Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Family and population studies have reported that blood pressure has a heritability of 30-50%, but simple genetic models do not readily explain the patterns of inheritance of hypertension. 2. Restriction fragment length polymorphisms were used to study allele frequencies of a selection of candidate genes that may be important in determining the genetic component of hypertension. These included the genes for renin, haptoglobin, neuropeptide Y and cardiac myosin beta heavy chain. 3. There was no significant association between alleles at any of these loci and the presence of hypertension in this population, suggesting that the contribution of variation at these loci to the genetic component of the variance in hypertension may be quite small.
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PMID:Polymorphisms of candidate genes in essential hypertension. 135 2

We isolated 7.4 mg of pure renin from 2 kg of rat kidneys using affinity chromatography on pepstatin-aminohexyl-Sepharose and an octapeptide renin inhibitor, H-77-Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that renin consists of two polypeptide chains linked by a disulfide bond, one of Mr = 36,000 (heavy chain) and the other of Mr = 3,000 (light chain). The amino-terminal 10-amino acid sequences of the heavy and the light chains were identical to the sequences beginning at Ser72 and Asp355, respectively, of the amino acid sequence of preprorenin deduced from the renin cDNA sequence. Amino acid sequencing of the carboxyl-terminal peptide of the heavy chain, generated by digestion with lysyl endopeptidase, showed that the carboxyl-terminal residue of the heavy chain is Phe. Thus, the propeptide of prorenin is cleaved after Thr71, followed by removal of two amino acids, Arg353 and Asn354, the result being formation of the heavy and light chains. Thus, the site of cleavage of rat prorenin is after a nonbasic amino acid, in contrast to the cleavage of the propeptide after a pair of basic amino acids in mouse submaxillary renin, human renal renin, and many secretory proteins. Treatment of renin with neuraminidase or glycopeptidase F had no apparent effect on the charge heterogeneity of renin. Glycosylation probably does not contribute to charge heterogeneity.
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PMID:Amino-terminal amino acid sequence and heterogeneity in glycosylation of rat renal renin. 201 14

Processing of renin involves sequential proteolytic cleavages of a preproform to the active mature forms. Preprorenin is rapidly internalized cotranslationally into the rough endoplasmic reticulum and hydrolyzed by signal peptidase to produce prorenin. In the Golgi, prorenin is converted (within 15 min) to a form of renin that is enzymatically active. Over the next 12 hr, a slow intracellular process removes a dipeptide near the carboxyl terminus, converting the one-chain renin into two chains joined by a single disulfide bond. This conversion occurs during formation, condensation, and packaging of renin granules. The resultant two-chain renin is approximately one-sixth as active as the one-chain form. The intact renin molecule is obligatory for enzymatic activity because heavy chain alone has little or no activity. Both one- and two-chain renins are secreted, but prorenin is not. Multiple isoelectric forms of prorenin, one-chain renin, and two-chain renin are also observed. This microheterogeneity probably results from minor differences in amino acid composition as a consequence of variations in cleavage positions during processing. Thus, these data suggest that renin synthesis and secretion is complex and may be subject to regulation at multiple steps. Furthermore, based on the results of this study, we also propose that renin can be secreted by two different pathways.
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PMID:Biosynthesis of renin: multiplicity of active and intermediate forms. 613 11

A monolayer cell culture of juxtaglomerular cells (JGC) was derived from the renal cortex of neonatal rats. The JGC had the characteristics of those within the kidney, including peripheral dense bodies and myofibrils indicating a smooth muscle origin; rough ER containing fluffy material consistent with protein synthesis; a prominent Golgi apparatus for packaging granules, and granules having the characteristics of secretory granules and lysosomes. Transplants of the cultured cells into syngeneic recipients survived for 2 weeks or longer and retained the features of JGC. The JGC granules fluoresced when treated with a rabbit antibody against pure rat renin, followed by fluorescein isothyocyanate conjugated F(ab')2 fragment of goat antirabbit IgG (Fc fragment) heavy chain specific. The latter indicated the presence of renin. The JGC were lysed in the presence of DFP, captopril, leupeptin, and EDTA, and were extracted in the presence of pepstatin. The lysate contained renin activity that was inhibited by a specific renin antibody. Nonspecific proteases were excluded by the antibody and its pH optimum. Angiotensin I-converting enzyme was detected in the lysate prepared without the use of EDTA and captopril. Angiotensins I and II/III were derived from the extract by additional extractions, TLC, and RIA, using highly specific antibodies. The angiotensins were confirmed by chromatography monitored by authentic angiotensins. We concluded that the cultured JGC contained renin, angiotensin I-converting enzyme, and angiotensin I and II/III.
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PMID:Juxtaglomerular cells grown as monolayer cell culture contain renin, angiotensin I-converting enzyme, and angiotensin I and II/III. 628 94

