|Other Names||Leucine-rich repeat serine/threonine-protein kinase 2, Dardarin, LRRK2, PARK8|
|Target/Specificity||The synthetic peptide sequence used to generate the antibody AP7099j was selected from the LRRK2 region of human PARK8 (LRRK2). A 10 to 100 fold molar excess to antibody is recommended. Precise conditions should be optimized for a particular assay.|
|Format||The synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml deionized water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Function||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. 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. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.|
|Cellular Location||Membrane; Peripheral membrane protein. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Endosome. Lysosome. Mitochondrion outer membrane Mitochondrion inner membrane. Mitochondrion matrix. Note=Predominantly associated with intracytoplasmic vesicular and membranous structures (By similarity). Localized in the cytoplasm and associated with cellular membrane structures Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes.|
|Tissue Location||Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, 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|
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Parkinson is the second most common neurodegenerative disease after Alzheimers. About 1 percent of people over the age of 65 and 3 percent of people over the age of 75 are affected by the disease. The mutation is the most common cause of Parkinson's disease identified to date. LRRK2, a genetic mutation, was recently found linked to about 5 percent of inherited cases of Parkinson's disease. By high-resolution recombination mapping and candidate gene sequencing in 46 families, 6 disease-segregating mutations (5 missense and 1 putative splice site mutation). It may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism. LRRK2 belongs to the ROCO protein family and includes a protein kinase domain of the MAPKKK class and several other major functional domains.
Shen J. Neuron. 2004. 44:575. Paisan-Ruiz C, et al. Neuron. 2004. 44(4):595. Zimprich A, et al. Neuron. 2004. 44(4):601. Wszolek ZK, et al. Neurology. 2004. 62(9):1619. Park YJ, et al. Transplant Proc. 2004. 36(2):353. Zimprich A, et al. Am J Hum Genet. 2004. 74:11. Bonifati V. Lancet Neurol. 2002. 1:83. Funayama M, et al.Ann Neurol. 2002. 51:296.
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