WordNet

a proteolytic enzyme secreted by the kidneys; catalyzes the formation of angiotensin and thus affects blood pressure

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/24 22:59:52」(JST)

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Renin (etymology and pronunciation), also known as an angiotensinogenase, is a protein and enzyme that participates in the body's renin-angiotensin aldosterone system (RAAS)—also known as the renin-angiotensin-aldosterone axis—that mediates extracellular volume (i.e., that of the blood plasma, lymph and interstitial fluid), and arterial vasoconstriction. Thus, it regulates the body's mean arterial blood pressure.

Renin is often improperly referred to as a hormone even though it has no peripheral receptors and rather has an enzymatic activity with which it hydrolyzes angiotensinogen to angiotensin I.

Biochemistry and physiology

Structure

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 kDa.^[4]

Secretion

The enzyme renin is secreted by the afferent arterioles of the kidney from specialized cells of the juxtaglomerular apparatus – the juxtaglomerular cells, in response to three stimuli:

A decrease in arterial blood pressure (that could be related to a decrease in blood volume) as detected by baroreceptors (pressure-sensitive cells). This is the most direct causal link between blood pressure and renin secretion (the other two methods operate via longer pathways).
A decrease in sodium load delivered to the distal tubule. This load is measured by the macula densa of the juxtaglomerular apparatus.
Sympathetic nervous system activity, which also controls blood pressure, acting through the beta₁ adrenergic receptors.

Human renin is secreted by at least 2 cellular pathways: a constitutive pathway for the secretion of the precursor prorenin and a regulated pathway for the secretion of mature renin.^[5]

Renin-angiotensin system

The renin-angiotensin system, showing role of renin at bottom.^[6]

The renin enzyme circulates in the blood stream and breaks down (hydrolyzes) angiotensinogen secreted from the liver into the peptide angiotensin I.

Angiotensin I is further cleaved in the lungs by endothelial-bound angiotensin-converting enzyme (ACE) into angiotensin II, the most vasoactive peptide.^[7]^[8] Angiotensin II is a potent constrictor of all blood vessels. It acts on the smooth muscle and, therefore, raises the resistance posed by these arteries to the heart. The heart, trying to overcome this increase in its 'load', works more vigorously, causing the blood pressure to rise. Angiotensin II also acts on the adrenal glands and releases aldosterone, which stimulates the epithelial cells in the distal tubule and collecting ducts of the kidneys to increase re-absorption of sodium, exchanging with potassium to maintain electrochemical neutrality, and water, leading to raised blood volume and raised blood pressure. The RAS also acts on the CNS to increase water intake by stimulating thirst, as well as conserving blood volume, by reducing urinary loss through the secretion of vasopressin from the posterior pituitary gland.

The normal concentration of renin in adult human plasma is 1.98-24.6 ng/L in the upright position.^[9]

Function

Renin activates the renin-angiotensin system by cleaving angiotensinogen, produced by the liver, to yield angiotensin I, which is further converted into angiotensin II by ACE, the angiotensin-converting enzyme primarily within the capillaries of the lungs. Angiotensin II then constricts blood vessels, increases the secretion of ADH and aldosterone, and stimulates the hypothalamus to activate the thirst reflex, each leading to an increase in blood pressure. Renin's primary function is therefore to eventually cause an increase in blood pressure, leading to restoration of perfusion pressure in the kidneys.

Renin is secreted from juxtaglomerular kidney cells, which sense changes in renal perfusion pressure, via stretch receptors in the vascular walls. The juxtaglomerular cells are also stimulated to release renin by signaling from the macula densa. The macula densa senses changes in sodium delivery to the distal tubule, and responds to a drop in tubular sodium load by stimulating renin release in the juxtaglomerular cells. Together, the macula densa and juxtaglomerular cells comprise the juxtaglomerular complex.

Renin secretion is also stimulated by sympathetic nervous stimulation, mainly through beta-1 adrenoceptor activation.

Renin can bind to ATP6AP2, which results in a fourfold 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.^[10]

The level of renin mRNA appears to be modulated by the binding of HADHB, HuR and CP1 to a regulatory region in the 3' UTR.^[11]

Genetics

The gene for renin, REN, spans 12 kb of DNA and contains 8 introns.^[12] It produces several mRNA that encode different REN isoforms.

