Angiotensin-Converting Enzyme 2 (ACE-2) is an endogenous transmural metalloprotein (zinc + protein base) receptor present on the surface of many types of cells. ACE-2 has three main functions, 1) amino acid transport facilitation, 2) down regulation of the renin-angiotensin system, 3) and receptor for the SARS-CoV-2 virus. Historically, it has also served as the entry point for previous viruses including SARS-CoV-1 and HcoV-NL63.

ACE-2 expressed in a variety of organ cells including lungs, cardiovascular system, gut, and kidneys. The wide distribution of ACE-2 in the body explains some symptoms of COVID-19 including respiratory distress, GI distress, and renal failure. Individual expression variation in number or configuration of ACE-2 receptors helps explain variation in symptomatic response. For instance, smoking has been shown to upregulate ACE-2 gene expression.

The renin-angiotensin system regulates blood pressure. When the kidney experiences decreased blood flow, such as from low water or sodium, they release renin. Renin then catalyzes the conversion of angiotensin into angiotensin I. An enzyme in the serum, angiotensin-converting enzyme (ACE) then converts angiotensin I into angiotensin II. Angiotensin II stimulates the secretion of aldosterone from the adrenals which increases reabsorption of salt and water by the kidneys and causes vasoconstriction of arterioles, increasing blood pressure. Cleaved, soluble ACE-2 converts Angiotensin II into Angiotensin (1-7) and serves as the counterbalance to the renin-angiotensin system.

Human ACE2 domains

SP = Signal peptide; TM = transmembrane domain; ID = Intracellular domain