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UniProtKB/Swiss-Prot O60260: Variant p.Arg402Cys

E3 ubiquitin-protein ligase parkin
Gene: PRKN
Variant information

Variant position:  402
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Arginine (R) to Cysteine (C) at position 402 (R402C, p.Arg402Cys).
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 polar (C)
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

Variant description:  In PARK2.
Any additional useful information about the variant.

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

Sequence information

Variant position:  402
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  465
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.

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




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.

Chain 1 – 465 E3 ubiquitin-protein ligase parkin
Region 234 – 465 TRIAD supradomain
Region 378 – 410 REP
Metal binding 418 – 418 Zinc 5
Metal binding 421 – 421 Zinc 5
Alternative sequence 298 – 465 Missing. In isoform 3.
Alternative sequence 369 – 465 Missing. In isoform 5.
Mutagenesis 403 – 403 W -> A. Decreased autoinhibition and increased E3 activity.
Mutagenesis 415 – 415 T -> N. Loss of activity and self-ubiquitination. Loss of monoubiquitination resulting in an increase in apoptosis. No effect on polyubiquitination or mitophagy.
Mutagenesis 421 – 421 C -> A. Impairs the ability of self-ubiquitination and to ubiquitinate SNCAIP.
Beta strand 401 – 403

Literature citations

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.