PIK3R4
PIK3R4, known as VPS15 or p150, is the regulatory subunit of the class III phosphatidylinositol 3-kinase complex that also contains the catalytic subunit VPS34 and BECN1. Despite a protein-kinase fold, PIK3R4 has no established lipid or protein kinase activity and functions as a scaffold: its WD40 repeats and C-terminal region bind VPS34 and BECN1, stabilizing the complex and regulating its recruitment to endosomal and autophagosomal membranes where PI3P is generated. PIK3R4 thereby controls endosome-to-Golgi trafficking, autophagy and membrane sorting. Mutations have been linked to a neurodevelopmental disorder with immunological features. Recombinant PIK3R4 supports VPS34-complex assembly and trafficking studies.
