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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q5S007: Variant p.Arg1441His

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
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Variant information Variant position: help 1441 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 Arginine (R) to Histidine (H) at position 1441 (R1441H, p.Arg1441His). 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 large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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 an increase in activity in phosphorylation of RAB8A and RAB10; decreases phosphorylation-dependent binding to YWHAG. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1441 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 LSKGQAEVDAMKPWLFNIKA R ASSSPVILVGTHLDVSDEKQ 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                         LSKGQAEVDAMKPWLFNIKARASSSPVILVGTHLDVSDEKQ

Mouse                         LSKGQAEVDAMKPWLFNIKARASSSPVILVGTHLDVSDEKQ
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
Domain 1328 – 1511 Roc
Modified residue 1444 – 1444 Phosphoserine
Mutagenesis 1441 – 1441 R -> G. Decreased membrane association when associated with D-727, D-728, or D-729. Inhibits autophosphorylation and RAB10 phosphorylation when associated with N-1348 or A-2017.
Helix 1431 – 1441



Literature citations
Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases.
Steger M.; Tonelli F.; Ito G.; Davies P.; Trost M.; Vetter M.; Wachter S.; Lorentzen E.; Duddy G.; Wilson S.; Baptista M.A.; Fiske B.K.; Fell M.J.; Morrow J.A.; Reith A.D.; Alessi D.R.; Mann M.;
Elife 5:0-0(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; COFACTOR; ACTIVITY REGULATION; INTERACTION WITH RAB8A; RAB10 AND RAB12; CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385; MUTAGENESIS OF ASP-1994; Rab29 activation of the Parkinson's disease-associated LRRK2 kinase.
Purlyte E.; Dhekne H.S.; Sarhan A.R.; Gomez R.; Lis P.; Wightman M.; Martinez T.N.; Tonelli F.; Pfeffer S.R.; Alessi D.R.;
EMBO J. 37:1-18(2018)
Cited for: FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292; CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385; MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348; ARG-1441; TYR-1699; ASP-2017 AND GLY-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; 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; 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;
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.