LRRK2
Gene Information
- Official Symbol: LRRK2
- Official Name: leucine rich repeat kinase 2
- Aliases and Previous Symbols: N/A
- Entrez ID: 120892
- UniProt: Q5S007
- Interactions: BioGRID
- PubMed articles: Open PubMed
- OMIM: 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}.
Pfam Domains GO Terms
Pfam Domains
| Ras |
| LRR 4 |
| Miro |
| Pkinase Tyr |
| Pkinase |
GO Terms
| 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
Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Compound Hit
| Screen | Score |
|---|---|
| Pyrazinamide 100μM R08 exp516 | -1.81 |
Most Correlated Genes in Chemogenomics
No correlation found to any other genes in chemogenomics.
Tissues where Essential in the Avana Dataset (DepMap 20Q1)
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
Expression Distribution
LRRK2 Expression in NALM6 Cells: -5.6
