KEGG   PATHWAY: hsa04614
Entry
hsa04614                    Pathway                                
Name
Renin-angiotensin system - Homo sapiens (human)
Description
The renin-angiotensin system (RAS) is a peptidergic system with endocrine characteristics regarding to the regulation of the blood pressure and hydro-electrolytic balance. In the classical RAS, the enzyme renin cleaves its substrate angiotensinogen (Agt) forming the decapeptide angiotensin I that is in turn cleaved by angiotensin-converting enzyme (ACE) to produce the angiotensin II (Ang II), a key player of this system. Ang II activates its AT1 receptor (AT1R), the principal receptor that mediates the majority of the known actions of Ang II in the kidney, including vasoconstriction, renal sodium (Na+) reabsorption, and aldosterone secretion, increasing blood pressure and contributing to the development of hypertension. In addition to (ACE)/Ang II/AT1R and AT2R axis, other signaling pathways in the RAS, such as ACE2/angiotensin-(1-7)/Mas and Ang IV/IRAP, and other active peptide of the RAS, with physiological relevance as Ang III, Ang A and alamandine, are now widely recognized.
Class
Organismal Systems; Endocrine system
Pathway map
hsa04614  Renin-angiotensin system
hsa04614

Network
  Element
N01743  Renin-angiotensin signaling pathway
Drug
D00150  Angiotensin II (INN)
D00251  Captopril (JP18/USP/INN)
D00357  Losartan potassium (JP18/USP)
D00362  Lisinopril (USP)
D00383  Trandolapril (JAN/USP/INN)
D00400  Valsartan (JP18/USP/INN)
D00421  Ramipril (USP/INN)
D00459  Quinapril hydrochloride (JP18/USP)
D00522  Candesartan (USAN/INN)
D00523  Irbesartan (JP18/USP/INN)
D00620  Benazepril hydrochloride (JAN/USP)
D00621  Enalapril maleate (JP18/USP)
D00622  Fosinopril sodium (USP)
D00623  Moexipril hydrochloride (USP)
D00624  Perindopril erbumine (JAN/USP)
D00626  Candesartan cilexetil (JP18/USP)
D00627  Telmisartan (JP18/USP/INN)
D01069  Cilazapril (USAN)
D01070  Candoxatril (JAN/USAN/INN)
D01119  Temocapril hydrochloride (JP18/USAN)
D01204  Olmesartan medoxomil (JP18/USP)
D01549  Imidapril hydrochloride (JP18)
D01667  Delapril hydrochloride (JAN/USAN)
D01900  Alacepril (JP18/INN)
D01922  Pratosartan (JAN/INN)
D01970  Omapatrilat (JAN/USAN/INN)
D02014  Angiotensin II (USAN)
D02082  Eprosartan mesylate (USAN)
D02939  Angiotensin amide (USAN)
D03077  Benazeprilat (USAN/INN)
D03208  Aliskiren (USAN/INN)
D03349  Candoxatrilat (USAN/INN)
D03440  Ceronapril (USAN/INN)
D03738  Enalkiren (USAN/INN)
D03741  Ditekiren (USAN)
D03743  Terlakiren (USAN/INN)
D03745  Zankiren hydrochloride (USAN)
D03752  Quinapril (INN)
D03753  Perindopril (USAN/INN)
D03756  Indolapril hydrochloride (USAN)
D03758  Libenzapril (USAN/INN)
D03763  Pivopril (USAN/INN)
D03765  Spirapril hydrochloride (USAN)
D03767  Zofenopril calcium (USAN)
D03769  Enalaprilat (USP)
D03772  Fosinoprilat (USAN/INN)
D03773  Quinaprilat (USAN/INN)
D03775  Spiraprilat (USAN/INN)
D03776  Zofenoprilat arginine (USAN)
D03929  Ecadotril (USAN/INN)
D04040  Eprosartan (USAN/INN)
D04126  Saralasin acetate (USAN)
D04243  Forasartan (USAN/INN)
D04312  Gemopatrilat (USAN/INN)
D05246  Olmesartan (USAN/INN)
D05801  Saprisartan potassium (USAN)
D06010  Tasosartan (USAN/INN)
D06076  Teprotide (USAN/INN)
D06412  Aliskiren fumarate (JAN/USAN)
D07499  Benazepril (INN)
D07699  Cilazapril (INN)
D07781  Delapril (INN)
D07892  Enalapril (INN)
D07992  Fosinopril (INN)
D08067  Azilsartan medoxomil (USAN)
D08068  Imidapril (INN)
D08131  Lisinopril (INN)
D08146  Losartan (INN)
D08225  Moexipril (INN)
D08529  Spirapril (INN)
D08566  Temocapril (INN)
D08688  Zofenopril (INN)
D08864  Azilsartan (JAN/USAN/INN)
D08865  Azilsartan kamedoxomil (USAN)
D09038  Remikiren (INN)
D10225  Sacubitril (JAN/USAN/INN)
D10226  Sacubitril valsartan sodium hydrate (JAN)
D10556  Fimasartan (INN)
D11142  Angiotensin II acetate (USAN)
D11580  Perindopril arginine
D12830  Rinvecalinase alfa (USAN/INN)
D12840  Zilebesiran sodium (JAN/USAN)
Other DBs
GO: 0002003
Organism
Homo sapiens (human) [GN:hsa]
Gene
183  AGT; angiotensinogen [KO:K09821]
5972  REN; renin [KO:K01380] [EC:3.4.23.15]
1636  ACE; angiotensin I converting enzyme [KO:K01283] [EC:3.4.15.1]
1215  CMA1; chymase 1 [KO:K01329] [EC:3.4.21.39]
1511  CTSG; cathepsin G [KO:K01319] [EC:3.4.21.20]
3817  KLK2; kallikrein related peptidase 2 [KO:K01325] [EC:3.4.21.35]
3816  KLK1; kallikrein 1 [KO:K01325] [EC:3.4.21.35]
2028  ENPEP; glutamyl aminopeptidase [KO:K11141] [EC:3.4.11.7]
290  ANPEP; alanyl aminopeptidase, membrane [KO:K11140] [EC:3.4.11.2]
5550  PREP; prolyl endopeptidase [KO:K01322] [EC:3.4.21.26]
59272  ACE2; angiotensin converting enzyme 2 [KO:K09708] [EC:3.4.17.23]
5476  CTSA; cathepsin A [KO:K13289] [EC:3.4.16.5]
1359  CPA3; carboxypeptidase A3 [KO:K08780] [EC:3.4.17.1]
4311  MME; membrane metalloendopeptidase [KO:K01389] [EC:3.4.24.11]
7064  THOP1; thimet oligopeptidase 1 [KO:K01392] [EC:3.4.24.15]
57486  NLN; neurolysin [KO:K01393] [EC:3.4.24.16]
5547  PRCP; prolylcarboxypeptidase [KO:K01285] [EC:3.4.16.2]
4142  MAS1; MAS1 proto-oncogene, G protein-coupled receptor [KO:K04303]
116512  MRGPRD; MAS related GPR family member D [KO:K08392]
185  AGTR1; angiotensin II receptor type 1 [KO:K04166]
186  AGTR2; angiotensin II receptor type 2 [KO:K04167]
4012  LNPEP; leucyl and cystinyl aminopeptidase [KO:K01257] [EC:3.4.11.3]
10159  ATP6AP2; ATPase H+ transporting accessory protein 2 [KO:K19514]
Compound
C00873  Angiotensin I
C02135  Angiotensin II
C15848  Angiotensin III
C15849  Angiotensin IV
C15850  Angiotensin (1-7)
C15851  Angiotensin (1-9)
C15852  Angiotensin (1-5)
C20970  Angiotensin A
C20971  Alamandine
C20972  Angiotensin (5-8)
C20973  Angiotensin (5-7)
Reference
PMID:17229979
  Authors
Kramkowski K, Mogielnicki A, Buczko W.
  Title
The physiological significance of the alternative pathways of angiotensin II production.
  Journal
J Physiol Pharmacol 57:529-39 (2006)
Reference
PMID:15549172
  Authors
Danilczyk U, Eriksson U, Oudit GY, Penninger JM.
  Title
Physiological roles of angiotensin-converting enzyme 2.
  Journal
Cell Mol Life Sci 61:2714-9 (2004)
DOI:10.1007/s00018-004-4241-6
Reference
PMID:15549171
  Authors
Warner FJ, Smith AI, Hooper NM, Turner AJ.
  Title
Angiotensin-converting enzyme-2: a molecular and cellular perspective.
  Journal
Cell Mol Life Sci 61:2704-13 (2004)
DOI:10.1007/s00018-004-4240-7
Reference
PMID:15833268
  Authors
Kurdi M, De Mello WC, Booz GW.
  Title
Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components.
  Journal
Int J Biochem Cell Biol 37:1357-67 (2005)
DOI:10.1016/j.biocel.2005.01.012
Reference
PMID:15109615
  Authors
Burrell LM, Johnston CI, Tikellis C, Cooper ME.
  Title
ACE2, a new regulator of the renin-angiotensin system.
  Journal
Trends Endocrinol Metab 15:166-9 (2004)
DOI:10.1016/j.tem.2004.03.001
Reference
PMID:16555051
  Authors
von Bohlen und Halbach O, Albrecht D.
