Summary

Name LRRK2
Full Name Leucine-rich repeat serine/threonine-protein kinase 2
Synonyms Dardarin | PARK8
Primary ID Q5S007
Links - -
Type protein
Relations 34
Pathways Parkinson
Function 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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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation SNCA 0.651
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ img/unknown.png phosphorylation LRRK2 0.2
Publications: 3 Organism: Homo Sapiens
Pathways:Parkinson
+ down-regulates activity img/direct_inhibition.png phosphorylation LRRK2 0.415
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation LRRK2 0.2
Publications: 5 Organism: Homo Sapiens
Pathways:Parkinson
+ up-regulates img/direct-activation.png phosphorylation AKT 0.388
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AKT1 0.388
Publications: 2 Organism: Homo Sapiens
Pathways:Parkinson
+ down-regulates img/direct_inhibition.png phosphorylation SH3GL2 0.487
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SNAPIN 0.534
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation ARHGEF7 0.47
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PRDX3 0.425
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LRRK2 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Parkinson
+ up-regulates activity img/direct-activation.png phosphorylation MSN 0.574
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RAB8A 0.339
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation RAB10 0.338
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation ARFGAP1 0.603
Publications: 2 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png binding LRRK2 0.47
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding LRRK2 0.603
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates quantity img/indirect-activation.png transcriptional regulation CADPS2 0.3
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding DVL3 0.495
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.549
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png Autophagy 0.7
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SH3GL1 0.481
Publications: 1 Organism: Homo Sapiens