Polymorphism of human transcobalamin II: substitution of proline and/or glutamine residues by arginine.

The sequence of transcobalamin II (TC II) cDNA amplified from human fibroblast and colon adenocarcinoma (Caco-2) and the electrophoretic mobility of TC II secreted by these cell lines were analyzed to get some insights into the structural basis for the expression of various polymorphic forms of human TC II. Based on relative anodic mobilities of TC II phenotypes expressed in human serum, TC II expressed in the fibroblast cell line studied and Caco-2 cells were assigned as the MX (medium/extremely slow) and S (slow) types, respectively. Nucleotide sequence analysis of TC II cDNA amplified from these cells revealed that residues Arg and Arg, Gln and Arg, and Gln and Pro were present at positions 234 and 259, respectively, in TC II alleles encoding the X, S and M types. Based on these results, we suggest that differences in the anodic mobilities of the various polymorphic forms of TC II such as the X, S and M types are due to charge difference on the protein caused by the replacement of uncharged residues by arginine at positions 234 and/or 259.