Mutations in the REN gene can be inherited, and are a cause of a rare inherited kidney disease, so far found to be present in only 2 families. This disease is autosomal dominant, meaning that it is characterized by a 50% chance of inheritance and is a slowly progressive chronic kidney disease that leads to the need for dialysis or kidney transplantation. Many – but not all – patients and families with this disease suffer from an elevation in serum potassium and unexplained anemia relatively early in life. Patients with a mutation in this gene can have a variable rate of loss of kidney function, with some individuals going on dialysis in their 40's while others may not go on dialysis until into their 70’s. This is a rare inherited kidney disease that exists in less than 1% of people with kidney disease.^[13]

Model organisms

*Ren1* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Non-Invasive Blood Pressure	Abnormal^[14]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal^[15]
Citrobacter infection	Abnormal^[16]
All tests and analysis from^[17]^[18]

Model organisms have been used in the study of REN function. A knockout mouse line, called Ren1^{Ren-1c Enhancer KO} was generated.^[19] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[17]^[20] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. Homozygous mutant animals had a decreased heart rate and an increased susceptibility to bacterial infection.^[17] A more detailed analysis of this line indicated plasma creatinine was also increased and males had lower mean arterial pressure than controls.^[19]

Clinical applications

An over-active 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.^[21]^[22] This is measured by the plasma renin activity (PRA).

In current medical practice, the renin-angiotensin-aldosterone-System's overactivity (and resultant hypertension) is more commonly reduced using either ACE inhibitors (such as ramipril and perindopril) or angiotensin II receptor blockers (ARBs, such as losartan, irbesartan or candesartan) rather than a direct oral renin inhibitor. ACE inhibitors or ARBs are also part of the standard treatment after a heart attack.

The differential diagnosis of kidney cancer in a young patient with hypertension includes juxtaglomerular cell tumor (reninoma), Wilms' tumor, and renal cell carcinoma, all of which may produce renin.^[23]

Measurement

Renin is usually measured as the plasma renin activity (PRA). PRA is measured specially in case of certain diseases that present with hypertension or hypotension. PRA is also raised in certain tumors.^[24] A PRA measurement may be compared to a plasma aldosterone concentration (PAC) as a PAC/PRA ratio.

Discovery and naming

The name renin = ren + -in, "kidney" + "compound". The most common pronunciation in English is /ˈriːnᵻn/ (long e); /ˈrɛnᵻn/ (short e) is also common, but using /ˈriːnᵻn/ allows one to reserve /ˈrɛnᵻn/ for rennin. Renin was discovered, characterized, and named in 1898 by Robert Tigerstedt, Professor of Physiology, and his student, Per Bergman, at the Karolinska Institute in Stockholm.^[25]^[26]

