Not to be confused with rennin, the active enzyme in rennet.
|-
| align="center" colspan="2" |
|-
| colspan="2" bgcolor="#dddddd" | Identifiers
|-
| bgcolor="#e7dcc3" | Symbol(s)
| bgcolor="#eeeeee" | [REN]
|-
| bgcolor="#e7dcc3" | Entrez
| bgcolor="#eeeeee" | [5972]
|- class="hiddenStructure"
| bgcolor="#e7dcc3" | OMIM
| bgcolor="#eeeeee" | [179820]
|-
| bgcolor="#e7dcc3" | RefSeq
| bgcolor="#eeeeee" | [NM_000537]
|-
| bgcolor="#e7dcc3" | UniProt
| bgcolor="#eeeeee" | [P00797]
|- class="hiddenStructure"
| bgcolor="#e7dcc3" | PDB
| bgcolor="#eeeeee" | []
|-
| colspan="2" bgcolor="#dddddd" | Other data
|- class="hiddenStructure"
| bgcolor="#e7dcc3" | EC number
| bgcolor="#eeeeee" | [3.4.23.15]
|-
| bgcolor="#e7dcc3" | Locus
| bgcolor="#eeeeee" | Chr. 1[q32]
|-
|}
Renin, also known as angiotensinogenase, is a circulating enzyme released mainly by juxtaglomerular cells in the JGA of the kidneys in response to low blood volume or low body NaCl content, mediated through the rapid release of prostaglandins. Although it has hormone-like actions, it cleaves a protein precursor in the circulation rather than working on a cellular target. Thus it is not truly a hormone. Fujino T, Nakagawa N, Yuhki K, Hara A, Yamada T, Takayama K, Kuriyama S, Hosoki Y, Takahata O, Taniguchi T, Fukuzawa J, Hasebe N, Kikuchi K, Narumiya S and Ushikubi F. (2004) Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP. J. Clin. Invest. 114:805-812. [Full Text] Sympathetic activation of membrane β1- and α1-adrenergic receptors on JGA cells also cause renin release, probably by altering tubular sodium content or macula densa function. Brenner & Rector's The Kidney, 7th ed., Saunders, 2004. pp.2118-2119.[Full Text with MDConsult subscription] The normal concentration in human plasma is 1.0-2.5 mg/ml.
The primary structure of renin precursor consists of 406 amino acids with a pre and a pro segment carrying 20 and 46 amino acids respectively. Mature renin contains 340 amino acids and has a mass of 37 kD. Cloning and sequence analysis of cDNA for human renin precursor. ; [PubMed] [Free text]
Renin can bind to ATP6AP2, which results in a 4-fold increase in the conversion of angiotensinogen to angiotensin I over that shown by soluble renin. In addition, renin binding results in phosphorylation of serine and tyrosine residues of ATP6AP2. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. 2002 Jun; [PubMed] [Free text]
Gene
The gene for renin, REN, spans 12 kb of DNA and contains 8 introns.Human renin gene: structure and sequence analysis. 1984 Aug; [PubMed] [Free text] It produces several mRNA that encode different REN isoforms.
Secretion
Human Renin is secreted by at least 2 cellular pathways: a constitutive pathway for the secretion of prorenin and a regulated pathway for the secretion of mature renin Different secretory pathways of renin from mouse cells transfected with the human renin gene. 1988 Mar 5; [PubMed] [Free text (PDF - 1.3MB)].
Clinical implications
An overactive renin-angiotension system leads to vasoconstriction and retention of sodium and water. These effects lead to hypertension. Therefore, renin inhibitors can be used for the treatment of hypertension.
Many analysts believe the first renin inhibitor to be launched will be Novartis' Rasilez (aliskiren), a first-in-class oral renin inhibitor currently undergoing Phase III clinical trials. Rasilez, an octanamide, is the first known representative of a new class of completely non-peptide, low-molecular weight, orally active transition-state renin inhibitors. Designed through the use of molecular modeling techniques, it is a potent and specific in vitro inhibitor of human renin (IC50 in the low nanomolar range), with a plasma half-life of ≈24 hours. Rasilez has good water solubility and low lipophilicity and is resistant to biodegradation by peptidases in the intestine, blood circulation, and the liver.
