UniProtKB/Swiss-Prot Q99497: Variant p.Ala104Thr

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

Variant position:  104
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 Alanine (A) to Threonine (T) at position 104 (A104T, p.Ala104Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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; loss of protection against metal cytotoxicity.
Any additional useful information about the variant.

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

Sequence information

Variant position:  104
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.

Active site 106 – 106 Nucleophile
Modified residue 106 – 106 Cysteine sulfinic acid (-SO2H); alternate
Lipidation 106 – 106 S-palmitoyl cysteine; alternate
Mutagenesis 106 – 106 C -> A. Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduces binding to OTUD7B.
Mutagenesis 106 – 106 C -> A. Reduced localization in lipid rafts; when associated with A-46.
Mutagenesis 106 – 106 C -> D. Abolishes oxidation and association with mitochondria. No effect on chaperone activity.
Mutagenesis 106 – 106 C -> S. Loss of protein and nucleic acid deglycase activity. No effect on mitochondrial translocation. Reduced protease activity. No effect on protection against metal cytotoxicity.
Beta strand 101 – 105

Literature citations

Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity.
Bjorkblom B.; Adilbayeva A.; Maple-Grodem J.; Piston D.; Okvist M.; Xu X.M.; Brede C.; Larsen J.P.; Moller S.G.;
J. Biol. Chem. 288:22809-22820(2013)

Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.
Clark L.N.; Afridi S.; Mejia-Santana H.; Harris J.; Louis E.D.; Cote L.J.; Andrews H.; Singleton A.; Wavrant De-Vrieze F.; Hardy J.; Mayeux R.; Fahn S.; Waters C.; Ford B.; Frucht S.; Ottman R.; Marder K.;
Mov. Disord. 19:796-800(2004)

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.