Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence

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Abstract
Cloned c[complementary]DNA sequences for human preangiotensinogen were 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 2 mRNA 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 are discussed. These are the Met codon located at the position exactly corresponding to the initiation site of rat preangiotensinogen mRNA and an additional Met 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 2 proteins are identical. However, the amino-terminal portions directly distal to angiotensin I diverge markedly between the 2 proteins and differ in their possible glycosylation sites. These structural differences may contribute to the known species specificity exhibited by renin.