References

^ "Drugs that physically interact with Renin view/edit references on wikidata".
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ Imai T, Miyazaki H, Hirose S, Hori H, Hayashi T, Kageyama R, Ohkubo H, Nakanishi S, Murakami K (Dec 1983). "Cloning and sequence analysis of cDNA for human renin precursor". Proceedings of the National Academy of Sciences of the United States of America. 80 (24): 7405–9. doi:10.1073/pnas.80.24.7405. PMC 389959. PMID 6324167.
^ Pratt RE, Flynn JA, Hobart PM, Paul M, Dzau VJ (Mar 1988). "Different secretory pathways of renin from mouse cells transfected with the human renin gene". The Journal of Biological Chemistry. 263 (7): 3137–41. PMID 2893797.
^ Boulpaep EL, Boron WF (2005). "Integration of Salt and Water Balance; The Adrenal Gland". Medical physiology: a cellular and molecular approach. St. Louis, MO: Elsevier Saunders. pp. 866–867, 1059. ISBN 1-4160-2328-3.
^ 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, Ushikubi F (Sep 2004). "Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP". The Journal of Clinical Investigation. 114 (6): 805–12. doi:10.1172/JCI21382. PMC 516260. PMID 15372104.
^ Brenner & Rector's The Kidney, 7th ed., Saunders, 2004, pp. 2118-2119 Full Text with MDConsult subscription
^ Hamilton Regional Laboratory Medicine Program - Laboratory Reference Centre Manual. [deadlink]
^ Nguyen G, Delarue F, Burcklé C, Bouzhir L, Giller T, Sraer JD (Jun 2002). "Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin". The Journal of Clinical Investigation. 109 (11): 1417–27. doi:10.1172/JCI14276. PMC 150992. PMID 12045255.
^ Adams DJ, Beveridge DJ, van der Weyden L, Mangs H, Leedman PJ, Morris BJ (Nov 2003). "HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression". The Journal of Biological Chemistry. 278 (45): 44894–903. doi:10.1074/jbc.M307782200. PMID 12933794.
^ Hobart PM, Fogliano M, O'Connor BA, Schaefer IM, Chirgwin JM (Aug 1984). "Human renin gene: structure and sequence analysis". Proceedings of the National Academy of Sciences of the United States of America. 81 (16): 5026–30. doi:10.1073/pnas.81.16.5026. PMC 391630. PMID 6089171.
^ Zivná M, Hůlková H, Matignon M, Hodanová K, Vylet'al P, Kalbácová M, Baresová V, Sikora J, Blazková H, Zivný J, Ivánek R, Stránecký V, Sovová J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gübler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S (2009). "Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure". Am. J. Hum. Genet. 85 (2): 204–13. doi:10.1016/j.ajhg.2009.07.010. PMC 2725269. PMID 19664745.
^ "Non-Invasive Blood Pressure data for Ren1". Wellcome Trust Sanger Institute.
^ "Salmonella infection data for Ren1". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Ren1". Wellcome Trust Sanger Institute.
^ ^a ^b ^c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ ^a ^b Adams DJ, Head GA, Markus MA, Lovicu FJ, van der Weyden L, Köntgen F, Arends MJ, Thiru S, Mayorov DN, Morris BJ (Oct 2006). "Renin enhancer is critical for control of renin gene expression and cardiovascular function". The Journal of Biological Chemistry. 281 (42): 31753–61. doi:10.1074/jbc.M605720200. PMID 16895910.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
^ Presentation on Direct Renin Inhibitors as Antihypertensive Drugs
^ Ram CV (Sep 2009). "Direct inhibition of renin: a physiological approach to treat hypertension and cardiovascular disease". Future Cardiology. 5 (5): 453–65. doi:10.2217/fca.09.31. PMID 19715410.
^ Méndez GP, Klock C, Nosé V (Feb 2011). "Juxtaglomerular cell tumor of the kidney: case report and differential diagnosis with emphasis on pathologic and cytopathologic features". International Journal of Surgical Pathology. 19 (1): 93–8. doi:10.1177/1066896908329413. PMID 19098017.
^ Hamilton Regional Laboratory Medicine Program - Laboratory Reference Centre Manual. Renin Direct.
^ Phillips MI, Schmidt-Ott KM (Dec 1999). "The Discovery of Renin 100 Years Ago". News in Physiological Sciences. 14: 271–274. PMID 11390864.
^ Tigerstedt R, Bergman PG (1898). "Niere und Kreislauf" [Kidney and Circulation]. Skandinavisches Archiv für Physiologie [Scandinavian Archives of Physiology] (in German). 8: 223–271. doi:10.1111/j.1748-1716.1898.tb00272.x.

External links

GeneReviews/NCBI/NIH/UW entry on Familial Juvenile Hyperuricemic Nephropathy Type 2
OMIM entries on Familial Juvenile Hyperuricemic Nephropathy Type 2
The MEROPS online database for peptidases and their inhibitors: A01.007
Renin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. レニン－アンギオテンシン系の概要 overview of the renin angiotensin system
2. 副腎疾患におけるレニン-アンギオテンシン-アルドステロン系の評価 assays of the renin angiotensin aldosterone system in adrenal disease
3. 高血圧治療におけるレニン・アンギオテンシン系阻害 renin angiotensin system inhibition in the treatment of hypertension
4. Diagnosis of primary aldosteronism
5. 低レニン性原発性（本態性）高血圧 low renin primary essential hypertension

English Journal

Effects of a domain-selective ACE inhibitor in a mouse model of chronic angiotensin II-dependent hypertension.

