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 the brain. Nectin 1 exists as nectin 1a and 1/HIgR, produced by alternative splicing. The cytoplasmic regions of Nectin 1a, but not Nectin 1/HIgR, 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 1, also designated HveC/ PRR1, allows the entry of herpes simplex virus type 1 (HSV-1) and HSV-2 into mammalian cells. The interaction of virus envelope glycoprotein D (gD) with nectin 1 is an essential step in the process leading to membrane fusion, the gD binding site is located at the first Ig-like domain of Nectin 1. Both the transinteraction of nectin and the interaction of nectin with afadin are necessary for their co-localization with E-cadherin and catenins at adherens junctions.
