======= LRRK2 =======
== Gene Information ==
* **Official Symbol**: LRRK2
* **Official Name**: leucine rich repeat kinase 2
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=120892|120892]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q5S007|Q5S007]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=LRRK2&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20LRRK2|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/609007|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: 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].
* **UniProt Summary**: 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. {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852}.
|Ras|
|LRR 4|
|Miro|
|Pkinase Tyr|
|Pkinase|
|negative regulation of thioredoxin peroxidase activity|
|negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation|
|regulation of thioredoxin peroxidase activity|
|peroxidase inhibitor activity|
|negative regulation of peroxidase activity|
|caveola neck|
|GTP-dependent protein kinase activity|
|Wnt signalosome assembly|
|amphisome|
|positive regulation of protein autoubiquitination|
|cytoplasmic side of mitochondrial outer membrane|
|negative regulation of protein processing involved in protein targeting to mitochondrion|
|negative regulation of late endosome to lysosome transport|
|regulation of peroxidase activity|
|negative regulation of vacuolar transport|
|beta-catenin destruction complex binding|
|regulation of protein processing involved in protein targeting to mitochondrion|
|multivesicular body, internal vesicle|
|regulation of CAMKK-AMPK signaling cascade|
|regulation of late endosome to lysosome transport|
|regulation of retrograde transport, endosome to Golgi|
|regulation of vacuolar transport|
|positive regulation of dopamine receptor signaling pathway|
|regulation of protein autoubiquitination|
|regulation of kidney size|
|regulation of branching morphogenesis of a nerve|
|negative regulation of protein targeting to mitochondrion|
|positive regulation of histone deacetylase activity|
|tangential migration from the subventricular zone to the olfactory bulb|
|positive regulation of synaptic vesicle endocytosis|
|regulation of synaptic vesicle transport|
|protein localization to endoplasmic reticulum exit site|
|positive regulation of deacetylase activity|
|negative regulation of establishment of protein localization to mitochondrion|
|positive regulation of microglial cell activation|
|autolysosome|
|regulation of histone deacetylase activity|
|positive regulation of synaptic vesicle recycling|
|intracellular distribution of mitochondria|
|regulation of neuron maturation|
|negative regulation of excitatory postsynaptic potential|
|neuron projection arborization|
|regulation of deacetylase activity|
|regulation of dopamine receptor signaling pathway|
|positive regulation of cellular response to drug|
|regulation of lysosomal lumen pH|
|Wnt signalosome|
|cellular response to manganese ion|
|locomotory exploration behavior|
|co-receptor binding|
|negative regulation of autophagosome assembly|
|presynaptic cytosol|
|positive regulation of neuroinflammatory response|
|positive regulation of nitric-oxide synthase biosynthetic process|
|regulation of synaptic vesicle endocytosis|
|negative regulation of response to reactive oxygen species|
|regulation of ER to Golgi vesicle-mediated transport|
|negative regulation of hydrogen peroxide-induced cell death|
|mitochondrion distribution|
|MAP kinase kinase activity|
|determination of adult lifespan|
|Golgi-associated vesicle|
|regulation of microglial cell activation|
|positive regulation of histone deacetylation|
|striatum development|
|response to manganese ion|
|inclusion body|
|regulation of nitric-oxide synthase biosynthetic process|
|regulation of protein kinase A signaling|
|positive regulation of tumor necrosis factor secretion|
|negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|negative regulation of cellular response to drug|
|regulation of mitochondrial depolarization|
|receptor signaling complex adaptor activity|
|positive regulation of protein deacetylation|
|regulation of hydrogen peroxide-induced cell death|
|regulation of mitochondrial fission|
|regulation of cell maturation|
|negative regulation of oxidoreductase activity|
|regulation of synaptic vesicle recycling|
|positive regulation of macrophage activation|
|regulation of cytoplasmic transport|
|subpallium development|
|GTP metabolic process|
|protein kinase A binding|
|negative regulation of nervous system process|
|exploration behavior|
|syntaxin-1 binding|
|negative regulation of response to drug|
|regulation of histone deacetylation|
|regulation of tumor necrosis factor secretion|
|endoplasmic reticulum exit site|
|Rho GTPase binding|
|dendrite cytoplasm|
|positive regulation of response to drug|
|regulation of neuroinflammatory response|
|regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|regulation of neuroblast proliferation|
|olfactory bulb development|
