LRRK2
Entrez ID: 120892
Full name: leucine rich repeat kinase 2
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: TKL: LRRK
Chromosomal location: 12q12
Substructure location: Gatekeeper: A-loop: G-loop: αC-helix:
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LRRK2
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed...
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). 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 (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).
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GO - Biological processes (BP):
activation of MAPK activity, activation of MAPKK activity, autophagy, calcium-mediated signaling, canonical Wnt signaling pathway, cellular protein localization, cellular response to dopamine, cellular response to manganese ion, cellular response to oxidative stress, cellular response to starvation,...
activation of MAPK activity, activation of MAPKK activity, autophagy, calcium-mediated signaling, canonical Wnt signaling pathway, cellular protein localization, cellular response to dopamine, cellular response to manganese ion, cellular response to oxidative stress, cellular response to starvation, 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, 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 hydrogen peroxide-induced cell death, negative regulation of late endosome to lysosome transport, negative regulation of macroautophagy, negative regulation of neuron death, negative regulation of neuron projection development, negative regulation of protein binding, negative regulation of protein phosphorylation, negative regulation of protein processing, negative regulation of protein processing involved in protein targeting to mitochondrion, negative regulation of protein targeting to mitochondrion, negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation, neuromuscular junction development, neuron death, 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 histone deacetylase activity, 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 phosphorylation, positive regulation of protein ubiquitination, positive regulation of synaptic vesicle endocytosis, positive regulation of tumor necrosis factor secretion, protein autophosphorylation, protein import into nucleus, protein localization to endoplasmic reticulum exit site, protein localization to mitochondrion, protein phosphorylation, reactive oxygen species metabolic process, 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 kidney size, regulation of locomotion, regulation of lysosomal lumen pH, regulation of membrane potential, regulation of mitochondrial depolarization, regulation of mitochondrial fission, regulation of neuroblast proliferation, regulation of neuron death, regulation of neuron maturation, regulation of protein kinase A signaling, regulation of protein stability, regulation of retrograde transport, endosome to Golgi, regulation of synaptic transmission, glutamatergic, regulation of synaptic vesicle exocytosis, regulation of synaptic vesicle transport, response to oxidative stress, spermatogenesis, striatum development, tangential migration from the subventricular zone to the olfactory bulb, Wnt signalosome assembly
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GO - Molecular function (MF):
actin binding, ATP binding, beta-catenin destruction complex binding, clathrin binding, co-receptor binding, GTPase activator activity, GTPase activity, GTP binding, GTP-dependent protein kinase activity, identical protein binding, ion channel binding, kinase activity, magnesium ion binding, MAP kin...
actin binding, ATP binding, beta-catenin destruction complex binding, clathrin binding, co-receptor binding, GTPase activator activity, GTPase activity, GTP binding, GTP-dependent protein kinase activity, identical protein binding, ion channel binding, kinase activity, magnesium ion binding, MAP kinase kinase activity, microtubule binding, peroxidase inhibitor activity, protein homodimerization activity, protein kinase A binding, protein kinase activity, protein serine/threonine kinase activity, receptor signaling complex adaptor activity, Rho GTPase binding, SNARE binding, syntaxin-1 binding, tubulin binding
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GO - Cellular component (CC):
cytosol, presynaptic cytosol, endoplasmic reticulum, endoplasmic reticulum exit site, endoplasmic reticulum membrane, endosome, multivesicular body, internal vesicle, extracellular exosome, extracellular space, Golgi apparatus, Golgi membrane, trans-Golgi network, autolysosome, lysosome, cytoplasmic...
cytosol, presynaptic cytosol, endoplasmic reticulum, endoplasmic reticulum exit site, endoplasmic reticulum membrane, endosome, multivesicular body, internal vesicle, extracellular exosome, extracellular space, Golgi apparatus, Golgi membrane, trans-Golgi network, autolysosome, lysosome, cytoplasmic side of mitochondrial outer membrane, mitochondrial inner membrane, mitochondrial matrix, mitochondrial membrane, mitochondrial outer membrane, mitochondrion, nucleoplasm, caveola neck, plasma membrane, amphisome, axon, cell, cell junction, cytoplasm, cytoplasmic vesicle, dendrite, dendrite cytoplasm, glutamatergic synapse, Golgi-associated vesicle, growth cone, inclusion body, intracellular membrane-bounded organelle, membrane raft, microvillus, neuron projection, neuronal cell body, perikaryon, postsynapse, ribonucleoprotein complex, synaptic vesicle membrane, terminal bouton, Wnt signalosome
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leucine rich repeat kinase 2
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A-loop
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*NOTE: the Kaplan plots were collected from OncoLnc