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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60260: Variant p.Arg42Pro

E3 ubiquitin-protein ligase parkin
Gene: PRKN
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Variant information Variant position: help 42 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help 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: help 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: help -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

Variant description: help In PARK2 and PARK; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding; decreases ubiquitination and degradation; increased aggregation; impairs the ability to ubiquitinate and degrade SYT11. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 42 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 465 The length of the canonical sequence.
Location on the sequence: help 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         SIFQLKEVVAKRQGVPADQLRVIFAGKELRNDWTVQNCDLD

Mouse                         SILQLKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLE

Rat                           SIFQLKEVVAKRQGVPADQLRVIFAGKELQNHLTVQNCDLE

Drosophila                    DIKNVKELVAPQLGLQPDDLKIIFAGKELSDATTIEQCDLG

Sequence annotation in neighborhood: help 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 41 – 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: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240; Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation.
Xiong H.; Wang D.; Chen L.; Choo Y.S.; Ma H.; Tang C.; Xia K.; Jiang W.; Ronai Z.; Zhuang X.; Zhang Z.;
J. Clin. Invest. 119:650-660(2009)
Cited for: FUNCTION; COMPONENT OF A COMPLEX COMPOSED OF PRKN; PARK7 AND PINK1; SUBCELLULAR LOCATION; UBIQUITINATION; CHARACTERIZATION OF VARIANT PARK2 PRO-42; Molecular chaperone-mediated rescue of mitophagy by a Parkin RING1 domain mutant.
Rose J.M.; Novoselov S.S.; Robinson P.A.; Cheetham M.E.;
Hum. Mol. Genet. 20:16-27(2011)
Cited for: CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND GLY-289; 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; Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and Parkinson's disease-like pathology.
Wang C.; Kang X.; Zhou L.; Chai Z.; Wu Q.; Huang R.; Xu H.; Hu M.; Sun X.; Sun S.; Li J.; Jiao R.; Zuo P.; Zheng L.; Yue Z.; Zhou Z.;
Nat. Commun. 9:81-81(2018)
Cited for: CHARACTERIZATION OF VARIANTS PARK PRO-42 AND TRP-275; FUNCTION;
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.