Affinage

Showing ACE — DCP1 is a alias.

ACE

Angiotensin-converting enzyme · UniProt P12821

Length
1306 aa
Mass
149.7 kDa
Annotated
2026-06-09
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACE (angiotensin-converting enzyme/CD143) is a membrane-bound dipeptidyl carboxypeptidase central to the renin-angiotensin and kinin systems, present as two mammalian isoforms with distinct biological roles: a double-domain somatic form whose two catalytic domains have different substrate affinities, and a single-domain germinal (testicular) form required for male fertility (PMID:12676162). The two isoforms are developmentally and cell-type specifically regulated in germ cells, with testicular ACE confined to spermatids and spermatozoa and somatic ACE appearing in fetal germ cells and germ cell neoplasms (PMID:10576213); in sperm, ACE activity supports sperm-egg binding while its product angiotensin II drives the acrosome reaction through a type 2 angiotensin receptor (PMID:9739417). Beyond classical peptidase function, ACE participates in cell-fate and immune processes: its enzymatic activity and downstream AGTR1/AGTR2 signaling regulate hemangioblast expansion and endothelial-versus-hematopoietic lineage choice (PMID:18728246), and it shapes myeloid biology, suppressing pro-inflammatory cytokine output through a non-catalytic, AMPK-dependent intracellular signaling role (PMID:21116821) while myeloid ACE overexpression reduces atherosclerotic plaque burden (PMID:31615657). ACE also exerts catalysis-independent effects, directly activating the bradykinin B1 receptor at its zinc-binding HEXXH motif when bound by nanomolar ACE inhibitors, elevating intracellular calcium and releasing NO (PMID:12489793), and its catalytic activity is augmented by heterodimerization with the bradykinin B2 receptor (PMID:18212275). Surface ACE shedding is governed by conformation, controlled by N-domain residues that regulate dimerization and by binding of lysozyme and bilirubin, such that an N-domain mutation disrupting lysozyme binding sharply elevates circulating ACE activity (PMID:27734897, PMID:20003136). ACE expression across the human vascular tree is markedly heterogeneous, being intense in lung capillaries and small muscular arteries but low in large vessels and most renal vasculature (PMID:21167844), and renal ACE is reciprocally regulated against ACE2 in diabetes (PMID:15078862).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 Medium

    Established that ACE function is not confined to systemic blood pressure control but operates directly in fertilization, linking the enzyme's product angiotensin II to sperm activation.

    Evidence Sperm-egg binding and acrosome reaction assays with captopril, angiotensin I/II, and receptor-specific antagonists

    PMID:9739417

    Open questions at the time
    • Does not identify which ACE isoform mediates sperm-egg binding
    • Mechanism by which ACE inhibition reduces binding without affecting capacitation unresolved
  2. 1999 Medium

    Resolved that ACE isoform expression in germ cells is developmental-stage specific, distinguishing testicular ACE in mature germ cells from somatic ACE in fetal and neoplastic germ cells.

    Evidence RT-PCR on laser-picked germ cells and isoform-specific immunohistochemistry on normal testes, fetal tissue, and testicular tumors

    PMID:10576213

    Open questions at the time
    • Functional consequence of somatic ACE re-expression in neoplasia not tested
    • Regulatory switch controlling isoform usage unknown
  3. 2002 High

    Demonstrated a catalysis-independent action of ACE inhibitors, showing they directly activate the bradykinin B1 receptor at a defined zinc-binding motif, revealing signaling effects distinct from peptidase inhibition.

    Evidence Calcium and NO assays with site-directed mutagenesis (H195A), peptide competition, and B1 antagonist

    PMID:12489793

    Open questions at the time
    • Physiological relevance of inhibitor-induced B1 activation in vivo not established
    • Whether endogenous ACE participates in this receptor activation unclear
  4. 2003 High

    Defined the two-isoform architecture of mammalian ACE and assigned distinct in vivo roles to the somatic and germinal forms and to the two somatic catalytic domains.

