Plexins are type 1 transmembrane (TM) receptors acting as key regulatory proteins in a wide variety of developmental, regenerative and pathological processes. They are involved in guidance and motility of vascular, lymphatic vessel, and neuron growth, and in cancer metastasis.

Plexin family includes 9 proteins: Plexin-A1-4, -B1-3, -C1 and -D1. Class A Plexins interact with the secreted class 3 Semaphorins, and require Neuropilins (nrps) as co-receptors.

Plexin protein signaling results in cytosolic GTPase-activating 

protein activity including direct interactions with Rho GTPases and transient/catalytic interactions with Ras GTPases^1,2.

Plexin structure consists of an extracellular semaphorin domain, three Plexin-Semaphorin-Integrin (PSI) domains, and three immunoglobulin, Plexin, and transcription factor (IPT) domains. In addition, a single-spanning transmembrane domain, and a cytosolic region (CYTO) homologous with Ras GTPase-activating proteins (GAPs)². The transmembrane region of Plexin-A3 is characterized by poly-glycine usually used for close helix-helix packing and aromatic residues that distort helix conformation and association. Plexin-A family members only have 22 residues spanning the membrane¹_.

Mutations in Plexins have been reported in melanoma, lung, breast, pancreatic, and prostate cancers, strongly suggesting that their signaling may play a role in cancer development. Plexins are widely expressed in the nervous system and in the developing cerebral cortex².