UniProtKB/Swiss-Prot P14920: Variant p.Glu121Lys

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 121 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: US 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 Glutamate (E) to Lysine (K) at position 121 (E121K, p.Glu121Lys). 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 acidic (E) to large size and basic (K) 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: Found in a patient with ALS; abolishes activity; impairs FAD binding; over 900-fold decreased affinity for D-alanine; over 200-fold decreased affinity for D-serine; leads to the formation of protein aggregates; increases the occurrence of cell death. Any additional useful information about the variant.

Sequence information

Variant position: 121 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 347 The length of the canonical sequence.
Location on the sequence: AIPDPSWKDTVLGFRKLTPR E LDMFPDYGYGWFHTSLILEG 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	1 – 347	D-amino-acid oxidase
Mutagenesis	120 – 120	R -> EL. Increases activity and FAD-binding. Decreases protein localization to peroxisomes with protein mislocalized to the nucleus and cytosol.
Helix	119 – 122

Literature citations

Characterization of E121K mutation of D-amino acid oxidase - Insights into mechanisms leading to amyotrophic lateral sclerosis.
Dave U.; Khan S.; Gomes J.;
Biochim. Biophys. Acta 1871:140947-140947(2023)
Cited for: CHARACTERIZATION OF VARIANT ALS LYS-121; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; BIOPHYSICOCHEMICAL PROPERTIES; SUBUNIT;
Aggregation of E121K mutant D-amino acid oxidase and ubiquitination-mediated autophagy mechanisms leading to amyotrophic lateral sclerosis.
Dave U.; Narain P.; Mishra D.; Gomes J.;
J. Neurol. Sci. 456:122845-122845(2024)
Cited for: CHARACTERIZATION OF VARIANT ALS LYS-121;