Plexin D1 is a type I transmembrane protein that is the prototype of the Plexin D subfamily in the Plexin family. It is expressed on multiple tissues including fetal neuronal and endothelial cells. Plexin D1 expression is also induced on tumor vasculature and tumor cells. The 1879 amino acid (aa) mature human Plexin D1 contains a large (1225 aa) extracellular domain with a 500 aa sema domain and three short MRS (Met-related sequences) cysteine-rich motifs. By alternative splicing, multiple Plexin-D1 isoforms may exist. Plexin D1 binds Sema4A to suppress angiogenesis. It also binds Sema3E directly to mediate repulsive vascular vessal guidance. In mouse, this interaction has been shown to be independent of Neuropilin and Sema3A. Over the extracellular region used as immunogen, human Plexin D1 shares 89% and 91% aa identity with the mouse and canine protein, respectively.