人类的克隆和表征钴胺传递蛋白II基因。
文章的细节
-
引用
复制到剪贴板 -
Regec Quadros EV, Platica O, Rothenberg SP
人类的克隆和表征钴胺传递蛋白II基因。
血。1995年5月15日,85 (10):2711 - 9。
- PubMed ID
-
7742531 (在PubMed]
- 文摘
-
钴胺传递蛋白II (TCII)是一个结合的血浆蛋白质维生素B12(氰钴胺素;Cbl)和促进细胞摄取维生素的受体介导内吞作用。遗传疾病的特点是TCII的先天不足,细胞内Cbl缺陷发生,导致巨成红细胞性贫血的早期发病,有时伴有神经功能障碍。定义TCII缺陷的遗传基础,我们克隆人类基因编码这种蛋白的特征。基因跨越至少18 kbp和包含9个外显子和八个内含子,用聚腺苷酸化信号序列位于下游509个基点的终止密码子和转录起始位点上游开始158个基点的ATG翻译网站开始。5 '侧翼DNA没有塔塔或CCAAT监管元素,但34-nucleotide伸展开始帽的上游网站包含四个衔接着组织5 ' -CCCC-3四聚体。这个序列是一个主题trans-active转录因子(ETF)调节表达表皮生长因子受体基因(EGFR),也缺乏塔塔和CCAAT监管元素。GC-rich序列结合SP1的蛋白质位于356核苷酸上游预备的第一个系列的四聚体。虽然这个GC序列是一个不寻常的位置对帽网站,507 - bp片段包含这个GC盒驱动氯霉素乙酰转移酶(CAT)报告基因瞬时转染后NIH 3 t3细胞。没有观察到当猫活动420 - bp片段包含ETF-binding领域缺乏这个GC盒但同样转染细胞系。 One consensus and two atypical motifs for the c-myc ligand are located downstream and upstream, respectively, of the GC box, and this could explain the elevated plasma TCII observed in some patients with multiple myeloma, as the c-myc product is overexpressed in some myeloma cells. Restriction endonuclease digestion of genomic DNA from eight normal subjects with Taq I, Hinfl, Msp I, and Bgl I identified three patterns of restriction fragment length polymorphism (RFLP). A number of the exon/intron splice junctions of human TCII, TCI, and IF genes are located in homologous regions of these proteins, providing evidence that these genes have evolved by duplication of an ancestral gene. This characterization of the TCII gene and the RFLP should facilitate the identification of the mutation(s) responsible for the genetic abnormalities of TCII expression.