LRRK2 a large multidomain protein kinase with a TKL-type kinase domain, multiple protein-protein interaction domains and a mitochondrial Rho domain (MIRO). May play a role in the etiology of Parkinson disease. May also have GTPase activity. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Interacts with PARK2, PRDX3 and TPCN2. Expressed throughout the adult brain, but at a lower level than in heart and liver. Expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas. Defects in LRRK2 are the cause of Parkinson disease type 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. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.11.1; Kinase, protein; LRRK family; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; TKL group
Chromosomal Location of Human Ortholog: 12q12
Cellular Component:  amphisome; autolysosome; axon; caveola neck; cell junction; cytoplasm; cytoplasmic side of mitochondrial outer membrane; cytoplasmic vesicle; cytosol; dendrite; dendrite cytoplasm; endoplasmic reticulum; endoplasmic reticulum exit site; endosome; glutamatergic synapse; Golgi apparatus; Golgi-associated vesicle; growth cone; inclusion body; intracellular membrane-bounded organelle; lysosome; microvillus; mitochondrial inner membrane; mitochondrial matrix; mitochondrial membrane; mitochondrial outer membrane; mitochondrion; multivesicular body, internal vesicle; neuron projection; neuronal cell body; nucleus; perikaryon; plasma membrane; postsynapse; presynaptic cytosol; ribonucleoprotein complex; synaptic vesicle membrane; terminal bouton; trans-Golgi network; Wnt signalosome
Molecular Function:  actin binding; ATP binding; beta-catenin destruction complex binding; clathrin binding; co-receptor binding; GTP binding; GTP-dependent protein kinase activity; GTPase activator activity; GTPase activity; identical protein binding; ion channel binding; kinase activity; magnesium ion binding; MAP kinase kinase activity; microtubule binding; peroxidase inhibitor activity; protein binding; protein homodimerization activity; protein kinase A binding; protein kinase activity; protein serine/threonine kinase activity; receptor signaling complex scaffold activity; Rho GTPase binding; SNARE binding; syntaxin-1 binding; tubulin binding
Biological Process:  activation of MAPK activity; activation of MAPKK activity; autophagy; calcium-mediated signaling; canonical Wnt signaling pathway; cellular protein localization; cellular response to dopamine; cellular response to manganese ion; cellular response to oxidative stress; cellular response to starvation; determination of adult lifespan; endocytosis; endoplasmic reticulum organization; excitatory postsynaptic potential; exploration behavior; Golgi organization; GTP metabolic process; intracellular distribution of mitochondria; intracellular signal transduction; locomotory exploration behavior; lysosome organization; MAPK cascade; mitochondrion localization; mitochondrion organization; negative regulation of autophagosome assembly; negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; negative regulation of excitatory postsynaptic potential; negative regulation of GTPase activity; negative regulation of hydrogen peroxide-induced cell death; negative regulation of late endosome to lysosome transport; negative regulation of macroautophagy; negative regulation of neuron death; negative regulation of neuron projection development; negative regulation of protein binding; negative regulation of protein phosphorylation; negative regulation of protein processing; negative regulation of protein processing involved in protein targeting to mitochondrion; negative regulation of protein targeting to mitochondrion; negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation; neuromuscular junction development; neuron death; neuron projection arborization; neuron projection morphogenesis; olfactory bulb development; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of autophagy; positive regulation of canonical Wnt signaling pathway; positive regulation of dopamine receptor signaling pathway; positive regulation of GTPase activity; positive regulation of histone deacetylase activity; positive regulation of MAP kinase activity; positive regulation of microglial cell activation; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of programmed cell death; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein autoubiquitination; positive regulation of protein binding; positive regulation of protein phosphorylation; positive regulation of protein ubiquitination; positive regulation of synaptic vesicle endocytosis; positive regulation of tumor necrosis factor secretion; protein autophosphorylation; protein import into nucleus; protein localization to endoplasmic reticulum exit site; protein localization to mitochondrion; protein phosphorylation; reactive oxygen species metabolic process; regulation of autophagy; regulation of branching morphogenesis of a nerve; regulation of CAMKK-AMPK signaling cascade; regulation of canonical Wnt signaling pathway; regulation of dendritic spine morphogenesis; regulation of dopamine receptor signaling pathway; regulation of ER to Golgi vesicle-mediated transport; regulation of kidney size; regulation of locomotion; regulation of lysosomal lumen pH; regulation of membrane potential; regulation of mitochondrial depolarization; regulation of mitochondrial fission; regulation of neuroblast proliferation; regulation of neuron death; regulation of neuron maturation; regulation of protein kinase A signaling; regulation of protein stability; regulation of retrograde transport, endosome to Golgi; regulation of synaptic transmission, glutamatergic; regulation of synaptic vesicle exocytosis; regulation of synaptic vesicle transport; response to oxidative stress; spermatogenesis; striatum development; tangential migration from the subventricular zone to the olfactory bulb; Wnt signalosome assembly
Disease: Parkinson Disease 8, Autosomal Dominant
Reference #:  Q5S007 (UniProtKB)
Alt. Names/Synonyms: augmented in rheumatoid arthritis 17; AURA17; Dardarin; leucine-rich repeat kinase 2; Leucine-rich repeat serine/threonine-protein kinase 2; LRRK2; PARK8; RIPK7; ROCO2
Gene Symbols: LRRK2
Molecular weight: 286,103 Da
Basal Isoelectric point: 6.35  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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LRRK2

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