UniProtKB/Swiss-Prot O60260 : Variant p.Arg42Pro
E3 ubiquitin-protein ligase parkin
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Variant information
Variant position:
42
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
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:
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:
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
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).following page
Variant description:
Any additional useful information about the variant.
Other resources:
Links to websites of interest for 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:
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 SIFQLKEVVAKRQGVPADQLR VIFAGKELRNDWTVQNCDLD
Mouse SILQLKEVVAKRQGVPADQLR VIFAGKELPNHLTVQNCDLE
Rat SIFQLKEVVAKRQGVPADQLR VIFAGKELQNHLTVQNCDLE
Drosophila DIKNVKELVAPQLGLQPDDLK IIFAGKELSDATTIEQCDLG
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
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.
