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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60260: Variant p.Cys441Arg

E3 ubiquitin-protein ligase parkin
Gene: PRKN
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Variant information Variant position: help 441 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 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: help 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: help -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: help In PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 441 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 CHVPVEKNGGCMHMKCPQPQ C RLEWCWNCGCEWNRVCMGDH 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                         CHVPVEKNGGCMHMKCPQPQCRLEWCWNCGCEWNRVCMGDH

Mouse                         CNVPIEKNGGCMHMKCPQPQCKLEWCWNCGCEWNRACMGDH

Rat                           CNVPIEKNGGCMHMKCPQPQCKLEWCWNCGCEWNRACMGDH

Drosophila                    CRTPTERDGGCMHMVCTRAGCGFEWCWVCQTEWTRDCMGAH
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
Zinc finger 418 – 449 RING-type 2; atypical
Region 234 – 465 TRIAD supradomain
Active site 431 – 431
Binding site 421 – 421
Binding site 436 – 436
Binding site 441 – 441
Binding site 446 – 446
Binding site 449 – 449
Binding site 457 – 457
Binding site 461 – 461
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)
Cited for: FUNCTION IN PROTECTION OF APOPTOSIS; CHARACTERIZATION OF VARIANTS PARK2 ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441; DOMAIN; 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.