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leucine-rich repeat serine/threonine-protein kinase 2; dardarin (LRRK2, PARK8)
Function:
1) may play a role in the phosphorylation of proteins involved in Parkinson disease
2) may also have GTPase activity
3) interacts with PARK2
Structure:
- belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family
- contains 12 LRR repeats (leucine-rich repeats)
- contains 1 protein kinase domain
- contains 1 Roc domain
Compartment:
- cytoplasm, peripheral membrane
- localized in the cytoplasm
- associated with cellular membrane structures
- associates with mitochondrial outer membrane
Expression:
- expressed in heart, liver> brain > placenta, lung, skeletal muscle, kidney, pancreas
- in brain, expressed in the cerebellum, cerebral cortex, medulla oblongata, spinal cord occipital pole, frontal lobe, temporal lobe & putamen
- expression is particularly high in areas with dopamine receptors
Pathology:
- defects in LRRK2 are the cause of Parkinson disease 8 (PARK8)
- LRRK2 G2019S mutation carriers with milder progression of motor symptoms than idiopathic Parkinson's disease, but no difference in cognitive function [2]
Related
LRRK2 gene Arg1441Gly & Gly2019Ser mutation
LRRK2 gene mutation
Parkinson's disease (paralysis agitans, PD)
General
leucine-rich repeat-containing protein (LRRC)
serine/threonine kinase
Properties
SIZE: entity length = 2527 aa
MW = 286 kD
COMPARTMENT: mitochondria
cytoplasm
MOTIF: coiled coil {319-348}
leucine-rich repeat
SITE: 983-1004
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1012-1033
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1036-1057
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1059-1080
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1084-1105
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1108-1129
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1130-1150
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1174-1196
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1197-1218
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1221-1241
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1246-1267
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 1269-1291
MOTIF: leucine residue (SEVERAL)
Roc {1328-1511}
MOTIF: GTP-binding site
SITE: 1341-1348
kinase domain
SITE: 1879-2138
MOTIF: aspartate residue {D1994}
GTP-binding site
SITE: 2098-2121
GTP-binding site
SITE: 2295-2298
STATE: active state
Database Correlations
OMIM correlations
MORBIDMAP 609007
UniProt Q5S007
PFAM correlations
Entrez Gene 120892
Kegg hsa:120892
ENZYME 2.7.11.1
References
- UniProt :accession Q5S007
- George J.
Genetic Mutation Slows Motor Symptoms in PD.
Research could inform trials of new anti-Parkinson's disease
drugs.
MedPage Today January 11, 2018
https://www.medpagetoday.com/neurology/parkinsonsdisease/70438
- Saunders-Pullman R, Mirelman A, Alcalay RN et al
Progression in the LRRK2-Asssociated Parkinson Disease
Population.
JAMA Neurol. Published online January 8, 2018
PMID: 29309488
https://jamanetwork.com/journals/jamaneurology/article-abstract/2668463