Information on EC 3.4.24.71 - endothelin-converting enzyme 1

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
3.4.24.71
-
RECOMMENDED NAME
GeneOntology No.
endothelin-converting enzyme 1
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of the -Trp21-/-Val- bond in big endothelin to form endothelin 1
show the reaction diagram
-
-
-
-
Hydrolysis of the -Trp21-/-Val- bond in big endothelin to form endothelin 1
show the reaction diagram
ECE-1 promotes the recycling and re-sensitization of NK1 receptors, by degrading endocytosed substance P in endothelial cell endosomes. ECE-1 promotes CGRP and somatostatin receptor recycling
-
Hydrolysis of the -Trp21-/-Val- bond in big endothelin to form endothelin 1
show the reaction diagram
ECE-1 regulates re-sensitization of substance P signalling in HMEC-1-NK1 receptor cells
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ECE-1
-
-
-
-
Endothelin-converting enzyme
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
138238-81-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bovine
-
-
Manually annotated by BRENDA team
killifish
UniProt
Manually annotated by BRENDA team
4 isoforms of endothelin-converting enzyme-1, ECE-1a-d
-
-
Manually annotated by BRENDA team
4 isozymes ECE-1a-d
-
-
Manually annotated by BRENDA team
4 variants of isozyme ECE-1, ECE-1a, 1b, 1c and 1d
-
-
Manually annotated by BRENDA team
Chinese population, ECE1 shows four isoforms, ECE-1a, ECE-1b, ECE-1c and ECE-1d, gene ECE-1b
-
-
Manually annotated by BRENDA team
isozymes ECE-1a, ECE-1b, ECE-1c, and ECE-1d
-
-
Manually annotated by BRENDA team
isozymes ECE-1a-d
-
-
Manually annotated by BRENDA team
C57BL/6
-
-
Manually annotated by BRENDA team
C57BL/6J
-
-
Manually annotated by BRENDA team
male C57Bl6 mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J
-
-
Manually annotated by BRENDA team
healthy and streptozotocin-induced diabetic rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rat
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
ECE-1 inhibition causes endosomal retention of the substance P neurokinin 1 receptor, beta-arrestins, and Src, resulting in markedly sustained ERK2 activation in the cytosol and nucleus, whereas ECE-1 overexpression attenuates ERK2 activation. ECE-1 inhibition also enhances substance P-induced expression and phosphorylation of the nuclear death receptor Nur77, resulting in cell death
malfunction
-
ECE-1 inhibition causes endosomal retention of the substance P neurokinin 1 receptor, beta-arrestins, and Src, resulting in markedly sustained ERK2 activation in the cytosol and nucleus. ECE-1 inhibition also enhances substance P-induced expression and phosphorylation of the nuclear death receptor Nur77, resulting in cell death
malfunction
-
siRNA-mediated knockdown of ECE-1 results in a significant reduction in FAK phosphorylation. Transient ECE-1 overexpression in PNT1-a cells increases FAK phosphorylation
metabolism
-
regulation of neuropeptide signaling at the cell surface involving ECE-1, detailed overview
physiological function
-
ECE-1 regulates the duration and subcellular location of substance P-induced, beta-arrestin-dependent ERK activation, overview
physiological function
-
involvement of ECE-1 in the development of atherosclerosis disease, overview
physiological function
-
by degrading substance P and destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling endocytic signalling and trafficking of the NK1R: promoting resensitization of G protein-mediated plasma membrane signalling, and terminating beta-arrestin-mediated endosomal signalling
physiological function
-
differential degradation by ECE-1 is a novel mechanism by which corticotropin-releasing factor receptor 1 is protected from overactivation by physiologically relevant high concentrations of higher affinity ligand to mediate distinct resensitization and downstream signaling
physiological function
-
ECE-1 influences PC cell invasion via both ET-1-mediated FAK phosphorylation and ET-1 independent mechanisms
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(7-methoxy-coumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl) + H2O
?
show the reaction diagram
-
fluorogenic substrate
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-2,4-dinitrophenyl-OH + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta peptide + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid-beta peptide + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid-beta peptide + H2O
?
show the reaction diagram
-
degradation
-
-
?
amyloid-beta peptide + H2O
?
show the reaction diagram
-
degradation
-
-
?
amyloid-beta peptide + H2O
amyloid-beta peptide + ?
