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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q5S007: Variant p.Arg1728His

Leucine-rich repeat serine/threonine-protein kinase 2
Gene: LRRK2
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Variant information Variant position: help 1728 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 1728 (R1728H, p.Arg1728His). 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. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1728 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 LINRLLEISPYMLSGRERAL R PNRMYWRQGIYLNWSPEAYC 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                         LINRLLEISPYMLSGRERALRPNRMYWRQGIYLNWSPEAYC

Mouse                         LINRLLEISPFMLSGRERALRPNRMYWRQGIYLNWSPEAYC
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 1546 – 1740 COR
Mutagenesis 1710 – 1710 N -> A. Impairs RAB29-stimulated kinase activity on RAB10, RAB29 and LRRK2.



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; Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls.
Paisan-Ruiz C.; Nath P.; Washecka N.; Gibbs J.R.; Singleton A.B.;
Hum. Mutat. 29:485-490(2008)
Cited for: VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143 AND HIS-2466; VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND LYS-2395;
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.