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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q5S007: Variant p.Thr2356Ile

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
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Variant information Variant position: help 2356 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 Threonine (T) to Isoleucine (I) at position 2356 (T2356I, p.Thr2356Ile). 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 (T) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In PARK8; shows decreased WD domain homodimerization; no effect on kinase activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 2356 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2527 The length of the canonical sequence.
Location on the sequence: help IETRTSQLFSYAAFSDSNII T VVVDTALYIAKQNSPVVEVW 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                         IETRTSQLFSYAAFSDSNIITVVVDTALYIAKQNSPVVEVW

Mouse                         IETKTNQLFSYAAFSDSNIIALAVDTALYIAKKNSPVVEVW
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 – 2527 Leucine-rich repeat serine/threonine-protein kinase 2
Repeat 2333 – 2377 WD 5
Mutagenesis 2343 – 2343 L -> D. Decreases WD domain homodimerization. No effect on kinase activity.
Mutagenesis 2344 – 2344 F -> A. Decreases WD domain homodimerization. No effect on kinase activity.
Mutagenesis 2345 – 2345 S -> D. Decreases WD domain homodimerization. No effect on kinase activity.
Mutagenesis 2346 – 2346 Y -> A. Decreases WD domain homodimerization. No effect on kinase activity.
Beta strand 2354 – 2367



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; Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data.
Khan N.L.; Jain S.; Lynch J.M.; Pavese N.; Abou-Sleiman P.M.; Holton J.L.; Healy D.G.; Gilks W.P.; Sweeney M.G.; Ganguly M.; Gibbons V.; Gandhi S.; Vaughan J.; Eunson L.H.; Katzenschlager R.; Gayton J.; Lennox G.; Revesz T.; Nicholl D.; Bhatia K.P.; Quinn N.; Brooks D.; Lees A.J.; Davis M.B.; Piccini P.; Singleton A.B.; Wood N.W.;
Brain 128:2786-2796(2005)
Cited for: VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356;
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.