show the reaction diagram
-
protein kinase C epsilon, PKCepsilon, stimulates the amyloid-beta peptide degradation by ECE-1 in mice leading to a decrease in plaque-associated astrocytosis and dystrophic neurites, overview
-
-
?
angiotensin-I + H2O
?
show the reaction diagram
-
degradation, no activity with angiotensin-II
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
-
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
activation
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
ECE-1 is a membrane-bound metalloprotease responsible for production of vasoactive endothelin-1 from inactive big ET-1
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
PKCepsilon regulates the expression of ECE-1 in the brain
-
-
?
big endothelin + H2O
endothelin 1 + ?
show the reaction diagram
-
ECE-1a, 1b, 1c and 1d are all equally active on endothelin
-
-
?
big endothelin + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
Big endothelin 1 + H2O
?
show the reaction diagram
-
key enzyme in endothelin production, generates potent vasoconstrictor endothelin from its inactive precursor
-
-
-
big endothelin-1 + H2O
endothelin + ?
show the reaction diagram
-
key enzyme in the biosynthesis of the endothelins
-
?
big endothelin-1 + H2O
endothelin + ?
show the reaction diagram
-
activation, ECE-1 is a critical enzyme in the production of the potent vasoconstrictor peptide endothelin, ET-1
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
P42892
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
final step of posttranslational processing of this peptide
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
most potent naturally occurring vasoconstrictor
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
activation
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
activation
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
ECE-1 inhibition in MCF-7 breast cancer cells leads to a significantly decreased ET-1 expression and reduced cell invasiveness, overview
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
short-term endothelin-1 release is not involved in the isometric tension in response to different agonists, e.g. 15-E2t-IsoP, of human umbilical vein ring with or without endothelium, overview
-
-
?
big endothelin-3 + H2O
endothelin-3 + ?
show the reaction diagram
-
-
-
-
-
big endothelin-3 + H2O
endothelin-3 + ?
show the reaction diagram
-
specific for this substrate, big-endothelin-1 is no substrate
-
?
big endothelin-I + H2O
endothelin + ?
show the reaction diagram
-
key enzyme in the biosynthesis of the endothelins
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
degradation
-
-
?
calcitonin gene-related peptide + H2O
?
show the reaction diagram
-
degradation, degradation, co-internalization with ECE-1 into early endosomes, calcitonin gene-related peptide degradation promotes CLR/RAMP1 recycling and beta-arrestin2 redistribution into the cytosol, ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/RAMP1 recycling and resensitization, whereas ECE-1 overexpression has the opposite effect, mechanism, overview
-
-
?
corticotropin-releasing factor + H2O
?
show the reaction diagram
-
ECE-1 cleaves urocortin-1 (Ucn1) at three different sites but cleaves corticotropin-releasing factor (CRF) at only one site. ECE-1 degrades Ucn1 at both extracellular (pH 7.4) and endosomal (pH 5.5), whereas CRF is degraded at acidic pH alone. At a low or basal level, ECE-1 can disrupt association of Ucn1 or CRF with CRF1 in endosomes and free the receptor to promote recycling and resensitization
-
-
?
Human big endothelin 1 + H2O
Endothelin 1 + big endothelin 1(21-38)
show the reaction diagram
-
best substrate
-
-
-
Human big endothelin 1 + H2O
Endothelin 1 + big endothelin 1(21-38)
show the reaction diagram
-
best substrate, cleavage site: Trp21-Val22
-
-
Human big endothelin 2 + H2O
?
show the reaction diagram
-
hydrolysis at about 40% the rate of big endothelin1
-
-
-
Human big endothelin 2 + H2O
?
show the reaction diagram
-
hydrolysis at 25% the rate of big endothelin1
-
-
-
Human big endothelin 3 + H2O
?
show the reaction diagram
-
hydrolysis at about 30% the rate of big endothelin1, big endothelin 3(1-41)amide
-
-
-
Human big endothelin 3 + H2O
?
show the reaction diagram
-
hydrolysis at 50% the rate of big endothelin1
-
-
-
insulin B chain + H2O
?
show the reaction diagram
-
-
-
-
?
neurotensin + H2O
?
show the reaction diagram
-
-
-
-
?
preendothelin + H2O
endothelin + ?
show the reaction diagram
-
-
-
?
preproendothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
proendothelin-1 + H2O
endothelin + ?
show the reaction diagram
A7LFV6
activation
-
-
?
