Matthijs G, Schollen E, Pirard M, Budarf M L, Van Schaftingen E, Cassiman J J
Center for Human Genetics, University of Leuven, Belgium.
Genomics. 1997 Feb 15;40(1):41-7. doi: 10.1006/geno.1996.4536.
We have cloned the human homologue of SEC53 or yeast phosphomannomutase (HGMW-approved symbol PMM1) from a liver cDNA library. This cDNA encodes a protein of 262 amino acids with a predicted molecular mass of 29 kDa and 54% identity with yeast phosphomannomutase. Expression of the human cDNA in Escherichia coli yielded an active phosphomannomutase, which was purified to homogeneity. Northern blot analysis of human tissues showed strong expression in liver, heart, brain, and pancreas and a lower expression in skeletal muscle. The gene was assigned to chromosome 22q13.1 by the use of hybrid cell lines and by fluorescence in situ hybridization. Most patients presenting with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken disease) have a greatly reduced phosphomannomutase activity; the gene encoding this enzyme is a likely candidate for CDG1. Since the CDG1 locus maps else where in the genome (16p13), mutations in the phosphomannomutase gene encoded by chromosome 22 are not a major cause of CDG1.
我们从肝脏cDNA文库中克隆出了SEC53或酵母磷酸甘露糖变位酶（HGMW认可的符号为PMM1）的人类同源物。该cDNA编码一种由262个氨基酸组成的蛋白质，预测分子量为29 kDa，与酵母磷酸甘露糖变位酶有54%的同源性。人类cDNA在大肠杆菌中的表达产生了一种活性磷酸甘露糖变位酶，该酶被纯化至同质。对人类组织的Northern印迹分析表明，其在肝脏、心脏、大脑和胰腺中表达强烈，在骨骼肌中表达较低。通过使用杂交细胞系和荧光原位杂交，该基因被定位到22q13.1染色体上。大多数患有1型糖基化缺陷糖蛋白综合征（CDG1或雅克恩病）的患者磷酸甘露糖变位酶活性大幅降低；编码该酶的基因可能是CDG1的候选基因。由于CDG1基因座定位于基因组的其他位置（16p13），22号染色体编码的磷酸甘露糖变位酶基因突变不是CDG1的主要病因。
