Human vitamin D binding protein, previously known as the group-specific component (Gc), was shown to consist of a single polypeptide chain of molecular weight 52000 as evidenced by gel electrophoresis and gel filtration under denaturing conditions. Quantitative analyses by carboxypeptidase A hydrolysis and by automated sequential Edman degradation identified leucine as the amino and carboxyl terminus in molar yields consistent with a molecular weight of 52 000. Peptide maps of tryptic hydrolysates obtained from S-[14C]carboxymethylated Gc revealed the expected number of peptides predicted from amino acid composition. The molecular basis of the major Gc proteins (Gc lfast, Gc lslow, and Gc 2SloW) was investigated. In addition to identical carboxyl-terminal sequences, all three major components exhibited an identical amino-terminal sequence of 20 residues. Tryptic peptide maps of these Gc components were similar; however, Gc 1 and Gc 2 differed by two peptides, whereas Gc lfast and Gc 1SloW differed by only one peptide. Sequence analysis of the characteristic peptides indicated that the difference between Gc lfast and Gc lslow is posttranslational in nature, involving carbohydrate dissimilarities. However, the difference between Gc 1 and Gc 2 was related to primary structure involving only a small number of amino acids. These results support the hypothesis that the major components of Gc occur as a result of two autosomal alleles at a single locus.
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