Semaphorin-6A (SEMA6A) (SEMA6A)

Semaphorin-6A (SEMA6A) is a transmembrane protein belonging to the class 6 semaphorin family, primarily recognized for its role as a chemorepellent in axon guidance and neuronal migration during central nervous system development. It functions as a ligand for Plexin-A2 and Plexin-A4 receptors, triggering signaling cascades that reorganize the actin cytoskeleton through interactions with molecules like Mical1 and RhoA. Beyond its neurobiological functions, SEMA6A is a critical regulator of angiogenesis, where it modulates the expression and activity of vascular endothelial growth factor receptor 2 (VEGFR2) to influence endothelial cell survival. In oncology, SEMA6A exhibits a complex role, often promoting tumor progression and drug resistance in melanoma and hepatocellular carcinoma, while acting as a tumor suppressor in lung cancer. As a potential gene therapy payload, SEMA6A is being explored for its ability to enhance post-ischemic recovery or to inhibit pathological angiogenesis in various disease models. Currently, there are no approved drugs targeting SEMA6A, but research into viral vector-mediated delivery and neutralizing antibodies is ongoing.

Other names

Semaphorin VIASema VIASEMA6A1SEMAQHT018KIAA1368Semaphorin-Q

SEMA6A acts as a ligand for Plexin-A2 and Plexin-A4 receptors to initiate intracellular signaling. It regulates the expression and signaling of VEGFR2 in endothelial cells to promote survival and angiogenesis. Additionally, it modulates the actin cytoskeleton through interactions with Mical1 and RhoA-dependent pathways.