    Evidence Mouse knockouts, comparative biochemistry with invertebrate homologues, and domain-specific substrate assays

    PMID:12676162

    Open questions at the time
    • Full repertoire of physiological substrates for each domain not catalogued
    • Structural basis of domain substrate-affinity differences not detailed here
  5. 2004 Medium

    Showed reciprocal regulation of ACE and ACE2 in diabetic kidney, indicating tissue-specific remodeling of the renin-angiotensin axis under metabolic disease.

    Evidence Western blot, immunohistochemistry, activity assay, and RT-PCR in db/db versus control mouse kidney and heart

    PMID:15078862

    Open questions at the time
    • Causal driver of the reciprocal ACE/ACE2 shift not identified
    • Tissue specificity (kidney vs heart) mechanism unexplained
  6. 2008 Medium

    Identified an enzymatic requirement for ACE in hematopoietic/endothelial cell-fate decisions, placing the renin-angiotensin system upstream of hemangioblast lineage commitment.

    Evidence Human embryonic stem cell differentiation with ACE inhibitor and AGTR1/AGTR2 antagonists, flow cytometry

    PMID:18728246

    Open questions at the time
    • Identity of the ACE substrate driving the effect not pinned down
    • In vivo developmental relevance not tested
  7. 2008 Medium

    Revealed a non-catalytic intracellular signaling role for ACE in macrophage polarization, decoupling its immune-modulatory function from peptidase activity.

    Evidence siRNA knockdown, overexpression in THP-1, ACE inhibitor as negative control, AMPKα1 knockout macrophages, cytokine measurement

    PMID:21116821

    Open questions at the time
    • Direct intracellular partners transducing the signal not identified
    • Link between AMPK phosphorylation and ACE-dependent cytokine suppression incompletely mapped
  8. 2008 Medium

    Established that ACE catalytic output is modulated by physical heterodimerization with the bradykinin B2 receptor, demonstrating receptor crosstalk regulating enzyme activity.

    Evidence CHO coexpression with FRET activity assay, icatibant blockade, and B2 receptor knockout mouse endothelial cells

    PMID:18212275

    Open questions at the time
    • Structural interface of the ACE-B2 heterodimer not defined
    • Whether dimerization alters substrate selectivity unknown
  9. 2009 Medium

    Mapped an N-domain region controlling ACE dimerization and shedding, mechanistically linking quaternary structure to release of soluble ACE.

    Evidence Site-directed mutagenesis (Q18H, L19E, Q22A) in CHO cells, mAb epitope mapping, cross-linking, flow cytometry

    PMID:20003136

    Open questions at the time
    • Identity of the sheddase acting on ACE not addressed
    • Physiological signals controlling dimerization in vivo unknown
  10. 2009 Medium

    Connected ACE inhibition to activation of the counter-regulatory ACE2-Ang(1-7)-Mas axis, showing part of the inhibitor's anti-fibrotic effect is mediated through Mas signaling.

    Evidence Rat CCl4 liver fibrosis model and AngII-treated hepatic stellate cells with perindopril and Mas antagonist A779

    PMID:19793108

    Open questions at the time
    • Direct effect of ACE on the Mas axis versus indirect substrate-level effect not separated
    • Generality beyond liver fibrosis not tested
  11. 2010 Medium

    Showed ACE and ACE2 engage integrins RGD-independently and can serve as adhesion substrates, extending ACE function into cell adhesion and integrin signaling.

    Evidence Co-IP with integrin subunits, adhesion assays, FAK phosphorylation and Akt western blot

    PMID:22523556

    Open questions at the time
    • Single Co-IP without mutagenesis to map the interaction interface
    • Functional adhesion role demonstrated mainly for ACE2 rather than ACE
  12. 2010 Medium

    Documented the heterogeneous, organ- and vessel-specific distribution of endothelial ACE across the human vascular tree, establishing where ACE-dependent peptide processing predominates.

    Evidence Systematic immunohistochemistry of the complete human vascular tree with a monoclonal antibody panel

    PMID:21167844

    Open questions at the time
    • Functional consequence of vascular-bed-specific ACE levels not tested
    • Regulatory basis of the expression heterogeneity unknown
  13. 2016 Medium

    Identified lysozyme and bilirubin as conformational regulators of ACE controlling its shedding, with a natural N-domain mutation sharply raising blood ACE activity.

