THE ORGANIZATION OF THE HUMAN-COMPLEMENT FACTOR-I GENE (IF) - A MEMBER OF THE SERINE-PROTEASE GENE FAMILY

The human complement factor I gene (IF) was cloned from a how-sorted c osmid library. The gene spans 63 kb and comprises 13 exons. The first exon, which encodes the leader sequence and 5' untranslated region, is separated from the body of the gene by a large intron of 36 kb. Facto r I is a mosaic protein, and there is a correlation between the genomi c organization and the modular structure of the protein. The second ex on encodes a module found only in complement C6 and C7 (FI/C6/C7); the third and fourth exons encode a single CD5 domain; and the fifth and sixth exons each encode a low-density Lipoprotein receptor module. Two very small exons, 21 and 36 bp, then separate the first six exons fro m the last five that encode the serine protease domain of factor I. Wi thin the serine protease gene family factor I has a unique genomic str ucture, but it bears a much closer resemblance to trypsin than it does to the other complement system serine proteases, factor B, C2, and C1 r/C1s. (C) 1994 Academic Press,Inc.