Home  |  Contact

UniProtKB/Swiss-Prot P00441: Variant p.Ile114Thr

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

Variant position:  114
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 Isoleucine (I) to Threonine (T) at position 114 (I114T, p.Ile114Thr).
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 medium size and hydrophobic (I) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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; destabilizes dimeric protein structure and increases tendency to form fibrillar aggregates.
Any additional useful information about the variant.

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

Sequence information

Variant position:  114
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.

Chain 2 – 154 Superoxide dismutase [Cu-Zn]
Metal binding 121 – 121 Copper; catalytic
Modified residue 99 – 99 Phosphoserine
Modified residue 103 – 103 Phosphoserine
Modified residue 106 – 106 Phosphoserine
Modified residue 108 – 108 Phosphoserine
Modified residue 123 – 123 N6-acetyllysine; alternate
Modified residue 123 – 123 N6-succinyllysine; alternate
Disulfide bond 58 – 147
Mutagenesis 112 – 112 C -> S. Enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with S-7; S-58 and S-147.
Mutagenesis 123 – 123 K -> A. Decreased succinylation.
Mutagenesis 123 – 123 K -> E. Mimicks constitutive succinylation state; decreased activity.
Mutagenesis 134 – 134 E -> Q. Abolishes dimerization; when associated with E-50 and E-51.
Beta strand 112 – 115

Literature citations

Two novel mutations in the gene for copper zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis.
Enayat Z.E.; Orrell R.W.; Claus A.; Ludolph A.; Bachus R.; Brockmueller J.; Ray-Chaudhuri K.; Radunovic A.; Shaw C.; Wilkinson J.; King A.; Swash M.; Leigh P.N.; de Belleroche J.; Powell J.;
Hum. Mol. Genet. 4:1239-1240(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-56 AND 120-154; VARIANTS ALS1 GLN-49; ARG-94; THR-113; THR-114; HIS-126 AND THR-150;

Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutants.
Hough M.A.; Grossmann J.G.; Antonyuk S.V.; Strange R.W.; Doucette P.A.; Rodriguez J.A.; Whitson L.J.; Hart P.J.; Hayward L.J.; Valentine J.S.; Hasnain S.S.;
Proc. Natl. Acad. Sci. U.S.A. 101:5976-5981(2004)

'Sporadic' motoneuron disease due to familial SOD1 mutation with low penetrance.
Suthers G.; Laing N.; Wilton S.; Dorosz S.; Waddy H.;
Lancet 344:1773-1773(1994)
Cited for: VARIANT ALS1 THR-114;

A missense mutation in the SOD1 gene in patients with amyotrophic lateral sclerosis from the Kii Peninsula and its vicinity, Japan.
Kikugawa K.; Nakano R.; Inuzuka T.; Kokubo Y.; Narita Y.; Kuzuhara S.; Yoshida S.; Tsuji S.;
Neurogenetics 1:113-115(1997)
Cited for: VARIANT ALS1 THR-114;

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)

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.