MOLECULAR-CLONING OF HUMAN E-CADHERIN SUGGESTS A NOVEL SUBDIVISION OFTHE CADHERIN SUPERFAMILY

The gene encoding full-length human E-cadherin has been cloned and seq uenced from liver and colon cDNA libraries (GenBank Accession #L08599) . The predicted molecular mass of the unglycosylated and unprocessed p rotein is 97,000. The human protein conserves most features of the cla ssical cadherins. In its cytoplasmic domain, two approximate to 30-35 aminoacid conserved sequence motifs are recognized. These cadherin hom ology domains have been termed ''CH2'' and ''CH3'', and are characteri stic of the classical cadherins, but absent or divergent in the more d istantly related cadherins such as desmosomal cadherin, T-cadherin, fa t, and the human ret oncogene. Given these findings and the importance of cytoplasmic interactions to cadherin function, a subclassification of the cadherin superfamily based on cytoplasmic domain homologies is proposed. This subclassification provides a framework in future studi es for understanding the distinct down-stream signaling cascades assoc iated with each cadherin. (C) 1994 Academic Press, Inc.