IDENTIFICATION OF HIGH-MOLECULAR-WEIGHT PROTEINS WITH MULTIPLE EGF-LIKE MOTIFS BY MOTIF-TRAP SCREENING

To identify large proteins with an EGF-like-motif in a systematic mann er, we developed a computer-assisted method called motif-trap screenin g. The method exploits 5'-end single-pass sequence data obtained from a pool of cDNAs whose sizes exceed 5 kb, Using this screening procedur e, we were able to identify five known and nine new genes for proteins with multiple EGF-like-motifs from 8000 redundant human brain cDNA cl ones. These new genes were found to encode a novel mammalian homologue of Drosophila fat protein, two seven-transmembrane proteins containin g multiple cadherin and EGF-like motifs, two mammalian homologues of D rosophila slit protein, an unidentified LDL receptor-like protein, and three totally uncharacterized proteins. The organization of the domai ns in the proteins, together with their expression profiles and fine c hromosomal locations, has indicated their biological significance, dem onstrating that motif-trap screening is a powerful tool for the discov ery of new genes that have been difficult to identify by conventional methods. (C) 1998 Academic Press.