ACE2

ACE2 belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angi

Full Name

Angiotensin I Converting Enzyme 2

Function

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 (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency. In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity.
Isoform 2: Non-functional as a carboxypeptidase. Acts as a receptor for human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63.
Isoform 2: Non-functional as a receptor for human coronavirus SARS-CoV-2.

Biological Process

Angiotensin maturation
Angiotensin-mediated drinking behavior
Blood vessel diameter maintenance
Negative regulation of signaling receptor activity
Positive regulation of amino acid transport
Positive regulation of cardiac muscle contraction
Positive regulation of gap junction assembly
Positive regulation of L-proline import across plasma membrane
Positive regulation of reactive oxygen species metabolic process
Proteolysis
Receptor-mediated virion attachment to host cell
Regulation of cardiac conduction
Regulation of cell population proliferation
Regulation of cytokine production
Regulation of inflammatory response
Regulation of systemic arterial blood pressure by renin-angiotensin
Regulation of transmembrane transporter activity
Regulation of vasoconstriction
Tryptophan transport
Viral entry into host cell

Cellular Location

Secreted; Cell membrane; Apical cell membrane; Cytoplasm; Cilium. Detected in both cell membrane and cytoplasm in neurons.
Isoform 2: Apical cell membrane

Topology

Extracellular: 18-740 aa
Helical: 741-761 aa
Cytoplasmic: 762-805 aa

PTM

N-glycosylation on Asn-90 may limit SARS infectivity.
Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1.
Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains.