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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:
a) reduction of renal perfusion pressure
b) 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
Related
angiotensin-1/renin activity in plasma
renin activity in renal vein
Specific
prorenin
General
aspartic proteinase; carboxyl acid protease
regulatory molecule
secreted protein
Properties
SIZE: entity length = 406 aa
MW = 45 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-23}
N-glycosylation site {N71}
aspartate residue {D104}
cysteine residue {C117}
MODIFICATION: cysteine residue {C124}
cysteine residue {C124}
MODIFICATION: cysteine residue {C117}
N-glycosylation site {N141}
cysteine residue {C283}
MODIFICATION: cysteine residue {C287}
cysteine residue {C287}
MODIFICATION: cysteine residue {C283}
aspartate residue {D292}
cysteine residue {C325}
MODIFICATION: cysteine residue {C362}
cysteine residue {C362}
MODIFICATION: cysteine residue {C325}
SECRETED-BY: hepatocyte
Database Correlations
OMIM correlations
UniProt P00797
PFAM correlations
Entrez Gene 5972
Kegg hsa:5972
ENZYME 3.4.23.15
References
- Tietz Textbook of Clinical Chemistry, 2nd ed.
Burtis CA & Ashwood ER (eds), WB Saunders Co,
Philadelphia PA, 1993, pg 1519
- UniProt :accession P00797
- Wikipedia; Note: renin entry
http://en.wikipedia.org/wiki/renin
Component-of
high molecular weight renin (HMW renin)