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; cell junction; cell soma; cytoplasm; cytoplasmic vesicle; cytosol; dendrite; dendrite cytoplasm; endoplasmic reticulum; endosome; Golgi apparatus; Golgi-associated vesicle; growth cone; inclusion body; intracellular; intracellular membrane-bound organelle; lysosome; membrane raft; microvillus; mitochondrial inner membrane; mitochondrial matrix; mitochondrial membrane; mitochondrial outer membrane; mitochondrion; neuron projection; nucleus; perikaryon; plasma membrane; postsynapse; 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; GTP binding; GTP-dependent protein kinase activity; GTPase activator activity; GTPase activity; identical protein binding; ion channel binding; kinase activity; 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; cellular protein localization; cellular response to manganese ion; cellular response to oxidative stress; cellular response to starvation; determination of adult lifespan; endocytosis; excitatory postsynaptic potential; Golgi organization and biogenesis; GTP metabolic process; intracellular distribution of mitochondria; lysosome organization and biogenesis; MAPK cascade; mitochondrion localization; mitochondrion organization; negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; negative regulation of excitatory postsynaptic potential; 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; 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 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 binding; positive regulation of protein import into nucleus, translocation; positive regulation of protein phosphorylation; positive regulation of protein ubiquitination; positive regulation of synaptic vesicle endocytosis; positive regulation of tumor necrosis factor secretion; protein amino acid phosphorylation; protein autophosphorylation; reactive oxygen species metabolic process; regulation of autophagy; regulation of branching morphogenesis of a nerve; regulation of CAMKK-AMPK signaling cascade; regulation of dopamine receptor signaling pathway; regulation of locomotion; 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 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 receptor signaling pathway through beta-catenin; 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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