Leucine Rich Repeat Kinase 1 (LRRK1)

LRRK1 has a domain organization similar to that of LRRK2, with 6 N-terminal ankyrin repeats, followed by 14 leucine-rich repeats, a RAS (see HRAS)-like GTPase domain (ROC domain), a C-terminal to ROC (COR) domain, a serine/threonine kinase domain, and 7 C-terminal WD40 repeats. Highest expression of LRRK1 was in testis, placenta, prostate, and muscle, with moderate expression in brain, pancreas, small intestine, stomach, and spleen. LRRK1 underwent intramolecular, but not intermolecular, autophosphorylation. Replacement of lys1269 with trp in the ATP-binding niche of the kinase domain of LRRK1 significantly reduced autophosphorylation activity. LRRK1 also functioned as a GDP/GTP-binding protein, and its kinase activity was stimulated upon binding of GTP to the ROC domain.