|negative regulation of protein maturation|
|negative regulation of protein processing|
|negative regulation of macroautophagy|
|olfactory lobe development|
|regulation of response to reactive oxygen species|
|multicellular organism aging|
|regulation of autophagosome assembly|
|regulation of cellular response to drug|
|negative regulation of organelle assembly|
|clathrin binding|
|modulation of excitatory postsynaptic potential|
|guanosine-containing compound metabolic process|
|negative regulation of intracellular protein transport|
|neuromuscular junction development|
|regulation of vacuole organization|
|regulation of dendritic spine morphogenesis|
|regulation of protein deacetylation|
|negative regulation of response to endoplasmic reticulum stress|
|regulation of protein targeting to mitochondrion|
|regulation of membrane depolarization|
|negative regulation of cellular response to oxidative stress|
|negative regulation of oxidative stress-induced cell death|
|mitochondrion localization|
|negative regulation of GTPase activity|
|negative regulation of response to oxidative stress|
|terminal bouton|
|regulation of macrophage activation|
|neuron death|
|negative regulation of mitochondrion organization|
|activation of MAPKK activity|
|tubulin binding|
|endoplasmic reticulum organization|
|regulation of morphogenesis of a branching structure|
|telencephalon cell migration|
|lytic vacuole organization|
|lysosome organization|
|purine ribonucleoside triphosphate metabolic process|
|negative regulation of intracellular transport|
|negative regulation of synaptic transmission|
|forebrain cell migration|
|purine ribonucleoside metabolic process|
|microvillus|
|regulation of oxidative stress-induced cell death|
|excitatory postsynaptic potential|
|purine nucleoside metabolic process|
|regulation of stem cell proliferation|
|SNARE binding|
|regulation of protein processing|
|ribonucleoside triphosphate metabolic process|
|chemical synaptic transmission, postsynaptic|
|purine nucleoside triphosphate metabolic process|
|synaptic vesicle membrane|
|regulation of protein maturation|
|regulation of synaptic transmission, glutamatergic|
|regulation of mitochondrial membrane potential|
|regulation of establishment of protein localization to mitochondrion|
|regulation of dendritic spine development|
|regulation of cellular response to oxidative stress|
|ribonucleoside metabolic process|
|protein localization to mitochondrion|
|regulation of synaptic vesicle exocytosis|
|kinase activity|
|peptidyl-threonine phosphorylation|
|positive regulation of proteasomal ubiquitin-dependent protein catabolic process|
|regulation of protein targeting|
|postsynapse|
|negative regulation of autophagy|
|regulation of response to endoplasmic reticulum stress|
|regulation of intracellular pH|
|kidney morphogenesis|
|regulation of response to oxidative stress|
|cellular response to dopamine|
|positive regulation of tumor necrosis factor production|
|response to dopamine|
|regulation of neural precursor cell proliferation|
|positive regulation of tumor necrosis factor superfamily cytokine production|
|canonical Wnt signaling pathway|
|regulation of dendrite morphogenesis|
|regulation of cellular pH|
|peptidyl-threonine modification|
|positive regulation of histone modification|
|nucleoside triphosphate metabolic process|
|positive regulation of protein binding|
|negative regulation of intrinsic apoptotic signaling pathway|
|regulation of oxidoreductase activity|
|protein import into nucleus|
|regulation of postsynapse organization|
|regulation of calcium-mediated signaling|
|positive regulation of ubiquitin-dependent protein catabolic process|
|regulation of pH|
|regulation of response to drug|
|positive regulation of endocytosis|
|regulation of postsynaptic membrane potential|
|cellular response to catecholamine stimulus|
|cellular response to monoamine stimulus|
|mitochondrial membrane|
|negative regulation of protein binding|
|positive regulation of chromatin organization|
|positive regulation of proteasomal protein catabolic process|
|regulation of neurotransmitter secretion|
|response to catecholamine|
|response to monoamine|
|nucleoside metabolic process|
|cellular monovalent inorganic cation homeostasis|
|negative regulation of cellular protein localization|
|regulation of synaptic vesicle cycle|
|reactive oxygen species metabolic process|
|import into nucleus|
|positive regulation of protein ubiquitination|
|positive regulation of autophagy|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|ion channel binding|
|growth cone|
|vacuole organization|
|cellular response to ammonium ion|
|Golgi organization|
|positive regulation of protein modification by small protein conjugation or removal|
|glycosyl compound metabolic process|
|perikaryon|
|protein localization to endoplasmic reticulum|
|regulation of nervous system process|
|positive regulation of inflammatory response|
|positive regulation of cytokine secretion|
|monovalent inorganic cation homeostasis|