A DNA coding for mouse submandibular gland (MSG) renin was used in studies of the biosynthesis and processing of MSG renin and precursors and as a probe for identification of the human renin gene. A 2 kilodalton signal peptide was demonstrated by cleavage of preprorenin (45 kilodaltons) in the presence of microsomal membranes from dog pancreas. Prior selection of renin mRNA by hybridization with its cDNA obviated the possibility that a protease translated from total MSG mRNA could be activated by the microsomal membranes and then act on the primary translation product. In vitro labelling experiments with female MSG demonstrated that prorenin (43 kilodaltons) is rapidly converted to renin (38 kilodaltons) and that testosterone stimulated synthesis by increasing transcription of renin mRNA. Electrophoresis under non-reducing conditions demonstrated 38 kilodalton renin which when reduced ran as two bands of 33 and 5 kilodaltons. Thus, native MSG renin has two chains linked by disulphide bonding. Hydrolysis of the 38 kilodalton single chain occurred only slowly during in vitro labelling. Prorenin bound only weakly to a pepstatin affinity column and could be activated by adding trypsin to column fractions. Both 38 kilodalton single and two chain renin bound strongly however, suggesting that both are active. Base sequencing of MSG renin cDNA indicated an Arg-Arg residue additional to the published amino acid sequence of the heavy chain. This may account for the two forms seen on isoelectric focusing. Mouse renin cDNA was used as a hybridization probe in screening a human genomic library in order to identify the human renin gene. The DNA in positive colonies had overlapping restriction maps and the coding region was found.
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PMID:Synthesis of mouse renin as a 2-5-33-5 kilodalton pre-pro-two-chain molecule and use of its cDNA to identify the human gene. 635 33

To determine the structural basis for the highly specific action of renin, structural features of the active site and the complete amino acid sequence of mouse submaxillary gland renin were determined. A rapid method was developed for a large scale purification of renin from mouse submaxillary gland. The active site of renin was shown to consist of 2 aspartyl residues, 2 tyrosyl residues and one arginyl residue, the structures analogous to the active site of pepsin and other acid proteases. Renin was found to consist of one heavy chain (Mr = 31,036) and one light chain (Mr = 5,458) connected by a disulfide bridge. Amino acid sequences of these chains were determined using overlapping peptides generated by cleavage with cyanogen bromide, trypsin, Staphylococcus aureus protease and Lysobacter enzymogenes endoproteinase Lys-C. Sequences involving 2 catalytically essential aspartyl residues 32 and 215, characteristic to acid proteases, were found identical with pepsin, penicillopepsin and chymosin. The sequence of L-chain was homologous with carboxyl terminal region of porcine pepsin in 46% of amino acid residues. H-chain showed 41% homology with 284 residues on the amino-terminal side of the porcine pepsin molecule. Residues identical in renin and acid proteases are distributed throughout the length of the molecules, suggesting a similarity in their overall structure.
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PMID:Structure of mouse submaxillary gland renin. 635 66

Biosynthetic processing of mouse submandibular gland renin involved sequential proteolytic cleavages of preprorenin to prorenin; the prorenin, in turn, rapidly converted to one-chain and slowly to two-chain renins that were both enzymatically active. One-chain and two-chain renins were purified by an eight-step purification including carboxymethyl cellulose and high performance liquid chromatography (HPLC). The specific activity of the purified one-chain renin was fivefold higher than the two-chain renin. Purified heavy-chain renin was obtained by dithiotreitol incubation of two-chain renin. The heavy chain, isolated by HPLC, retained less than 4% of the activity of the native two-chain, indicating that light-chain renin is essential for enzymatic activity. Previous data indicate that both one-chain and two-chain renins are secreted. One-chain renin is immediately secreted into the media after synthesis, whereas two-chain renin is secreted later. These results suggest that renin may be secreted by two separate pathways--an early pathway from the golgi and another pathway from the secretory granules. Our data indicate that renin biosynthesis and secretion are complex and may be controlled at multiple points.
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PMID:Purification and characterization of one-chain and two-chain renins from mouse submandibular gland. 637 89

