ISOLATION AND SEQUENCING OF CDNAS FOR PROTEINS WITH MULTIPLE DOMAINS OF GLY-XAA-YAA REPEATS IDENTIFY A DISTINCT FAMILY OF COLLAGENOUS PROTEINS

We have isolated overlapping mouse cDNAs encoding a collagenous polype ptide that we have designated alpha 1(XVIII) collagen. Nucleotide sequ ence analysis shows that alpha 1(XVIII) collagen contains 10 triple-he lical domains separated and flanked by non-triple-helical regions. Wit hin the non-triple helical regions, there are several Ser-Gly-containi ng sequences that conform to consensus sequences for glycosaminoglycan attachment sites in proteoglycan core proteins. Northern blots show t hat alpha 1(XVIII) transcripts are present in multiple organs, with th e highest levels in liver, lung, and kidney. We have also isolated ove rlapping cDNAs encoding human alpha 1(XV) collagen, and their sequence extends a published partial alpha 1(XV) sequence to the 3' end. Compa rison of the alpha 1(XV) and alpha 1(XVIII) sequences reveals a striki ng similarity in the lengths of the six most carboxyl-terminal triple- helical domains. In addition, within the carboxyl non-triple-helical d omain NC1 of the two chains, a region of 177 amino acid residues shows about 60% identity at the amino acid level. We suggest, therefore, th at alpha 1(XV) and alpha 1(XVIII) collagens are structurally related. Their structure is different from that of other known collagen types. We conclude that they belong to a subfamily of extracellular matrix pr oteins and we suggest the designation multiplexins (for protein with m ultiple triple-helix domains and interruptions) for members of this su bfamily.