A Human Homolog of Angiotensin-converting Enzyme

By S. Tipnis, N. Hooper, R. Hyde, E. Karran, G. Christie, A. Turner. Journal of Biological Chemistry, 2000

1,976 citations recorded by the source corpus.

A novel human zinc metalloprotease that has considerable homology to human angiotensin-converting enzyme (ACE) (40% identity and 61% similarity) has been identified. This metalloprotease (angiotensin-converting enzyme homolog (ACEH)) contains a single HEXXH zinc-binding domain and conserves other critical residues typical of the ACE family. The predicted protein sequence consists of 805 amino acids, including a potential 17-amino acid N-terminal signal peptide sequence and a putative C-terminal membrane anchor. Expression in Chinese hamster ovary cells of a soluble, truncated form of ACEH, lacking the transmembrane and cytosolic domains, produces a glycoprotein of 120 kDa, which is able to cleave angiotensin I and angiotensin II but not bradykinin or Hip-His-Leu. In the hydrolysis of the angiotensins, ACEH functions exclusively as a carboxypeptidase. ACEH activity is inhibited by EDTA but not by classical ACE inhibitors such as captopril, lisinopril, or enalaprilat. Identification of the genomic sequence of ACEH has shown that the ACEH gene contains 18 exons, of which several have considerable size similarity with the first 17 exons of human ACE. The gene maps to chromosomal location Xp22. Northern blotting analysis has shown that the ACEH mRNA transcript is ∼3.4 kilobase pairs and is most highly expressed in testis, kidney, and heart. This is the first report of a mammalian homolog of ACE and has implications for our understanding of cardiovascular and renal function.

Subfields: Cardiology and Cardiovascular Medicine, Cell Biology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/4f7316b3b0bdc7784711e6a8d03a4a42bf88f680

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In Cardiology and Cardiovascular Medicine

Citations in the corpus

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis (2004, result): “These data are consistent with previous findings that low levels of ACE2 mRNA are found in many tissues and that ACE2 mRNA is highly expressed in renal, cardiovascular, and gastrointestinal tissues [8,10,12].”
Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System (2020, background): “2, 3, 15, 16, [23] [24] [25] [26] [27] While many metallopeptidases cluster in small inter-related gene families (eg, the neprilysin [NEP] family), unusually, no human homolog of the vasoactive zinc-peptidase ACE (angiotensin converting enzyme) had been identified at the turn of the century.”
Role of the ACE2/Angiotensin 1–7 axis of the Renin-Angiotensin System in Heart Failure (2016, methodology): “unaffected by ACE inhibitors (ACEi), such as captopril and lisinopril.(32,33,36) Further research revealed a major difference in”
Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2 (2005, background): “Evidence of a role for ACE2 in the human heart is provided by (1) the study of Crackower et al11 in ACE2-null mice, (2) the demonstration that Ang-(1–7) was increased in the hearts of patients receiving ACE inhibitors,13 and (3) the finding of ACE2 upregulation in ventricular membrane preparations f”
Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. (2004, background): “Adding a new level of complexity to the RAS, recently a renin receptor has been reported in the heart, kidney, brain, placenta and liver, which may function to increase the catalytic activity of renin [13], and an ACE homologue, ACE2, has been isolated [14,15] and found to play an essential role in ”
Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes (2009, background): “Since its discovery in 2000 [2, 3], ACE2 has been implicated in heart function, hypertension, and diabetes, with its effects being mediated, in part, through its ability to convert angiotensin II to angiotensin 1–7.”
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus (2003, background): “Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2”
SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways (2020, neutral): “2010; Tipnis et al.”
The protein expression profile of ACE2 in human tissues (2020, positive): “Early studies based on multi-tissue Northern blotting and QRT-PCR have suggested moderate to high transcript expression of ACE2 in kidney, testis, heart, and the intestinal tract, while the expression was low or absent in lung (Tipnis et al , 2000; Harmer et al , 2002).”
The pivotal link between ACE2 deficiency and SARS-CoV-2 infection (2020, positive): “The catalytic efficiency of ACE2 is 400 times higher on angiotensin II than on angiotensin I. [6] ACE2 shows a 40% structural identity to ACE, [4] although ACE-inhibitors do not block ACE2 because of the different conformational structure of the catalytic site.”
COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection (2021, background): “Moreover, chronic activation of RAAS is associated with Ang II/AT1 deleterious effects, exacerbating the inflammation, fibrosis, apoptosis, antidiuretic hormone (ADH) and aldosterone release, and ultimately water and sodium retention [9, 10] Discovered in 2000 [11] as an ACE homolog with distinguish”
Renin‐angiotensin system revisited (2008, background): “Angiotensin-converting enzyme 2 was discovered and cloned rather recently [38, 39] .”