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Mutational Analysis of the Human Protein C Gene

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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.
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