LRRK2 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. Plays an important role in recuiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. 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. 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 mouse Ortholog: 15|15 E3
Cellular Component:  amphisome; autolysosome; axon; basolateral plasma membrane; caveola neck; cell projection; cytoplasm; cytoplasmic side of mitochondrial outer membrane; cytoplasmic vesicle; cytoskeleton; 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; membrane; membrane raft; microvillus; mitochondrial inner membrane; mitochondrial matrix; mitochondrial membrane; mitochondrial outer membrane; mitochondrion; multivesicular body, internal vesicle; neuron projection; neuronal cell body; perikaryon; plasma membrane; presynaptic cytosol; ribonucleoprotein complex; synapse; synaptic vesicle; 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; hydrolase activity; identical protein binding; JUN kinase kinase kinase activity; kinase activity; magnesium ion binding; MAP kinase kinase kinase activity; nucleotide binding; peroxidase inhibitor activity; protein binding; protein homodimerization activity; protein kinase A binding; protein kinase activity; protein serine/threonine kinase activity; protein-containing complex binding; signaling receptor binding; signaling receptor complex adaptor activity; small GTPase binding; SNARE binding; syntaxin-1 binding; transferase activity; transmembrane transporter binding; tubulin binding
Biological Process:  autophagy; calcium-mediated signaling; cell differentiation; cellular response to dopamine; cellular response to manganese ion; cellular response to organic cyclic compound; cellular response to oxidative stress; cellular response to reactive oxygen species; cellular response to starvation; cellular response to tumor necrosis factor; 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; JNK cascade; 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 macroautophagy; negative regulation of neuron projection development; negative regulation of NF-kappaB transcription factor activity; negative regulation of protein binding; negative regulation of protein phosphorylation; negative regulation of protein processing; negative regulation of protein targeting to mitochondrion; negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation; neuromuscular junction development; 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 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 kinase activity; positive regulation of protein phosphorylation; positive regulation of protein ubiquitination; positive regulation of synaptic vesicle endocytosis; positive regulation of tumor necrosis factor production; protein autophosphorylation; protein import into nucleus; protein localization; protein localization to endoplasmic reticulum exit site; protein phosphorylation; 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 gene expression; regulation of kidney size; regulation of locomotion; regulation of lysosomal lumen pH; regulation of membrane potential; regulation of mitochondrial depolarization; regulation of neuroblast proliferation; regulation of neuron death; regulation of neuron maturation; regulation of protein kinase A signaling; regulation of protein stability; regulation of reactive oxygen species metabolic process; regulation of retrograde transport, endosome to Golgi; regulation of synaptic transmission, glutamatergic; regulation of synaptic vesicle endocytosis; regulation of synaptic vesicle exocytosis; regulation of synaptic vesicle transport; response to oxidative stress; synaptic vesicle recycling; tangential migration from the subventricular zone to the olfactory bulb; Wnt signalosome assembly
Reference #:  Q5S006 (UniProtKB)
Alt. Names/Synonyms: 4921513O20Rik; 9330188B09Rik; AW561911; cI-4; cI-46; D630001M17Rik; Gm927; leucine-rich repeat kinase 2; Leucine-rich repeat serine/threonine-protein kinase 2; Lrrk2; OTTMUSP00000022827
Gene Symbols: Lrrk2
Molecular weight: 284,732 Da
Basal Isoelectric point: 6.38  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein