Affinage

ECE1

Endothelin-converting enzyme 1 · UniProt P42892

Length
770 aa
Mass
87.2 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 32 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ECE-1 is a zinc-dependent, type II integral membrane metalloprotease that catalyzes the final, rate-limiting step in endothelin biosynthesis, cleaving big endothelin-1 at Trp21-Val22 to generate the active vasoconstrictor ET-1 (PMID:8062389, PMID:7805846). Catalysis depends on a HEXXH (HELTH) zinc-binding active site, and the enzyme converts big ET-1, -2, and -3, with substrate recognition occurring at both the P1 scissile position and the C-terminal region of big ET-1 (PMID:7805846, PMID:9422810, PMID:9450558). A single gene on chromosome 1p36 produces four isoforms (a–d) from alternative promoters that share catalytic activity but differ only in their N-terminal cytoplasmic tails; di-leucine-based motifs in these tails act as autonomous targeting signals that route ECE-1b to intracellular endosomal-lysosomal compartments while ECE-1a, -1c, and -1d reach the cell surface (PMID:9396733, PMID:10462527, PMID:10377252, PMID:9657986, PMID:10491078, PMID:8530372). ECE-1 abundance and activity are controlled post-translationally: isoform half-lives are set by intracellular degradation (PMID:9657986, PMID:12827039), PKC phosphorylation increases plasma-membrane ECE-1 and ET-1 secretion while the TIMAP-PP1c phosphatase complex reverses this (PMID:26806547), the calcimimetic R-568 inhibits the enzyme by ejecting active-site zinc (PMID:23911580), and the tetraspanin Tspan8 physically associates with ECE-1 to amplify big ET-1 conversion (PMID:37835445). Transcription of the isoform promoters is driven by cardiac and vascular regulators including Nkx2-5 and an arterial endothelial enhancer cooperatively bound by Sox17, FoxC2, and Etv2 (PMID:12824294, PMID:10682850, PMID:25179465). In vivo, ECE-1 acts redundantly with ECE-2 in cardiac outflow and aortic arch artery remodeling, with residual ET activation indicating additional non-ECE proteases, and ECE-1-mediated ET-1 production drives pro-fibrotic signaling in the kidney (PMID:10811845, PMID:12950083, PMID:32768584). Beyond ET-1 generation, ECE-1 promotes cancer cell invasion and proliferation through both ET-1-dependent and ET-1-independent routes, including modulation of FAK phosphorylation and direct interaction with the AKT pleckstrin homology domain to facilitate AKT membrane translocation and activation (PMID:18781169, PMID:20725143, PMID:37897251).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1994 High

    Established the core identity and function of ECE-1: that a single membrane metalloprotease executes the rate-limiting conversion of big ET-1 to mature ET-1, the molecular basis of endothelin production.

    Evidence cDNA transfection with functional ET-1 secretion assay; enzyme purification, peptide sequencing, and recombinant activity reconstitution identifying the HEXXH zinc motif

    PMID:7805846 PMID:8062389

    Open questions at the time
    • Cleavage at Trp21-Val22 defined for ET-1 but full substrate scope not yet mapped
    • No structural model of the catalytic ectodomain
  2. 1997 Medium

    Defined the gene architecture and isoform diversity, showing multiple promoters generate catalytically equivalent isoforms differing only in N-terminal tails — the basis for differential localization despite shared enzymology.

    Evidence Genomic cloning, FISH mapping, molecular cloning, immunofluorescence, and kinetic enzyme assays across isoforms in cultured cells

    PMID:8530372 PMID:9141502 PMID:9396733

    Open questions at the time
    • Why distinct subcellular pools are needed for an enzyme with one substrate not resolved
    • Tissue-specific isoform usage only partly characterized
  3. 1999 High

    Identified the molecular targeting signals that route ECE-1b intracellularly, showing di-leucine motifs are autonomous retention signals sufficient to redirect even a heterologous protease.

    Evidence Chimeric protein and ECE/NEP domain-swap construction, point mutagenesis, and EM immunocytochemistry in CHO and MDCK cells; identification of a fourth isoform ECE-1d

    PMID:10377252 PMID:10462527 PMID:10491078

    Open questions at the time
    • Adaptor proteins reading the di-leucine motifs not identified
    • Functional consequence of intracellular versus surface processing pools unclear
  4. 2000 High

    Tested ECE-1 sufficiency in vivo through genetics, revealing redundancy with ECE-2 and the existence of additional ET-activating proteases — refining ECE-1 from sole to principal converting enzyme.

    Evidence ECE-1/ECE-2 double-knockout mice with quantitative ET-1/ET-2 peptide measurement; antisense knockdown in pulmonary artery smooth muscle cells

    PMID:10811845 PMID:11160849

    Open questions at the time
    • Identity of the residual non-ECE ET-converting protease(s) unknown
    • Cell-type-specific reliance on ECE-1 versus alternatives unmapped
  5. 2003 Medium

    Connected ECE-1 to developmental morphogenesis and its transcriptional control, placing the gene within endothelin-pathway neural crest function and cardiac regulatory networks.

    Evidence Compound mutant mouse epistasis for aortic arch remodeling; EMSA, reporter mutagenesis, and overexpression linking Nkx2-5 to isoform promoters; enzyme kinetics defining big ET-1 recognition

    PMID:12824294 PMID:12827039 PMID:12950083 PMID:9450558

    Open questions at the time
    • Direct downstream developmental targets of ECE-1-generated ET-1 not defined
    • Promoter regulation studied largely in cell lines
  6. 2014 Medium

    Resolved multilayered control of ECE-1 expression — an arterial endothelial enhancer and post-transcriptional 3'UTR/alternative polyadenylation regulation tuning protein output.

    Evidence Transgenic mouse enhancer reporter with Sox17/FoxC2/Etv2 binding-site mutagenesis; 3'UTR reporter assays with APA-site mutagenesis in prostate cancer cells

    PMID:24497914 PMID:25179465

    Open questions at the time
    • Whether APA regulation operates in vascular tissue not shown
    • trans-factors controlling APA choice unidentified
  7. 2016 Medium

    Defined post-translational regulation of ECE-1 surface abundance through a phosphorylation cycle, identifying a specific kinase and phosphatase complex acting on the enzyme.

    Evidence Reciprocal co-IP for TIMAP-PP1c-ECE-1, TIMAP siRNA, PKC activation, membrane fractionation, and ET-1 secretion assays

    PMID:26806547

    Open questions at the time
    • Phosphorylation sites on ECE-1 not mapped
    • Which isoforms are PKC substrates not resolved
    • Single lab, no reciprocal phosphatase validation in vivo
  8. 2023 Medium

    Extended ECE-1 function beyond proteolysis, demonstrating activity amplification by a tetraspanin partner and an ET-1-independent scaffolding role in promoting AKT activation and tumor growth.

    Evidence Mass spectrometry and co-IP for Tspan8 association with KO mouse validation; co-IP/co-localization mapping ECE-1 to the AKT PH domain with AKT-inhibitor rescue and xenograft assays

    PMID:37835445 PMID:37897251

    Open questions at the time
    • Structural basis of the ECE-1–AKT PH domain interaction unknown
    • Whether the AKT-promoting role requires catalytic activity not tested
    • Mechanism by which Tspan8 amplifies activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how ECE-1's distinct subcellular pools and isoform-specific functions are integrated, and whether its non-catalytic AKT-scaffolding activity operates in normal physiology beyond cancer.
  • No high-resolution structure of full-length ECE-1 or its complexes
  • Identity of residual ET-converting proteases unresolved
  • Catalytic versus scaffolding contributions to disease phenotypes not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005764 lysosome 2 GO:0005768 endosome 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 2
Partners
AKT1ECE2PPP1CATIMAPTSPAN8
Complex memberships
TIMAP-PP1c-ECE-1 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ECE-1 is a membrane-bound neutral metalloprotease that catalyzes the proteolytic conversion of big endothelin-1 (38-residue) to active endothelin-1 (21-residue) by cleavage at Trp21-Val22. Transfection of ECE-1 cDNA into cultured cells conferred the ability to secrete mature ET-1, and ECE-1 interacts with big ET-1 at the cell surface. cDNA transfection into cultured cells, functional secretion assay, cell-surface interaction assay Cell High 8062389
1994 ECE-1 is a zinc metalloprotease containing the HEXXH (HELTH) catalytic motif. Purified bovine ECE-1 was confirmed by peptide sequencing and the recombinant human enzyme has the same catalytic activity as the native enzyme. Enzyme purification, tryptic peptide sequencing, heterologous expression in cultured cells and Xenopus oocytes, activity assay FEBS letters High 7805846
1997 ECE-1 exists as three isoforms (ECE-1a, ECE-1b, ECE-1c) generated from a single gene via alternative promoters, differing only in their N-terminal cytoplasmic tails. ECE-1a and ECE-1c localize to the cell surface, whereas ECE-1b localizes intracellularly with significant co-localization with the trans-Golgi network marker. All three isoforms have similar kinetic constants (Km, kcat, Vmax) for processing big endothelin-1, -2, and -3. Molecular cloning, immunofluorescence microscopy, subcellular localization, kinetic enzyme assays The Biochemical journal High 9396733
1999 Two di-leucine-based motifs in the N-terminal cytoplasmic tail of ECE-1b are responsible for its intracellular localization. One motif (LL) is unique to ECE-1b and responsible for its exclusive intracellular retention; a second motif (LV) is shared with ECE-1c and accounts for ECE-1c's reduced cell-surface expression relative to ECE-1a. Mutation of both motifs causes strong cell-surface appearance of ECE-1b. Chimeric protein construction, point mutagenesis, electron microscopy immunocytochemistry in CHO cells Journal of cell science High 10462527
1999 A nine amino-acid segment in the cytosolic tail of ECE-1b containing two leucine residues is sufficient to redirect neprilysin (NEP) from the cell surface to an intracellular compartment, establishing this segment as an autonomous intracellular retention/targeting signal. ECE/NEP chimeric protein construction, transfection in MDCK cells, site-directed mutagenesis, subcellular localization The Biochemical journal High 10377252
1998 ECE-1b localizes to early and late endosomes (not cell surface) in polarized MDCK cells. Phosphoramidon treatment increases ECE-1b protein level by slowing its lysosomal degradation (half-life extended from 2.8 h to 7.5 h), without changing mRNA levels, indicating rapid turnover of ECE-1b through endosomal-lysosomal compartments. Cell-surface biotinylation, immunofluorescence, anti-Rab5/Rab7 co-localization, pulse-chase immunoprecipitation, Western blot, Northern blot, confocal microscopy The Biochemical journal High 9657986
1999 A fourth isoform, ECE-1d, is generated from an additional promoter upstream of the third exon of the ECE-1 gene. ECE-1d has comparable converting activity to the other isoforms and is expressed at the cell surface, though less strongly than ECE-1a. Molecular cloning, promoter mapping, functional expression assay, cell-surface localization European journal of biochemistry Medium 10491078
2000 Genetic epistasis analysis using ECE-1/ECE-2 double-knockout mice showed that ECE-2 contributes to cardiac outflow and atrioventricular valve development redundantly with ECE-1, but significant residual ET-1/ET-2 remained in double-null embryos, indicating that additional proteases distinct from ECE-1 and ECE-2 can activate ET-1 in vivo. Homologous recombination knockout mice, compound mutant analysis, ET-1/ET-2 peptide measurement The Journal of clinical investigation High 10811845
2003 ECE-1 (Ece1) and Tbx1 define distinct, non-interacting pathways in aortic arch morphogenesis. Ece1 is required for regression of cranial arch arteries and growth of caudal arch arteries (linked to endothelin-1 pathway neural crest function), whereas Tbx1 is required for early formation and growth of pharyngeal arch arteries. Compound Ece1/Tbx1 mutants showed no genetic interaction. Genetic epistasis in compound mutant mice, morphological analysis of pharyngeal arch artery remodeling Developmental dynamics Medium 12950083
2003 The homeobox transcription factor Nkx2-5 activates all three ECE-1 isoform promoters (ECE-1a, ECE-1b, ECE-1c) in cardiomyoblasts. The ECE-1b promoter contains an Nkx2-5 consensus site required for direct activation; ECE-1a and ECE-1c promoters are activated indirectly. Stable Nkx2-5 overexpression increases ECE-1 isoform mRNA levels. Transient transfection reporter assays, gel shift assays (EMSA), site-directed mutagenesis of promoter elements, stable overexpression with RNase protection assay, Northern blot, real-time PCR FASEB journal Medium 12824294
1997 The ECE-1 gene is organized into 19 exons spanning >68 kb, mapped to chromosome 1p36. Two isoform mRNAs (ECE-1a and ECE-1b) are transcribed from two distinct promoters with different tissue distributions. Genomic cloning, exon-intron mapping, FISH chromosomal localization, tissue distribution analysis The Journal of biological chemistry Medium 8530372
2000 The ECE-1c promoter contains two positive regulatory regions (-142/-240 and -240/-490) likely binding GATA and ETS transcription factors, multiple transcriptional start sites (~-110, -140, and -350 bp), and a crucial E2F cis-element required for basal ECE-1c promoter activity as demonstrated by site-directed mutagenesis. Reporter gene assays with serial deletion mutants, transfection into endothelial and epithelial cells, site-directed mutagenesis, RNase protection assay, 5'-RACE FEBS letters Medium 10682850
2014 An arterial-specific enhancer in the human ECE1 locus is cooperatively activated by the transcription factors Sox17, FoxC2, and Etv2 through a conserved FOX:ETS composite motif and a SOX binding site. In transgenic mice, enhancer activity is restricted to arterial endothelium and endocardium by embryonic day 9.5. Transgenic mouse reporter assays, in vivo enhancer activity analysis, transcription factor binding site mutagenesis Developmental biology Medium 25179465
2016 The TIMAP-protein phosphatase 1 (PP1c) complex physically interacts with ECE-1 and dephosphorylates it. PKC phosphorylates ECE-1, increasing its plasma membrane level and ET-1 secretion; TIMAP depletion reduces PP1c activity toward ECE-1, leading to elevated ECE-1 membrane abundance and elevated ET-1 production. Thus, PKC-phosphorylated ECE-1 is a TIMAP-PP1c substrate. Co-immunoprecipitation (protein-protein interaction), TIMAP siRNA knockdown, PKC activation, Western blot membrane fractionation, ET-1 secretion assay The international journal of biochemistry & cell biology Medium 26806547
2008 siRNA-mediated knockdown of ECE-1 in prostate cancer stromal or epithelial cells reduces PC-3 epithelial cell invasion and migration. Re-addition of ET-1 only partially recovers invasion, indicating both ET-1-dependent and ET-1-independent functions for ECE-1. ECE-1 inhibition reduces focal adhesion kinase (FAK) phosphorylation; conversely, ECE-1 overexpression increases FAK phosphorylation, linking ECE-1 to FAK-mediated invasion signaling. siRNA/shRNA knockdown, Matrigel invasion assay, ET-1 rescue experiment, ECE-1 specific inhibitor treatment, Western blot for FAK phosphorylation, transient overexpression British journal of cancer / Canadian journal of physiology and pharmacology Medium 18781169 20725143
2008 ECE-1c and ECE-1a isoforms have opposing effects on prostate cancer cell invasion: ECE-1c overexpression increases PC-3 invasiveness through Matrigel, whereas ECE-1a expression suppresses invasion. Transient ECE-1a expression in stromal cells counteracts the pro-invasive effect of ECE-1c in epithelial cells. Transient isoform-specific overexpression, siRNA knockdown, Matrigel invasion assay, co-culture experiments British journal of cancer Medium 18781169
2014 ECE-1 expression is post-transcriptionally regulated by alternative polyadenylation (APA). The ECE-1 3'UTR markedly inhibits protein expression, and APA produces transcripts with truncated 3'UTRs that promote elevated ECE-1 protein expression. Abolition of APA sites in a reporter construct reduced protein expression in prostate cancer cells. Reporter assay with 3'UTR constructs, APA site mutagenesis, comparison of 3'UTR length variants PloS one Medium 24497914
2013 R-568 (calcimimetic) inhibits ECE-1 enzymatic activity by expelling zinc from the enzyme's active site, as demonstrated by restoration of activity upon addition of exogenous zinc and reduced zinc content in immunoprecipitated ECE-1 from R-568-treated cells. This results in decreased ET-1 synthesis despite increased ECE-1 protein levels. ECE-1 activity assay, zinc supplementation rescue experiment, immunoprecipitation with zinc measurement, Western blot, ELISA for ET-1 Pharmacological research Medium 23911580
2023 ECE-1 physically interacts with the pleckstrin homology (PH) domain of AKT and facilitates AKT translocation to the plasma membrane for activation, promoting lung cancer cell proliferation independent of its canonical ET-1 producing function. ECE-1 knockdown reduces AKT activation and tumor growth; AKT inhibition counteracts the growth-inhibitory effect of ECE-1 knockdown. Co-immunoprecipitation, immunofluorescence co-localization, RNA sequencing, ECE-1 knockdown (siRNA/shRNA), AKT inhibitor rescue, in vitro and xenograft tumor growth assays The journal of gene medicine Medium 37897251
2001 Antisense oligodeoxynucleotide knockdown of ECE-1c in bovine pulmonary artery smooth muscle cells markedly reduced ECE-1c mRNA and ECE-1 protein, but basal and TNFα-stimulated ET-1 release were largely unaffected, indicating that an endopeptidase distinct from ECE-1 is mainly responsible for big ET-1 processing in VSMC. Antisense oligodeoxynucleotide treatment, RT-PCR, Western blot, ET-1 ELISA Molecular pharmacology Medium 11160849
1997 ECE activity in human vascular smooth muscle (endothelium-denuded umbilical vein) is phosphoramidon-sensitive and can convert big ET-1, big ET-2(1-37), big ET-2(1-38), and big ET-3 to their mature biologically active forms, demonstrating broader substrate specificity than ET-1 alone. Pharmacological inhibition with phosphoramidon, functional vasoconstriction assay, radioimmunoassay for ET immunoreactivity British journal of pharmacology Medium 9422810
2003 ECE-1 inhibition reduces ET-1 expression and cell invasiveness in MCF-7 breast cancer cells (54.3% of controls) using the selective ECE-1 inhibitor RO 67-7447. Selective ECE-1 inhibitor treatment, ET-1 expression assay, cell invasion assay Breast cancer research and treatment Low 17295044
2006 siRNA-mediated knockdown of ECE-1 in oral squamous cell carcinoma (SCC) cells reduces SCC cell proliferation. ET-1 alone stimulates proliferation of oral SCC cells, and this is blocked by antagonists of either ETA or ETB receptors. siRNA knockdown, ECE-specific inhibitor, cell proliferation assay, receptor antagonist experiments International journal of cancer Low 16217751
1997 ECE-1 has an ectodomain structurally related to neutral endopeptidase 24.11 (NEP), and is a type II integral membrane protein expressed predominantly in endothelial cells. Multiple isoforms (ECE-1a, ECE-1b, ECE-1c, and ECE-2) exist with different characteristics. Sequence analysis, comparative biochemistry, structural homology analysis FASEB journal Medium 9141502
2008 ERK signaling pathway activation in hepatic stellate cells (after bile duct ligation) regulates ECE-1 expression: inhibition of ERK in stellate cells from BDL-injured liver leads to decreased ECE-1 expression, linking TGF-β/ERK signaling to ECE-1 transcriptional regulation in liver fibrosis. Pharmacological ERK inhibition, qRT-PCR for ECE-1, stellate cell isolation, phospho-Smad3 and MAP kinase Western blot The American journal of pathology Low 18753413
2008 ECE protein is expressed in the embryonic chick heart in endothelial cells, mesenchymal cells, myocytes, and is enriched in trabeculae and nascent ventricular conduction system. ET receptor blockade with bosentan delayed activation sequence maturation, and hemodynamic loading modifies myocardial ECE expression, supporting a role for ECE in cardiac conduction system differentiation. Immunohistochemistry with custom antibody, in vivo ET receptor blockade (bosentan), experimental hemodynamic loading, Western blot Developmental dynamics Low 18489007
2023 Tspan8 (tetraspanin) physically associates with ECE-1 and amplifies its activity in converting big ET-1 to ET-1, as demonstrated in colon carcinoma cells transduced with Tspan8 and in ileum tissue from tspan8 knockout mice versus wild-type mice. Mass spectrometry, Western blot co-immunoprecipitation, Tspan8 transduction in Isreco1 cells, tspan8 knockout mouse tissue analysis, ECE-1 activity assay Cancers Medium 37835445
2020 ECE-1 knockout mice show reduced kidney fibrosis, tubular injury, macrophage infiltration, fibroblast number, and myofibroblast formation after unilateral ureteral obstruction, associated with reduced TGF-β1 and α-SMA protein levels, demonstrating that ECE-1-mediated ET-1 activation drives pro-fibrotic signaling in the kidney. ECE-1 knockout mice, unilateral ureteral obstruction model, histopathology, immunostaining (F4/80, FSP-1, α-SMA), qRT-PCR, Western blot Life sciences Medium 32768584
2003 Phosphoramidon differentially affects ECE-1 isoforms: it increases intracellular ECE-1a and ECE-1b protein levels by prolonging their half-lives (via inhibition of intracellular degradation) but does not affect ECE-1c protein levels. mRNA levels are unchanged, indicating post-translational regulation. Metabolic pulse-chase labeling, immunoprecipitation, Western blot, Northern blot, immunocytochemistry in CHO cell lines stably expressing individual ECE-1 isoforms Journal of cardiovascular pharmacology Medium 12827039
1997 ECE-1 in endothelial cells (EA.hy926) is an integral membrane protein, as demonstrated by detergent solubilization and temperature-induced phase separation. Greater than 75% of total ECE activity could be immunoprecipitated with a monoclonal antibody raised against neutral endopeptidase E-24.11, indicating a shared epitope between ECE and NEP. Detergent phase separation, antibody immunoprecipitation of enzymatic activity Journal of cardiovascular pharmacology Low 8587468
1997 ECE-1 inhibition by phosphoramidon in big ET-1-stimulated human umbilical vein smooth muscle preparations blocks vasoconstriction in a concentration-dependent manner, confirming that smooth muscle ECE converts big ET-1 to active ET-1 via a phosphoramidon-sensitive mechanism. Ex vivo vascular preparation, phosphoramidon pharmacological inhibition, concentration-response analysis British journal of pharmacology Low 9422810
1997 Big ET-1 peptide analogues [Phe21]big ET-1(18-34) and [Ala31]big ET-1(18-34) inhibit ECE-1 activity in different fashions: [Phe21]big ET-1(18-34) is a competitive inhibitor (Ki=20.6 µM) and [Ala31]big ET-1(18-34) is a noncompetitive inhibitor (Ki=35.6 µM), indicating ECE-1 recognizes big ET-1 both at the P1 position and at the C-terminal region through distinct mechanisms. Kinetic analysis of ECE-1 inhibition using solubilized membranes from ECE-1-expressing CHO-K1 cells, competitive vs. noncompetitive inhibitor determination FEBS letters Medium 9450558

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell 795 8062389
1997 Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 344 9141502
1993 Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. Infection and immunity 208 8359888
1995 Organization of the gene encoding the human endothelin-converting enzyme (ECE-1). The Journal of biological chemistry 186 8530372
1997 Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations. The Biochemical journal 176 9396733
1994 Molecular characterization of human and bovine endothelin converting enzyme (ECE-1). FEBS letters 168 7805846
2006 Phylogenetic analysis of the "ECE" (CYC/TB1) clade reveals duplications predating the core eudicots. Proceedings of the National Academy of Sciences of the United States of America 151 16754863
2000 Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development. The Journal of clinical investigation 149 10811845
1999 A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter molecular cloning and characterization. European journal of biochemistry 135 10491078
1999 Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart. The American journal of physiology 80 10199843
2021 A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis. PLoS pathogens 63 34506615
2007 On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer. Breast cancer research and treatment 60 17295044
2020 The role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 54 32170981
2006 Molecular characterization of a novel coronavirus associated with epizootic catarrhal enteritis (ECE) in ferrets. Virology 54 16499943
2018 Upregulation of miR-199a-5p Protects Spinal Cord Against Ischemia/Reperfusion-Induced Injury via Downregulation of ECE1 in Rat. Cellular and molecular neurobiology 43 29948551
2009 Expressions of ECE-CYC2 clade genes relating to abortion of both dorsal and ventral stamens in Opithandra (Gesneriaceae). BMC evolutionary biology 37 19811633
2000 ET-1 in the myocardial interstitium: relation to myocyte ECE activity and expression. American journal of physiology. Heart and circulatory physiology 36 10843904
1997 Endothelin converting enzyme (ECE) activity in human vascular smooth muscle. British journal of pharmacology 36 9422810
2006 Endothelin system in oral squamous carcinoma cells: specific siRNA targeting of ECE-1 blocks cell proliferation. International journal of cancer 35 16217751
2004 Zinc-metalloproteases in insects: ACE and ECE. Insect biochemistry and molecular biology 35 15147752
1998 Recombinant human endothelin-converting enzyme ECE-1b is located in an intracellular compartment when expressed in polarized Madin-Darby canine kidney cells. The Biochemical journal 33 9657986
2008 Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion. British journal of cancer 31 18781169
2014 Prediction of thyroid extracapsular extension with cervical lymph node metastases (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 24863948
2014 An arterial-specific enhancer of the human endothelin converting enzyme 1 (ECE1) gene is synergistically activated by Sox17, FoxC2, and Etv2. Developmental biology 27 25179465
2003 Vascular ECE-1 mRNA expression decreases in response to estrogens. Life sciences 27 14519446
2013 Combining phylogenetic and syntenic analyses for understanding the evolution of TCP ECE genes in eudicots. PloS one 26 24019982
2005 Dual ECE/NEP inhibition on cardiac and neurohumoral function during the transition from hypertrophy to heart failure in rats. Hypertension (Dallas, Tex. : 1979) 26 15897363
2003 Endothelin converting enzyme (ECE) activity in normal pregnancy and preeclampsia. Hypertension in pregnancy 26 14572358
2001 A three-dimensional model of endothelin-converting enzyme (ECE) based on the X-ray structure of neutral endopeptidase 24.11 (NEP). Protein engineering 26 11438756
1999 Two di-leucine-based motifs account for the different subcellular localizations of the human endothelin-converting enzyme (ECE-1) isoforms. Journal of cell science 26 10462527
2000 Cellular expression of isoforms of endothelin-converting enzyme-1 (ECE-1c, ECE-1b and ECE-1a) and endothelin-converting enzyme-2. Journal of cardiovascular pharmacology 24 11078322
2023 CircNDC80 promotes glioblastoma multiforme tumorigenesis via the miR-139-5p/ECE1 pathway. Journal of translational medicine 23 36635757
2008 Cardiac expression patterns of endothelin-converting enzyme (ECE): implications for conduction system development. Developmental dynamics : an official publication of the American Association of Anatomists 22 18489007
2002 Molecular isolation and characterization of novel four subisoforms of ECE-2. Biochemical and biophysical research communications 22 12054617
1995 Temporal expression of ECE-1, ET-1, ET-3, ETA, and ETB receptor mRNAs after balloon angioplasty in the rat. Journal of cardiovascular pharmacology 22 8587369
2008 Divergent transforming growth factor-beta signaling in hepatic stellate cells after liver injury: functional effects on ECE-1 regulation. The American journal of pathology 19 18753413
2004 Sustained improvement of cardiac function and prevention of cardiac remodeling after long-term dual ECE-NEP inhibition in rats with congestive heart failure. Journal of cardiovascular pharmacology 19 15085059
2002 N-[2-(Indan-1-yl)-3-mercapto-propionyl] amino acids as highly potent inhibitors of the three vasopeptidases (NEP, ACE, ECE): In vitro and In vivo activities. Bioorganic & medicinal chemistry letters 18 12113828
2005 Triple ACE-ECE-NEP inhibition in heart failure: a comparison with ACE and dual ECE-NEP inhibition. Journal of cardiovascular pharmacology 16 16116347
2002 Toward an optimal joint recognition of the S1' subsites of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE), and neutral endopeptidase (NEP). Journal of medicinal chemistry 16 11906289
1999 The expression of endothelin-1 and endothelin-converting enzyme-1 (ECE-1) are independently regulated in bovine aortic endothelial cells. Journal of cardiovascular pharmacology 16 10218741
2020 Endothelin converting enzyme-1 (ECE-1) deletion in association with Endothelin-1 downregulation ameliorates kidney fibrosis in mice. Life sciences 15 32768584
2012 A polymorphic microsatellite repeat within the ECE-1c promoter is involved in transcriptional start site determination, human evolution, and Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 15 23175834
2009 Solid-state structural characterization of cutinase-ECE-pincer-metal hybrids. Chemistry (Weinheim an der Bergstrasse, Germany) 15 19219875
2008 C-338A polymorphism of the endothelin-converting enzyme (ECE-1) gene and the susceptibility to sporadic late-onset Alzheimer's disease and coronary artery disease. Disease markers 15 18334739
2006 Genomic organisation of the mouse gene encoding endothelin-converting enzyme-1 (ECE-1) and mRNA expression of ECE-1 isoforms in murine tissues. Gene 15 16540265
2003 Ece1 and Tbx1 define distinct pathways to aortic arch morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 15 12950083
2010 ECE-1 influences prostate cancer cell invasion via ET-1-mediated FAK phosphorylation and ET-1-independent mechanisms. Canadian journal of physiology and pharmacology 14 20725143
2000 Characterization of the c-specific promoter of the gene encoding human endothelin-converting enzyme-1 (ECE-1). FEBS letters 14 10682850
1999 The N-terminal segment of endothelin-converting enzyme (ECE)-1b contains a di-leucine motif that can redirect neprilysin to an intracellular compartment in Madin-Darby canine kidney (MDCK) cells. The Biochemical journal 14 10377252
2020 Garlic alters the expression of putative virulence factor genes SIR2 and ECE1 in vulvovaginal C. albicans isolates. Scientific reports 13 32107396
2010 Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction. Peptides 13 20600419
2001 Effect of an antisense oligodeoxynucleotide to endothelin-converting enzyme-1c (ECE-1c) on ECE-1c mRNA, ECE-1 protein and endothelin-1 synthesis in bovine pulmonary artery smooth muscle cells. Molecular pharmacology 13 11160849
2023 Functional analysis of the Candida albicans ECE1 Promoter. Microbiology spectrum 12 36786567
2014 Endothelin-converting enzyme-1 (ECE-1) is post-transcriptionally regulated by alternative polyadenylation. PloS one 12 24497914
2003 Endothelin-converting enzyme-1 (ECE-1) is a downstream target of the homeobox transcription factor Nkx2-5. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 12824294
2000 Immunohistochemical localization of ECE-1 in the human placenta. Placenta 12 10736246
1987 Molecular cloning of an endogenous cat retroviral element (ECE 1)--a recombinant between RD-114 and FeLV-related sequences. Brief report. Archives of virology 12 2821968
2002 Attenuation of SAH-induced cerebral vasospasm by a selective ECE inhibitor. Neuroreport 11 11893909
2001 Effect of ECE and NEP inhibition on cigarette smoke-induced cell proliferation in the rat lung. Inhalation toxicology 11 11445889
2015 Molecular cloning, sequence characteristics, and tissue expression analysis of ECE1 gene in Tibetan pig. Gene 10 26115769
1996 Human endothelin converting enzyme gene (ECE1) mapped to chromosomal region 1p36.1. Cytogenetics and cell genetics 10 8641140
2012 The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 9 22693153
2016 TIMAP-protein phosphatase 1-complex controls endothelin-1 production via ECE-1 dephosphorylation. The international journal of biochemistry & cell biology 8 26806547
2007 Functional neuroprotective effect of CGS 26303, a dual ECE inhibitor, on ischemic-reperfusion spinal cord injury in rats. Experimental biology and medicine (Maywood, N.J.) 8 17259328
2005 Novel, selective indole-based ECE inhibitors: lead optimization via solid-phase and classical synthesis. Bioorganic & medicinal chemistry letters 8 16085415
2023 A non-canonical role of endothelin converting enzyme 1 (ECE1) in promoting lung cancer development via directly targeting protein kinase B (AKT). The journal of gene medicine 7 37897251
2013 Regulation of endothelin-converting enzyme-1 (ECE-1) by the calcimimetic R-568. Pharmacological research 7 23911580
2018 A stress-enhanced model for discovery of disease-modifying gene: Ece1-suppresses the toxicity of α-synuclein A30P. Neurobiology of disease 6 29524599
2006 Selective indole-based ECE inhibitors: synthesis and pharmacological evaluation. ChemMedChem 6 16892341
