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J Biol Chem, Vol. 273, Issue 25, 15866-15871, June 19, 1998
,,, and
From the Department of Membrane Biochemistry, Tokyo Metropolitan
Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan and
the N-Glycolylneuraminic acid (NeuGc) is
abundantly expressed in most mammals, but it is not detectable in
humans. The expression of NeuGc is controlled by cytidine
monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase
activity. We previously cloned a cDNA for mouse CMP-NeuAc
hydroxylase and found that the human genome contains a homologue. We
report here the molecular basis for the absence of NeuGc in humans. We
cloned a cDNA for human CMP-NeuAc hydroxylase from a HeLa cell
cDNA library. The cDNA encodes a 486-amino acid protein, and
its deduced amino acid sequence lacks a domain corresponding to the
N-terminal 104 amino acids of the mouse CMP-NeuAc hydroxylase protein,
although the human protein is highly identical (93%) to the rest of
the mouse hydroxylase protein. The N-terminal truncation of the human
hydroxylase is caused by deletion of a 92-base pair-long exon in human
genomic DNA. The human hydroxylase expressed in COS-7 cells exhibited no enzymatic activity, and a mouse hydroxylase mutant, which lacks the
N-terminal domain, was also inactive. A chimera composed of the human
hydroxylase and the N-terminal domain of the mouse hydroxylase displayed the enzyme activity. These results indicate that the human
homologue of CMP-NeuAc hydroxylase is inactive because it lacks an
N-terminal domain that is essential for enzyme activity. The absence of
NeuGc in human glycoconjugates is due to a partial deletion in the gene
that encodes CMP-NeuAc hydroxylase.
Department of Biological Chemistry, Faculty of
Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto
606-8304, Japan
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