{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:05:20Z","timestamp":1782903920406,"version":"3.54.5"},"reference-count":101,"publisher":"Portland Press Ltd.","issue":"18","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin\u2013angiotensin system (RAS) and providing a cardioprotective role. Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. However, it does convert a number of other regulatory peptides in vitro and in vivo. Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles.<\/jats:p>","DOI":"10.1042\/cs20200476","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T09:27:14Z","timestamp":1601371634000},"page":"2489-2501","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Discovery and characterization of ACE2 \u2013 a 20-year journey of surprises from vasopeptidase to COVID-19"],"prefix":"10.1042","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5811-3484","authenticated-orcid":false,"given":"Nigel\u00a0M.","family":"Hooper","sequence":"first","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-3145","authenticated-orcid":false,"given":"Daniel\u00a0W.","family":"Lambert","sequence":"additional","affiliation":[{"name":"School of Clinical Dentistry and Neuroscience Institute, University of Sheffield, Sheffield S10 2TA, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-8198","authenticated-orcid":false,"given":"Anthony\u00a0J.","family":"Turner","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT,U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"2021113011161345900_B1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1084\/jem.103.3.295","article-title":"The Preparation and Function of the Hypertensin-Converting Enzyme","volume":"103","author":"Skeggs","year":"1956","journal-title":"J. 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