The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (PubMed:24687852). It also mediates homodimerization and regulates kinase activity (PubMed:30635421).
The COR domain mediates homodimerization; it also mediates homotetramerization via interaction with the protein kinase domain.
The Roc domain mediates homodimerization and regulates kinase activity.
The protein expressed by the gene LRRK2 is a serine/threonine-protein kinase that phosphorylates a wide range of proteins involved in neuronal plasticity, autophagy, and vesicle trafficking. It serves as a key regulator of RAB GTPases by affecting the GTP/GDP exchange and interaction partners of RABs through phosphorylation, targeting proteins like RAB3A, RAB3B, and others. LRRK2 manages the GDP/GTP exchange for RAB8A by phosphorylating 'Thr-72', inhibiting RAB8A's interaction with GDI1/GDI2, and influencing primary ciliogenesis to enhance SHH signaling in the brain. It works with RAB29 in retromer-dependent recycling of proteins between lysosomes and the Golgi. The protein is involved in shaping neuronal morphology in the CNS, synaptic vesicle trafficking, and recruiting SEC16A to assist in ER to Golgi transport. It enhances autophagy via the CaMKK/AMPK pathway and relates to nicotinic acid adenine dinucleotide phosphate receptors and lysosomal activity. LRRK2 phosphorylates PRDX3 and APP, influencing neuron apoptosis. Independently, it inhibits MAPT degradation, fostering MAPT oligomerization. Additionally, LRRK2 possesses GTPase activity that regulates its kinase activity. This supplementary information is collated from multiple sources and compiled automatically.
Parkinson disease 8
PARK8
A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.
None
The disease is caused by variants affecting the gene represented in this entry.
Autophosphorylated at Ser-1292; autophosphorylation is stimulated by RAB29 (PubMed:28202711, PubMed:28720718, PubMed:29127255, PubMed:29212815, PubMed:30635421, PubMed:38127736). Phosphorylation of Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with YWHAG (PubMed:28202711). Phosphorylation of Ser-910 and/or Ser-935 facilitates interaction with SFN (PubMed:28202711).
Ubiquitinated by TRIM1; undergoes 'Lys-48'-linked polyubiquitination leading to proteasomal degradation.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed in neutrophils (at protein level) (PubMed:29127255). Expressed in the brain. Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.
PARK8, LRRK2, Leucine-rich repeat serine/threonine-protein kinase 2, Dardarin
Proteins
Immunology & Infectious Disease
286103Da
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