Semaphorin 3A is one of six Class 3 secreted semaphorins which share ~40-50% aa identity. Class 3 semaphorins are potent chemo- repellents that function in axon and/or vascular guidance during development. The 772aa mouse Sema3C contains a 20aa signal sequence, an ~500aa N-terminal Sema domain that forms a b-propeller structure similar to that found in integrin molecules, a PSI domain, a furin- type cleavage site, an Ig-like domain, and a C-terminal basic domain. Covalent dimerization plus cleavage at the C-terminus are required for activity of class 3 semaphorins. The 95kD mature mouse Sema3A shares at least 95% aa identity with human, rat, equine and canine Sema3A, and 90% and 86% aa identity with chick and zebrafish Sema3A, r espectively. Type 3 semaphorins transduce signals through transmembrane plexins, either directly or by binding associated neuropilin receptors. Sema3A signaling is transduced by plexin A1-4, indirectly via neuropilin-1. Sema3A activity is mediated by small GTPases that influence actin rearrangement and integrin activity. It is important in developmental organization of central and peripheral nerves, including those in heart , lung, kidneys, bones, teeth, and visual and olfactory systems. Gradients of Sema3A repel axons, but attract dendrites. Sema3A affect vasculogenesis by inhibiting integrin function and, with Sema3F, promoting apoptosis of endothelial cells. It is thought to suppress cancer-related angiogenesis. In the immune system, Sema3A influences T cell proliferation, migration, response to activation, and interactions with dendritic cells. It negatively regulates platelet activation. Expression of Sema3A in relevant parts of the nervous system may be increased in Alzheimer's disease, multiple sclerosis, ischemia and schizophrenia.