CDNA CLONING, SEQUENCING AND CHROMOSOMAL ASSIGNMENT OF THE GENE FOR MOUSE COMPLEMENT FACTOR-I (C3B C4B INACTIVATOR) - IDENTIFICATION OF A SPECIES-SPECIFIC DIVERGENT SEGMENT IN FACTOR-I/

Factor I is an essential regulatory serine proteinase of the complemen t cascade. It cleaves and inactivates the C3b and C4b constituents of the C3 and C5 convertases and thereby regulates many complement-mediat ed activities. The human protein is a heterodimer composed of a 50 kDa non-catalytic subunit (which contains several domains, i.e. FIM, CD5, LDLr type A) disulfide linked to a 38 kDa catalytic subunit. Recent c haracterization of Xenopus factor I cDNA revealed a 29 residue negativ ely charged region in its heavy chain which is absent in the human pro tein (Kunnath-Muglia et al., Molec. Immun. 30, 1249-1256, 1993). We re port the complete cDNA sequence of mouse factor I as well as a partial chicken factor I cDNA sequence. Alignment of these two sequences with the published sequences for human and Xenopus proteins (a) demonstrat es an overall conservation of primary structure and domain organizatio n of mouse factor I, and (b) defines a divergent segment (D segment) i n each species. In Xenopus protein, the D segment includes the 29 resi due negatively charged region. In each of the four species examined, t he D segment differed in length, sequence, organization, and number of repeated subregions. These differences reflect a considerable evoluti on of D segment. The significance of the diversity of the D segment is at present unclear. We also report the chromosomal localization of th e mouse factor I gene (Cfi) to distal chromosome 3 near Egf.