UniProtKB/Swiss-Prot Q5S007: Variant p.Arg1441Cys

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
Chromosomal location: 12q12
Variant information

Variant position:  1441
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Arginine (R) to Cysteine (C) at position 1441 (R1441C, p.Arg1441Cys).
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 large size and basic (R) to medium size and polar (C)
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

Variant description:  In PARK; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate.
Any additional useful information about the variant.

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

Sequence information

Variant position:  1441
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.



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.

Chain 1 – 2527 Leucine-rich repeat serine/threonine-protein kinase 2
Domain 1328 – 1511 Roc
Helix 1431 – 1441

Literature citations

Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.
Zimprich A.; Biskup S.; Leitner P.; Lichtner P.; Farrer M.; Lincoln S.J.; Kachergus J.M.; Hulihan M.M.; Uitti R.J.; Calne D.B.; Stoessl A.J.; Pfeiffer R.F.; Patenge N.; Carballo Carbajal I.; Vieregge P.; Asmus F.; Mueller-Myhsok B.; Dickson D.W.; Meitinger T.; Strom T.M.; Wszolek Z.K.; Gasser T.;
Neuron 44:601-607(2004)

Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity.
West A.B.; Moore D.J.; Biskup S.; Bugayenko A.; Smith W.W.; Ross C.A.; Dawson V.L.; Dawson T.M.;
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005)

Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease.
Di Fonzo A.; Tassorelli C.; De Mari M.; Chien H.F.; Ferreira J.; Rohe C.F.; Riboldazzi G.; Antonini A.; Albani G.; Mauro A.; Marconi R.; Abbruzzese G.; Lopiano L.; Fincati E.; Guidi M.; Marini P.; Stocchi F.; Onofrj M.; Toni V.; Tinazzi M.; Fabbrini G.; Lamberti P.; Vanacore N.; Meco G.; Leitner P.; Uitti R.J.; Wszolek Z.K.; Gasser T.; Simons E.J.; Breedveld G.J.; Goldwurm S.; Pezzoli G.; Sampaio C.; Barbosa E.; Martignoni E.; Oostra B.A.; Bonifati V.;
Eur. J. Hum. Genet. 14:322-331(2006)
Cited for: VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019;

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; 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; PRO-1628; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397;

A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations.
Zabetian C.P.; Samii A.; Mosley A.D.; Roberts J.W.; Leis B.C.; Yearout D.; Raskind W.H.; Griffith A.;
Neurology 65:741-744(2005)
Cited for: VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019;

LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance.
Gaig C.; Ezquerra M.; Marti M.J.; Munoz E.; Valldeoriola F.; Tolosa E.;
Arch. Neurol. 63:377-382(2006)
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019;

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.