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Classical cadherins have a well conserved cytoplasmic domains. Chordate classic cadherins have an extracellular domain organization composed of five cadherin repeats. Chordate classical cadherins can be further sub-divided into type I and type II. Type I cadherins have a His-Arg-Val sequence in the N-terminal cadherin repeat. Type II cadherins are all chordate classical cadherins not in type I.

Nonchordate classic cadherins have an extracellular domain organization composed of at least two cadherin repeats. In contrast to chordates, nonchordate classic cadherins have a variable number of repeats in the extracellular domain (e.g. HMR-1 in C. elegans has 2 repeats, and DN-cadherin in Drosophila has 15 repeats). Also, they have additional domains that are inserted between the cadherin repeats and the transmembrane domain. These domains include one or two Laminin A G domains, several cysteine-rich repeats with similarity to the epidermal growth factor (EGF).

Desmosomal cadherins are expressed in desmosomes and are essential for desmosome formation. They contain 5 extracellular cadherin repeats like chordate classical cadherins. Tyrosine receptor kinase (RET) cadherins have a tyrosine kinase domain in its cytoplasmic domain. The extracellular domain contains one cadherin repeat.

Fat-like cadherins have a very large extracellular domains with many cadherin repeats (19 in CDH-3, 27 in Dachsous, 34 in Fat, hFat, and rFAT). As well, Fat, hFat, rFAT and CDH-3 contain epidermal growth factor (EGF)-like and Laminin AG-domain-like regions. These regions are localized between the cadherin and transmembrane domains. Fat-like cadherins may function in adhesion or signaling, or both.

Flamingo cadherins contain a seven-pass transmembrane receptor which shows some similarity to the secretin family of G-protein linked receptors. The large extracellular domain of Flamingo contains nine cadherin repeats, two globular laminin motifs, and four cystein-rich EGF motifs. Also present is a subdomain located between the last cadherin repeat and the first EGF domain which is highly conserved across species. This region is known as the Flamingo box.


Chordate Classic CadherinType I Classic CadherinType II Classic CadherinNon-chordate Classic CadherinDesmosomal CadherinTyrosine Kinase ReceptorFAT-like CadherinFlamingo Cadherin