Using the polymerase chain reaction, we have isolated numerous rat and
human cDNAs of which the deduced amino acid sequences are highly homo
logous to the sequences of the extracellular domain of cadherins. The
entire putative coding sequences for two human proteins defined by two
of these cDNAs have been determined. The overall structure of these m
olecules is very similar to that of classic cadherins, but they have s
ome unique features. The extracellular domains are composed of six or
seven subdomains that are very similar to those of cadherins, but have
characteristic properties. The cytoplasmic domains, on the other hand
, have no significant homology with those of classic cadherins. Since
various cDNAs with almost identical features were obtained also from X
enopus, Drosophila and Caenorhabditis elegans, it appears that similar
molecules are expressed in a variety of organisms. We have tentativel
y named these proteins protocadherins. They are highly expressed in br
ain and their expression appears to be developmentally regulated. The
proteins expressed from the two full-length cDNAs in L cells were appr
oximately 170 or 150 kDa in size, and were localized mainly at cell-ce
ll contact sites. Moreover, the transfectants showed cell adhesion act
ivity.