Regulation of Expression and Function of Type I Classical Cadherins

The cadherin superfamily is made of transmembrane glycoproteins involved in calcium-dependent cell-cell adhesion and cell-cell recognition (reviewed in Gul et al. 2015). The human type I subfamily of classical cadherins includes CDH1 (E-cadherin), CDH2 (N-cadherin), CDH3 (P-cadherin), CDH4 (R-cadherin), and CDH15 (M-cadherin) (reviewed in Gul et al. 2015). Like other classical cadherins, Type I cadherins possess five extracellular cadherin domains (EC1-5), which drive cell-cell adhesion through formation of trans-dimers, usually trans-homodimers (also known as homotypic dimers), between two identical cadherin molecules expressed on plasma membranes on two adjacent cells (reviewed in Brasch et al. 2012). Type I classical cadherins contain a conserved tryptophan residue at the second position of their EC1 domain, while Type II cadherins contain two conserved tryptophan residues at positions 2 and 4 of their EC1 domain (reviewed in Brasch et al. 2012). These tryptophan residues directly participate in formation of cadherin trans-dimers (reviewed in Brasch et al. 2012). Type I cadherin also contain a conserved diproline motif, with two proline residues at position 5 and 6 of their EC1 domain (reviewed in Brasch et al. 2012). The diproline motif increases the specificity of Type I cadherins for binding identical cadherin molecules, thus favoring formation of homotypic dimers, while Type II cadherins also engage in formation of heterotypic dimers (reviewed in Brasch et al. 2012).

Summary from Reactome (R-HSA-9764274), read 2026-09-23.