LRRK2 Antibody – Mouse Monoclonal

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, Jul 2008]

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.

Protein type: Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; EC 2.7.11.1; TKL group; LRRK family

Chromosomal Location of Human Ortholog: 12q12

Cellular Component: dendrite cytoplasm; Golgi apparatus; extracellular space; mitochondrion; lysosome; dendrite; terminal button; trans-Golgi network; inclusion body; cytosol; lipid raft; mitochondrial outer membrane; cell soma; mitochondrial matrix; cytoplasm; mitochondrial inner membrane; cytoplasmic vesicle; endosome; neuron projection; synaptic vesicle membrane; endoplasmic reticulum; perikaryon; axon; mitochondrial membrane; plasma membrane; cell junction

Molecular Function: GTPase activity; tubulin binding; identical protein binding; GTP-dependent protein kinase activity; clathrin binding; Rho GTPase binding; protein homodimerization activity; GTP binding; actin binding; GTPase activator activity; protein kinase activity; MAP kinase kinase activity; protein serine/threonine kinase activity; SNARE binding; protein binding; protein kinase A binding; syntaxin-1 binding; kinase activity; glycoprotein binding; ATP binding

Biological Process: regulation of synaptic transmission, glutamatergic; activation of MAPKK activity; positive regulation of protein binding; activation of MAPK activity; protein amino acid autophosphorylation; regulation of neuron maturation; determination of adult life span; protein amino acid phosphorylation; positive regulation of MAP kinase activity; tangential migration from the subventricular zone to the olfactory bulb; negative regulation of protein amino acid phosphorylation; regulation of dopamine receptor signaling pathway; small GTPase mediated signal transduction; regulation of mitochondrial depolarization; negative regulation of protein binding; neuromuscular junction development; positive regulation of autophagy; positive regulation of dopamine receptor signaling pathway; olfactory bulb development; MAPKKK cascade; peptidyl-threonine phosphorylation; endocytosis; regulation of locomotion; regulation of membrane potential; peptidyl-serine phosphorylation; positive regulation of programmed cell death; positive regulation of protein ubiquitination; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; intracellular distribution of mitochondria; autophagy; positive regulation of protein amino acid phosphorylation; response to oxidative stress; regulation of excitatory postsynaptic membrane potential; neurite morphogenesis; positive regulation of GTPase activity

Disease: Parkinson Disease 8, Autosomal Dominant