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Gene Review

REN  -  renin

Homo sapiens

Synonyms: Angiotensinogenase, Renin
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Disease relevance of REN


Psychiatry related information on REN


High impact information on REN

  • The renin angiotensin aldosterone system has an important role antagonizing the vasodilatory cyclic GMP system [11].
  • Moreover, adenosine tonically inhibits the renal release of renin and stimulates NaCl transport in the cortical proximal tubule but inhibits it in medullary segments including the medullary thick ascending limb [12].
  • Recently, some of the in vivo targets and mechanisms leading to changes in neuronal adaptation, smooth muscle relaxation and growth, intestinal water secretion, bone growth, renin secretion, and other important functions have been identified [13].
  • Morphology, physiology, and molecular biology of renin secretion [14].
  • We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1 [15].

Chemical compound and disease context of REN


Biological context of REN


Anatomical context of REN


Associations of REN with chemical compounds


Physical interactions of REN

  • RNase degradation assays confirm that 3'-UTR binding proteins are able to protect and stabilize REN mRNA in vitro [21].
  • RnBP has been shown to bind and inactivate renin, a key player of the blood pressure regulating renin-angiotensin system [33].
  • The M6P-R is a clearance receptor that binds exclusively the glycosylated forms of renin and prorenin [34].
  • Angiotensin receptor antagonists inhibit the renin angiotensin system at different levels from ACE inhibitors by selectively blocking the binding of angiotensin II to AT1 receptors [35].
  • Genetic and molecular properties of human and rat renin-binding proteins with reference to the function of the leucine zipper motif [36].

Enzymatic interactions of REN

  • Previous studies have demonstrated that the mouse proprotein convertase PC1 (mPC1) accurately cleaves human prorenin to generate active renin and that this processing event appears to require co-packaging in secretory granules [37].
  • Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RIA [38].

Regulatory relationships of REN

  • Recombinant RnBP inhibited porcine renin activity in a dose dependent manner [39].
  • As the renin gene is negatively regulated by calcium in the same way as the parathormone (PTH) gene, we hypothesized that a similar molecular transcriptional mechanism could be involved [40].
  • The angiotensin II (Ang II) type 1 (AT1) receptor is highly expressed on juxtaglomerular (G) cells and is assumed to be involved in the negative short loop feedback regulation of renin secretion and in the suppression of Ang II-mediated JG cell proliferation and/or growth [41].
  • These results suggest that intrarenal ANG II content can be regulated independently of renal renin content [42].
  • BACKGROUND: Renin Angiotensin system is involved in renal function and its polymorphisms may influence diabetic nephropathy [43].

