Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic poly peptide

Abstract

Recent identification of natriuretic-diuretic activity in peptides isolated from human and rat atrial tissue implicates them in the control of extracellular fluid volume and electrolytic homeostasis. The presence of multiple forms of the peptides ranging from 3,000 to 13,000 molecular weight (MW) suggests they may all derive from the same precursor. The established amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha- hANP ), a 28-residue peptide with potent natriuretic activity, provided the means to elucidate the structure of the precursor for alpha- hANP and the gene encoding it. Here we report the cloning and sequence analysis of the cDNA of human atrial mRNA encoding a precursor of alpha- hANP . The cDNA encodes gamma-human atrial natriuretic polypeptide (gamma- hANP ) of 13,000 MW, whose C-terminal 28 amino acid residues may be processed as alpha- hANP .

Atrial Natriuretic Peptide Prohormone Gene Expression: Hormones and Diseases That Upregulate its Expression

“…2). Exon 3 encodes for the terminal tyrosine (i.e., a.a. 126 of the ANP prohormone) in humans and 3 a.a. (Try-Arg-Arg) in rat, rabbit, cow, and mouse (2)(3)(4)(5). Deletion of this terminal tyrosine residue encoded by exon 3 does affect slightly binding of ANP but does not appear to contribute to biologic activity, as there is no apparent decrease in biologic activity when this terminal tyrosine is not present (1).…”

“…The signal peptide is cleaved from the preprohormone (151 a.a.) in the endoplasmic reticulum. The resulting prohormone of 126 a.a. is the storage form for the four atrial natriuretic peptide hormones within tissues (3)(4)(5)(6). The first 16 a.a. of this prohormone encoded by exon 1 are, after proteolytic processing of the ANP prohormone, also the first 16 a.a. of a peptide hormone named long-acting natriuretic hormone (LANH) (Fig.…”

“…Deletion of this terminal tyrosine residue encoded by exon 3 does affect slightly binding of ANP but does not appear to contribute to biologic activity, as there is no apparent decrease in biologic activity when this terminal tyrosine is not present (1). Exon 2 encodes for the rest of the prohormone (2)(3)(4)(5).…”

“…2). Exon 1 encodes the 5 -untranslated region, the signal peptide, and the first 16 a.a. of the ANP prohormone (2)(3)(4)(5). The signal peptide is cleaved from the preprohormone (151 a.a.) in the endoplasmic reticulum.…”

Natriuretic Peptides and Analytical Barriers

“…ANP is synthesized as a 151-amino acid prepropeptide, preproANP, which is stored in atrial intracellular granules (10 ). PreproANP is secreted and cleaved to the mature peptide, ANP, in response to atrial stretch, angiotensin II, endothelin, or sympathetic-mediated stimulation.…”