    Evidence Natural ACE mutation (Arg532Trp) characterization, binding identification, conformational mAb fingerprinting, electron microscopy

    PMID:27734897

    Open questions at the time
    • Quantitative contribution of conformational regulation to physiological ACE shedding unclear
    • Structural details of lysozyme/bilirubin binding sites not fully resolved
  14. 2016 Medium

    Used the C. elegans ACE ortholog acn-1 to place ACE-family activity in a longevity pathway, showing its reduction extends lifespan dependent on daf-16 but distinct from known longevity axes.

    Evidence C. elegans lifespan assays with captopril and acn-1 reduction plus systematic epistasis with daf-16, daf-2, age-1, and other mutants

    PMID:26918946

    Open questions at the time
    • Relevance to mammalian ACE longevity effects not established
    • Molecular substrate of acn-1 in aging unknown
  15. 2019 Medium

    Demonstrated through cell-type-specific genetics that myeloid ACE overexpression paradoxically reduces atherosclerosis, defining a protective immune role for ACE in plaque biology.

    Evidence ACE10 transgenic myeloid-overexpression mouse crossed to ApoE-/-, atherogenic diet, bone marrow transplantation, plaque quantification

    PMID:31615657

    Open questions at the time
    • Whether the protective effect is catalytic or non-catalytic not resolved
    • Human relevance of myeloid ACE overexpression untested
  16. 2022 Medium

    Dissected a radiation-responsive ACE pathway in myeloid cells, linking ACE activation to NADPH oxidase 2- and AT1 receptor-dependent ROS and tissue inflammation.

    Evidence Irradiated human monocytes/THP-1 with ACE activity, ROS, NOX2 and AT1 inhibitor assays plus rat partial-body irradiation with lisinopril

    PMID:35093482

    Open questions at the time
    • Mechanism by which radiation activates ACE not defined
    • Reconciliation with protective myeloid ACE roles unresolved
  17. 2022 Low

    Correlated ACE-1 protein, activity, and angiotensin II with normal brain aging and early Alzheimer's disease, raising the question of an ACE role in neurodegeneration.

    Evidence Fluorogenic activity assays and ELISA in post-mortem normal-aging (n=121) and AD (n=60) brain cohorts

    PMID:35396835

    Open questions at the time
    • Correlative post-mortem data with no mechanistic intervention
    • Causal direction between ACE changes and AD pathology unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ACE's catalytic and non-catalytic functions are integrated and reconciled across contexts where it appears both pro-inflammatory and protective, and what the direct intracellular partners of its signaling role are.
  • No identified intracellular signaling effectors downstream of non-catalytic ACE
  • Catalytic versus non-catalytic basis of myeloid phenotypes not separated
  • No structural model of ACE-receptor heterodimers

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0098631 cell adhesion mediator activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1474165 Reproduction 2
Partners
ACE2AGTR1AGTR2BDKRB1BDKRB2LYZ

