UniProtKB/SwissProt variant VAR

E3 ubiquitin-protein ligase parkin
Gene: PRKN
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Variant information Variant position:

418 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 Cysteine (C) to Arginine (R) at position 418 (C418R, p.Cys418Arg). 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 medium size and polar (C) to large size and basic (R) 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; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression; fails to ubiquitinate SYT11 but does not loose ability to bind SYT11. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1554252200 [ dbSNP | Ensembl ]

Sequence information Variant position:

418 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:

AEQARWEAASKETIKKTTKP C PRCHVPVEKNGGCMHMKCPQ 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                         AEQARWEAASKETIKKTTKPCPRCHVPVEKNGGCMHMKCPQ

Mouse                         AEQARWEEASKETIKKTTKPCPRCNVPIEKNGGCMHMKCPQ

Rat                           AEQARWEEASKETIKKTTKPCPRCNVPIEKNGGCMHMKCPQ

Drosophila                    AAEARWDEASNVTIKVSTKPCPKCRTPTERDGGCMHMVCTR

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
Zinc finger	418 – 449	RING-type 2; atypical
Region	234 – 465	TRIAD supradomain
Active site	431 – 431
Binding site	418 – 418
Binding site	421 – 421
Binding site	436 – 436
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.
Mutagenesis	429 – 429	G -> E. Reduced self-ubiquitination.
Mutagenesis	430 – 430	G -> D. Loss of self-ubiquitination.
Mutagenesis	431 – 431	C -> A. Loss of activity.
Mutagenesis	431 – 431	C -> S. Impairs the ability to ubiquitinate target proteins. No effect on translocation to mitochondria.
Mutagenesis	433 – 433	H -> NA. Impaired activity.

Literature citations
The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI.
Huynh D.P.; Scoles D.R.; Nguyen D.; Pulst S.M.;
Hum. Mol. Genet. 12:2587-2597(2003)
Cited for: INTERACTION WITH SYT11; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS PARK2 GLY-289 AND ARG-418; Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease.
da Costa C.A.; Sunyach C.; Giaime E.; West A.; Corti O.; Brice A.; Safe S.; Abou-Sleiman P.M.; Wood N.W.; Takahashi H.; Goldberg M.S.; Shen J.; Checler F.;
Nat. Cell Biol. 11:1370-1375(2009)
Cited for: FUNCTION IN PROTECTION OF APOPTOSIS; CHARACTERIZATION OF VARIANTS PARK2 ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441; DOMAIN; 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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60260: Variant p.Cys418Arg