| Research Abstract |
Immunoglobulin(Ig)-, fibronectin type Ill(FN-Ill)-, and cadhefin-related sequences are often found in multiple repeats in the extracellular regions of cell adhesion molecules. The amino acid sequences of 82 different cadherin-like repeats from 13 known members of the cadhefin superfamily were compared for six highly conserved regions, and a frequency matrix represented as amino acids versus position matrix was calculated based on the alignment. Using the frequency matrix, further members of the cadhefin superfamily were searched in protein database. It was found that the ret protein, a receptor protein tyrosine kinase, contains cadherin-like repeats in the extracellular region. A similar analysis was also carried out for the FN-Ill superfamily. Nine receptor protein tyrosine kinases were shown to exhibit significant similarities in sequence with known FN-Ill-like repeats. Several receptor protein tyrosine kinases have already been reported to have Ig-like repeats in their extracellular regions. Thus these receptor protein tyrosine kinases, together with the remaining receptors whose structures are not yet characterized, are possible to be classified into at least four distinct groups based on the structural differences in the extracellular domains. This classification was also supported from an evolutional viewpoint : A molecular phylogenetic tree inferred from the shared kinase domains revealed a close relationship between the branching patterns in tree and the grouping based on the structural differences.
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