ACE (angiotensin I converting enzyme; HGNC:2707, NCBI Gene ID 1636) is a human locus mapped to chromosome band 17q23.3 that encodes endothelial zinc metallopeptidase ACE (1,306 aa somatic; 732 aa testicular; EC 3.4.15.1). ACE acts in conversion of Angiotensin I to vasoconstrictor Angiotensin II & degradation of vasodilator Bradykinin, together with AGT (Angiotensinogen Precursor Gene), KLKB1 (Plasma Prekallikrein / Bradykinin Gene), and NOS3 (Endothelial Nitric Oxide Synthase Gene). Encodes endothelial angiotensin-converting enzyme, the zinc metallopeptidase generating angiotensin II and degrading bradykinin.
Approved Symbol
ACE
Chromosomal Locus
17q23.3
Encoded Product
Endothelial zinc metallopeptidase ACE (1,306 aa somatic; 732 aa testicular; EC 3.4.15.1)
Primary Pathway
Conversion of Angiotensin I to vasoconstrictor Angiotensin II & degradation of vasodilator Bradykinin
Clinical / Therapeutic Role
Direct target of ACE inhibitors (lisinopril, enalapril, ramipril); intron 16 I/D polymorphism in endurance vs. power physiology
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 26-exon gene on chromosome 17q23.3 that arose from an ancient tandem gene duplication: a somatic promoter drives transcription of exons 1–26 (excluding exon 13) to produce a two-domain enzyme with homologous N- and C-terminal HEXXH zinc-binding catalytic sites, whereas a sperm-specific promoter inside intron 12 drives transcription of single-domain testicular ACE.
Cellular & Tissue Expression Profile: Anchored via a C-terminal transmembrane helix at highest density on the luminal surface of pulmonary capillary endothelial cells, renal proximal tubule brush border, vascular endothelium, and macrophages.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Cleaves the C-terminal His-Leu dipeptide from inactive decapeptide Angiotensin I (derived from AGT) to generate the potent octapeptide vasoconstrictor and aldosterone secretagogue Angiotensin II, while simultaneously inactivating the vasodilatory nonapeptide bradykinin (derived from KLKB1/KNG1 cleavage) by sequential C-terminal dipeptide removal.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: A common 287-bp Alu repeat insertion/deletion (I/D) polymorphism inside intron 16 accounts for ~47% of the variance in serum ACE activity (DD homozygotes have nearly twice the plasma and tissue ACE levels of II homozygotes, with the I allele enriched in high-altitude mountaineers and endurance athletes and the D allele associated with power hypertrophy), while biallelic loss-of-function mutations cause fatal autosomal recessive renal tubular dysgenesis.
Therapeutic & Clinical Pharmacology: Direct molecular target of ACE inhibitors (captopril, enalapril, lisinopril, ramipril, perindopril)—first-line small molecules designed from Bothrops jararaca venom peptides that coordinate the catalytic Zn2+ ion to treat hypertension, HFrEF, and diabetic nephropathy (with bradykinin accumulation explaining ACE-inhibitor cough and angioedema).