|positive regulation of cellular protein catabolic process|
|protein import|
|regulation of neurotransmitter transport|
|positive regulation of canonical Wnt signaling pathway|
|calcium-mediated signaling|
|regulation of histone modification|
|regulation of tumor necrosis factor production|
|regulation of dendrite development|
|cellular response to starvation|
|regulation of tumor necrosis factor superfamily cytokine production|
|regulation of ubiquitin-dependent protein catabolic process|
|negative regulation of neuron projection development|
|ribonucleoprotein complex|
|activation of MAPK activity|
|regulation of intrinsic apoptotic signaling pathway|
|protein localization to nucleus|
|mitochondrial outer membrane|
|regulation of regulated secretory pathway|
|negative regulation of binding|
|trans-Golgi network|
|regulation of macroautophagy|
|peptidyl-serine phosphorylation|
|positive regulation of chromosome organization|
|positive regulation of Wnt signaling pathway|
|positive regulation of binding|
|regulation of mitochondrion organization|
|negative regulation of cell projection organization|
|negative regulation of protein transport|
|regulation of proteasomal protein catabolic process|
|response to ammonium ion|
|negative regulation of establishment of protein localization|
|regulation of chromatin organization|
|cellular response to metal ion|
|response to starvation|
|protein autophosphorylation|
|locomotory behavior|
|peptidyl-serine modification|
|regulation of protein ubiquitination|
|regulation of cytokine secretion|
|regulation of endocytosis|
|negative regulation of neuron death|
|magnesium ion binding|
|positive regulation of protein catabolic process|
|regulation of proteolysis involved in cellular protein catabolic process|
|regulation of synapse organization|
|regulation of protein binding|
|regulation of organelle assembly|
|cellular response to inorganic substance|
|regulation of exocytosis|
|membrane raft|
|negative regulation of neuron differentiation|
|negative regulation of apoptotic signaling pathway|
|regulation of synapse structure or activity|
|regulation of protein modification by small protein conjugation or removal|
|regulation of intracellular protein transport|
|cellular response to nutrient levels|
|protein kinase activity|
|microtubule binding|
|cellular response to oxidative stress|
|regulation of cellular protein catabolic process|
|lysosome|
|negative regulation of cellular catabolic process|
|cytoplasmic vesicle|
|telencephalon development|
|autophagy|
|positive regulation of MAP kinase activity|
|process utilizing autophagic mechanism|
|nucleocytoplasmic transport|
|cellular response to extracellular stimulus|
|nuclear transport|
|kidney development|
|actin binding|
|positive regulation of protein secretion|
|endosome|
|synapse organization|
|aging|
|regulation of canonical Wnt signaling pathway|
|GTPase activator activity|
|renal system development|
|regulation of protein stability|
|positive regulation of peptide secretion|
|negative regulation of neurogenesis|
|axon|
|regulation of cell morphogenesis involved in differentiation|
|negative regulation of catabolic process|
|regulation of neuron death|
|negative regulation of nervous system development|
|purine ribonucleotide metabolic process|
|urogenital system development|
|neuron projection|
|ribonucleotide metabolic process|
|activation of protein kinase activity|
|GTPase activity|
|purine nucleotide metabolic process|
|regulation of autophagy|
|negative regulation of cell development|
|cellular response to external stimulus|
|ribose phosphate metabolic process|
|second-messenger-mediated signaling|
|regulation of inflammatory response|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|glutamatergic synapse|
|regulation of chromosome organization|
|regulation of intracellular transport|
|negative regulation of proteolysis|
|regulation of neurotransmitter levels|
|cell-cell signaling by wnt|
|positive regulation of proteolysis|
|Wnt signaling pathway|
|regulation of Wnt signaling pathway|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|purine-containing compound metabolic process|
|mitochondrial matrix|
|response to metal ion|
|MAPK cascade|
|neuronal cell body|
|negative regulation of organelle organization|
|regulation of binding|
|regulation of protein catabolic process|
|response to oxidative stress|
|forebrain development|
|GTP binding|
|signal transduction by protein phosphorylation|
|mitochondrial inner membrane|
|regulation of apoptotic signaling pathway|
|cellular response to drug|
|positive regulation of secretion by cell|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|positive regulation of GTPase activity|
|positive regulation of cell activation|
|endomembrane system organization|
|dendrite|
|chemical synaptic transmission|
|anterograde trans-synaptic signaling|
|positive regulation of protein transport|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of membrane potential|
|establishment of protein localization to organelle|
