Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins, casomorphins and dynorphin A (By similarity). By cleavage of angiotensin II, may be an important regulator of heart function (PubMed:12075344, PubMed:12967627). By cleavage of angiotensin II, may also have a protective role in acute lung injury (PubMed:16001071). Plays an important role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19, regulating its trafficking on the cell surface and its activity (PubMed:19185582, PubMed:18424768, PubMed:22677001). angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine angiotensin I + H2O = angiotensin-(1-9) + L-leucine bradykinin(1-8) + H2O = bradykinin(1-7) + L-phenylalanine H2O + neurotensin = L-leucine + neurotensin-(1-12) H2O + kinetensin = kinetensin-(1-8) + L-leucine dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine apelin-13 + H2O = apelin-12 + L-phenylalanine [Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine apelin-17 + H2O = apelin-16 + L-phenylalanine Binds 1 zinc ion per subunit. Binds 1 Cl(-) ion per subunit. Homodimer. Interacts with the catalytically active form of TMPRSS2 (By similarity). Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine (PubMed:19185582). Interacts with ITGA5:ITGB1 (By similarity). Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781 (By similarity). Interacts (via PDZ-binding motif) with SLC9A3R1 (via PDZ domains); the interaction may enhance ACE2 membrane residence (By similarity). (Microbial infection) Weakly interacts with SARS-CoV S protein. Detected in both cell membrane and cytoplasm in neurons. Expressed in heart, kidney and forebrain (at protein level). Expressed in the small intestine, with expression in the intestinal brush border (at protein level) (PubMed:19185582, PubMed:22677001). Ubiquitously expressed, with highest levels in ileum, kidney and lung. In lung, expressed on vascular endothelial and airway epithelial cells. Also expressed at high levels in lung secretory club and goblet cells as well as in alveolar type 2 cells (PubMed:32425701). Down-regulated in lung after acute injury. Exposure to cigarette smoke increases ACE2 expression up to 80% more in lungs (PubMed:32425701). The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interaction with proteins that mediate endocytic trafficking and autophagy. Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1 (By similarity). Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains. Mice are viable and fertile, exhibit normal kidney and lung function, but show a severe reduction in cardiac contractility, and are highly sensitive to severe acute lung failure (PubMed:12075344). Mutant males exhibit an absence of SLC6A19 in small intestine brush border membranes, but normal SLC6A19 expression in kidney (PubMed:19185582). Abolished sodium-dependent transport of isoleucine in intestinal rings (PubMed:19185582). Transgenic mice overexpressing ACE2 in the heart appear healthy but show conduction disturbances and ventricular arrhythmias which leads to sudden death (PubMed:12075344). Belongs to the peptidase M2 family.