Refetoff S, Murata Y, Mori Y, Janssen O E, Takeda K, Hayashi Y
Department of Medicine, University of Chicago, IL 60637-1470, USA.
Horm Res. 1996;45(3-5):128-38. doi: 10.1159/000184775.
Thyroxine-binding globulin (TBG), the principal thyroid hormone transport protein in human serum, is synthesized by the liver and secreted into the bloodstream as a 54-kD acidic glycoprotein made up of a single polypeptide chain of 395 amino acids and four heterosaccharide units. The carbohydrate chains are important for the correct posttranslational folding, secretion and degradation of the molecule but are not required for hormone binding. TBG, encoded by a single gene copy located on Xq22, consists of five exons spanning 5.5 kbp. An upstream sequence of 218 nucleotides containing a hepatocyte nuclear factor 1 binding motif imparts to the gene a strong liver-specific transcriptional activity. Inherited TBG defects produce three phenotypes based on the level of TBG in serum of affected hemizygotes: complete TBG deficiency (TBG-CD), partial TBG deficiency (TBG-PD) and TBG excess (TBG-E). The molecular basis of the TBG defect has been identified in 12 of 16 known TBG variants. TBG-CD is caused by either premature termination of translation or an amino acid substitution resulting in failure of secretion. Point mutations resulting in single amino acid substitutions are responsible for the alteration of the properties and/or concentration of TBG-PD variants. Gene duplication and triplication has been recently identified in subjects with TBG-E.
甲状腺素结合球蛋白（TBG）是人类血清中主要的甲状腺激素转运蛋白，由肝脏合成并作为一种54-kD的酸性糖蛋白分泌到血液中，该蛋白由一条包含395个氨基酸的单多肽链和四个杂糖单元组成。糖链对于分子的正确翻译后折叠、分泌和降解很重要，但激素结合并不需要它们。TBG由位于Xq22的单个基因拷贝编码，由跨越5.5 kbp的五个外显子组成。一个包含肝细胞核因子1结合基序的218个核苷酸的上游序列赋予该基因很强的肝脏特异性转录活性。基于受影响半合子血清中TBG的水平，遗传性TBG缺陷产生三种表型：完全性TBG缺乏症（TBG-CD）、部分性TBG缺乏症（TBG-PD）和TBG过多症（TBG-E）。在16种已知的TBG变体中，有12种已确定了TBG缺陷的分子基础。TBG-CD是由翻译提前终止或氨基酸取代导致分泌失败引起的。导致单个氨基酸取代的点突变是TBG-PD变体性质和/或浓度改变的原因。最近在患有TBG-E的受试者中发现了基因重复和三倍体现象。
