title: Structure and evolution of the human genes encoding protein C and coagulation factor IX.
abstract: Human protein C is a vitamin K-dependent plasma protein that serves as a feedback down-regulator of the coagulation cascade by specifically degrading the protein cofactors VIIIa and Va. The protein C precursor consists of the following domains: leader peptide, "gla" region, two epidermal growth factor segments, and the activation peptide/serine protease. Comparison of amino acid sequences reveals that protein C and factor IX are homologous. A comparison of the genes for protein C and factor IX shows that all seven of the introns within the protein coding regions are in identical positions and correspond to protein structure-function domain boundries. However, the base compositions of the two genes (coding and noncoding regions) are remarkably different: approximately 60% guanine + cytosine (G + C) for protein C versus approximately 40% G + C for factor IX. One possible explanation for this phenomenon is that the factor IX gene (located on the X chromosome) has undergone extensive deoxycytosine methylation and subsequent spontaneous deamination mutagenesis, resulting in a net C to thymine (and G to adenine) transition. This would suggest that the protein C gene may represent a more primitive form of the gene duplication precursor.
mesh_terms: D000595:Amino Acid Sequence; D001482:Base Composition; D001483:Base Sequence; D005075:Biological Evolution; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D005164:Factor IX / Q000235:genetics*; D005796:Genes; D006801:Humans; D007438:Introns; D008745:Methylation; D011486:Protein C / Q000235:genetics*
chemical_list: D003062:Codon; D011486:Protein C; D005164:Factor IX; D004247:DNA