Description
Nectins are a small family of Ca++-independent immunoglobulin (Ig)-like cell adhesion molecules (CAMs) that organize intercellular junctions. They are highly homologous to the human receptor for poliovirus, and as such have been alternately named poliovirus receptor-related proteins. The 65 kDa long isoform of human Nectin-2/CD112 (Nectin-2δ) consists of a 329 amino acid (aa) extracellular region (ECD) with three immunoglobulin-like domains, a 21 aa transmembrane segment, and a 157 aa cytoplasmic domain. Within the ECD, human Nectin-2 shares 72% aa sequence identity with mouse Nectin-2. Alternative splicing generates a short 60 kDa isoform with a 94 aa cytoplasmic tail. Nectin-2 localizes to adherens junctions between neurons, endothelial cells, epithelial cells, and fibroblasts. It forms homodimers in cis, followed by dimers in trans (between cells). It does not cis-dimerize with other Nectins but forms cis-dimers between its two splice forms. Notably, a Nectin-2 cis-dimer on one cell can heterodimerize with a Nectin-3 cis-dimer on a neighboring cell. Nectin-2 additionally binds to DNAM-1/CD226 on NK cells and triggers NK cell cytolytic activity. Nectin-2 is known to bind pseudorabies virus and herpes simplex virus-2 (HSV-2), but not HSV-1 or poliovirus. Nectin-2 is a component of cardiac intercalated discs and limits fibrosis and dysfunction resulting from pressure overload