UniProtKB/Swiss-Prot Q99497: Variant p.Ala104Thr

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 104 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 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
Variant description: In PARK7; loss of protection against metal cytotoxicity; decreased detoxification activity on methylglyocal-adducted CoA. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs774005786 [ dbSNP | Ensembl ]

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.
Location on the sequence: ESAAVKEILKEQENRKGLIA A ICAGPTALLAHEIGFGSKVT 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
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. Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduces binding to OTUD7B. Removes the glycations and restores histone 3. 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. No effect on methylglyoxal-adducted glutathione or CoA.
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)
Cited for: FUNCTION; COPPER-BINDING; CHARACTERIZATION OF VARIANTS PARK7 THR-104 AND ALA-149; MUTAGENESIS OF CYS-106; 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; 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)
Cited for: VARIANT PARK7 THR-104; VARIANTS GLN-98 AND SER-171;