Nakanishi H, Nakayama K, Yokota A, Tachikawa H, Takahashi N, Jigami Y
Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
Yeast. 2001 Apr;18(6):543-54. doi: 10.1002/yea.707.
The Saccharomyces cerevisiae HUT1 gene (scHUT1) and the Schizosaccharomyces pombe hut1(+) gene (sphut1(+)) encode hydrophobic proteins with approximately 30% identity to a human UDP-galactose transporter-related gene (UGTrel1) product. These proteins show a significant similarity to the nucleotide sugar transporter and are conserved in many eukaryotic species, but their physiological functions are not known. Both scHUT1 and sphut1(+) genes are non-essential for cell growth under normal conditions, and their disruptants show no defects in the modification of O- and N-linked oligosaccharides, but are sensitive to a membrane-permeable reducing agent, dithiothreitol (DTT). Consistent with this phenotype, scHUT1 has genetic interaction with ERO1, which plays an essential role in the oxidation of secretory proteins at the endoplasmic reticulum (ER). Overexpression of the MPD1 or MPD2 genes, which were isolated as multicopy suppressors of protein disulphide isomerase (PDI) depletion, could not replace the essential function of PDI in Delta hut1 S. cerevisiae cells. Our results indicate that scHut1p and spHut1p are functional homologues, and their physiological function is to maintain the optimal environment for the folding of secretory pathway proteins in the ER.
酿酒酵母HUT1基因（scHUT1）和粟酒裂殖酵母hut1(+)基因（sphut1(+)）编码的疏水蛋白与一种人类UDP-半乳糖转运体相关基因（UGTrel1）产物具有约30%的同源性。这些蛋白与核苷酸糖转运体显示出显著的相似性，并且在许多真核生物物种中保守，但它们的生理功能尚不清楚。在正常条件下，scHUT1和sphut1(+)基因对细胞生长均非必需，它们的缺失突变体在O-连接和N-连接寡糖的修饰方面没有缺陷，但对膜通透性还原剂二硫苏糖醇（DTT）敏感。与这种表型一致，scHUT1与ERO1存在遗传相互作用，ERO1在内质网（ER）分泌蛋白的氧化过程中起关键作用。作为蛋白质二硫键异构酶（PDI）缺失的多拷贝抑制子而分离得到的MPD1或MPD2基因的过表达，不能替代Δhut1酿酒酵母细胞中PDI的必需功能。我们的结果表明，scHut1p和spHut1p是功能同源物，它们的生理功能是在内质网中维持分泌途径蛋白折叠的最佳环境。
