Human DNAX accessory molecule 1 (DNAM-1/CD226) is a 65 kDa type I transmembrane glycoprotein in the immunoglobulin superfamily. Mature human DNAM-1 contains an extracellular domain (ECD) with two Ig-like C2-set domains and a cytoplasmic region that contains motifs for binding PDZ domains and band 4.1 family proteins. DNAM-1 is expressed on multiple lymphoid and myeloid cells and interacts with CD155 and CD112. Ligation of DNAM-1 promotes the activation of NK cells, CD8+ T cells, and mast cells, dendritic cell maturation, megakaryocyte and activated platelet adhesion to vascular endothelial cells, and monocyte extravasation; it inhibits the forrmation of osteoclasts. Plateletendothelium, interactions mediated by DNAM-1, enable the metastasis of tumor cells to the lung.