  Title
The CNS renin-angiotensin system.
  Journal
Cell Tissue Res 326:599-616 (2006)
DOI:10.1007/s00441-006-0190-8
Reference
PMID:12793984
  Authors
Schmaier AH
  Title
The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction.
  Journal
Am J Physiol Regul Integr Comp Physiol 285:R1-13 (2003)
DOI:10.1152/ajpregu.00535.2002
Reference
PMID:12419208
  Authors
Eriksson U, Danilczyk U, Penninger JM.
  Title
Just the beginning: novel functions for angiotensin-converting enzymes.
  Journal
Curr Biol 12:R745-52 (2002)
DOI:10.1016/S0960-9822(02)01255-1
Reference
PMID:16286563
  Authors
Dielis AW, Smid M, Spronk HM, Hamulyak K, Kroon AA, ten Cate H, de Leeuw PW.
  Title
The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.
  Journal
Hypertension 46:1236-42 (2005)
DOI:10.1161/01.HYP.0000193538.20705.23
Reference
PMID:16581295
  Authors
Kuba K, Imai Y, Penninger JM.
  Title
Angiotensin-converting enzyme 2 in lung diseases.
  Journal
Curr Opin Pharmacol 6:271-6 (2006)
DOI:10.1016/j.coph.2006.03.001
Reference
PMID:12505055
  Authors
Erdos EG, Jackman HL, Brovkovych V, Tan F, Deddish PA.
  Title
Products of angiotensin I hydrolysis by human cardiac enzymes potentiate bradykinin.
  Journal
J Mol Cell Cardiol 34:1569-76 (2002)
DOI:10.1006/jmcc.2002.2080
Reference
PMID:12372844
  Authors
Shrimpton CN, Smith AI, Lew RA.
  Title
Soluble metalloendopeptidases and neuroendocrine signaling.
  Journal
Endocr Rev 23:647-64 (2002)
DOI:10.1210/er.2001-0032
Reference
PMID:12019279
  Authors
Jackman HL, Massad MG, Sekosan M, Tan F, Brovkovych V, Marcic BM, Erdos EG.
  Title
Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A.
  Journal
Hypertension 39:976-81 (2002)
DOI:10.1161/01.HYP.0000017283.67962.02
Reference
PMID:15173164
  Authors
Lundequist A, Tchougounova E, Abrink M, Pejler G.
  Title
Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II.
  Journal
J Biol Chem 279:32339-44 (2004)
DOI:10.1074/jbc.M405576200
Reference
PMID:17362841
  Authors
Kehoe PG, Wilcock GK.
  Title
Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?
  Journal
Lancet Neurol 6:373-8 (2007)
DOI:10.1016/S1474-4422(07)70077-7
Reference
PMID:25332897
  Authors
Ferrao FM, Lara LS, Lowe J
  Title
Renin-angiotensin system in the kidney: What is new?
  Journal
World J Nephrol 3:64-76 (2014)
DOI:10.5527/wjn.v3.i3.64
Reference
PMID:24273531
  Authors
Zhuo JL, Ferrao FM, Zheng Y, Li XC
  Title
New frontiers in the intrarenal Renin-Angiotensin system: a critical review of classical and new paradigms.
  Journal
Front Endocrinol (Lausanne) 4:166 (2013)
DOI:10.3389/fendo.2013.00166
Reference
PMID:21951628
  Authors
Unger T, Paulis L, Sica DA
  Title
Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches.
  Journal
Eur Heart J 32:2739-47 (2011)
DOI:10.1093/eurheartj/ehr253
Reference
PMID:18793332
  Authors
Fyhrquist F, Saijonmaa O
  Title
Renin-angiotensin system revisited.
  Journal
J Intern Med 264:224-36 (2008)
DOI:10.1111/j.1365-2796.2008.01981.x
Reference
PMID:23692861
  Authors
Yugandhar VG, Clark MA
  Title
Angiotensin III: a physiological relevant peptide of the renin angiotensin system.
  Journal
Peptides 46:26-32 (2013)
DOI:10.1016/j.peptides.2013.04.014
Reference
PMID:24760442
  Authors
Etelvino GM, Peluso AA, Santos RA
  Title
New components of the renin-angiotensin system: alamandine and the MAS-related G protein-coupled receptor D.
  Journal
Curr Hypertens Rep 16:433 (2014)
DOI:10.1007/s11906-014-0433-0
Related
pathway
hsa04270  Vascular smooth muscle contraction
hsa04610  Complement and coagulation cascades
hsa04924  Renin secretion
hsa04925  Aldosterone synthesis and secretion
KO pathway
ko04614   
LinkDB

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