KEGG   PATHWAY: oas04614
Entry
oas04614                    Pathway                                
Name
Renin-angiotensin system - Ovis aries (sheep)
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
oas04614  Renin-angiotensin system
oas04614

Other DBs
GO: 0002003
Organism
Ovis aries (sheep) [GN:oas]
Gene
101119440  AGT; angiotensinogen [KO:K09821]
443310  REN; renin precursor [KO:K01380] [EC:3.4.23.15]
554335  ACE; angiotensin-converting enzyme isoform X1 [KO:K01283] [EC:3.4.15.1]
105613829  angiotensin-converting enzyme-like protein Ace3 isoform X1 [KO:K01283] [EC:3.4.15.1]
101112678  LOW QUALITY PROTEIN: mast cell protease 2 [KO:K01329] [EC:3.4.21.39]
101107261  mast cell protease 2 precursor [KO:K01329] [EC:3.4.21.39]
114109029  mast cell protease 2-like [KO:K01329] [EC:3.4.21.39]
101121553  cathepsin G-like [KO:K01319] [EC:3.4.21.20]
101121298  cathepsin G-like [KO:K01319] [EC:3.4.21.20]
100048991  KLK1; kallikrein-1 precursor [KO:K01325] [EC:3.4.21.35]
101117763  ENPEP; glutamyl aminopeptidase [KO:K11141] [EC:3.4.11.7]
101104860  ANPEP; aminopeptidase N [KO:K11140] [EC:3.4.11.2]
101110768  PREP; prolyl endopeptidase isoform X2 [KO:K01322] [EC:3.4.21.26]
101103622  ACE2; angiotensin-converting enzyme 2 isoform X2 [KO:K09708] [EC:3.4.17.23]
101113615  CTSA; lysosomal protective protein isoform X2 [KO:K13289] [EC:3.4.16.5]
101123173  CPA3; mast cell carboxypeptidase A [KO:K08780] [EC:3.4.17.1]
101112618  MME; neprilysin isoform X2 [KO:K01389] [EC:3.4.24.11]
101119557  THOP1; thimet oligopeptidase [KO:K01392] [EC:3.4.24.15]
101123582  NLN; neurolysin, mitochondrial [KO:K01393] [EC:3.4.24.16]
101107644  PRCP; lysosomal Pro-X carboxypeptidase [KO:K01285] [EC:3.4.16.2]
101112233  MAS1; proto-oncogene Mas [KO:K04303]
101115243  mas-related G-protein coupled receptor member D [KO:K08392]
121817522  mas-related G-protein coupled receptor member D-like [KO:K08392]
443107  AGTR1; type-1 angiotensin II receptor [KO:K04166]
443335  AGTR2; type-2 angiotensin II receptor [KO:K04167]
101102729  LNPEP; leucyl-cystinyl aminopeptidase isoform X2 [KO:K01257] [EC:3.4.11.3]
101103453  ATP6AP2; renin receptor isoform X1 [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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
oas04270  Vascular smooth muscle contraction
oas04610  Complement and coagulation cascades
oas04924  Renin secretion
oas04925  Aldosterone synthesis and secretion
KO pathway
ko04614   
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