C1r and C1s are the serine proteases that form the catalytic unit of the C1 complex, the first component of complement. In the present study, we found that the genes encoding murine C1r and C1s are duplicated. One set of these genes, referred to as c1rA and c1sA, are primarily expressed in the liver and are therefore the homologues of the human C1r and C1s genes. The other two genes, termed c1rB and c1sB, are expressed exclusively in male reproductive tissues, specifically the coagulating gland and the prostate. The predicted C1rB and C1sB proteins share 96 and 93% amino acid identity with C1rA and C1sA respectively. Most of the substitutions are clustered in the serine protease domains, suggesting differences in catalytic efficiencies and/or substrate specificities or alternatively adaptation to different physiological environments. The high homology of C1rB and C1sB with C1rA and C1sA in the non-catalytic regions indicates that they are probably capable of assembling the C1 complex. The expression of alternative genes encoding isomorphs of activating components of complement in male reproductive tissues raises the possibility of new mechanisms of complement activation in the male genital tract or of novel functions for complement proteases in reproduction.
Abbreviations used: CCP, complement control protein; CS, connecting segment; CUB, C1r/C1s, sea urchin epidermal growth factor (uEGF) and human bone morphogenetic protein-1; DAF, decay accelerating factor; EST, expressed sequence tag; LPS, lipopolysaccharide; MCP, membrane cofactor protein; ORF, open reading frame; RACE, rapid amplification of cDNA ends; RT, reverse transcriptase; SP, serine protease; UTR, untranslated region.