BACE2

Angiotensin-converting enzyme 2 UniProt accession Q9BYF1

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:10924499, PubMed:10969042, PubMed:11815627, PubMed:14504186, PubMed:19021774). 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)

Source: UniProt

Homodimer (PubMed:32132184). Interacts with the catalytically active form of TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine (By similarity).

Interacts with ITGA5:ITGB1 (PubMed:15276642, PubMed:33102950). Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781 (PubMed:33436498). Interacts (via PDZ-binding motif) with NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane residence (PubMed:34189428)

(Microbial infection) Interacts with SARS coronavirus/SARS-CoV spike protein

(Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein (via RBD domain)

(Microbial infection) Interacts with human coronavirus NL63 spike protein

(Microbial infection) Interacts with human coronavirus NL63/HCoV-NL63 spike glycoprotein

(Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein; the interaction is increased by AVP/Arg-vasopressin with which they may form a complex

Source: UniProt
Secreted Cell membrane — Single-pass type I membrane protein, Cytoplasm, Cell projection, cilium, Apical cell membrane Apical cell membrane
Source: UniProt

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:10924499, PubMed:10969042, PubMed:12459472, PubMed:15231706, PubMed:15671045, PubMed:32170560, PubMed:32715618). In lung, expressed at low levels in some alveolar type 2 cells, the expression seems to be individual-specific (at protein level) (PubMed:15141377, PubMed:32170560, PubMed:32425701, PubMed:32715618, PubMed:33432184). Expressed in nasal epithelial cells (at protein level) (PubMed:32333915, PubMed:33432184).

Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal epithelial cells, cornea, gallbladder and nasal goblet secretory cells (PubMed:32327758, PubMed:32358202, PubMed:32413319). Coexpressed with TMPRSS4 within mature enterocytes (PubMed:32404436)

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

Source: UniProt

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 interaction with proteins that mediate endocytic trafficking and autophagy

Source: UniProt

Click a pathway to open the interactive Reactome viewer.

Pathway list and interactive viewer: Reactome

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to BACE2, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 1

NCT ID Condition Brief Title Phase Status
NCT04335136 COVID-19 Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 PHASE2 COMPLETED
NCT04422457 Solid Tumor Specific Molecular Imaging of DX600 Labeled by PET Radionuclide Targeting ACE2 in Patients NA COMPLETED
NCT00192803 NIDDM Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs PHASE4 UNKNOWN
NCT04375046 COVID-19 Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP Could be Promising Treatment for COVID-19 Infection- and Its Inflammatory Complications Better Than Recombinant Human ACE2 PHASE1 UNKNOWN
NCT04640610 Adenoidectomy, Tonsillectomy Angiotensin-converting Enzyme 2 (ACE2) Expression in Tonsils and Adenoids N/A WITHDRAWN
NCT04870164 COVID-19 Safety, Tolerability and PK of Ensovibep (MP0420 - a New Candidate With Potential for Treatment of COVID-19) PHASE1 TERMINATED
NCT04990557 COVID-19 Respiratory Infection CRISPR/Cas9-modified Human T Cell ( PD-1and ACE2 Knockout Engineered T Cells ) for Inducing Long-term Immunity in COVID-19 Patients PHASE1, PHASE2 UNKNOWN
NCT04382950 COVID Combination of Recombinant Bacterial ACE2 Receptors -Like Enzyme of B38-CAP and Isotretinoin Could be Promising Treatment for COVID-19 Infection- and Its Inflammatory Complications PHASE1 UNKNOWN
NCT06194630 Lung Cancer, Healthy Human Application of 68Ga-labeled ACE2 Targeting Probe PET/CT Imaging in Tracing ACE2 Expression and Diagnosis of Lung Cancer EARLY_PHASE1 UNKNOWN
NCT04318301 COVID-19, Hypertension Hypertension in Patients Hospitalized With COVID-19 N/A COMPLETED