Peptidase M2, peptidyl-dipeptidase A (IPR001548)

Short name: Peptidase_M2

Overlapping homologous superfamilies


Family relationships



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 [PMID: 7674922].

Peptidyl-dipeptidase A (angiotensin-converting enzyme or ACE, EC 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 [PMID: 7674922]. 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 [PMID: 7674922]. The testis-specific form contains only the C-terminal domain, arising from a duplicated promoter region present in intron 12 of the gene [PMID: 7674922]. 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 [PMID: 7674922, PMID: 1851160]. 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 [PMID: 17439247, PMID: 18457420].

An ACE homolog, 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 [PMID: 14754895, PMID: 17464936].

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 [PMID: 12633854, PMID: 9629165].

GO terms

Biological Process

GO:0006508 proteolysis

Molecular Function

GO:0008237 metallopeptidase activity
GO:0008241 peptidyl-dipeptidase activity

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.