Burger D1, Reudelhuber TL2, Mahajan A3, Chibale K3, Sturrock ED4, Touyz RM.Author information 1*Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.2†Clinical Research Institute of Montreal, Montreal, Canada.3‡Department of Chemistry and South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch, South Africa.4§Institute of Infectious Diseases and Molecular Medicine and Division of Medical Biochemistry, University of Cape Town, Cape Town, South Africa.AbstractThe somatic isozyme of ACE (angiotensin I-converting enzyme) comprises two distinct zinc-dependent catalytic domains with different substrate specificities for angiotensin I (cleaved selectively by the C-domain) and bradykinin (cleaved equally efficiently by both the N- and C-domains). Classical ACEIs (ACE inhibitors) target both domains, with side effects such as cough and angio-oedema being attributed, in part, to N-domain inhibition, probably through bradykinin accumulation. We questioned whether a novel C-domain-selective ACEI (lisW-S) has anti-hypertensive effects without influencing bradykinin status. AngII (angiotensin II)-dependent hypertension was studied in mice that express active human renin in the liver (TtRhRen). Compared with wild-type littermates, TtRhRen mice displayed cardiac hypertrophy and had significantly elevated SBP [systolic BP (blood pressure)] as determined by tail cuff sphygmomanometry (150±3 compared with 112±5 mmHg; P<0.05) and telemetry (163±3 compared with 112±2 mmHg; P<0.01). Treatment with the non-selective ACEI lisinopril (1 mg/kg of body weight per day via an osmotic mini-pump for 2 weeks) reduced SBP (127±3 compared with. 154±6; P<0.05). Similarly, treatment with the C-domain selective ACEI lisW-S (lisinopril-tryptophan; 3.6 mg/kg of body weight per day via an osmotic mini-pump for 2 weeks) reduced BP. Treatment with lisinopril or lisW-S significantly reduced levels of AngII in kidneys (~4-fold; P<0.001). Ang-(2-8) [angiotensin-2-8)] was significantly reduced by lisinopril, but not by lisW-S. Plasma bradykinin levels were significantly increased only in the lisinopril group. These data suggest that C-domain-selective ACEIs reduce BP and AngII levels similarly to classical ACEIs. C-domain-selective ACEIs have the potential to avoid undesirable effects on the bradykinin system common to classic ACEIs and may represent a novel approach to the treatment of hypertension.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 Jul 1;127(1):57-63. doi: 10.1042/CS20130808.
The somatic isozyme of ACE (angiotensin I-converting enzyme) comprises two distinct zinc-dependent catalytic domains with different substrate specificities for angiotensin I (cleaved selectively by the C-domain) and bradykinin (cleaved equally efficiently by both the N- and C-domains). Classical ACE
PMID 24506807

Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodelling.

McKinney CA1, Fattah C1, Loughrey CM1, Milligan G2, Nicklin SA1.Author information 1*Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, U.K.2†Institute of Molecular Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, U.K.AbstractThe RAS (renin-angiotensin system) is integral to cardiovascular physiology; however, dysregulation of this system largely contributes to the pathophysiology of CVD (cardiovascular disease). It is well established that AngII (angiotensin II), the main effector of the RAS, engages the AT1R (angiotensin type 1 receptor) and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodelling of the heart and vasculature, ultimately leading to the development and progression of various CVDs, including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centred on the actions of ACE2 (angiotensin-converting enzyme 2) and the resultant production of Ang-(1-7) [angiotensin-(1-7)] from AngII, antagonizes the actions of AngII via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9) [angiotensin-(1-9)], has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. The present review will discuss the role of the counter-regulatory RAS peptides Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodelling of the heart and vasculature.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 Jun 1;126(12):815-27. doi: 10.1042/CS20130436.
The RAS (renin-angiotensin system) is integral to cardiovascular physiology; however, dysregulation of this system largely contributes to the pathophysiology of CVD (cardiovascular disease). It is well established that AngII (angiotensin II), the main effector of the RAS, engages the AT1R (angiotens
PMID 24593683

The central renin-angiotensin system and sympathetic nerve activity in chronic heart failure.

Zucker IH, Xiao L, Haack KK.Author information *Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, U.S.A.AbstractCHF (chronic heart failure) is a multifactorial disease process that is characterized by overactivation of the RAAS (renin-angiotensin-aldosterone system) and the sympathetic nervous system. Both of these systems are chronically activated in CHF. The RAAS consists of an excitatory arm involving AngII (angiotensin II), ACE (angiotensin-converting enzyme) and the AT1R (AngII type 1 receptor). The RAAS also consists of a protective arm consisting of Ang-(1-7) [angiotensin-(1-7)], the AT2R (AngII type 2 receptor), ACE2 and the Mas receptor. Sympatho-excitation in CHF is driven, in large part, by an imbalance of these two arms, with an increase in the AngII/AT1R/ACE arm and a decrease in the AT2R/ACE2 arm. This imbalance is manifested in cardiovascular-control regions of the brain such as the rostral ventrolateral medulla and paraventricular nucleus in the hypothalamus. The present review focuses on the current literature that describes the components of these two arms of the RAAS and their imbalance in the CHF state. Moreover, the present review provides additional evidence for the relevance of ACE2 and Ang-(1-7) as key players in the regulation of central sympathetic outflow in CHF. Finally, we also examine the effects of exercise training as a therapeutic strategy and the molecular mechanisms at play in CHF, in part, because of the ability of exercise training to restore the balance of the RAAS axis and sympathetic outflow.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 May;126(10):695-706. doi: 10.1042/CS20130294.
CHF (chronic heart failure) is a multifactorial disease process that is characterized by overactivation of the RAAS (renin-angiotensin-aldosterone system) and the sympathetic nervous system. Both of these systems are chronically activated in CHF. The RAAS consists of an excitatory arm involving AngI
PMID 24490814

Japanese Journal

レニン-アンジオテンシン-アルドステロン系を阻害する薬物 : ACE阻害薬とAT₁受容体拮抗薬の特徴

日本獣医腎泌尿器学会誌 8(1), 60-65, 2015-11
NAID 40020657678

心腎連関における交感神経系の関与 (特集循環器疾患と交感神経系)

循環器内科 = Cardioangiology 78(5), 492-498, 2015-11
NAID 40020657337

Atp6ap2/(プロ)レニン受容体の網膜発生期における細胞極性への関与 (平成26年度日本眼科学会学術奨励賞受賞論文総説)

日本眼科学会雑誌 119(11), 787-798, 2015-11
NAID 40020648059

Related Pictures

★リンクテーブル★

リンク元	「レニン」「prorenin」
拡張検索	「renin-angiotensin-aldosterone system」「aldosterone renin ratio」「formylkynurenine」

「レニン」

Search
PMC	articles
PubMed	articles
NCBI	proteins

renin
Identifiers
EC number	3.4.23.15
CAS number	9015-94-5
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

REN
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4XX4, 1BBS, 1BIL, 1BIM, 1HRN, 1RNE, 2BKS, 2BKT, 2FS4, 2G1N, 2G1O, 2G1R, 2G1S, 2G1Y, 2G20, 2G21, 2G22, 2G24, 2G26, 2G27, 2I4Q, 2IKO, 2IKU, 2IL2, 2REN, 2V0Z, 2V10, 2V11, 2V12, 2V13, 2V16, 2X0B, 3D91, 3G6Z, 3G70, 3G72, 3GW5, 3K1W, 3KM4, 3O9L, 3OAD, 3OAG, 3OOT, 3OQF, 3OQK, 3OWN, 3Q3T, 3Q4B, 3Q5H, 3SFC, 3VCM, 3VSW, 3VSX, 3VUC, 3VYD, 3VYE, 3VYF, 4AMT, 4GJ5, 4GJ6, 4GJ7, 4GJ8, 4GJ9, 4GJA, 4GJB, 4GJC, 4GJD, 4PYV, 4Q1N, 4RYC, 4RYG, 4RZ1, 4S1G, 4XX3
Identifiers
Aliases	REN, HNFJ2, renin
External IDs	OMIM: 179820 MGI: 97898 HomoloGene: 20151 GeneCards: 5972
Targeted by Drug
	aliskiren
Gene ontology
Molecular function	• insulin-like growth factor receptor binding; • aspartic-type endopeptidase activity; • endopeptidase activity; • peptidase activity; • receptor binding; • hydrolase activity;
Cellular component	• cytoplasm; • membrane; • plasma membrane; • intracellular; • extracellular space; • extracellular region; • lysosome;
Biological process	• response to immobilization stress; • regulation of blood volume by renin-angiotensin; • male gonad development; • regulation of MAPK cascade; • kidney development; • renin-angiotensin regulation of aldosterone production; • cell maturation; • beta-amyloid metabolic process; • response to organic substance; • angiotensin maturation; • proteolysis; • mesonephros development; • regulation of blood pressure; • response to lipopolysaccharide; • cellular response to drug; • protein catabolic process; • drinking behavior; • hormone-mediated signaling pathway; • response to cGMP; • response to cAMP; • response to drug;
	Sources:Amigo / QuickGO
Orthologs
	5972
	19701
	ENSG00000143839
	ENSMUSG00000070645
	P00797
	P06281
	NM_000537
	NM_031192
	NP_000528.1
	NP_112469.1
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: renin
関: アンジオテンシノゲン、アンジオテンシン

