Protein / target

Angiotensin-converting enzyme 2

Encoded byACE2Q9BYF1Homo sapiensSwiss-Prot

UniProt: Q9BYF1 Ensembl: ENSG00000130234 HGNC: HGNC:13557 NCBI Gene: 59272

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Metallocarboxypeptidase

Strongest disease association

COVID-19

Via encoding gene ACE2 · Genetic evidence · score 0.63

Research activity

Actively researched

31 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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)

Subcellular location

SecretedCell membraneCytoplasmCell projection, ciliumApical cell membrane

Domains and Gene Ontology detail (49)

Domains & features

Peptidase M2Collectrin-like

Gene Ontology

Capical plasma membrane
Cbrush border membrane
Ccell surface
Ccilium
Cendocytic vesicle membrane
Cendoplasmic reticulum lumen
Cextracellular exosome
Cextracellular region
Cextracellular space
Cmembrane
Cmembrane raft
Cplasma membrane

805 aa · 92 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOMetabolic enzyme activityUniProt · GOProteolysisGOImmune signallingGO

View supporting evidence

Cell proliferation & survival

·regulation of cell population proliferation

Metabolic enzyme activity

·Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system th…
·positive regulation of reactive oxygen species metabolic process

Proteolysis

·carboxypeptidase activity
·endopeptidase activity
·metallocarboxypeptidase activity
·metallopeptidase activity

Immune signalling

·regulation of cytokine production
·regulation of inflammatory response

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene ACE2

Gene-level evidence surfaced through the gene ACE2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

COVID-19

0.80Well supported

Genetic evidence dominant · Open Targets 0.68

Severe Acute Respiratory Syndrome

0.54Limited support

Pathway evidence dominant · Open Targets 0.56 · no direct causal or clinical evidence

Idiopathic Pulmonary Fibrosis

0.32Preliminary

Animal model evidence dominant · Open Targets 0.13 · no direct causal or clinical evidence

Lung carcinoma

0.30Preliminary

Animal model evidence dominant · Open Targets 0.13 · no direct causal or clinical evidence

Neurodegenerative Diseases

0.30Preliminary

Pathway evidence dominant · Open Targets 0.42 · no direct causal or clinical evidence

View evidence synthesis (5)

COVID-19Well supported

0.80

agreement 0.68–0.92

Genetic55%Pathway33%Literature13%

Open Targets aggregate 0.68 · 3 independent evidence families

Severe Acute Respiratory SyndromeLimited support

0.54

agreement 0.40–0.68

Pathway52%Animal model30%Literature17%

Open Targets aggregate 0.56 · 3 independent evidence families · no direct causal or clinical evidence

Idiopathic Pulmonary FibrosisPreliminary

0.32

agreement 0.15–0.50

Animal model62%Literature38%

Open Targets aggregate 0.13 · 2 independent evidence families · no direct causal or clinical evidence

Lung carcinomaPreliminary

0.30

agreement 0.13–0.48

Animal model59%Literature42%

Open Targets aggregate 0.13 · 2 independent evidence families · no direct causal or clinical evidence

Neurodegenerative DiseasesPreliminary

0.30

agreement 0.12–0.47

Pathway89%Literature11%

Open Targets aggregate 0.42 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

COVID-190.68

Severe Acute Respiratory Syndrome0.56

Neurodegenerative Diseases0.42

Alzheimer's Disease0.21

Parkinson's Disease0.21

Multiple Sclerosis0.18

Lysosomal Storage Diseases0.18

Autoimmune disorder of central nervous system0.14

Idiopathic Pulmonary Fibrosis0.13

Lung carcinoma0.13

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)

SM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.