Three minor forms of renin from the submaxillary glands of male mice called D1, D2, and E have been purified to homogeneity. Their amino acid compositions are identical to the principal form of mouse submaxillary gland renin (renin A), except for 1, 1, and 2 extra arginine residues, respectively. The electrophoretic mobility of renin D2 does not change upon reduction, indicating that its heavy and light chains are linked by more than a disulfide bond. The light chain of renin D1 has an electrophoretic mobility different from the light chain of renin A. Renin D2 is proposed to be renin A with an arginine-arginine dipeptide connecting the carboxyl terminus of the heavy chain to the NH2 terminus of the light chain, with the light chain missing the carboxyl-terminal arginine of renin A. Renin D1 is suggested to be renin D2 with the peptide bond between an arginine and the NH2 terminus of the light chain cleaved. Renin E is proposed to be renin D1 plus the carboxyl-terminal arginine of the light chain. A fourth minor form of male mouse submaxillary renin, called renin B/A, has been purified to homogeneity in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in isoelectric focusing. Renin B/A seems to be a second renin gene product which is difficult to separate from renin A. Renin B/A has an amino acid composition significantly different from renin A, and all three preparations of B/A had compositions significantly different from one another. For renin B/A, the light chain sequence and the first 53 NH2-terminal residues of its heavy chain sequence were identical to renin A.
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PMID:Mouse submaxillary gland renin. Purification and properties of minor forms, which include several differently processed forms of the major gene product and a second gene product. 637 3

The amino acid sequence of porcine spleen cathepsin D heavy chain has been determined and, hence, the complete structure of this enzyme is now known. The sequence of heavy chain was constructed by aligning the structures of peptides generated by cyanogen bromide, trypsin, and endo-proteinase Lys C cleavages. The structure of the light chain has been published previously. The cathepsin D molecule contains 339 amino acid residues in two polypeptide chains: a 97-residue light chain and a 242-residue heavy chain, with a combined Mr of 36,779 (without carbohydrate). There are two carbohydrate units linked to asparagine residues 70 and 192. The disulfide bond arrangement in cathepsin D is probably similar to that of pepsin, because the positions of six half-cystine residues are conserved. The active site aspartyl residues, corresponding to aspartic acid-32 and -215 of pepsin, are located at residues 33 and 224 in the cathepsin D molecule. The amino acid sequence around these aspartyl residues is strongly conserved. Cathepsin D shows a strong homology with other acid proteases. When the sequence of cathepsin D, renin, and pepsin are aligned, 32.7% of the residues are identical. The homology is observed throughout the length of the molecules, indicating that three-dimensional structures of all three molecules are similar.
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PMID:Amino acid sequence of porcine spleen cathepsin D. 658 85

The complete amino acid sequences of the heavy chain and light chain of mouse submaxillary gland renin have been determined. The heavy chain consists of 288 amino acid residues having a Mr of 31,036 calculated from the sequence. The light chain contains 48 amino acid residues with a Mr of 5,458. The sequence of the heavy chain was determined by automated Edman degradations of the cyanogen bromide peptides and tryptic peptides generated after citraconylation, as well as other peptides generated therefrom. The sequence of the light chain was derived from sequence analyses of the peptides generated by cyanogen bromide cleavage or by digestion with Staphylococcus aureus protease. The sequences in the active site regions in renin containing two catalytically essential aspartyl residues 32 and 215 were found identical with those in pepsin, chymosin, and penicillopepsin. Comparison of the amino acid sequence of renin with that of porcine pepsin indicated a 42% sequence identity of the heavy chain with the amino-terminal and middle regions and a 46% identity of the light chain with the carboxyl-terminal region of the porcine pepsin sequence. Residues identical in renin and pepsin are distributed throughout the length of the molecules, suggesting a similarity in their overall structures.
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PMID:Amino acid sequence of mouse submaxillary gland renin. 681 55


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