Nectins are a small family of Ca++independent immunoglobulin (Ig)-like cell adhesion molecules (CAMs) that organize intercellular junctions. The Nectin family has at least four members, all of which show alternate splicing (except for Nectin-4), a transmembrane (TM) region (except for Nectin-1 gamma), and three extracellular Ig-domains. Nectin-2 is a 60 or 65 kDa type I transmembrane (TM) glycoprotein that is found on a variety of cell types. It has two splice forms. Nectin-2 delta is a 65 kDa long form and is synthesized as a 538 amino acid precursor. It contains a 31 amino acid (aa) signal sequence, a 329 aa extracellular region, a 21 aa TM segment, and a 157 aa cytoplasmic domain. The extracellular region contains one N terminal 85 aa V-type Ig domain and two 45-55 aa C2-type Ig domains. The V-domain is believed to mediate Nectin binding to its ligands. The short, 60 kDa isoform of Nectin-2 (Nectin-2 alpha) has the same signal sequence and extracellular domain as Nectin-2 delta, but differs in the TM and cytoplasmic region. In this case, the cytoplasmic tail is only 94 aa in length. Nectin-2 is known to bind the pseudorabies virus, and herpes simplex virus2 (HSV2), but not HSV1. As a cell adhesion molecule, Nectin-2 will form cis-homodimers (same cell), followed by trans-dimers (across cells). Nectin-2 will not cis-dimerize with other Nectins, but will cis-dimerize with its two splice forms. Notably, a Nectin-2 cis-dimer on one cell will heterodimerize with a Nectin-3 cis-dimer on another cell. Nectin-2 is found concentrated in adherens junctions, and exists on neurons, endothelial cells, epithelial cells and fibroblasts.