UniProtKB/Swiss-Prot Q5S007: Variant p.Met2397Thr

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

2397 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Methionine (M) to Threonine (T) at position 2397 (M2397T, p.Met2397Thr). 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 hydrophobic (M) to medium size and polar (T) 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
Other resources:

Links to websites of interest for the variant.

Variant rs3761863 [ dbSNP | Ensembl ]

Sequence information Variant position:

2397 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:

DKKTEKLCGLIDCVHFLREV M VKENKESKHKMSYSGRVKTL 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                         DKKTEKLCGLIDCVHFLREVMVKENKESKHKMSYSGRVKTL

Mouse                         DKKTEKLCELIDCVHFLKEVMVKLNKESKHQLSYSGRVKAL

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	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.
Turn	2397 – 2399

Literature citations
Lrrk2 pathogenic substitutions in Parkinson's disease.
Mata I.F.; Kachergus J.M.; Taylor J.P.; Lincoln S.; Aasly J.; Lynch T.; Hulihan M.M.; Cobb S.A.; Wu R.-M.; Lu C.-S.; Lahoz C.; Wszolek Z.K.; Farrer M.J.;
Neurogenetics 6:171-177(2005)
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598; PRO-1628; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385; VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397; LRRK2 gene in Parkinson disease: mutation analysis and case control association study.
Paisan-Ruiz C.; Lang A.E.; Kawarai T.; Sato C.; Salehi-Rad S.; Fisman G.K.; Al-Khairallah T.; St George-Hyslop P.H.; Singleton A.; Rogaeva E.;
Neurology 65:696-700(2005)
Cited for: VARIANTS PARK8 VAL-1371 AND SER-2019; VARIANTS HIS-1398 AND THR-2397; Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence of purifying selection and independent origin of the p.Arg1628Pro mutation in Europe.
Rubio J.P.; Topp S.; Warren L.; St Jean P.L.; Wegmann D.; Kessner D.; Novembre J.; Shen J.; Fraser D.; Aponte J.; Nangle K.; Cardon L.R.; Ehm M.G.; Chissoe S.L.; Whittaker J.C.; Nelson M.R.; Mooser V.E.;
Hum. Mutat. 33:1087-1098(2012)
Cited for: VARIANTS LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; PRO-1628; THR-1646; THR-1647; ASP-2081 AND THR-2397;

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.