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UniProtKB/Swiss-Prot O60260: Variant p.Ala46Pro

E3 ubiquitin-protein ligase parkin
Gene: PRKN
Variant information

Variant position:  46
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 Alanine (A) to Proline (P) at position 46 (A46P, p.Ala46Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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.
Any additional useful information about the variant.



Sequence information

Variant position:  46
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:   LKEVVAKRQGVPADQLRVIF  A GKELRNDWTVQNCDLDQQSI
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                         LKEVVAKRQGVPADQLRVIFAGKELRNDWTVQNCDLDQQSI

Mouse                         LKEVVAKRQGVPADQLRVIFAGKELPNHLTVQNCDLEQQSI

Rat                           LKEVVAKRQGVPADQLRVIFAGKELQNHLTVQNCDLEQQSI

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.

TypePositionsDescription
Chain 1 – 465 E3 ubiquitin-protein ligase parkin
Domain 1 – 76 Ubiquitin-like
Modified residue 65 – 65 Phosphoserine; by PINK1
Alternative sequence 1 – 191 Missing. In isoform 4.
Alternative sequence 1 – 79 Missing. In isoform 3.
Mutagenesis 65 – 65 S -> A. Loss of phosphorylation. Undergoes autoubiquitination in the presence of phosphorylated ubiquitin.
Mutagenesis 65 – 65 S -> E. Phosphomimetic mutant; still requires PINK1 for activation. PRKN is activated in presence of phosphorylated ubiquitin.


Literature citations

A new point mutation on exon 2 of parkin gene in Parkinson's disease.
Xu Y.; Liu Z.; Wang Y.; Tao E.; Chen G.; Chen B.;
Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19:409-411(2002)
Cited for: VARIANT PARK2 PRO-46;

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.