The Ra-reactive factor (RaRF) found in vertebrate sera activates the C4 and C2 components of complement. The C4/C2-activating component of mouse RaRF has been found to contain a 100-kDa serine protease called P100. In the present study, we cloned a cDNA with cDNA of mouse RaRF P100 as a probe from a human liver cDNA library. An open reading frame of 2097 nucleotides encoding a protein of 699 residues was found in the cloned cDNA of 4489 nucleotides. This protein exhibits 87.4% amino acid homology with mouse P100, and 36.4% and 37.1% homologies with that of the C1r and C1s subcomponents of human complement, respectively. The characteristic nodules and domain of C1r and C1s were highly conserved in this protein. This indicates that the P100, together with the C1r and C1s, forms a unique protein family having the same module/domain constitution.