UniProtKB/SwissProt variant VAR

Variant information

Variant position:

388

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Cysteine (C) to Arginine (R) at position 388 (C388R, p.Cys388Arg).

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

Involvement in disease:

Parkinson disease 6 (PARK6) [MIM:605909]: An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive. {ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:15349860, ECO:0000269|PubMed:15349870, ECO:0000269|PubMed:15505171, ECO:0000269|PubMed:15596610, ECO:0000269|PubMed:15955953, ECO:0000269|PubMed:15970950, ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16207217, ECO:0000269|PubMed:16207731, ECO:0000269|PubMed:16257123, ECO:0000269|PubMed:16401616, ECO:0000269|PubMed:16482571, ECO:0000269|PubMed:16632486, ECO:0000269|PubMed:16966503, ECO:0000269|PubMed:17030667, ECO:0000269|PubMed:18286320, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22043288, ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:24784582}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In PARK6.

Any additional useful information about the variant.

Sequence information

Variant position:

388

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

581

The length of the canonical sequence.

Location on the sequence:

ILVELDPDGCPWLVIADFGC C LADESIGLQLPFSSWYVDRG

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                         ILVELDPDGC-PWLVIADFGCCLADESIGLQLPFSSWYVDRG

Mouse                         ILVEWDSDGC-PWLVISDFGCCLADQHVGLRLPFNSSSVER

Rat                           ILVEWDSDGC-PWLVISDFGCCLADERVGLQLPFNSSSVER

Caenorhabditis elegans        ILLEYDFDDEIPQLVVADFGCALACDN--WQVDYESDEVSL

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	78 – 581	Serine/threonine-protein kinase PINK1, mitochondrial
Topological domain	111 – 581	Cytoplasmic
Domain	156 – 511	Protein kinase
Modified residue	402 – 402	Phosphoserine; by autocatalysis
Mutagenesis	384 – 384	D -> A. Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with ALA-219 and ALA-362.

Literature citations

Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism.
Li Y.; Tomiyama H.; Sato K.; Hatano Y.; Yoshino H.; Atsumi M.; Kitaguchi M.; Sasaki S.; Kawaguchi S.; Miyajima H.; Toda T.; Mizuno Y.; Hattori N.;
Neurology 64:1955-1957(2005)
Cited for: VARIANT PARK6 ARG-388;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BXM7: Variant p.Cys388Arg