Other interactions of REN


Analytical, diagnostic and therapeutic context of REN


  1. Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma. Juillerat-Jeanneret, L., Celerier, J., Chapuis Bernasconi, C., Nguyen, G., Wostl, W., Maerki, H.P., Janzer, R.C., Corvol, P., Gasc, J.M. Br. J. Cancer (2004) [Pubmed]
  2. Genetic determination of plasma aldosterone levels in essential hypertension. Pojoga, L., Gautier, S., Blanc, H., Guyene, T.T., Poirier, O., Cambien, F., Benetos, A. Am. J. Hypertens. (1998) [Pubmed]
  3. Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients. Filler, G., Yang, F., Martin, A., Stolpe, J., Neumayer, H.H., Hocher, B. Pediatric transplantation. (2001) [Pubmed]
  4. Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol. Mulatero, P., Curnow, K.M., Aupetit-Faisant, B., Foekling, M., Gomez-Sanchez, C., Veglio, F., Jeunemaitre, X., Corvol, P., Pascoe, L. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  5. Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene. Kayes-Wandover, K.M., Tannin, G.M., Shulman, D., Peled, D., Jones, K.L., Karaviti, L., White, P.C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  6. Cyclooxygenase-2 inhibitors: a painful lesson. Sanghi, S., MacLaughlin, E.J., Jewell, C.W., Chaffer, S., Naus, P.J., Watson, L.E., Dostal, D.E. Cardiovascular & hematological disorders drug targets. (2006) [Pubmed]
  7. Mild high-renin essential hypertension. Neurogenic human hypertension? Esler, M., Julius, S., Zweifler, A., Randall, O., Harburg, E., Gardiner, H., DeQuattro, V. N. Engl. J. Med. (1977) [Pubmed]
  8. Forebrain pathways mediating stress-induced hormone secretion. Van de Kar, L.D., Blair, M.L. Frontiers in neuroendocrinology. (1999) [Pubmed]
  9. Blood-pressure response to moderate sodium restriction and to potassium supplementation in mild essential hypertension. Richards, A.M., Nicholls, M.G., Espiner, E.A., Ikram, H., Maslowski, A.H., Hamilton, E.J., Wells, J.E. Lancet (1984) [Pubmed]
  10. Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq. Murray, J.C., Nishimura, D.Y., Buetow, K.H., Ardinger, H.H., Spence, M.A., Sparkes, R.S., Falk, R.E., Falk, P.M., Gardner, R.J., Harkness, E.M. Am. J. Hum. Genet. (1990) [Pubmed]
  11. The molecular basis of hypertension. Garbers, D.L., Dubois, S.K. Annu. Rev. Biochem. (1999) [Pubmed]
  12. Adenosine and kidney function. Vallon, V., Mühlbauer, B., Osswald, H. Physiol. Rev. (2006) [Pubmed]
  13. Function of cGMP-dependent protein kinases as revealed by gene deletion. Hofmann, F., Feil, R., Kleppisch, T., Schlossmann, J. Physiol. Rev. (2006) [Pubmed]
  14. Morphology, physiology, and molecular biology of renin secretion. Hackenthal, E., Paul, M., Ganten, D., Taugner, R. Physiol. Rev. (1990) [Pubmed]
  15. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Gribouval, O., Gonzales, M., Neuhaus, T., Aziza, J., Bieth, E., Laurent, N., Bouton, J.M., Feuillet, F., Makni, S., Ben Amar, H., Laube, G., Delezoide, A.L., Bouvier, R., Dijoud, F., Ollagnon-Roman, E., Roume, J., Joubert, M., Antignac, C., Gubler, M.C. Nat. Genet. (2005) [Pubmed]
  16. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Linz, W., Wiemer, G., Gohlke, P., Unger, T., Schölkens, B.A. Pharmacol. Rev. (1995) [Pubmed]
  17. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. Mackins, C.J., Kano, S., Seyedi, N., Schäfer, U., Reid, A.C., Machida, T., Silver, R.B., Levi, R. J. Clin. Invest. (2006) [Pubmed]
  18. Monocyte infiltration and adhesion molecules in a rat model of high human renin hypertension. Mervaala, E.M., Müller, D.N., Park, J.K., Schmidt, F., Löhn, M., Breu, V., Dragun, D., Ganten, D., Haller, H., Luft, F.C. Hypertension (1999) [Pubmed]
  19. Response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to long-term administration of captopril in patients with severe, treatment-resistant malignant hypertension. McCaa, C.S., Langford, H.G., Cushman, W.C., McCaa, R.E. Clin. Sci. (1979) [Pubmed]
  20. HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression. Adams, D.J., Beveridge, D.J., van der Weyden, L., Mangs, H., Leedman, P.J., Morris, B.J. J. Biol. Chem. (2003) [Pubmed]
  21. Posttranscriptional control of renin synthesis: identification of proteins interacting with renin mRNA 3'-untranslated region. Skalweit, A., Doller, A., Huth, A., Kähne, T., Persson, P.B., Thiele, B.J. Circ. Res. (2003) [Pubmed]
  22. Genetic evidence that lethality in angiotensinogen-deficient mice is due to loss of systemic but not renal angiotensinogen. Ding, Y., Stec, D.E., Sigmund, C.D. J. Biol. Chem. (2001) [Pubmed]
  23. Baroreflex sensitivity and variants of the renin angiotensin system genes. Ylitalo, A., Airaksinen, K.E., Hautanen, A., Kupari, M., Carson, M., Virolainen, J., Savolainen, M., Kauma, H., Kesäniemi, Y.A., White, P.C., Huikuri, H.V. J. Am. Coll. Cardiol. (2000) [Pubmed]
  24. The brain renin-angiotensin system in transgenic mice carrying a highly regulated human renin transgene. Morimoto, S., Cassell, M.D., Sigmund, C.D. Circ. Res. (2002) [Pubmed]
