UniProtKB/Swiss-Prot P00441: Variant p.Gly86Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 86 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 MARCHF5; leading to the degradation of mitochondrial SOD1. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs121912436 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
Chain	2 – 154	Superoxide dismutase [Cu-Zn]
Binding site	72 – 72
Binding site	81 – 81
Binding site	84 – 84
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; Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.
Rosen D.R.; Siddique T.; Patterson D.; Figlewicz D.A.; Sapp P.; Hentati A.; Donaldson D.; Goto J.; O'Regan J.P.; Deng H.-X.; Rahmani Z.; Krizus A.; McKenna-Yasek D.; Cayabyab A.; Gaston S.M.; Berger R.; Tanzi R.E.; Halperin J.J.; Herzfeldt B.; van den Bergh R.; Hung W.-Y.; Bird T.; Deng G.; Mulder D.W.; Smyth C.; Laing N.G.; Soriano E.; Pericak-Vance M.A.; Haines J.; Rouleau G.A.; Gusella J.S.; Horvitz H.R.; Brown R.H. Jr.;
Nature 362:59-62(1993)
Cited for: VARIANTS ALS1 ARG-38; VAL-39; ASP-42; SER-42; ARG-44; ARG-86; ALA-94; CYS-94; GLY-101; VAL-107 AND THR-114; Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase.
Deng H.-X.; Hentati A.; Tainer J.A.; Iqbal Z.; Cayabyab A.; Hung W.-Y.; Getzoff E.D.; Hu P.; Herzfeldt B.; Roos R.P.; Warner C.; Deng G.; Soriano E.; Smyth C.; Parge H.E.; Ahmed A.; Roses A.D.; Hallewell R.A.; Pericak-Vance M.A.; Siddique T.;
Science 261:1047-1051(1993)
Cited for: VARIANTS ALS1 VAL-5; ARG-38; VAL-39; ASP-42; SER-42; ARG-44; ARG-86; ALA-94; CYS-94; GLY-101; VAL-107; THR-114; PHE-145 AND GLY-149; 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;