Candidate Genes Diabetic Retinopathy

Angiotensin I Converting Enzyme

Official Symbol
ACE
Alternative Names
Peptidase P, Kininase II, Carboxycathepsin, Dipeptidyl carboxypeptidase 1
Description
This gene encodes an enzyme exopeptidase involved in catalyzing the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This enzyme plays a key role in the renin- angiotensin system. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme or cardiovascular pathophysiologies. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, and two most abundant spliced variants encode the somatic form and the testicular form, respectively, that are equally active.
Location
17q23.3
Map
Chr 17
Start: 61,554,432 bp from pter
End: 61,599,209 bp from pter
Size: 44,778 bases
Orientation: plus strand
Exons and Introns
26 exons and 58 distinct introns (54 gt-ag, 3 gc-ag, 1 other).
Nucleotide Sequence
Aminoacid Sequence
Variation
rs4343 A/G
Motif
Pfam: Peptidase_M2

PROSITE: Zinc_Protease
Ec No.
3.4.15.1 
Catalytic Activity
Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.
Active Site
Zinc binding motif HEXXH
Cofactor

Binds 3 chloride ions per subunit

Binds 2 zinc ions per subunit.

Biophysico

chemical  Properties

Kinetic parameters:

KM=2.51 mM for Hip-His-Leu
Enzyme Regulation
Strongly activated by chloride. Specifically inhibited by lisinopril, captopril and enalaprilat
Induction
Up-regulated in failing heart
Pathway

ACE inhibitor pathway

ACE Inhibitor Pathway, Pharmacodynamics

Pathway

Renin-Angiotensin-Aldosterone-System-acting drug pathway (PD)

Renin-Angiotensin-Aldosterone-System-acting Drug Pathway (PD)

Interactors

Protein interactors
Bradykinin receptor 2
Catechol –O- methyltransferase
Angiotensin II receptor 2
Non protein interactors

Zinc
Post Translational Modification
Phosphorylated by CK2 on Ser-1299; which allows membrane retention
Molecular Weight
149714  da
Molecular Class
Enzyme: Hydrolase 
Molecular Function

Actin binding
Bradykinin receptor binding
Carboxypeptidase activity
Chloride ion binding
Drug binding
Metallopeptidase activity
Zinc ion binding
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. A

Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety
3D Structure

------------------------pdb3nxq