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Renin

Renin is a member of the family of aspartic proteases. These proteases have two highly conserved aspartic residues in the active cleft, which work optimally at acidic pH. In this aspect, renin is an exception, as it cleaves its substrate angiotensinogen at neutral pH in blood plasma. Renin is produced in juxtaglomerular (JG) cells as prorenin, which contains a 43-amino-acid prosegment that covers the active cleft. The prosegment inactivates the protease and thereby prevents intracellular proteolysis, but it is also thought to be important for folding, stability, and intracellular sorting of proteases. Renin generates angiotensin I by cleaving its unique substrate angiotensinogen. This first step is indispensable for the subsequent formation of angiotensin II. Thus renin is essential for sodium homeostasis and blood pressure regulation. The (Pro) renin receptor can also act as a signalling receptor for (pro)renin, independent from the formation of Ang I. Binding of (pro)renin to the (P)RR activates the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (Erk1/2) in several cell types, including mesangial cells, collecting duct cells, VSMCs, monocytes, and neurons. Activation of Erk1/2 increases cell proliferation and stimulates production of transforming growth factor-β1 (TGF-β1), resulting in the upregulation of profibrotic factors, such as the plasminogen-activated inhibitor-1 (PAI-1), fibronectin, and collagen.

References

1.Manne Krop,et al. Pflugers Arch. 2013 Jan; 465(1): 87–97.

Metabolic Enzyme/Protease

11β-HSD(15) 15-PGDH(1) ACC(10) ACE(9) AChE(29) Adenylate Cyclase(10) ALDH(14) Aldose Reductase(5) Aminopeptidase(17) BACE(18) Casein Kinase(41) CAT(5) Cathepsin(8) CETP(10) COMT(2) CPG2(1) CYPs(6) Decarboxylase(3) Dehydrogenase(87) DGAT(4) Dopamine beta-hydroxylase(2) DPP(28) Elastase(6) FAAH(19) Factor Xa(22) Fatty Acid Synthase(16) Ftase(2) FXR(22) Glucokinase(1) GSNOR(2) Guanylate Cyclase(9) HMGCR(17) IDH(7) IDO(20) IMPDH(2) LDH(2) LDL(5) Lipase(13) Lipid(9) MAGL(3) MAO(51) MMP(48) NAMPT(7) Neprilysin(6) Other Targets(9) P450(87) PAI-1(7) Phosphatase(49) Phospholipase(43) PPAR(86) Protein Phosphatase/PTP(6) Renin(7) Retinoid Receptor(23) SCD(6) Steroid Sulfatase (STS)(2) Thioredoxin(1) TPH(5) Transferase(24) Vitamin(39) Xanthine Oxidase (XAO)(6)