Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3)

Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3) is a multi-domain, ER- and plasma membrane-localized protein that facilitates non-vesicular lipid transfer and lipid signaling, particularly phosphatidylinositol and phosphatidic acid, at membrane contact sites[1][3]. It acts as a receptor that binds CCL18, enabling cancer cell migration and metastasis via PTK2B phosphorylation. PITPNM3 is implicated in several cancers as a metastasis-promoting gene and is mutated in hereditary retinal diseases like cone-rod dystrophy 5[2][3]. Its structure includes FFAT, DDHD, and LNS2 domains involved in membrane targeting and protein-protein interactions, with multiple transcript variants encoding different isoforms[1]. Experimental drug inhibitors have started to target PITPNM3, blocking its oncogenic signaling without major cytotoxicity[2].

Other names

NIR1PITPnm3NIR-1RDGBA3ACKR6Phosphatidylinositol transfer protein, membrane-associated 3Cone rod dystrophy 5Retinal degeneration B alpha 3Pyk2 N-terminal domain-interacting receptor 1Atypical chemokine receptor 6CORD5

Inhibition of PITPNM3 disrupts PTK2B phosphorylation and downstream signaling involved in cancer cell migration and invasion[2]