2002 Effects of the ECE/NEP inhibitor CGS 34225 on the big ET-1-induced pressor response and plasma atrial natriuretic peptide concentration in conscious rats. Clinical science (London, England : 1979) 6 12193065
2024 DNA damage repair factor Rad18 controls virulence partially via transcriptional suppression of genes HWP1 and ECE1 in Candida albicans. Virulence 5 39573927
2014 Polymorphisms of ECE1 may contribute to susceptibility to ischemic stroke in Han Chinese of Northern China. Cell biochemistry and biophysics 5 24595843
2013 Blood pressure, artery size, and artery compliance parallel bone size and strength in mice with differing ece1 expression. Journal of biomechanical engineering 5 23699715
2012 ECE1 polymorphisms may contribute to the susceptibility of sporadic congenital heart disease in a Chinese population. DNA and cell biology 5 22731820
2012 Dynamic changes in the secondary structure of ECE-1 and XCE account for their different substrate specificities. BMC bioinformatics 5 23113990
2005 Fasting influences steroidogenesis, vascular endothelial growth factor (VEGF) levels and mRNAs expression for VEGF, VEGF receptor type 2 (VEGFR-2), endothelin-1 (ET-1), endothelin receptor type A (ET-A) and endothelin converting enzyme-1 (ECE-1) in newly formed pig corpora lutea. Domestic animal endocrinology 5 15760668
2004 In vivo properties of thiol inhibitors of the three vasopeptidases NEP, ACE and ECE are improved by introduction of a 7-azatryptophan in P2' position. The journal of peptide research : official journal of the American Peptide Society 5 15009531
2002 Synthesis of triazole-Tethered pyrrolidine libraries: novel ECE inhibitors. Bioorganic & medicinal chemistry letters 5 12067547
1987 Molecular pathogenesis of equine coital exanthema (ECE): temperature sensitivity (TS) and restriction endonuclease (RE) fragment profiles of several field isolates. Archives of virology 5 3028334
2024 siRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated Damage in a Monocrotaline Model. Current molecular pharmacology 4 38465437
2020 Association of ECE1 gene polymorphisms and essential hypertension risk in the Northern Han Chinese: A case-control study. Molecular genetics & genomic medicine 4 32107880
2020 Phenylethanol Glycosides Protect Myocardial Hypertrophy Induced by Abdominal Aortic Constriction via ECE-1 Demethylation Inhibition and PI3K/PKB/eNOS Pathway Enhancement. Evidence-based complementary and alternative medicine : eCAM 4 32595726
2016 Association between ECE1 gene polymorphisms and risk of intracerebral haemorrhage. The Journal of international medical research 4 27036146
2019 The -839(A/C) Polymorphism in the ECE1 Isoform b Promoter Associates With Osteoporosis and Fractures. Journal of the Endocrine Society 3 31637345
2003 The effects of phosphoramidon on the expression of human endothelin-converting enzyme-1 (ECE-1) isoforms. Journal of cardiovascular pharmacology 3 12827039
1998 Synthesis of novel substituted pyridines as inhibitors of endothelin converting enzyme-1 (ECE-1). Bioorganic & medicinal chemistry letters 3 9873497
2024 Candida Albicans Candidalysin ECE1 Gene - A Potent Virulence Factor for Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders. Indian journal of dental research : official publication of Indian Society for Dental Research 2 39787422
2023 The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity. Cancers 2 37835445
2019 Effects of ECE-1b rs213045 and rs2038089 polymorphisms on the development of contrast-induced acute kidney injury in patients with acute coronary syndrome. The Journal of international medical research 2 31777301
2018 ECE-1 overexpression in head and neck cancer is associated with poor tumor differentiation and patient outcome. Oral diseases 2 29978582
2017 Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR. Hypertension research : official journal of the Japanese Society of Hypertension 2 28298655
1997 [Phe21]big endothelin-1(18-34) and [Ala31]big endothelin-1(18-34) inhibit the human endothelin-converting enzyme-1 (ECE-1) expressed in CHO-K1 cells in a different fashion. FEBS letters 2 9450558
1995 Expression of ECE and related membrane peptidases in the EA.hy926 cell line. Journal of cardiovascular pharmacology 2 8587468
2025 ECE vs DISP Mechanisms in Anodic Electrolysis of Benzyl Alcohols: Computational Prediction of Microscopic Rate Constants. The journal of physical chemistry. C, Nanomaterials and interfaces 1 40959779
2023 Mutation analysis of the ECE1 gene in late-onset Alzheimer's disease. Neurobiology of aging 1 37271044
2022 Susceptibility of ECE1 polymorphisms to Hirschsprung's disease in southern Chinese children. Frontiers in pediatrics 1 36619519
2025 High-fat diet-induced dyslipidemia drives retinal ECE-1 and ET-1 upregulation. Frontiers in endocrinology 0 40951441
2024 The Analysis of ECE1 and PPARG Variants in the Development of Osteopenia and Osteoporosis in Postmenopausal Women. Biomedicines 0 39062013
2012 In-silico characterization of ECE-1 inhibitors. Computers in biology and medicine 0 22245098

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