Nucleotide sequence of complementary DNA and derived amino acid sequence of murine complement protein C3

The nucleotide sequences coding for murine complement component C3 have been determined from a cloned genomic DNA fragment and several overlapping cloned complementary DNA fragments. The amino acid sequence of the protein was deduced. The mature β and α subunits contain 642 and 993 amino acids respectively. Including a 24 amino acid signal peptide and four arginines in the β—α transition region, which are probably not contained in the mature protein, the unglycosylated single chain precursor protein preproC3 would have a molecular mass of 186484 Da and consist of 1663 amino acid residues. The C3 messenger RNA would be composed of a 56 + 2 nucleotide long 5' non-translated region, 4992 nucleotides of coding sequence, and a 3' non-translated region of 39 nucleotides, excluding the poly A tail. The β chain contains only three cysteine residues, the α chain 24, ten of which are clustered in the carboxy terminal stretch of 175 amino acids. Two potential carbohydrate attachment sites are predicted for the α chain, none for the β chain. From a comparison with human C3 cDNA sequence (of which over 80% has been determined) an extensive overall sequence homology was observed. Human and murine preproC3 would be of very similar length and share several noteworthy properties: the same order of the subunits in the precursor, the same basic residue multiplet in the β-a transition region, and a glutamine residue in the thioester region. The equivalent position of the known factor I cleavage sites in human C3a could be located in the murine C3 α chain and the size and sequence of the resulting peptide were deduced. A comparison of the amino acid sequences of murine G3 and human alpha2-macroglobulin is given. Several areas of strong sequence homology are observed, and we conclude that the two genes must have evolved from a common ancestor.