UniProtKB/Swiss-Prot Q99497: Variant p.Glu64Asp

Protein 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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

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.
Any additional useful information about 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.

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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         VQCSRDVVICPDASLEDA-KKEGPYDVVVLPGG--NLGAQNLSE

Mouse                         VQCSRDVMICPDTSLEDA-KTQGPYDVVVLPGG--NLGAQN

Rat                           VQCSRDVVICPDTSLEEA-KTQGPYDVVVLPGG--NLGAQN

Bovine                        VQCSRDVVICPDASLEDA-KKEGPYDVVVLPGG--NLGAQN

Chicken                       VQCSRDVLICPDASLEDA-RKEGPYDVIVLPGG--NLGAQN

Zebrafish                     VQCSREVMICPDSSLEDA-HKQGPYDVVLLPGG--LLGAQN

Slime mold                    VTSTFGVKVQVDVLLGEVVKSLDEFDALAIPGGFENYSFYE

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
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.
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.


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)
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;

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.