POLYMORPHISM OF HUMAN TRANSCOBALAMIN-II - SUBSTITUTION OF PROLINE ANDOR GLUTAMINE RESIDUES BY ARGININE/

The sequence of transcobalamin II (TC II) cDNA amplified from human fi broblast and colon adenocarcinoma (Caco-2) and the electrophoretic mob ility of TC II secreted by these cell lines were analyzed to get some insights into the structural basis for the expression of various polym orphic forms of human TC II. Based on relative anodic mobilities of TC II phenotypes expressed in human serum, TC II expressed in the fibrob last cell line studied and Caco-2 cells were assigned as the MX (mediu m/extremely slow) and S (slow) types, respectively. Nucleotide sequenc e analysis of TC II cDNA amplified from these cells revealed that resi dues Arg and Arg, Gin and Arg, and Gin and Pro were present at positio ns 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 ano dic 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.