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Publication : Molecular cloning and characterization of a human multisubstrate specific nucleotide-sugar transporter homologous to Drosophila fringe connection.

First Author  Suda T Year  2004
Journal  J Biol Chem Volume  279
Issue  25 Pages  26469-74
PubMed ID  15082721 Mgi Jnum  J:324202
Mgi Id  MGI:7276125 Doi  10.1074/jbc.M311353200
Citation  Suda T, et al. (2004) Molecular cloning and characterization of a human multisubstrate specific nucleotide-sugar transporter homologous to Drosophila fringe connection. J Biol Chem 279(25):26469-74
abstractText  Nucleotide-sugar transporters are crucial components in the synthesis of glycoconjugates. We identified a novel human nucleotide-sugar transporter gene, hfrc1, which is homologous to Drosophila melanogaster fringe connection, Caenorhabditis elegans sqv-7, and human UGTrel7. HFRC1 was localized within the Golgi apparatus following its transient expression in HCT116 cells. In human tissues, hfrc1 and UGTrel7 exhibited similar tissue distributions, although hfrc1 transcripts showed a 10 times greater abundance than those of UGTrel7. The heterologous expression of HFRC1 in the yeast revealed the multisubstrate specific transport activity of HFRC1 (for UDP-N-acetylglucosamine (UDP-GlcNAc), UDP-glucose (UDP-Glc), and GDP-mannose (GDP-Man), with apparent K(m) values of 8.0, 2.1, and 0.14 microm, respectively). In the mammalian cells, HFRC1 transported UDP-GlcNAc and UDP-Glc, but not GDP-Man. Overexpression of the hfrc1 gene in HCT116 cells modulated the cell surface heparan sulfate expression status. These results suggest that HFRC1 takes part in the synthesis of heparan sulfate by regulating the level of UDP-GlcNAc, a donor substrate for the heparan sulfate synthases.
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