Cloning, mapping and RNA analysis of the human methionine synthase gene
Cloning, mapping and RNA analysis of the human methionine synthase gene
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DOI：
10.1093/hmg/5.12.1851
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发表时间：
1996-12-01
影响因子：
3.5
通讯作者：
Kruger, WD
中科院分区：
文献类型：
--
作者：
Li, YN;Gulati, S;Kruger, WD
血浆同型半胱氨酸水平升高是出生缺陷和血管疾病的危险因素。蛋氨酸合酶 (MS) 是一种钴胺素依赖性酶，可催化同型半胱氨酸甲基化为蛋氨酸。 MS 活性受损预计会导致血浆同型半胱氨酸水平升高。此外，该基因的缺陷可能是在许多人类肿瘤细胞系中观察到的蛋氨酸依赖性的基础。我们在此描述了人类 MS cDNA 的分离和表征。它包含一个由 3798 个核苷酸组成的开放阅读框，编码由 1265 个氨基酸组成的蛋白质，预计分子量为 140 kDa。人 MS 的氨基酸序列与大肠杆菌酶 (METH) 的氨基酸序列有 55% 相同，与预测的秀丽隐杆线虫酶有 64% 相同。源自纯化猪 MS 的 7 个肽序列与人蛋白质具有显着相似性。Northern 分析表明 MS RNA 存在于多种组织中。我们已将人类基因定位到染色体位置 1q43，该区域在 1q 缺失综合征个体中发现为单体区域。 MS cDNA 的分离现在可以直接确定该基因的突变是否会导致叶酸相关的神经管缺陷、心血管疾病和出生缺陷。
Elevated levels of plasma homocysteine is a risk factor in both birth defects and vascular disease. Methionine synthase (MS) is a cobalamin dependent enzyme which catalyzes methylation of homocysteine to methionine. Impaired MS activity is expected to lead to increased levels of plasma homocysteine. In addition, defects in this gene may underlie the methionine-dependence observed in a number of human tumor cell lines, We describe here the isolation and characterization of the human MS cDNA. It contains an open reading frame of 3798 nucleotides encoding a protein of 1265 amino acids with a predicted molecular mass of 140 kDa. The amino acid sequence of the human MS is 55% identical with that of the Escherichia coli enzyme (METH) and 64% identical with the predicted Caenorhabditis elegans enzyme, Seven peptide sequences derived from purified porcine MS have substantial similarity to the human protein, Northern analysis indicates that the MS RNA is present in a wide variety of tissues. We have mapped the human gene to chromosomal location 1q43, a region found monosomic in individuals with deletion 1q syndrome. The isolation of the MS cDNA will now allow the direct determination of whether mutations in this gene contribute to folate-related neural tube defects, cardiovascular diseases, and birth defects.