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ACE exists as two isoforms in mammals: a single-domain germinal (testicular) isoform required for male fertility, and a double-domain somatic isoform with a key role in the renin-angiotensin system. Both somatic domains are catalytically active but have different substrate affinities. Mouse knockout experiments demonstrated these two domains have clearly distinct biological roles. Mouse knockout experiments, comparative biochemistry with invertebrate homologues, enzymatic substrate assays The international journal of biochemistry & cell biology High 12676162
2008 ACE (CD143) enzymatic activity is required for hemangioblast expansion from human embryonic stem cells, and ACE/renin-angiotensin system signaling through AGTR1 and AGTR2 receptors directly regulates hemangioblast differentiation toward endothelial or hematopoietic lineages. Human embryonic stem cell differentiation assays, ACE inhibitor treatment, AGTR1/AGTR2-specific inhibitors, flow cytometry for ACE+CD45-CD34+/- hemangioblasts Blood Medium 18728246
2008 ACE modulates macrophage polarization independently of its enzymatic activity: overexpression of ACE in macrophages reduced pro-inflammatory cytokine production (TNF-α, IL-6, MCP-1), and this effect was insensitive to ACE inhibition but sensitive to ACE siRNA knockdown, indicating a non-catalytic intracellular signaling role. Adipocyte-derived lipids upregulate ACE expression via AMPK phosphorylation. siRNA knockdown of ACE, ACE overexpression in THP-1 cells, ACE inhibitor treatment (negative control), AMPK inhibition, AMPKα1 knockout mouse macrophages, cytokine measurements Basic research in cardiology Medium 21116821
2008 ACE activity is modulated by its heterodimerization with the bradykinin B2 receptor: coexpression of the kinin B2 receptor with somatic ACE in CHO cells augmented ACE catalytic activity, and this effect was blocked by the B2 receptor antagonist icatibant. Endothelial cells from kinin B2 receptor knockout mice showed decreased ACE activity. Coexpression in CHO cells with FRET-based enzymatic activity assay, B2 receptor antagonist icatibant, kinin B2 receptor knockout mouse endothelial cells Hypertension (Dallas, Tex. : 1979) Medium 18212275
2002 ACE inhibitors at nanomolar concentrations directly activate the bradykinin B1 receptor at its Zn-binding HEXXH motif (residues 195-199) independently of ACE enzymatic activity and without peptide ligands, elevating intracellular calcium and releasing NO. Site-directed mutagenesis of H195 to alanine abolished ACE inhibitor-induced B1 receptor activation but not peptide ligand activation. Cell-based calcium assay, NO measurement, site-directed mutagenesis (H195A), synthetic peptide competition, B1 receptor antagonist International immunopharmacology High 12489793
2016 Lysozyme (a blood protein) and bilirubin (a low-molecular-weight effector) bind to ACE and regulate its conformation and shedding from endothelial cell surfaces. An ACE mutation (Arg532Trp in the N domain) that disrupts the lysozyme binding site increases blood ACE activity 7-fold by increasing shedding. Novel ACE gene mutation characterization, protein binding identification, conformational analysis using monoclonal antibody panel (ACE phenotyping), electron microscopy Scientific reports Medium 27734897
2009 Fine epitope mapping of anti-ACE monoclonal antibodies 9B9 and 3G8 identified that a region in the N-terminal N domain (involving residues Q18, L19, Q22) regulates ACE dimerization and shedding. Point mutations Q18H, L19E, and Q22A in full-length somatic ACE increased cell-surface ACE expression, basal shedding, and the amount of cross-linked ACE dimer. Site-directed mutagenesis (Q18H, L19E, Q22A) of full-length somatic ACE expressed in CHO cells, monoclonal antibody epitope mapping, cross-linking and western blot, flow cytometry Tissue antigens Medium 20003136
2004 ACE and ACE2 are co-expressed in renal tubules, with ACE protein markedly reduced and ACE2 protein increased in kidneys of diabetic (db/db) mice compared to controls, accompanied by a corresponding decrease in renal ACE enzymatic activity. This reciprocal pattern was not observed in heart tissue. Western blot, immunohistochemistry, fluorometric ACE activity assay, RT-PCR for mRNA; comparison of db/db diabetic vs db/m control mice Hypertension (Dallas, Tex. : 1979) Medium 15078862
2010 ACE and ACE2 bind integrin subunits in an RGD-independent manner and can act as cell adhesion substrates. Cellular expression of ACE2 enhanced cell adhesion. Soluble ACE2 suppressed integrin signaling mediated by FAK and altered Akt expression levels. Co-immunoprecipitation (Co-IP) of ACE/ACE2 with integrin subunits, cell adhesion assays, FAK phosphorylation measurement, Akt western blot PloS one Medium 22523556