分類

産生組織

傍糸球体装置の類上皮細胞から輸入細動脈に分泌される

標的組織

血中のアンジオテンシノゲン

作用

アンジオテンシノゲンを分解しアンジオテンシンI(ANG I)を生成する

分泌の調整 (PT. 480)

1. 交感神経刺激

循環中枢からの刺激→レニン放出↑　β1受容体を介する

立位　→　交感神経亢進(おそらく脳への血行を保つため)　→　レニン放出↑

2. 腎動脈圧

腎動脈圧↓→レニン放出↑

腎動脈圧↑→レニン放出↓

腎臓の輸入細動脈の圧受容器による

cf.腎動脈の動脈狭窄により血流↓→レニン・アンジオテンシン・アルドステロン系↑→血圧↑

3. 遠位尿細管濾液中のNaCl濃度↓

遠位尿細管濾液中のNaCl濃度↓→レニン放出↑

緻密斑細胞により検出される

血漿濃度や輸入細動脈圧の減少はGFRを減少させ、それによって遠位尿細管濾液中のNaCl濃度を減少させる

4. アンジオテンシンII

ネガティブフィードバック制御を受ける。
アンジオテンシンII↑→レニン↓

分子機構

プロテアーゼであり、アンジオテンシノゲンからアミノ酸を４残基除去する

臨床関連

レニン活性(PRA)、レニン濃度(PRC)

「prorenin」

　　[★]

プロレニン

関: renin

「renin-angiotensin-aldosterone system」

　　[★] レニン-アンギオテンシン-アルドステロン系 RAAS

「aldosterone renin ratio」

　　[★] アルドステロン・レニン比

「formylkynurenine」

　　[★] ホルミルキヌレニン

[1] "Drugs that physically interact with Renin view/edit references on wikidata".

[2] "Human PubMed Reference:".

[3] "Mouse PubMed Reference:".

[pmid6324167-4] Imai T, Miyazaki H, Hirose S, Hori H, Hayashi T, Kageyama R, Ohkubo H, Nakanishi S, Murakami K (Dec 1983). "Cloning and sequence analysis of cDNA for human renin precursor". Proceedings of the National Academy of Sciences of the United States of America. 80 (24): 7405–9. doi:10.1073/pnas.80.24.7405. PMC 389959. PMID 6324167.

[pmid2893797-5] Pratt RE, Flynn JA, Hobart PM, Paul M, Dzau VJ (Mar 1988). "Different secretory pathways of renin from mouse cells transfected with the human renin gene". The Journal of Biological Chemistry. 263 (7): 3137–41. PMID 2893797.

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v t e Proteases: aspartate proteases (EC 3.4.23)

Vertebrate	Pepsin Chymosin Renin Signal peptide peptidase Beta secretase 1 2

Pathogenic	Plasmepsin HIV-1 protease

Plant	Nepenthesin

Cathepsin	D E

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

匿名

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案内

案内

renin