Summary: A family of proteins that mediate AXONAL GUIDANCE. Semaphorins act as repulsive cues for neuronal GROWTH CONES and bind to receptors on their filopodia. At least 20 different molecules have been described and divided into eight classes based on domain organization and species of origin. Classes 1 and 2 are invertebrate, classes 3-7 are vertebrate, and class V are viral. Semaphorins may be secreted (classes 2, 3, and V), transmembrane (classes 1, 4, 5, and 6), or membrane-anchored (class 7). All semaphorins possess a common 500-amino acid extracellular domain which is critical for receptor binding and specificity, and is also found in plexins and scatter factor receptors. Their C termini are class-specific and may contain additional sequence motifs.