2022 Radiation directly activates ACE within myeloid immune cells, increasing ACE activity and reactive oxygen species (ROS) generation via NADPH oxidase 2 and type 1 angiotensin receptor signaling. ACE inhibition with lisinopril blocked radiation-induced ACE activation and ROS production in human monocytes and reduced lung myeloid cell infiltration in vivo. In vitro radiation of human monocytes/THP-1 cells with ACE activity measurement, ROS assay, NADPH oxidase 2 inhibitor, AT1 receptor inhibitor; rat partial body irradiation model with lisinopril treatment, flow cytometry for lung immune cells, BAL cytokine measurement International journal of radiation oncology, biology, physics Medium 35093482
2019 Myeloid-specific ACE overexpression (ACE10 mouse model) paradoxically reduced atherosclerotic plaque burden in ApoE-deficient mice on an atherogenic diet. Bone marrow transplantation demonstrated this effect was mediated by myeloid-lineage ACE, as ACE10 bone marrow recipients showed significantly reduced lesion areas compared to wild-type bone marrow recipients. ACE10 transgenic mouse model with myeloid-specific ACE overexpression, ApoE-/- cross, atherogenic diet, bone marrow transplantation, plaque quantification Biochemical and biophysical research communications Medium 31615657
2010 ACE expression in the vascular endothelium is heterogeneous and vessel-, organ-, and species-specific: in humans, small muscular arteries and arterioles display high ACE immunoreactivity while large arteries, veins, and renal vasculature show little or no ACE. In the lung, all capillary endothelial cells are intensely ACE-positive. This pattern was determined by direct immunohistochemistry of the entire human vascular tree. Immunohistochemistry of serial sections from the complete human vascular tree using a panel of monoclonal antibodies, comparison with other endothelial markers Microvascular research Medium 21167844
1998 ACE (kininase II) is functionally involved in human sperm-egg interactions: inhibition of ACE by captopril decreased binding of human spermatozoa to zona-free hamster oocytes. ACE inhibition did not affect capacitation or the acrosome reaction. Angiotensin II (an ACE product) dose-dependently induced the acrosome reaction via calcium-dependent, protein kinase-mediated signaling through a type 2 angiotensin II receptor on sperm heads. Sperm-egg binding assay with captopril (ACE inhibitor), acrosome reaction assay with angiotensin I/II, pertussis toxin treatment, type 1 and type 2 receptor-specific antagonists, calcium dependency assays Andrologia Medium 9739417
1999 In normal adult testes, testicular ACE isoform (tACE) is expressed only in spermatids and spermatozoa but not in spermatogonia or spermatocytes. By contrast, somatic ACE (sACE) mRNA and protein are expressed in fetal germ cells and in intratubular germ cell neoplasms and seminomas, indicating isoform-specific and developmental-stage-specific regulation of ACE expression in germ cells. RT-PCR on laser-assisted cell-picked germ cells, immunohistochemistry with isoform-specific monoclonal antibodies on normal testes, fetal tissues, and 22 testicular tumor specimens Laboratory investigation; a journal of technical methods and pathology Medium 10576213
2016 ACE inhibitor captopril extends C. elegans lifespan via inhibition of the ACE homolog acn-1. Reducing acn-1 activity extended lifespan and delayed age-related degeneration. The lifespan extension required daf-16 but was additive with caloric restriction, mitochondrial insufficiency, and daf-2/age-1 mutations, placing acn-1 in a distinct longevity pathway. C. elegans lifespan assays with captopril, acn-1 RNAi/genetic reduction, double-mutant epistasis with daf-16, daf-2, age-1, sir-2.1, hsf-1, rict-1, caloric restriction, and mitochondrial insufficiency mutants PLoS genetics Medium 26918946
2009 ACE inhibitor treatment upregulates ACE2 expression and Mas receptor mRNA in both CCl4-injured rat liver in vivo and angiotensin II-treated hepatic stellate cells in vitro. ACE inhibitor-mediated suppression of angiotensin II-induced connective tissue growth factor (CTGF) expression was ameliorated by Mas receptor blockade with A779, indicating that ACE inhibitors act partly through upregulation of the ACE2-Ang(1-7)-Mas axis. In vivo rat CCl4 liver fibrosis model with perindopril treatment (immunohistochemistry, western blot, RT-PCR); in vitro hepatic stellate cell treatment with AngII ± ACE inhibitor ± Mas antagonist A779; CTGF western blot Clinical and experimental pharmacology & physiology Medium 19793108
2022 In normal aging human brain, ACE-1 protein levels and angiotensin II correlate positively with age, while ACE-1 enzyme activity is inversely related to age. In early/intermediate Alzheimer's disease (Braak stage III-IV), ACE-1 enzyme activity is elevated in the temporal cortex independently of normal age-related changes in ACE-1 protein. Fluorogenic peptide activity assays for ACE-1 and ACE-2, ELISA for ACE-1, ACE-2 protein and Ang-II, in post-mortem brain tissue from normal aging cohort (n=121) and AD cohort (n=60) stratified by Braak stage The journals of gerontology. Series A, Biological sciences and medical sciences Low 35396835