  25. Proprotein conversion is determined by a multiplicity of factors including convertase processing, substrate specificity, and intracellular environment. Cell type-specific processing of human prorenin by the convertase PC1. Benjannet, S., Reudelhuber, T., Mercure, C., Rondeau, N., Chrétien, M., Seidah, N.G. J. Biol. Chem. (1992) [Pubmed]
  26. Prohormone convertase PC5 is a candidate processing enzyme for prorenin in the human adrenal cortex. Mercure, C., Jutras, I., Day, R., Seidah, N.G., Reudelhuber, T.L. Hypertension (1996) [Pubmed]
  27. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Loghman-Adham, M., Soto, C.E., Inagami, T., Cassis, L. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  28. Glial-specific ablation of angiotensinogen lowers arterial pressure in renin and angiotensinogen transgenic mice. Sherrod, M., Davis, D.R., Zhou, X., Cassell, M.D., Sigmund, C.D. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  29. Angiotensinogen concentrations and renin clearance : implications for blood pressure regulation. Bohlender, J., Ménard, J., Ganten, D., Luft, F.C. Hypertension (2000) [Pubmed]
  30. Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. Paillard, F., Chansel, D., Brand, E., Benetos, A., Thomas, F., Czekalski, S., Ardaillou, R., Soubrier, F. Hypertension (1999) [Pubmed]
  31. Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule. Lavoie, J.L., Lake-Bruse, K.D., Sigmund, C.D. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  32. cAMP controls human renin mRNA stability via specific RNA-binding proteins. Morris, B.J., Adams, D.J., Beveridge, D.J., van der Weyden, L., Mangs, H., Leedman, P.J. Acta Physiol. Scand. (2004) [Pubmed]
  33. Human renin binding protein: complete genomic sequence and association of an intronic T/C polymorphism with the prorenin level in males. Knöll, A., Schunkert, H., Reichwald, K., Danser, A.H., Bauer, D., Platzer, M., Stein, G., Rosenthal, A. Hum. Mol. Genet. (1997) [Pubmed]
  34. Renin/prorenin receptors. Nguyen, G. Kidney Int. (2006) [Pubmed]
  35. Losartan renography for the detection of renal artery stenosis: comparison with captopril renography and evaluation of dose and timing. Günay, E.C., Oztürk, M.H., Ergün, E.L., Altun, B., Salanci, B.V., Uğur, O., Cil, B., Hekimoğlu, B., Caner, B. Eur. J. Nucl. Med. Mol. Imaging (2005) [Pubmed]
  36. Genetic and molecular properties of human and rat renin-binding proteins with reference to the function of the leucine zipper motif. Inoue, H., Takahashi, S., Fukui, K., Miyake, Y. J. Biochem. (1991) [Pubmed]
  37. Proteolytic processing of human prorenin in renal and non-renal tissues. Reudelhuber, T.L., Ramla, D., Chiu, L., Mercure, C., Seidah, N.G. Kidney Int. (1994) [Pubmed]
  38. Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. Sato, N., Katsuya, T., Nakagawa, T., Ishikawa, K., Fu, Y., Asai, T., Fukuda, M., Suzuki, F., Nakamura, Y., Higaki, J., Ogihara, T. Life Sci. (2000) [Pubmed]
  39. Effects of Nucleotides on the Interaction of Renin with GlcNAc 2-Epimerase (Renin Binding Protein, RnBP). Takahashi, S., Hori, K., Ogasawara, H., Hiwatashi, K., Sugiyama, T. J. Biochem. (2006) [Pubmed]
  40. Implication of Ref-1 in the repression of renin gene transcription by intracellular calcium. Fuchs, S., Philippe, J., Corvol, P., Pinet, F. J. Hypertens. (2003) [Pubmed]
  41. Angiotensin II type 1 receptor expression in two cases of juxtaglomerular cell tumor: correlation to negative feedback of renin secretion by angiotensin II. Tanabe, A., Naruse, M., Naruse, K., Ito, F., Yoshimoto, T., Seki, T., Demura, R., Demura, H., Toma, H., Inagami, T. Horm. Metab. Res. (1999) [Pubmed]
  42. Intrarenal angiotensin II augmentation in angiotensin II dependent hypertension. Navar, L.G., Harrison-Bernard, L.M. Hypertens. Res. (2000) [Pubmed]
  43. Relationship between polymorphisms in the renin-angiotensin system and nephropathy in type 2 diabetic patients. Fradin, S., Goulet-Salmon, B., Chantepie, M., Grandhomme, F., Morello, R., Jauzac, P., Reznik, Y. Diabetes Metab. (2002) [Pubmed]
  44. Renin inhibits N-acetyl-D-glucosamine 2-epimerase (renin-binding protein). Takahashi, S., Kumagai, M., Shindo, S., Saito, K., Kawamura, Y. J. Biochem. (2000) [Pubmed]
  45. Salt sensitivity of Japanese from the viewpoint of gene polymorphism. Katsuya, T., Ishikawa, K., Sugimoto, K., Rakugi, H., Ogihara, T. Hypertens. Res. (2003) [Pubmed]
  46. Juxtaglomerular cell tumor of kidney with CD34 and CD117 immunoreactivity: report of 5 cases. Kim, H.J., Kim, C.H., Choi, Y.J., Ayala, A.G., Amirikachi, M., Ro, J.Y. Arch. Pathol. Lab. Med. (2006) [Pubmed]
  47. The Pal3 promoter sequence is critical for the regulation of human renin gene transcription by peroxisome proliferator-activated receptor-gamma. Todorov, V.T., Desch, M., Schubert, T., Kurtz, A. Endocrinology (2008) [Pubmed]
  48. Specific prorenin/renin binding (ProBP). Identification and characterization of a novel membrane site. Sealey, J.E., Catanzaro, D.F., Lavin, T.N., Gahnem, F., Pitarresi, T., Hu, L.F., Laragh, J.H. Am. J. Hypertens. (1996) [Pubmed]
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