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Cadherin definitions


Defining the cadherin superfamily

Definitions prepared by Frans Van Roy and Paco Hulpiau (Feb 2010):

Cadherins are calcium-dependent transmembrane proteins that generally mediate cell-cell adhesion or cell-cell recognition and are characterized by the presence of at least two consecutive extracellular cadherin-specific motifs, called cadherin repeats, with conserved calcium-binding amino acid residues.

The cadherin superfamily can be phylogenetically divided into three major families: the major cadherin family, the protocadherin family and the cadherin-related family.

All members of the major cadherin (CDH) gene family encode proteins with an ectodomain comprising at least five consecutive cadherin repeats showing high sequence conservation within the family. The family includes the “classical” type I and type II cadherin genes, encoding proteins with a single transmembrane domain and a cytoplasmic domain containing two conserved motifs for binding to members of the armadillo protein family. Further, the family includes type-III, type-IV and desmosomal cadherins, often encoding longer ectodomains with additional motifs, a single transmembrane domain and a cytoplasmic domain containing at least one conserved motif for armadillo protein binding. Finally, the family includes Flamingo/CELSR genes encoding proteins, which typically have a longer ectodomain, a seven-pass membrane domain and an unrelated cytoplasmic domain compared to other cadherins. These subfamilies are phylogenetically grouped together in one major cadherin branch.

The protocadherin (PCDH) gene family encodes proteins with an ectodomain comprising six or seven cadherin repeats with high sequence conservation within the family and weaker homology to the cadherin repeats of members of the major cadherin family. Further, protocadherins have a single transmembrane domain and a distinct, protocadherin-specific, cytoplasmic domain. Protocadherins can be further subdivided into clustered and non-clustered protocadherins on the basis of particular genomic organizations.

The cadherin-related (CDHR) genes do not fit into the above two families as they are phylogenetically clearly separated. The encoded proteins comprise at least two typical, consecutive cadherin motifs, but often more than the typical members of the cadherin and protocadherin families. Their overall domain organization differs from the members of the major cadherin family and the protocadherin family, and includes different and unique cytoplasmic domains.


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