LRRK2

This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq]

LRRK2

Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882).
Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421).
Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371).
Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392).
Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392).
Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148).
Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371).
Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044).
Plays a role in synaptic vesicle trafficking (PubMed:24687852).
Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882).
Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985).
The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985).
Phosphorylates PRDX3 (PubMed:21850687).
By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718).
Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385).
In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).

AutophagyIEA:UniProtKB-KW
Calcium-mediated signalingManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Canonical Wnt signaling pathwayManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Cellular protein localizationISS:ParkinsonsUK-UCL
Cellular response to dopamineManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Cellular response to manganese ionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Cellular response to organic cyclic compoundManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to oxidative stressManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Cellular response to starvationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Determination of adult lifespanManual Assertion Based On ExperimentIMP:BHF-UCL
EndocytosisManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Endoplasmic reticulum organizationManual Assertion Based On ExperimentIMP:UniProtKB
Excitatory postsynaptic potentialISS:ParkinsonsUK-UCL
Exploration behaviorManual Assertion Based On ExperimentIMP:BHF-UCL
Golgi organizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
GTP metabolic processManual Assertion Based On ExperimentIDA:BHF-UCL
Intracellular distribution of mitochondriaManual Assertion Based On ExperimentIMP:BHF-UCL
Intracellular signal transductionISS:ParkinsonsUK-UCL
JNK cascadeManual Assertion Based On ExperimentIDA:BHF-UCL
Locomotory exploration behaviorIEA:Ensembl
Lysosome organizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrion localizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Mitochondrion organizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of autophagosome assemblyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of excitatory postsynaptic potentialISS:ParkinsonsUK-UCL
Negative regulation of GTPase activityManual Assertion Based On ExperimentIDA:MGI
Negative regulation of hydrogen peroxide-induced cell deathManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of late endosome to lysosome transportManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of macroautophagyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of neuron deathManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of neuron projection developmentIEA:Ensembl
Negative regulation of protein bindingManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of protein phosphorylationISS:ParkinsonsUK-UCL
Negative regulation of protein processingManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of protein processing involved in protein targeting to mitochondrion1 PublicationIC:ParkinsonsUK-UCL
Negative regulation of protein targeting to mitochondrionManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Neuromuscular junction developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Neuron deathManual Assertion Based On ExperimentIMP:BHF-UCL
Neuron projection arborizationIEA:Ensembl
Neuron projection morphogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Olfactory bulb developmentManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
PhosphorylationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of autophagyManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Positive regulation of dopamine receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of histone deacetylase activityIEA:Ensembl
Positive regulation of MAP kinase activityManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of microglial cell activationIEA:Ensembl
Positive regulation of nitric-oxide synthase biosynthetic processIEA:Ensembl
Positive regulation of programmed cell deathManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processISS:BHF-UCL
Positive regulation of protein autoubiquitinationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of protein bindingManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of protein kinase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of synaptic vesicle endocytosisIEA:Ensembl
Positive regulation of tumor necrosis factor productionIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein import into nucleusIEA:Ensembl
Protein localization to endoplasmic reticulum exit siteManual Assertion Based On ExperimentIMP:UniProtKB
Protein localization to mitochondrionManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Protein phosphorylationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Reactive oxygen species metabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of autophagyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of branching morphogenesis of a nerveManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of CAMKK-AMPK signaling cascadeManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Regulation of dendritic spine morphogenesisManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of dopamine receptor signaling pathwayISS:ParkinsonsUK-UCL
Regulation of ER to Golgi vesicle-mediated transportISS:UniProtKB
Regulation of kidney sizeISS:BHF-UCL
Regulation of locomotionManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of lysosomal lumen pHManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of membrane potentialManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of mitochondrial depolarizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of mitochondrial fissionManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of neuroblast proliferationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of neuron deathManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of neuron maturationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of protein kinase A signalingISS:ParkinsonsUK-UCL
Regulation of protein stabilityManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of retrograde transport, endosome to GolgiManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Regulation of synaptic transmission, glutamatergicISS:ParkinsonsUK-UCL
Regulation of synaptic vesicle exocytosisManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of synaptic vesicle transportISS:ParkinsonsUK-UCL
Response to oxidative stressManual Assertion Based On ExperimentIMP:BHF-UCL
Signal transductionManual Assertion Based On ExperimentIBA:GO_Central
SpermatogenesisIEA:Ensembl
Striatum developmentIEA:Ensembl
Tangential migration from the subventricular zone to the olfactory bulbManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Wnt signalosome assemblyManual Assertion Based On ExperimentIPI:ParkinsonsUK-UCL

Cytoplasmic vesicle
Perikaryon
Golgi apparatus membrane
Cell projection, axon
Cell projection, dendrite
Endoplasmic reticulum membrane
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane
Endosome
Lysosome
Mitochondrion outer membrane
Colocalized with RAB29 along tubular structures emerging from Golgi apparatus (PubMed:23395371).
Localizes to endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER) (PubMed:25201882).

Parkinson disease 8 (PARK8):
A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.

Autophosphorylated (PubMed:28202711, PubMed:28720718, PubMed:29127255, PubMed:29212815, PubMed:30635421).
Phosphorylation of Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with YWHAG (PubMed:28202711).
Phosphorylation of Ser-910 and/or Ser-935 facilitates interaction with SFN (PubMed:28202711).