|positive regulation of catabolic process|
|positive regulation of secretion|
|trans-synaptic signaling|
|mitochondrion organization|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|negative regulation of phosphorylation|
|nucleotide metabolic process|
|positive regulation of cytokine production|
|nucleoside phosphate metabolic process|
|negative regulation of hydrolase activity|
|positive regulation of establishment of protein localization|
|synaptic signaling|
|regulation of protein secretion|
|positive regulation of defense response|
|neuron projection morphogenesis|
|regulation of GTPase activity|
|plasma membrane bounded cell projection morphogenesis|
|negative regulation of transport|
|regulation of cell morphogenesis|
|cell projection morphogenesis|
|regulation of peptide secretion|
|regulation of neuron projection development|
|response to nutrient levels|
|negative regulation of intracellular signal transduction|
|cell part morphogenesis|
|regulation of anatomical structure size|
|regulation of protein serine/threonine kinase activity|
|response to extracellular stimulus|
|positive regulation of protein kinase activity|
|response to inorganic substance|
|regulation of cellular protein localization|
|nucleobase-containing small molecule metabolic process|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|spermatogenesis|
|cell junction|
|regulation of vesicle-mediated transport|
|endocytosis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|male gamete generation|
|behavior|
|positive regulation of kinase activity|
|organelle localization|
|regulation of system process|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|positive regulation of organelle organization|
|cellular cation homeostasis|
|regulation of cell activation|
|cellular ion homeostasis|
|positive regulation of programmed cell death|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|import into cell|
|intracellular membrane-bounded organelle|
|gamete generation|
|regulation of cytokine production|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|negative regulation of cellular component organization|
|cation homeostasis|
|regulation of protein transport|
|regulation of cell projection organization|
|negative regulation of cell differentiation|
|inorganic ion homeostasis|
|cell morphogenesis|
|regulation of proteolysis|
|regulation of cellular response to stress|
|protein localization to organelle|
|regulation of peptide transport|
|brain development|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|positive regulation of hydrolase activity|
|head development|
|ion homeostasis|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|regulation of secretion|
|neuron development|
|regulation of neurogenesis|
|cellular component morphogenesis|
|multicellular organismal reproductive process|
|sexual reproduction|
|regulation of cellular catabolic process|
|multicellular organism reproduction|
|regulation of kinase activity|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|organophosphate metabolic process|
|negative regulation of apoptotic process|
|cellular homeostasis|
|negative regulation of programmed cell death|
|regulation of cellular localization|
|response to organic cyclic compound|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|animal organ morphogenesis|
|regulation of cellular component biogenesis|
|cell migration|
|protein phosphorylation|
|regulation of transferase activity|
|central nervous system development|
|regulation of locomotion|
|Golgi apparatus|
|positive regulation of transport|
|negative regulation of cell death|
|multi-organism reproductive process|
|regulation of catabolic process|
|intracellular protein transport|
|response to organonitrogen compound|
|endoplasmic reticulum|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|response to drug|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|carbohydrate derivative metabolic process|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|identical protein binding|
|cell motility|
|localization of cell|
|response to nitrogen compound|
|cell death|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|cell projection organization|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|locomotion|
|negative regulation of cell communication|
|negative regulation of signaling|
|nervous system process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|protein transport|
|intracellular transport|
|generation of neurons|
|peptide transport|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|amide transport|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|homeostatic process|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|nitrogen compound transport|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|system process|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp516|Pyrazinamide 100μM R08 exp516]]|-1.81|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 6392
* **Expression level (log2 read counts)**: -5.6
{{:chemogenomics:nalm6 dist.png?nolink |}}