Nectin is a Ca2+-independent homophilic cell adhesion molecule that belongs to the immunoglobulin superfamily. Human Nectin is identical to the poliovirus receptor-related protein (PRR) and is identified to be the alphaherpesvirus entry mediator. Nectin constitutes a family consisting of at least Nectin 1, 2 and 3. Nectin 2 and 3 are ubiquitously expressed, whereas Nectin 1 is abundantly expressed in brain. Nectin 3, also designated as PRR3, has three splicing variants: Nectin 3α, 3β and 3γ. Nectin 3 is a transmembrane protein whose extracellular region contains three Ig-like domains. Nectin 3α and 3β, but not Nectin 3γ, have a C-terminal conserved motif (E/A-X-Y-V). This motif interacts with the PDZ domain of the F-Actin-binding protein, afadin, through which it is linked to the Actin cytoskeleton. Nectin 3α co-localizes with Nectin 2 at cadherin-based adheren junctions and interacts with afadin.