Target 48 Neurodegeneration
Gene
LRRK2
Uniprot
Q5S007
Protein
Leucine-rich repeat serine/threonine-protein kinase 2
See alternative names Dardarin
Uniprot Function Description
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). 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:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). 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). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal 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:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290).
Sample type
Recommended sample types are plasma and serum. A range of additional sample types are compatible with the technology (PEA), including citrate plasma, heparin plasma, cerebrospinal fluid, (CSF), tissue and cell lysates, fine needle biopsies, microdialysis fluid, cell culture media, dried blood spots, synovial fluid, saliva, plaque extract and microvesicles. Please note that protein expression levels are expected to vary between different sample types. Certain assays are differentially affected by interfering substances such as hemolysate. Download any of our Data Validation documents or contact support@olink.com for more information.
Precision
Precision (repeatability) is calculated from quantified data (pg/mL) within the limits of quantification: LOQ.
Analytical measuring range
The technical data reported below refers to the measured values generated during the assay validation process using recombinant antigens. Per default, Olink Target 48 products deliver data in absolute protein concentrations (pg/mL) using the Calibrator built into the system.
Sensitivity plot
The calibrator curve shown below visualizes the analytical measuring range determined during the validation process using recombinant antigen. Please note that this is shown for reference only and CANNOT be used to e.g. convert NPX values to absolute concentrations. The vertical dotted lines represent lower limit of quantification (LLOQ) and upper limit of quantification (ULOQ) respectively. The solid horizontal line indicates the limit of detection (LOD).
Sample distribution plot
The plot below shows the levels of protein measured in a number of human samples (for further information please see the Validation Data Document which can be found in the Document download center). The data is shown to give an idea of the data range to expect but cannot cover protein levels that may be seen under all potential conditions.
Plasma
Human EDTA plasma samples were acquired for assay performance evaluation. Protein values indicate range, and group comparisons should be interpreted with caution.
Cerebrospinal fluid (CSF)
Human CSF samples were acquired for assay performance evaluation. Protein values indicate range, and group comparisons should be interpreted with caution.
Biomarker Validation Data
Additional validation data, as well as a more detailed description of how the Olink panels are quality controlled can be found in our Data Validation documents – go to Document download center