Kageyama R, Ohkubo H, Nakanishi S
Biochemistry. 1984 Jul 31;23(16):3603-9. doi: 10.1021/bi00311a006.
Cloned cDNA sequences for human preangiotensinogen have been isolated from a human liver cDNA library by hybridization with a restriction fragment derived from a previously cloned cDNA for rat preangiotensinogen. Analyses by nucleotide sequence determination, S1 nuclease mapping, and RNA blot hybridization indicate that human preangiotensinogen is encoded by two mRNAs that differ only in the length of the 3'-untranslated region. The deduced amino acid sequence shows that the mature angiotensinogen consists of 452 amino acid residues with the angiotensin sequence at its amino-terminal portion. Two potential initiation sites have been discussed. These are the methionine codon located at the position exactly corresponding to the initiation site of rat preangiotensinogen mRNA and an additional methionine codon positioned nearest the 5' end of the mRNA. The amino acid sequences starting at either of the initiation sites and preceding the angiotensin sequence constitute a large number of hydrophobic amino acid residues, thus representing the signal peptide characteristic of the secretory proteins. Human and rat preangiotensinogens show that 63.6% of the amino acid positions of the two proteins are identical. However, the amino-terminal portions directly distal to angiotensin I diverge markedly between the two proteins and differ in their possible glycosylation sites. These structural differences may contribute to the known species specificity exhibited by renin.
通过与源自先前克隆的大鼠血管紧张素原前体cDNA的限制性片段杂交，从人肝cDNA文库中分离出了人血管紧张素原前体的克隆cDNA序列。通过核苷酸序列测定、S1核酸酶图谱分析和RNA印迹杂交分析表明，人血管紧张素原前体由两种mRNA编码，这两种mRNA仅在3'-非翻译区的长度上有所不同。推导的氨基酸序列表明，成熟的血管紧张素原由452个氨基酸残基组成，其氨基末端部分含有血管紧张素序列。已经讨论了两个潜在的起始位点。一个是位于与大鼠血管紧张素原前体mRNA起始位点完全对应的位置的甲硫氨酸密码子，另一个是位于mRNA 5'端最靠近的额外甲硫氨酸密码子。从任一起始位点开始并在血管紧张素序列之前的氨基酸序列构成大量疏水氨基酸残基，因此代表分泌蛋白的信号肽特征。人和大鼠血管紧张素原前体表明，这两种蛋白质63.6%的氨基酸位置是相同的。然而，两种蛋白质中血管紧张素I直接远端的氨基末端部分明显不同，并且它们可能的糖基化位点也不同。这些结构差异可能导致肾素表现出已知的物种特异性。
