Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published September 6, 1984 | public
Journal Article

Nucleotide Sequence of Complementary DNA and Derived Amino Acid Sequence of Murine Complement Protein C3

Abstract

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 186 484 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 - α transition region, and a glutamine residue in the thioester region. The equivalent position of the known factor I cleavage sites in human C3 α 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 C3 and human α_2-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.

Additional Information

© 1984 The Royal Society. This is publication number 3363IMM from the Research Institute of Scripps Clinic. This work was supported by grants numbers AI-19222 and AI-19651 from the National Institutes of Health (United States Public Health Service Grants) and Investigatorship A.H.A. 80-841 from the American Heart Association. We thank Ms Tertia Belt, Dr Michael C. Carroll and Professor Rodney R. Porter, F.R.S., for permission to screen their human liver cDNA library and for their hospitality. We thank Dr Lars Sottrup-Jensen for making the human alpha2- macroglobulin sequence available to us prior to publication, and for helpful discussions. We thank Dr Russell Doolittle for a computer comparison of C3 and alpha2-macroglobulin sequences. The Research Institute of Scripps Clinic and the Department of Immunology have provided generous support in setting up this laboratory. We thank Keith Dunn for the expert assistance with the preparation of this manuscript.

Additional details

Created:
August 19, 2023
Modified:
October 19, 2023