Semaphorin 4D (Sema4D/CD100, previously sem J, G, or C-like 2) is a widely expressed 150kD type I transmembrane glycoprotein of the Class 4 Semaphorin family with activity in the immune and nervous systems. The 861aa Semaphorin 4D contains a 710aa extracellular domain (ECD) with a sema domain and an immunoglobulin-like domain. Within the ECD region used as an immunogen, mouse Semaphorin 4D shares 87% and 93% aa identity with human and rat Semaphorin 4D, respectively. A soluble, active 120kD form is produced proteolytically upon activation of B and T cells. Semaphorin 4D binds CD72 on B cells and dendritic cells and Plexin B1 elsewhere. In developing neurons, Semaphorin 4D assists in guidance. Semaphorin 4D is pro-angiogenic when expressed by tumor-associated macrophages.