ACE2

Domain

The extracellular region of the ACE2 enzyme is composed of two domains. The first is a zinc metallopeptidase domain (residues 19-611). The second domain is located at the C-terminus (residues 612-740) and is 48% identical to human collectrin.

The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interation with proteins that mediate endocytic trafficking and autophagy.

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 (PubMed:27217402). 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 (PubMed:10969042, PubMed:10924499, PubMed:11815627, PubMed:19021774, PubMed:14504186). Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin (PubMed:10969042, PubMed:11815627). 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 (PubMed:11815627, PubMed:27217402, PubMed:28293165). 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 (PubMed:18424768, PubMed:19185582).

Isoform 2

Non-functional as a carboxypeptidase.

(Microbial infection) Acts as a receptor for human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63.

Isoform 2

(Microbial infection) Non-functional as a receptor for human coronavirus SARS-CoV-2.

Post-translational modifications

N-glycosylation on Asn-90 may limit SARS infectivity.

Proteolytic cleavage by ADAM17 generates a secreted form (PubMed:15983030, PubMed:33713620). 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.

Sequence similarities

Belongs to the peptidase M2 family.

Tissue specificity

Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells (at protein level) (PubMed:15141377). Expressed in enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level) (PubMed:15141377). Expressed in the renal proximal tubule and the small intestine (at protein level) (PubMed:18424768). Expressed in heart, kidney, testis, and gastrointestinal system (at protein level) (PubMed:10969042, PubMed:10924499, PubMed:15231706, PubMed:12459472, PubMed:15671045, PubMed:32715618, PubMed:32170560). In lung, expressed at low levels in some alveolar type 2 cells, the expression seems to be individual-specific (at protein level) (PubMed:32425701, PubMed:15141377, PubMed:32715618, PubMed:32170560, PubMed:33432184). Expressed in nasal epithelial cells (at protein level) (PubMed:33432184, PubMed:32333915). Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal epithelial cells, cornea, gallbladder and nasal goblet secretory cells (PubMed:32413319, PubMed:32327758, PubMed:32358202). Coexpressed with TMPRSS4 within mature enterocytes (PubMed:32404436).

Isoform 2

Expressed in nasal and bronchial epithelial cells (at protein level).

Cellular localization

• Processed angiotensin-converting enzyme 2
• Secreted
• Cell membrane
• Single-pass type I membrane protein
• Cytoplasm
• Cell projection
• Cilium
• Apical cell membrane
• Detected in both cell membrane and cytoplasm in neurons.
• Isoform 2
• Apical cell membrane

Alternative names

• Angiotensin-converting enzyme 2
• Angiotensin-converting enzyme homolog
• Angiotensin-converting enzyme-related carboxypeptidase
• Metalloprotease MPROT15
• ACEH
• ACE-related carboxypeptidase
• UNQ868/PRO1885
• ACE2

Database links

• entrezGene:59272
• omim:300335
• swissprot:Q9BYF1

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

92463Da