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes & development 737 16815998
2005 A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA (New York, N.Y.) 368 16177138
2006 ACE polymorphisms. Circulation research 318 16690893
1988 ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene. Molecular and cellular biology 238 3043194
2005 The translational regulator CPEB1 provides a link between dcp1 bodies and stress granules. Journal of cell science 234 15731006
2004 Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice: a renoprotective combination? Hypertension (Dallas, Tex. : 1979) 205 15078862
2014 Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. The Cochrane database of systematic reviews 169 25148386
2008 Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells. Blood 158 18728246
2003 The angiotensin converting enzyme (ACE). The international journal of biochemistry & cell biology 150 12676162
2002 The DEAD box protein Dhh1 stimulates the decapping enzyme Dcp1. The EMBO journal 147 12032091
2015 ACE and ACE2 in kidney disease. World journal of nephrology 144 25664248
2012 A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation. Nature structural & molecular biology 142 23142987
2020 A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance. British journal of pharmacology 126 32333398
1997 Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema. The British journal of dermatology 125 9068723
2008 Structural basis of dcp2 recognition and activation by dcp1. Molecular cell 116 18280239
1982 Angiotensin converting enzyme (ACE) inhibitors. Annual review of pharmacology and toxicology 114 6282189
2014 The activation of the decapping enzyme DCP2 by DCP1 occurs on the EDC4 scaffold and involves a conserved loop in DCP1. Nucleic acids research 102 24510189
2007 Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues. Blood 100 17993616
2003 Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. Journal of cellular physiology 95 12767053
2009 Reinventing the ACE inhibitors: some old and new implications of ACE inhibition. Hypertension research : official journal of the Japanese Society of Hypertension 92 19911001
2012 Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling. PloS one 83 22523556
2008 Similar modes of interaction enable Trailer Hitch and EDC3 to associate with DCP1 and Me31B in distinct protein complexes. Molecular and cellular biology 80 18765641
2021 Angiotensin converting enzyme (ACE). Clinica chimica acta; international journal of clinical chemistry 76 34728179
1992 Cough and ACE inhibitors. Archives of internal medicine 76 1497404
2003 Angiotensin-converting enzyme (CD143) is abundantly expressed by dendritic cells and discriminates human monocyte-derived dendritic cells from acute myeloid leukemia-derived dendritic cells. Experimental hematology 75 14662338
1989 Cooperative activation of a eukaryotic transcription factor: interaction between Cu(I) and yeast ACE1 protein. Proceedings of the National Academy of Sciences of the United States of America 75 2664778
1986 Adverse reactions with angiotensin converting enzyme (ACE) inhibitors. Medical toxicology 75 3023783
2021 Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 73 33676010
2012 DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PloS one 72 22808171
2009 Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors. Clinical and experimental pharmacology & physiology 72 19793108
1992 Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. Drug safety 72 1536695
2002 Using ACE inhibitors appropriately. American family physician 71 12182524
2015 Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae. Chemical science 67 29142718
2007 A divergent Sm fold in EDC3 proteins mediates DCP1 binding and P-body targeting. Molecular and cellular biology 66 17923697
2019 ACE inhibitor-mediated angioedema. International immunopharmacology 65 31835086
1994 The angiotensin-converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction. Clinical genetics 58 7988087
2006 Expression of Magnaporthe grisea avirulence gene ACE1 is connected to the initiation of appressorium-mediated penetration. Eukaryotic cell 57 17142568
2009 Activities of angiotensin-converting enzymes ACE1 and ACE2 and inhibition by bioactive peptides in porcine ocular tissues. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 55 19232015
