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Complete amino acid sequence and maturation of the mouse submaxillary gland renin precursor

Abstract

Renin, a protease which cleaves the prohormone angiotensinogen, releasing angiotensin I, has a major role in regulating blood pressure and electrolyte balance. However, the primary structure and the active structure of the enzyme remain unknown. The presence of an inactive form of the enzyme, activable by partial proteolysis, has led to the proposal that renin is synthesized as an inactive precursor1. Kidney juxtaglomerular cells constitute the principal source of renin, but its concentration in this tissue is too low to allow determination of its primary structure by conventional techniques. In some strains of mice, the male submaxillary glands synthesize and secrete very large amounts of an enzyme which appears indistinguishable from renal renin by immunological and physicochemical criteria2,3, thereby representing a unique opportunity to delineate the detailed features of renin. We now present the analysis of bacterial DNA recombinant clones harbouring an essentially complete transcript of renin mRNA isolated from the mouse submaxillary gland. The deduced amino acid sequence shows that renin is synthesized as a 44,209 molecular weight (Mr) precursor. Comparison with other known acid proteases shows a good alignment of renin and acid protease sequences in the neighbourhood of residues involved in the active site. N-terminal sequence analysis of renin reveals that the precursor is converted by a protein cleavage into active renin consisting of two chains of Mr 35,000 and 3,000.

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Panthier, JJ., Foote, S., Chambraud, B. et al. Complete amino acid sequence and maturation of the mouse submaxillary gland renin precursor. Nature 298, 90–92 (1982). https://doi.org/10.1038/298090a0

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