This group of metallopeptidases belong to the MEROPS peptidase family M2 (clan MA(E)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA. The catalytic residues and zinc ligands have been identified, the zinc ion being ligated to two His residues within the motif HEXXH, showing that the enzyme belongs to the glu-zincin sub-group of metalloproteases [].Peptidyl-dipeptidase A (angiotensin-converting enzyme or ACE, ) is a mammalian enzyme responsible for cleavage of dipeptides from the C-termini of proteins, notably converting decapeptide angiotensin I to the octapeptide angiotensin II []. The enzyme exists in two differentially transcribed forms, the most common of which is from lung endothelium; this contains two homologous domains that have arisen by gene duplication []. The testis-specific form contains only the C-terminal domain, arising from a duplicated promoter region present in intron 12 of the gene []. Both enzymatic forms are membrane proteins that are anchored by means of a C-terminal transmembrane domain. Both domains of the endothelial enzyme are active, but have differing kinetic constants [, ]. ACE is well-known as a key part of the renin-angiotensin system that regulates blood pressure and ACE inhibitors are important for the treatment of hypertension [, ].An ACE homologue, ACE2 (MEROPS identifier M02.006), has been identified in humans that differs from ACE; it preferentially removes carboxy-terminal hydrophobic or basic amino acids and appears to be important in cardiac function [, ]. ACE3 is a non-peptidase homologue included in this entry which lacks Glu378 in the HEXXH motif.A number of insect enzymes have been shown to be similar to peptidyl-dipeptidase A, these containing a single catalytic domain [, ].
Angiotensinogen is a component of the renin-angiotensin system (RAS), a hormone system that regulates blood pressure and fluid balance. It is also known as the renin substrate, and is a non-inhibitory member of the serpin family of proteinase inhibitors (MEROPS inhibitor family I4, clan ID, MEROPS identifier I04.953).Angiotensinogen is catalytically cleaved by renin to produce angiotensin I in response to lowered blood pressure. Angiotensin converting enzyme (ACE), subsequently removes a dipeptide to produce angiotensin II, the physiologically active peptide, which functions in the regulation of volume and mineral balance of body fluids [, ]. Angiotensin I and angiotensin II can be further processed to generate angiotensin III, which stimulates aldosterone release [], and angiotensin IV. Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 []and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4 [, ].Angiotensinogen is synthesised in the liver and secreted in plasma [, , , ]. Angiotensinogen appears to be associated with a predisposition to essential hypertension; it is also associated with pregnancy-induced hypertension (pih) (preeclampsia), a heterogeneous disorder that complicates 5-7% of all pregnancies and remains a leading cause of maternal, foetal and neonatal morbidity and mortality [].The entry represents the full precursor sequence of angiotensinogen.
Angiotensinogen is a component of the renin-angiotensin system (RAS), a hormone system that regulates blood pressure and fluid balance. It is also known as the renin substrate, and is a non-inhibitory member of the serpin family of proteinase inhibitors (MEROPS inhibitor family I4, clan ID, MEROPS identifier I04.953).Angiotensinogen is catalytically cleaved by renin to produce angiotensin I in response to lowered blood pressure. Angiotensin converting enzyme (ACE), subsequently removes a dipeptide to produce angiotensin II, the physiologically active peptide, which functions in the regulation of volume and mineral balance of body fluids [, ]. Angiotensin I and angiotensin II can be further processed to generate angiotensin III, which stimulates aldosterone release [], and angiotensin IV. Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 []and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4 [, ].Angiotensinogen is synthesised in the liver and secreted in plasma [, , , ]. Angiotensinogen appears to be associated with a predisposition to essential hypertension; it is also associated with pregnancy-induced hypertension (pih) (preeclampsia), a heterogeneous disorder that complicates 5-7% of all pregnancies and remains a leading cause of maternal, foetal and neonatal morbidity and mortality [].This entry represents the serpin domain of angiotensinogen.
