Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity

Cell Mol Life Sci. 2015 Feb;72(4):645-58. doi: 10.1007/s00018-014-1763-4. Epub 2014 Oct 19.


Cell-cell adhesive processes are central to the physiology of multicellular organisms. A number of cell surface molecules contribute to cell-cell adhesion, and the dysfunction of adhesive processes underlies numerous developmental defects and inherited diseases. The nectins, a family of four immunoglobulin superfamily members (nectin-1 to -4), interact through their extracellular domains to support cell-cell adhesion. While both homophilic and heterophilic interactions among the nectins are implicated in cell-cell adhesion, cell-based and biochemical studies suggest heterophilic interactions are stronger than homophilic interactions and control a range of physiological processes. In addition to interactions within the nectin family, heterophilic associations with nectin-like molecules, immune receptors, and viral glycoproteins support a wide range of biological functions, including immune modulation, cancer progression, host-pathogen interactions and immune evasion. We review current structural and molecular knowledge of nectin recognition processes, with a focus on the biochemical and biophysical determinants of affinity and selectivity that drive distinct nectin associations. These proteins and interactions are discussed as potential targets for immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cadherins / chemistry
  • Cadherins / metabolism
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism*
  • Herpesvirus 1, Human / metabolism
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunoglobulins / chemistry
  • Nectins
  • Protein Interaction Domains and Motifs
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Virus Internalization


  • Cadherins
  • Cell Adhesion Molecules
  • Immunoglobulins
  • NECTIN1 protein, human
  • Nectins
  • Protein Isoforms