Mutational Analysis of the Human Protein C Gene
The single gene for protein C is located at position q13–q14 on chromosome 2 (1). Two groups have described human genomic clones of protein C isolated from phage l charon libraries using cDNA for human protein C as hybridization probes (2,3). The gene is approximately 11 kb long and is composed of 9 exons and 8 introns. In common with factors VII, IX and X the exons encode specific structural domains of the protein C molecule. Exon 1 encodes the 5′ untranslated region, exon 2 encodes the signal peptide and 6 amino acids of the propeptide, exon 3 encodes the remainder of the propeptide and the Gla domain (residues 1–45), exon 4 encodes the connecting segment between the Gla domain and the first EGF-like domain, exons 5 and 6 encode for the EGF-like domains (residues 49–91 and 92–137), exon 7 encodes the activation peptide (residues 157–169), the C-terminus of the light chain and the first 29 amino acids of the heavy chain. Exons 8 and 9 encode the remaining heavy chain sequence.
KeywordsVortex Microwave Phenol Urea Lithium
- 2.Beckmann, R. J., Schmidt, R. J., Sonterre, R. F., Plutzky, J., Crabtree, G. R., and Long, G. L. (1985) The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs. Nucleic Acids Res. 13, 5233–5247.CrossRefPubMedGoogle Scholar
- 4.Reitsma, P. H., Bernardi, F., Doig, R. G., Gandrille, S., Greengard, J. S., Ireland, H., et al. (1995) Protein C deficiency: a database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardisation Committee of the ISTH. Thromb. Haemostasis 73, 876–889.Google Scholar