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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; Kinase, protein; LRRK family; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; TKL group
Chromosomal Location of Human Ortholog: 12q12
Cellular Component: axon; cell soma; cytoplasm; cytoplasmic vesicle; cytosol; dendrite; dendrite cytoplasm; endoplasmic reticulum; endosome; extracellular space; Golgi apparatus; Golgi-associated vesicle; growth cone; inclusion body; intracellular; intracellular membrane-bound organelle; lysosome; microvillus; mitochondrial inner membrane; mitochondrial matrix; mitochondrial membrane; mitochondrial outer membrane; mitochondrion; neuron projection; nucleus; perikaryon; plasma membrane; terminal button
Molecular Function: actin binding; clathrin binding; glycoprotein binding; GTP binding; GTP-dependent protein kinase activity; GTPase activator activity; GTPase activity; identical protein binding; kinase activity; MAP kinase kinase activity; microtubule binding; 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; calcium-mediated signaling; cellular response to starvation; determination of adult life span; endocytosis; Golgi organization and biogenesis; GTP metabolic process; intracellular distribution of mitochondria; lysosome organization and biogenesis; MAPKKK cascade; mitochondrion localization; mitochondrion organization and biogenesis; negative regulation of macroautophagy; negative regulation of protein amino acid phosphorylation; negative regulation of protein binding; neurite morphogenesis; neuromuscular junction development; olfactory bulb development; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of autophagy; positive regulation of dopamine receptor signaling pathway; positive regulation of MAP kinase activity; positive regulation of programmed cell death; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein amino acid phosphorylation; positive regulation of protein binding; positive regulation of protein ubiquitination; protein amino acid autophosphorylation; protein amino acid phosphorylation; regulation of autophagy; regulation of dopamine receptor signaling pathway; regulation of excitatory postsynaptic membrane potential; regulation of locomotion; regulation of membrane potential; regulation of mitochondrial depolarization; regulation of neuron maturation; regulation of synaptic transmission, glutamatergic; response to oxidative stress; tangential migration from the subventricular zone to the olfactory bulb; Wnt receptor signaling pathway through beta-catenin
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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