Protein / target
Angiotensin-converting enzyme
Protein at a glance
Biological role
Mitogen-activated protein kinase kinase binding
Primary system
Nervous system
Strongest disease association
renal tubular dysgenesis
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
22 approved · 2 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (PubMed:15615692, PubMed:20826823, PubMed:2558109, PubMed:4322742, PubMed:7523412, PubMed:7683654). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:10913258, PubMed:1320019, PubMed:1851160, PubMed:19773553, PubMed:7683654, PubMed:7876104). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (PubMed:11432860, PubMed:1851160, PubMed:19773553, PubMed:23056909, PubMed:4322742). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (PubMed:15615692, PubMed:2558109, PubMed:4322742, PubMed:6055465, PubMed:6270633, PubMed:7683654). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (PubMed:15615692, PubMed:6208535, PubMed:6270633, PubMed:656131). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (PubMed:2982830, PubMed:6270633, PubMed:656131). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:26403559, PubMed:7876104, PubMed:8257427, PubMed:8609242). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (PubMed:10336644, PubMed:2983326, PubMed:7683654, PubMed:9371719). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (PubMed:10336644, PubMed:19773553, PubMed:7876104)
Subcellular location
Domains and Gene Ontology detail (59)Hide
Domains & features
Gene Ontology
- Cendosome
- Cexternal side of plasma membrane
- Cextracellular exosome
- Cextracellular region
- Cextracellular space
- Clysosome
- Cplasma membrane
- Factin binding
- Fbradykinin receptor binding
- Fcalmodulin binding
- Fchloride ion binding
- Fendopeptidase activity
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Proteolysis
- ·endopeptidase activity
- ·exopeptidase activity
- ·metallocarboxypeptidase activity
- ·metallodipeptidase activity
Metabolic enzyme activity
- ·amyloid-beta metabolic process
- ·hormone metabolic process
- ·regulation of angiotensin metabolic process
Kinase signalling
- ·mitogen-activated protein kinase binding
- ·mitogen-activated protein kinase kinase binding
Transcriptional regulation
- ·negative regulation of gene expression
- ·post-transcriptional regulation of gene expression
Synaptic signalling
- ·Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of…
Chloride transport
- ·chloride ion binding
View underlying pathways (1)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Angiotensin-converting enzyme inhibitor
Appears in clinical studies involving hypertensive disorder, myocardial infarction, congestive heart failure, diabetic kidney disease
Angiotensin-converting enzyme inhibitor
Appears in clinical studies involving hypertensive disorder, heart failure, stroke disorder, diabetes mellitus
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Show all associationsHide all associations
Open Targets ranks 2,523 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 24 total
cardiovascular disorder · congestive heart failure
hypertensive disorder · heart failure · congestive heart failure
hypertensive disorder · essential hypertension · Hypertension
Hypertension · hypertensive disorder · dilated cardiomyopathy
hypertensive disorder · myocardial infarction · congestive heart failure
cardiovascular disorder · hypertensive disorder
hypertensive disorder · diabetes mellitus · stroke disorder
hypertensive disorder
Stroke · coronary artery disorder · hypertensive disorder
cardiovascular disorder · Hypertension · type 2 diabetes mellitus
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- New publicationRelation between renal dysfunction and cardiovascular outcomes after myocardial infarction.
- New publicationValsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.
- New publicationA novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.