UniProtKB/Swiss-Prot Q99497: Variant p.Glu64Asp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 64 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 Glutamate (E) to Aspartate (D) at position 64 (E64D, p.Glu64Asp). 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: Similar physico-chemical property. Both residues are medium size and acidic. 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 PARK7; no apparent effect on protein stability; impaired mitochondrial morphology; no effect on detoxification activity on methylglyocal-adducted CoA. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs74315353 [ dbSNP | Ensembl ]

Sequence information

Variant position: 64 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 189 The length of the canonical sequence.
Location on the sequence: VQCSRDVVICPDASLEDAKK E GPYDVVVLPGGNLGAQNLSE 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
Modified residue	67 – 67	Phosphotyrosine
Lipidation	46 – 46	S-palmitoyl cysteine
Lipidation	53 – 53	S-palmitoyl cysteine
Mutagenesis	46 – 46	C -> A. Reduces protein stability. No effect on oxidation.
Mutagenesis	46 – 46	C -> A. Reduces protein stability. No effect on oxidation. Reduced localization in lipid rafts; when associated with A-106.
Mutagenesis	46 – 46	C -> S. No effect on mitochondrial translocation neither on deglycase activity.
Mutagenesis	51 – 51	V -> A. Disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide.
Mutagenesis	53 – 53	C -> A. Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide.
Mutagenesis	53 – 53	C -> S. No effect on mitochondrial translocation neither on deglycase activity.

Literature citations

Parkinson's disease-related DJ-1 functions in thiol quality control against aldehyde attack in vitro.
Matsuda N.; Kimura M.; Queliconi B.B.; Kojima W.; Mishima M.; Takagi K.; Koyano F.; Yamano K.; Mizushima T.; Ito Y.; Tanaka K.;
Sci. Rep. 7:12816-12816(2017)
Cited for: FUNCTION; MUTAGENESIS OF LEU-10; GLU-18; CYS-106 AND ALA-179; CHARACTERIZATION OF VARIANTS PARK7 ILE-26; ASP-64; THR-104; ALA-149; LYS-163 AND PRO-166; CHARACTERIZATION OF VARIANT SER-39; Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).
Hering R.; Strauss K.M.; Tao X.; Bauer A.; Woitalla D.; Mietz E.M.; Petrovic S.; Bauer P.; Schaible W.; Mueller T.; Schoels L.; Klein C.; Berg D.; Meyer P.T.; Schulz J.B.; Wollnik B.; Tong L.; Krueger R.; Riess O.;
Hum. Mutat. 24:321-329(2004)
Cited for: VARIANT PARK7 ASP-64; X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS); Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1.
Goerner K.; Holtorf E.; Odoy S.; Nuscher B.; Yamamoto A.; Regula J.T.; Beyer K.; Haass C.; Kahle P.J.;
J. Biol. Chem. 279:6943-6951(2004)
Cited for: CHARACTERIZATION OF VARIANTS PARK7 ASP-64 AND PRO-166; Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1.
Krebiehl G.; Ruckerbauer S.; Burbulla L.F.; Kieper N.; Maurer B.; Waak J.; Wolburg H.; Gizatullina Z.; Gellerich F.N.; Woitalla D.; Riess O.; Kahle P.J.; Proikas-Cezanne T.; Kruger R.;
PLoS ONE 5:E9367-E9367(2010)
Cited for: VARIANT ASP-64; FUNCTION;