A NATURALLY-OCCURRING 46-AMINO ACID DELETION OF CYTIDINE MONOPHOSPHO-N-ACETYLNEURAMINIC ACID HYDROXYLASE LEADS TO A CHANGE IN THE INTRACELLULAR-DISTRIBUTION OF THE PROTEIN

Cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase i s a key enzyme for the expression of N-glycolylneuraminic acid. The mo lecular cloning of this enzyme from mouse liver has been described in our previous report (Kawano T, Koyama S, Takematsu H, Kozutsumi Y, Kaw asaki H, Kawashima S, Kawasaki T, Suzuki A (1995) J Biol Chem 270: 164 58-63). During the cDNA cloning, a cDNA containing a truncated open re ading frame (ORF) was isolated. This clone encodes a protein of 531 am ino acids which lacks 46 amino acids in the middle of the normal full- length protein. The percentage of this mRNA containing the truncated O W our of the total population of CMP-NeuAc hydroxylase mRNA in various mouse tissues was about 10-25%. The truncated protein was expressed i n COS-1 cells, but did not show any enzymatic activity. The truncated protein was localized to the region which appeared to be the endoplasm ic reticulum, whereas the full-length protein with normal enzymatic ac tivity was detected in the cytosol. These data suggest that this natur ally occurring 46-amino acid deletion leads to a change in the intrace llular distribution of CMP-NeuAc hydroxylase, and a loss in the activi ty of this enzyme.