1993 Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure. Clinical pharmacokinetics 55 8462229
2012 Angiotensin-converting enzyme (CD143) specifies emerging lympho-hematopoietic progenitors in the human embryo. Blood 54 22282502
2009 DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa. Proceedings of the National Academy of Sciences of the United States of America 53 19966221
2004 The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer. International journal of oncology 53 15492809
2023 Bifidobacterium adolescentis orchestrates CD143+ cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1. Cancer communications (London, England) 52 37533188
1990 The DNA and Cu binding functions of ACE1 are interdigitated within a single domain. The New biologist 51 2088504
2010 Heterogeneous distribution of angiotensin I-converting enzyme (CD143) in the human and rat vascular systems: vessel, organ and species specificity. Microvascular research 50 21167844
2007 Demystifying the ACE polymorphism: from genetics to biology. Current pharmaceutical design 50 17504229
1993 Regulation of metallothionein genes by the ACE1 and AMT1 transcription factors. The Journal of biological chemistry 49 8509391
2016 Structure of the Dcp2-Dcp1 mRNA-decapping complex in the activated conformation. Nature structural & molecular biology 45 27183195
2010 Dcp1 links coactivators of mRNA decapping to Dcp2 by proline recognition. RNA (New York, N.Y.) 45 21148770
2003 Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension. Journal of human hypertension 45 14504631
2000 Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene interactions with the apolipoprotein E epsilon4 allele as risk factors in Alzheimer's disease and in Parkinson's disease with coexisting Alzheimer pathology. Journal of medical genetics 45 11015454
2016 Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span. PLoS genetics 44 26918946
2016 Structural basis of mRNA-cap recognition by Dcp1-Dcp2. Nature structural & molecular biology 44 27694842
2010 Adipocyte-derived lipids increase angiotensin-converting enzyme (ACE) expression and modulate macrophage phenotype. Basic research in cardiology 44 21116821
2009 Dcp1-bodies in mouse oocytes. Molecular biology of the cell 43 19812249
2016 Structure of the active form of Dcp1-Dcp2 decapping enzyme bound to m7GDP and its Edc3 activator. Nature structural & molecular biology 42 27694841
1989 Copper and the ACE1 regulatory protein reversibly induce yeast metallothionein gene transcription in a mouse extract. Proceedings of the National Academy of Sciences of the United States of America 42 2682650
2018 High-throughput immunophenotypic characterization of bone marrow- and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers: identification of angiotensin-converting enzyme (CD143) as a marker differentially expressed between adult and perinatal tissue sources. Stem cell research & therapy 40 29338788
2001 Haa1, a protein homologous to the copper-regulated transcription factor Ace1, is a novel transcriptional activator. The Journal of biological chemistry 40 11504737
1998 Effect of angiotensin converting enzyme (ACE) and angiotensins on human sperm functions. Andrologia 40 9739417
2012 Angiotensin converting enzyme (ACE) inhibitory, antihypertensive and antihyperlipidaemic activities of protein hydrolysates from Rhopilema esculentum. Food chemistry 38 23442666
2001 Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis. Journal of internal medicine 37 11168787
2018 Structure of the activated Edc1-Dcp1-Dcp2-Edc3 mRNA decapping complex with substrate analog poised for catalysis. Nature communications 36 29559651
2004 APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease. Neuroreport 36 15106838
2004 Zinc-metalloproteases in insects: ACE and ECE. Insect biochemistry and molecular biology 35 15147752
2002 Activation of bradykinin B1 receptor by ACE inhibitors. International immunopharmacology 35 12489793
2002 ACE inhibition and atherogenesis. Canadian journal of physiology and pharmacology 32 12025972
2022 Pharmacologic ACE-Inhibition Mitigates Radiation-Induced Pneumonitis by Suppressing ACE-Expressing Lung Myeloid Cells. International journal of radiation oncology, biology, physics 31 35093482
