(a) Structural features shared by plexins, semaphorins, and PRGF receptors. Plexins are divided into four subfamilies (A–D) based on sequence similarity, structural features, and tissue distribution. All plexins include a highly conserved cytoplasmic domain (SP domain, green box and oval) and, in the extracellular portion, a sema domain (yellow) and one or more MRS motifs (orange), which are also present in semaphorins and PRGF receptors. Almost 20 semaphorins are known in humans, falling into five subclasses (3 to 7). As an example, a class 4 transmembrane semaphorin is depicted. (b) Protein alignment of an MRS conserved domain. Two or three MRS repeats are found in plexins, whereas only one is present in PRGF receptors and semaphorins. The alignment shows the first MRS motif of human plexin-A1, -A3, -B1, -C1, and -D1, as well as the Drosophila plexin-A and -B, the mouse plexin-A2, and the MRSs from Sema-3F, Sema-4D, and Met. The number and the spacing of cysteine residues (yellow) are conserved.