UniProtKB/Swiss-Prot Q99497: Variant p.Glu64Asp

Protein/nucleic acid deglycase DJ-1
Gene: PARK7
Chromosomal location: 1p36.23
Variant information

Variant position:  64
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

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

Involvement in disease:  Parkinson disease 7 (PARK7) [MIM:606324]: A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease). {ECO:0000269|PubMed:12446870, ECO:0000269|PubMed:12851414, ECO:0000269|PubMed:12953260, ECO:0000269|PubMed:14607841, ECO:0000269|PubMed:14713311, ECO:0000269|PubMed:15254937, ECO:0000269|PubMed:15365989, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PARK7; no apparent effect on protein stability; impaired mitochondrial morphology.
Any additional useful information about the variant.

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

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.

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.

Modified residue 67 – 67 Phosphotyrosine
Lipidation 46 – 46 S-palmitoyl cysteine
Lipidation 53 – 53 S-palmitoyl cysteine
Mutagenesis 46 – 46 C -> A. Reduced localization in lipid rafts; when associated with A-106.
Mutagenesis 46 – 46 C -> A. Reduces protein stability. No effect on oxidation.
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

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)

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)

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)

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.