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UniProtKB/Swiss-Prot P00441: Variant p.Gly38Arg

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

Variant position:  38
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 38 (G38R, p.Gly38Arg).
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; mild form; ubiquitinated by RNF19A. 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:  38
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:   IINFEQKESNGPVKVWGSIK  G LTEGLHGFHVHEFGDNTAGC
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 47 – 47 Copper; catalytic
Metal binding 49 – 49 Copper; catalytic
Cross 33 – 33 1-(tryptophan-3-yl)-tryptophan (Trp-Trp) (interchain with W-33)
Mutagenesis 58 – 58 C -> A. Exhibits very slow copper acquisition.
Mutagenesis 58 – 58 C -> S. Enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with S-7; S-112 and S-147.
Beta strand 30 – 38


Literature citations

Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis.
Hart P.J.; Liu H.; Pellegrini M.; Nersissian A.M.; Gralla E.B.; Valentine J.S.; Eisenberg D.;
Protein Sci. 7:545-555(1998)
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF VARIANT ALS1 ARG-38;

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;

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.