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Background
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ACE2 cDNA encodes a deduced 805-amino acid protein containing a potential 17-amino acid N-terminal signal peptide and a putative 22-amino acid C-terminal membrane anchor. It also possesses a zinc metalloprotease consensus sequence and a conserved glutamine residue that may function as a third zinc ligand. ACE2 is expressed predominantly in vascular endothelial cells of the heart and kidney. ACE converts angiotensin I to angiotensin II, ACE2 converts angiotensin I to angiotensin 1-9, which has 9 amino acids. Angiotensin II is a potent blood vessel constrictor, while angiotensin 1-9 does not impact blood vessels but is cleaved by ACE to a shorter peptide, angiotensin 1-7, which is a blood vessel dilator. Spike (S) proteins of coronaviruses, including the SARS coronavirus, bind with cellular receptors to mediate infection of target cells. ACE2 binds the S1 domain of the SARS coronavirus S protein. SARS coronavirus replicates efficiently on ACE2-transfected but not mock-transfected 293T cells. Anti-ACE2 but not anti-ACE1 antibody blocks viral replication on Vero E6 cells. It has been proposed that ACE2 is a functional receptor for SARS coronavirus.
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Background
References
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- Douglas, G.C., et al., Endocrinology 145(10):4703-4711 (2004).
- Turner, A.J., et al., Trends Pharmacol. Sci. 25(6):291-294 (2004).
- Towler, P., et al., J. Biol. Chem. 279(17):17996-18007 (2004).
- Wong, S.K., et al., J. Biol. Chem. 279(5):3197-3201 (2004).
- Li, W., et al., Nature 426(6965):450-454 (2003).
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