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UniProtKB/Swiss-Prot O60260: Variant p.Cys441Arg

E3 ubiquitin-protein ligase parkin
Gene: PRKN
Variant information

Variant position:  441
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 441 (C441R, p.Cys441Arg).
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.
Any additional useful information about the variant.

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

Sequence information

Variant position:  441
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
Zinc finger 418 – 449 RING-type 2; atypical
Region 234 – 465 TRIAD supradomain
Active site 431 – 431
Metal binding 421 – 421 Zinc 5
Metal binding 436 – 436 Zinc 5
Metal binding 441 – 441 Zinc 5
Metal binding 446 – 446 Zinc 6
Metal binding 449 – 449 Zinc 6
Metal binding 457 – 457 Zinc 6
Metal binding 461 – 461 Zinc 6; via tele nitrogen
Alternative sequence 298 – 465 Missing. In isoform 3.
Alternative sequence 369 – 465 Missing. In isoform 5.
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.
Mutagenesis 444 – 444 E -> QA. Impaired activity.
Turn 439 – 441

Literature citations

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)

Complex relationship between parkin mutations and Parkinson disease.
West A.; Periquet M.; Lincoln S.; Luecking C.B.; Nicholl D.; Bonifati V.; Rawal N.; Gasser T.; Lohmann E.; Deleuze J.-F.; Maraganore D.; Levey A.; Wood N.W.; Duerr A.; Hardy J.; Brice A.; Farrer M.;
Am. J. Med. Genet. 114:584-591(2002)
Cited for: VARIANTS PARK2 GLU-82; CYS-256; TRP-275; GLU-328 AND ARG-441;

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.