renin; angiotensinogenase (REN)

Function

• highly specific endopeptidase
• only known function is to generate angiotensin I from angiotensinogen in plasma, initiating a cascade of reactions that results in elevation of blood pressure & increased Na+ retention by the kidney
• cleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I
• interaction with ATP6AP2 results in a 5-fold increased efficiency in angiotensinogen processing
• renin binds to RENBP forming a protein complex called HMW renin that inhibits renin activity
• angiotensin I is converted in lungs to vasoconstrictor angiotensin II

Kinetic parameters:

• KM=1 uM for angiotensinogen (in absence of ATP6AP2)
• KM=0.15 uM for angiotensinogen (in presence of membrane-bound ATP6AP2)

Structure

belongs to the peptidase A1 family

Compartment

• secreted
• membrane: associated with membranes via binding to ATP6AP2

Alternative splicing

named isoforms=2

Expression

• renin is produced within juxtaglomerular cells after processing & cleavage of prorenin, which is produced in the liver
• primary stimuli for renin release include:
  • reduction of renal perfusion pressure
  • hyponatremia
• other factors effecting renin release include:
  • sympathetic nervous system
  • angiotensin II
  • vasopressin
  • endothelin
  • prostaglandins
  • atrial natriuretic factor (perhaps)

Pathology

• defects in REN are a cause of renal tubular dysgenesis
• defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2

More general terms

• aspartic proteinase; carboxyl acid protease
• secreted protein
• regulatory molecule

More specific terms

• prorenin

Additional terms

• angiotensin-1/renin activity in plasma
• renin activity in renal vein

Component of

• high molecular weight renin (HMW renin)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5972
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5972
• OMIM: https://mirror.omim.org/entry/179820
• OMIM: https://mirror.omim.org/entry/267430
• OMIM: https://mirror.omim.org/entry/613092
• UniProt: http://www.uniprot.org/uniprot/P00797.html