2021 Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging. International journal of molecular sciences 31 34947975
2000 CD143 in the development of atherosclerosis. Atherosclerosis 31 10781632
1999 Angiotensin-converting enzyme (CD143) in neoplastic germ cells. Laboratory investigation; a journal of technical methods and pathology 31 10576213
2008 ACE activity is modulated by kinin B2 receptor. Hypertension (Dallas, Tex. : 1979) 30 18212275
1993 Cardioprotection by angiotensin-converting enzyme (ACE) inhibitors. The Canadian journal of cardiology 30 8513428
1992 Pharmacokinetic optimisation of angiotensin converting enzyme (ACE) inhibitor therapy. Clinical pharmacokinetics 30 1505143
2011 The peptide network regulated by angiotensin converting enzyme (ACE) in hematopoiesis. Cell cycle (Georgetown, Tex.) 29 21441775
2009 Fine epitope mapping of monoclonal antibodies 9B9 and 3G8 to the N domain of angiotensin-converting enzyme (CD143) defines a region involved in regulating angiotensin-converting enzyme dimerization and shedding. Tissue antigens 29 20003136
1995 Angiotensin converting enzyme (ACE) inhibitors and kinin metabolism: evidence that ACE inhibitors may inhibit a kininase other than ACE. Clinical and experimental pharmacology & physiology 29 8846511
2018 ACE phenotyping in Gaucher disease. Molecular genetics and metabolism 28 29478818
1992 ACE-inhibitors and atherosclerosis. European journal of epidemiology 28 1324185
2005 [Angiotensin I-converting enzyme (ACE) for sarcoidosis diagnosis]. Pathologie-biologie 27 15781381
2005 The angiotensin-converting enzyme (ACE) gene family of Anopheles gambiae. BMC genomics 26 16329762
2011 Inflammation alters angiotensin converting enzymes (ACE and ACE-2) balance in rat heart. Inflammation 25 21053061
2006 Testicular isoform of angiotensin I-converting enzyme (ACE, CD143) on the surface of human spermatozoa: revelation and quantification using monoclonal antibodies. American journal of reproductive immunology (New York, N.Y. : 1989) 25 16364013
2006 Monoclonal antibodies to native mouse angiotensin-converting enzyme (CD143): ACE expression quantification, lung endothelial cell targeting and gene delivery. Tissue antigens 25 16451197
2004 Decapping reaction of mRNA requires Dcp1 in fission yeast: its characterization in different species from yeast to human. Journal of biochemistry 24 15671491
2016 Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding. Scientific reports 23 27734897
1994 ACE inhibitors and cough. Angiology 23 8092546
1989 Enzymes in sarcoidosis. Angiotensin-converting-enzyme (ACE). Clinics in laboratory medicine 23 2556234
2022 Dysregulation of ACE-1 in Normal Aging and the Early Stages of Alzheimer's Disease. The journals of gerontology. Series A, Biological sciences and medical sciences 22 35396835
2012 Extensive Ace2 duplication and multiple mutations on Ace1 and Ace2 are related with high level of organophosphates resistance in Aphis gossypii. Environmental toxicology 22 22489048
2002 ACE genotype and ACE inhibitor response in kidney disease: a perspective. American journal of kidney diseases : the official journal of the National Kidney Foundation 22 12148094
2005 ACE inhibitors and chronotherapy. Clinical and experimental hypertension (New York, N.Y. : 1993) 21 15835380
2007 Molecular cloning and characterization of the complete acetylcholinesterase gene (Ace1) from the mosquito Aedes aegypti with implications for comparative genome analysis. Insect biochemistry and molecular biology 20 17550823
2022 Role and Interaction Between ACE1, ACE2 and Their Related Genes in Cardiovascular Disorders. Current problems in cardiology 19 35245599
2021 Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients. Vascular pharmacology 18 34774774
2020 Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. The Cochrane database of systematic reviews 18 33089502
2019 Overexpression of myeloid angiotensin-converting enzyme (ACE) reduces atherosclerosis. Biochemical and biophysical research communications 18 31615657
1996 ACE inhibitors and proteinuria. Pharmacy world & science : PWS 18 9010883
1990 Haemodynamic effects of ACE inhibitors. European heart journal 17 2193808
1993 Nephroprotective effect of ACE inhibitors. Drugs 16 7512474

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