UniProtKB/Swiss-Prot Q99497: Variant p.Leu166Pro

Protein DJ-1
Gene: PARK7
Chromosomal location: 1p36.23
Variant information

Variant position:  166
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 Leucine (L) to Proline (P) at position 166 (L166P, p.Leu166Pro).
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 hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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). 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; reduces protein stability and leads to increased degradation; interferes with homodimerization; abolishes interaction with PIAS2; strongly reduces chaperone activity; ubiquitinated by PARK2, leading to its recognition by HDAC6 and targeting to aggresome where is degraded.
Any additional useful information about the variant.

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



Sequence information

Variant position:  166
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:   VEKDGLILTSRGPGTSFEFA  L AIVEALNGKEVAAQVKAPLV
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                         VEKDGLILTSRGPGTSFEFALAIVEALNGKEVAAQVKAPLV

Mouse                         VEKDGLILTSRGPGTSFEFALAIVEALVGKDMANQVKAPLV

Rat                           VEKDGLILTSRGPGTSFEFALAIVEALSGKDMANQVKAPLV

Bovine                        VEKDGLILTSRGPGTSFEFALKIVEVLVGKEVADQVKAPLV

Chicken                       VEKDGNILTSRGPGTSFEFGLAIVEALMGKEVAEQVKAPLI

Zebrafish                     VQKDGNVITSRGPGTSFEFALTIVEELMGAEVAAQVKAPLI

Slime mold                    IVIDKNVITSYNPQTAPYVAFELLSRLSDENKAKKVKTLMG

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 148 – 148 N6-acetyllysine
Modified residue 182 – 182 N6-succinyllysine
Mutagenesis 166 – 166 L -> P. Reduced localization in lipid rafts.
Helix 161 – 173


Literature citations

L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system.
Miller D.W.; Ahmad R.; Hague S.; Baptista M.J.; Canet-Aviles R.; McLendon C.; Carter D.M.; Zhu P.-P.; Stadler J.; Chandran J.; Klinefelter G.R.; Blackstone C.; Cookson M.R.;
J. Biol. Chem. 278:36588-36595(2003)
Cited for: DEGRADATION BY THE PROTEASOME; SUBCELLULAR LOCATION; INTERACTION WITH PIAS2; HOMODIMERIZATION; MUTAGENESIS OF LYS-130; CHARACTERIZATION OF VARIANT PARK7 PRO-166;

A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization.
Moore D.J.; Zhang L.; Dawson T.M.; Dawson V.L.;
J. Neurochem. 87:1558-1567(2003)
Cited for: DEGRADATION BY THE PROTEASOME; CHARACTERIZATION OF VARIANTS PARK7 ILE-26 AND PRO-166;

Mutations in the DJ-1 gene associated with autosomal recessive early-onset Parkinsonism.
Bonifati V.; Rizzu P.; van Baren M.J.; Schaap O.; Breedveld G.J.; Krieger E.; Dekker M.C.J.; Squitieri F.; Ibanez P.; Joosse M.; van Dongen J.W.; Vanacore N.; van Swieten J.C.; Brice A.; Meco G.; van Duijn C.M.; Oostra B.A.; Heutink P.;
Science 299:256-259(2003)
Cited for: VARIANT PARK7 PRO-166; SUBCELLULAR LOCATION;

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;

Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6.
Olzmann J.A.; Li L.; Chudaev M.V.; Chen J.; Perez F.A.; Palmiter R.D.; Chin L.S.;
J. Cell Biol. 178:1025-1038(2007)
Cited for: CHARACTERIZATION OF VARIANT PARK7 PRO-166;

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.