UniProtKB/Swiss-Prot O60260: Variant p.Arg42Pro

E3 ubiquitin-protein ligase parkin
Gene: PARK2
Chromosomal location: 6q25.2-q27
Variant information

Variant position:  42
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 Arginine (R) to Proline (P) at position 42 (R42P, p.Arg42Pro).
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 large size and basic (R) to medium size and hydrophobic (P)
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 2 (PARK2) [MIM:600116]: A neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually before 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent. 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 PARK2; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding.
Any additional useful information about the variant.



Sequence information

Variant position:  42
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  465
The length of the canonical sequence.

Location on the sequence:   SIFQLKEVVAKRQGVPADQL  R VIFAGKELRNDWTVQNCDLD
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                         SIFQLKEVVAKRQGVPADQLRVIFAGKELRNDWTVQNCDLD

Mouse                         SILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLE

Rat                           SIFQLKEVVAKRQGVPADQLRVIFAGKELQNHLTVQNCDLE

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
Chain 1 – 465 E3 ubiquitin-protein ligase parkin
Domain 1 – 76 Ubiquitin-like
Alternative sequence 1 – 191 Missing. In isoform 4.
Alternative sequence 1 – 79 Missing. In isoform 3.
Beta strand 38 – 45


Literature citations

Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase.
Shimura H.; Hattori N.; Kubo S.; Mizuno Y.; Asakawa S.; Minoshima S.; Shimizu N.; Iwai K.; Chiba T.; Tanaka K.; Suzuki T.;
Nat. Genet. 25:302-305(2000)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240;

Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease.
Shimura H.; Schlossmacher M.G.; Hattori N.; Frosch M.P.; Trockenbacher A.; Schneider R.; Mizuno Y.; Kosik K.S.; Selkoe D.J.;
Science 293:263-269(2001)
Cited for: UBIQUITINATION OF AN O-GLYCOSYLATED ISOFORM OF SNCAIP; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240;

Evaluation of 50 probands with early-onset Parkinson's disease for parkin mutations.
Hedrich K.; Marder K.; Harris J.; Kann M.; Lynch T.; Meija-Santana H.; Pramstaller P.P.; Schwinger E.; Bressman S.B.; Fahn S.; Klein C.;
Neurology 58:1239-1246(2002)
Cited for: VARIANTS PARK2 PRO-42; LEU-192; CYS-256; TRP-275; ASP-430 AND LEU-437;

Novel parkin mutations detected in patients with early-onset Parkinson's disease.
Bertoli-Avella A.M.; Giroud-Benitez J.L.; Akyol A.; Barbosa E.; Schaap O.; van der Linde H.C.; Martignoni E.; Lopiano L.; Lamberti P.; Fincati E.; Antonini A.; Stocchi F.; Montagna P.; Squitieri F.; Marini P.; Abbruzzese G.; Fabbrini G.; Marconi R.; Dalla Libera A.; Trianni G.; Guidi M.; De Gaetano A.; Boff Maegawa G.; De Leo A.; Gallai V.; de Rosa G.; Vanacore N.; Meco G.; van Duijn C.M.; Oostra B.A.; Heutink P.; Bonifati V.;
Mov. Disord. 20:424-431(2005)
Cited for: VARIANTS PARK2 PRO-42; CYS-402; ASN-415 AND ARG-418;

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.