ACE2: Angiotensin-Converting Enzyme 2 - Key Regulator of Cardiovascular and Pulmonary Function
Comprehensive genomic and proteomic overview of ACE2, the entry receptor for SARS-CoV-2 and a critical modulator of the renin-angiotensin system.
Gene Information Card
| Symbol | ACE2 |
|---|---|
| Full Name | Angiotensin converting enzyme 2 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 59272 ncbi.nlm.nih.gov/gene/59272 |
| Ensembl ID | ENSG00000130234 |
| UniProt ID | Q9BYF1 |
| OMIM ID | 300335 |
| HGNC ID | 13557 |
| Aliases | ACEH, DKFZp564A032, MGC102953 |
Description
ACE2 (angiotensin-converting enzyme 2) encodes a protein belonging to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases. The encoded protein acts as a carboxypeptidase, cleaving angiotensin I to angiotensin 1-9 and angiotensin II to angiotensin 1-7, thereby counterbalancing the vasoconstrictive and proliferative effects of angiotensin II. ACE2 is a functional receptor for the spike glycoprotein of SARS-CoV-2, mediating viral entry into host cells. It is expressed predominantly in the heart, kidneys, testes, and gastrointestinal tract, and plays a critical role in cardiovascular, renal, and pulmonary homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| COVID-19 | ACE2 serves as the primary entry receptor for SARS-CoV-2; viral binding downregulates ACE2, contributing to acute lung injury and multi-organ dysfunction. | ClinVar, NCBI |
| Hypertension | ACE2 deficiency leads to increased angiotensin II levels, promoting vasoconstriction and elevated blood pressure; ACE2 activation is protective. | OMIM, NCBI |
| Heart failure | Reduced ACE2 activity is associated with cardiac hypertrophy and fibrosis; ACE2 overexpression attenuates heart failure in animal models. | NCBI, UniProt |
| Diabetic nephropathy | ACE2 loss in renal tubules exacerbates albuminuria and glomerular injury; ACE2 activation reduces kidney damage. | OMIM, NCBI |
| Acute respiratory distress syndrome (ARDS) | ACE2 downregulation by SARS-CoV-2 spike protein worsens lung inflammation and edema; recombinant ACE2 is under investigation. | ClinVar, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 169.5 | High |
| Testis | 78.2 | High |
| Kidney | 63.1 | High |
| Heart | 42.8 | Medium |
| Adipose tissue | 20.3 | Medium |
| Lung | 8.9 | Low |
| Liver | 4.2 | Low |
| Brain | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colon) | 120.5 | High expression; used in SARS-CoV-2 infection models |
| HPAEC (pulmonary artery endothelial) | 45.2 | Moderate expression; relevant to lung vascular function |
| HEK 293 (embryonic kidney) | 30.1 | Moderate expression; common for recombinant ACE2 studies |
| Huh-7 (hepatoma) | 12.3 | Low expression |
| A549 (lung carcinoma) | 5.8 | Low expression; often used for viral entry assays |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2285666 (c.439+4A>G) | Intronic variant | 0.30 (global) | Associated with altered ACE2 expression and COVID-19 susceptibility |
| rs2074192 (c.2160A>G) | Synonymous | 0.45 (global) | Linked to hypertension and cardiovascular risk |
| p.Asn720Asp (rs41303171) | Missense | 0.01 (global) | May reduce SARS-CoV-2 spike binding affinity |
| p.Ser19Pro (rs73635825) | Missense | 0.005 (global) | Rare; potential impact on protein stability |
| p.Lys26Arg (rs143936283) | Missense | 0.002 (global) | Rare; functional significance unknown |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., catalytic site variants) reduce angiotensin II cleavage, leading to increased angiotensin II levels, promoting hypertension, cardiac hypertrophy, and renal injury.
Gain of Function (GOF)
Gain-of-function variants (e.g., increased expression or catalytic activity) enhance angiotensin 1-7 production, providing protective effects against cardiovascular and pulmonary diseases.
Dominant Negative (DN)
No well-characterized dominant-negative mutations have been reported for ACE2.
View complete mutation data：
Gene Ontology (GO)
| • peptidase activity (GO:0008233) | • metallocarboxypeptidase activity (GO:0004181) |
| • proteolysis (GO:0006508) | • angiotensin maturation (GO:0002003) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • receptor activity (GO:0004872) | • identical protein binding (GO:0042802) |
| • protein binding (GO:0005515) | • cytoplasm (GO:0005737) |
Pathways
• Renin-angiotensin system (RAS) - ACE2 converts Ang II to Ang 1-7
• counteracting ACE activity.
• SARS-CoV-2 infection pathway - ACE2 is the cellular entry receptor for SARS-CoV-2 spike protein.
• Regulation of blood pressure by ACE2 - ACE2/Ang 1-7/Mas receptor axis mediates vasodilation.
• Tryptophan metabolism - ACE2 indirectly influences amino acid transport via neutral amino acid transporter B(0)AT1.
Protein Summary
ACE2 is a type I transmembrane metallocarboxypeptidase of 805 amino acids (UniProt Q9BYF1). It consists of an N-terminal catalytic domain, a single transmembrane helix, and a short C-terminal cytoplasmic tail. The catalytic domain contains a HEXXH zinc-binding motif essential for enzymatic activity. ACE2 cleaves a single residue from the C-terminus of angiotensin II (Ang II) to generate angiotensin 1-7 (Ang 1-7), which acts via the Mas receptor to promote vasodilation, anti-inflammation, and anti-fibrosis. ACE2 also serves as the primary receptor for SARS-CoV-2 spike protein, facilitating viral entry. The protein is heavily glycosylated and expressed on the apical surface of epithelial cells in the lung, intestine, kidney, and heart. Soluble ACE2, generated by ADAM17-mediated shedding, circulates in plasma and may neutralize SARS-CoV-2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BACE2 Knockout HEK293 Cell Line | EDJ-KQ2355 | Human | 25825 | Details Get a Quote |
| ACE2 Knockout HEK293 Cell Line | EDJ-KQ17852 | Human | 59272 | Details Get a Quote |
| BACE2 Knockout HCT 116 Cell Line | EDJ-KQ21465 | Human | 25825 | Details Get a Quote |
| BACE2 Knockout A-549 Cell Line | EDJ-KQ22787 | Human | 25825 | Details Get a Quote |
| BACE2 Knockout HeLa Cell Line | EDJ-KQ22789 | Human | 25825 | Details Get a Quote |
| ACE2 Knockout HeLa Cell Line | EDJ-KQ56960 | Human | 59272 | Details Get a Quote |
| ACE2 Knockout A-549 Cell Line | EDJ-KQ65466 | Human | 59272 | Details Get a Quote |
| ACE2 Knockout HCT 116 Cell Line | EDJ-KQ73901 | Human | 59272 | Details Get a Quote |
| ACE2 Overexpression HEK293 Stable Cell Line | EDJ-GQ96 | Human | 59272 | Details Get a Quote |
| ACE2 Overexpression HEK293T Stable Cell Line | EDJ-GQ97 | Human | 59272 | Details Get a Quote |
| ACE2 Overexpression HeLa Stable Cell Line | EDJ-GQ98 | Human | 59272 | Details Get a Quote |
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