Complete cDNA sequence of the fourth component of murine complement.

We have used the method of Okayama and Berg to construct cDNA clones that span the entire length of the fourth component of murine complement (C4) from mouse strain B10.WR. The cDNA sequence spans 5372 nucleotides and encodes a pre-pro-C4 molecule 1738 amino acids in length; it includes 56 and 99 untranslated bases at the 5' and 3' ends, respectively, of the C4 mRNA. The deduced pre-pro-C4 molecule includes a 19 amino acid signal peptide and two highly basic interchain regions that presumably are excised during maturation of the protein. The nucleotide sequence shows 79% identity with the human C4 cDNA sequence over the length of the protein-coding region. A comparison of the B10.WR C4 sequence with those of C4 and sex-limited protein (Slp) from mouse strain FM (i) suggests that the difference in hemolytic activity between the C4 proteins from B10.WR and FM is due to structural changes distant from both the C1 cleavage site and the internal thioester site and (ii) raises the possibility that the C4 gene from B10.WR has undergone genetic exchange with its adjoining Slp genes.