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UniProtKB/Swiss-Prot Q5S007: Variant p.Val2390Met

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
Variant information

Variant position:  2390
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 Valine (V) to Methionine (M) at position 2390 (V2390M, p.Val2390Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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 PARK8; shows decreased WD domain homodimerization; no effect on kinase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  2390
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2527
The length of the canonical sequence.

Location on the sequence:   SPVVEVWDKKTEKLCGLIDC  V HFLREVMVKENKESKHKMSY
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                         SPVVEVWDKKTEKLCGLIDCVHFLREVMVKENKESKHKMSY

Mouse                         SPVVEVWDKKTEKLCELIDCVHFLKEVMVKLNKESKHQLSY

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 – 2527 Leucine-rich repeat serine/threonine-protein kinase 2
Mutagenesis 2391 – 2391 H -> D. Increases kinase activity.
Mutagenesis 2394 – 2394 R -> E. Decreases WD domain homodimerization. Increases kinase activity and autophosphorylation at Ser-1292.
Mutagenesis 2395 – 2395 E -> R. Decreases WD domain homodimerization. No effect on kinase activity.
Mutagenesis 2408 – 2408 M -> AE. No effect on WD domain homodimerization. No effect on kinase activity.
Mutagenesis 2409 – 2409 S -> A. Decreases WD domain homodimerization.
Helix 2389 – 2393


Literature citations

Crystal structure of the WD40 domain dimer of LRRK2.
Zhang P.; Fan Y.; Ru H.; Wang L.; Magupalli V.G.; Taylor S.S.; Alessi D.R.; Wu H.;
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019)
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; DOMAIN; PHOSPHORYLATION AT SER-935 AND SER-1292; CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189; ILE-2356; ARG-2385; MET-2390 AND ILE-2439; MUTAGENESIS OF ASP-2017; LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395; MET-2408 AND SER-2409;

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.