Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O60260: Variant p.Cys431Phe

E3 ubiquitin-protein ligase parkin
Gene: PRKN
Feedback?
Variant information Variant position: help 431 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 Phenylalanine (F) at position 431 (C431F, p.Cys431Phe). 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 aromatic (F) 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; impaired E3 ubiquitin-protein ligase toward ZNF746 and BCL2. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 431 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 IKKTTKPCPRCHVPVEKNGG C MHMKCPQPQCRLEWCWNCGC 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                         IKKTTKPCPRCHVPVEKNGGCMHMKCPQPQCRLEWCWNCGC

Mouse                         IKKTTKPCPRCNVPIEKNGGCMHMKCPQPQCKLEWCWNCGC

Rat                           IKKTTKPCPRCNVPIEKNGGCMHMKCPQPQCKLEWCWNCGC

Drosophila                    IKVSTKPCPKCRTPTERDGGCMHMVCTRAGCGFEWCWVCQT
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 418 – 418
Binding site 421 – 421
Binding site 436 – 436
Binding site 441 – 441
Binding site 446 – 446
Binding site 449 – 449
Alternative sequence 298 – 465 Missing. In isoform 3.
Alternative sequence 369 – 465 Missing. In isoform 5.
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.
Mutagenesis 444 – 444 E -> QA. Impaired activity.
Beta strand 429 – 431



Literature citations
Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.
Chen D.; Gao F.; Li B.; Wang H.; Xu Y.; Zhu C.; Wang G.;
J. Biol. Chem. 285:38214-38223(2010)
Cited for: FUNCTION; INTERACTION WITH BCL2; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ARG-240; PHE-431 AND LEU-437; PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease.
Shin J.H.; Ko H.S.; Kang H.; Lee Y.; Lee Y.I.; Pletinkova O.; Troconso J.C.; Dawson V.L.; Dawson T.M.;
Cell 144:689-702(2011)
Cited for: FUNCTION; INTERACTION WITH ZNF746; CHARACTERIZATION OF VARIANTS PARK2 TRP-275; ASP-430 AND PHE-431; Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism.
Maruyama M.; Ikeuchi T.; Saito M.; Ishikawa A.; Yuasa T.; Tanaka H.; Hayashi S.; Wakabayashi K.; Takahashi H.; Tsuji S.;
Ann. Neurol. 48:245-250(2000)
Cited for: VARIANT PARK2 PHE-431;
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.