A. Loss of zinc binding and enhanced tendency to form aggregates; when associated with A-81.
Mutagenesis 84 – 84 D -> S. Destabilization of dimer and loss of zinc binding; when associated with S-81.
Beta strand 84 – 90


Literature citations

Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis.
Cao X.; Antonyuk S.V.; Seetharaman S.V.; Whitson L.J.; Taylor A.B.; Holloway S.P.; Strange R.W.; Doucette P.A.; Valentine J.S.; Tiwari A.; Hayward L.J.; Padua S.; Cohlberg J.A.; Hasnain S.S.; Hart P.J.;
J. Biol. Chem. 283:16169-16177(2008)
Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF VARIANT ALS1 ARG-86; CHARACTERIZATION OF VARIANT ALS1 ARG-86;

Crystal structure of human Cu-Zn superoxide dismutase mutant G85R (P21).
RIKEN structural genomics initiative (RSGI);
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF VARIANT ALS1 ARG-86;

Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds.
Ratovitski T.; Corson L.B.; Strain J.; Wong P.; Cleveland D.W.; Culotta V.C.; Borchelt D.R.;
Hum. Mol. Genet. 8:1451-1460(1999)
Cited for: CHARACTERIZATION OF VARIANTS ALS1 VAL-5; ARG-38; ARG-47; GLN-49; ARG-86 AND THR-114;

Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity.
Niwa J.; Ishigaki S.; Hishikawa N.; Yamamoto M.; Doyu M.; Murata S.; Tanaka K.; Taniguchi N.; Sobue G.;
J. Biol. Chem. 277:36793-36798(2002)
Cited for: CHARACTERIZATION OF VARIANTS ALS1 ARG-38; ARG-47; ARG-86 AND ALA-94; INTERACTION WITH RNF19A; UBIQUITINATION;

Complete loss of post-translational modifications triggers fibrillar aggregation of SOD1 in the familial form of amyotrophic lateral sclerosis.
Furukawa Y.; Kaneko K.; Yamanaka K.; O'Halloran T.V.; Nukina N.;
J. Biol. Chem. 283:24167-24176(2008)
Cited for: CHARACTERIZATION OF VARIANTS ALS1 ARG-38; ARG-86 AND ARG-94; MUTAGENESIS OF CYS-7; 51-PHE-GLY-52; CYS-58; HIS-81; ASP-84; CYS-112 AND CYS-147; IDENTIFICATION BY MASS SPECTROMETRY;

Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation.
Yonashiro R.; Sugiura A.; Miyachi M.; Fukuda T.; Matsushita N.; Inatome R.; Ogata Y.; Suzuki T.; Dohmae N.; Yanagi S.;
Mol. Biol. Cell 20:4524-4530(2009)
Cited for: CHARACTERIZATION OF VARIANTS ALS1 ARG-86 AND ALA-94; UBIQUITINATION BY MARCH5; SUBCELLULAR LOCATION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.