Semaphorin-4D is an 863-aa polypeptide containing a secretory signal sequence, a single transmembrane domain, an immunoglobulin (Ig)-like domain, and a conserved 500-amino acid sema domain. It was first identified as a cell surface protein of resting T cells and was the first semaphorin believed to be involved in the immune system. In addition to playing a functional role in the immune system it may also act in the nervous system. It induces B-cells to aggregate and improves their viability in vitro. It is strongly expressed in skeletal muscle, peripheral blood lymphocytes, spleen and thymus. It is expressed at lower levels in testes, brain, kidney, small intestine, prostate, heart, placenta, lung and pancreas, but not in colon or liver.