Somatostatin-14 + H2O
?
show the reaction diagram
-
i.e. SST-14, degradation of rat substrate internalized via recombinantly expressed somatostatin receptor subtype sst2A into HEK-293 cells
-
-
?
Substance P + H2O
?
show the reaction diagram
-
-
-
-
?
Substance P + H2O
?
show the reaction diagram
-
-
-
-
?
urocortin-1 + H2O
?
show the reaction diagram
-
ECE-1 cleaves urocortin-1 (Ucn1) at three different sites but cleaves corticotropin-releasing factor (CRF) at only one site. ECE-1 cleaves Ucn1 at Arg-34, which allows this ligands to bind and activate CRF1. ECE-1 degrades Ucn1 at both extracellular (pH 7.4) and endosomal (pH 5.5), whereas CRF is degraded at acidic pH alone. At a low or basal level, ECE-1 can disrupt association of Ucn1 or CRF with CRF1 in endosomes and free the receptor to promote recycling and resensitization
-
-
?
M7-methoxycoumarin-4-ylacetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)-OH + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
no substrate is the big endothelin 1(1-31) fragment
-
-
-
additional information
?
-
-
endothelin-converting enzyme function as vasopeptidase
-
-
-
additional information
?
-
-
isoforms of endothelin-converting enzyme-1, ECE-1a-d, are present in early endosomes, where they degrade neuropeptides and regulate post-endocytic sorting of receptors, ECE-1 does not regulate either the resensitization of receptors for peptides that are not ECE-1 substrates, e.g. angiotensin II, or the recycling of the bradykinin B2 receptor, which transiently interacts with beta-arrestins
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in endothelin processing
-
-
-
additional information
?
-
-
the enzyme is involved in chalizia, a granulomatous lesions of the eyelid
-
-
-
additional information
?
-
-
the enzyme plays a crucial role in the regulation of vascular tone and endothelial function
-
-
-
additional information
?
-
-
activity with octreotide
-
-
-
additional information
?
-
-
ECE-1 and endosomal acidification regulate the duration of substance P-induced ERK2 activation
-
-
-
additional information
?
-
-
endothelin-converting enzyme-1 degrades substance P in early endosomes of epithelial cells and neurons to destabilize the endosomal mitogen-activated protein kinase signalosome and terminate signaling
-
-
-
additional information
?
-
-
ECEs can hydrolyze several other biologically active peptides in vitro by cleavage on the amino side of hydrophobic residues
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
amyloid beta peptide + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid-beta peptide + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid-beta peptide + H2O
?
show the reaction diagram
-
degradation
-
-
?
amyloid-beta peptide + H2O
?
show the reaction diagram
-
degradation
-
-
?
angiotensin-I + H2O
?
show the reaction diagram
-
degradation, no activity with angiotensin-II
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
-
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
activation
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
ECE-1 is a membrane-bound metalloprotease responsible for production of vasoactive endothelin-1 from inactive big ET-1
-
-
?
big endothelin + H2O
endothelin + ?
show the reaction diagram
-
PKCepsilon regulates the expression of ECE-1 in the brain
-
-
?
big endothelin + H2O
endothelin 1 + ?
show the reaction diagram
-
-
-
-
?
big endothelin + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
Big endothelin 1 + H2O
?
show the reaction diagram
-
key enzyme in endothelin production, generates potent vasoconstrictor endothelin from its inactive precursor
-
-
-
big endothelin-1 + H2O
endothelin + ?
show the reaction diagram
-
key enzyme in the biosynthesis of the endothelins
-
?
big endothelin-1 + H2O
endothelin + ?
show the reaction diagram
-
ECE-1 is a critical enzyme in the production of the potent vasoconstrictor peptide endothelin, ET-1
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
P42892
-
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
final step of posttranslational processing of this peptide
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
most potent naturally occurring vasoconstrictor
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
activation
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
activation
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
ECE-1 inhibition in MCF-7 breast cancer cells leads to a significantly decreased ET-1 expression and reduced cell invasiveness, overview
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
short-term endothelin-1 release is not involved in the isometric tension in response to different agonists, e.g. 15-E2t-IsoP, of human umbilical vein ring with or without endothelium, overview
-
-
?
big endothelin-3 + H2O
endothelin-3 + ?
show the reaction diagram
-
specific for this substrate, big-endothelin-1 is no substrate
-
?
big endothelin-I + H2O
endothelin + ?
show the reaction diagram
-
key enzyme in the biosynthesis of the endothelins
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
degradation
-
-
?
preendothelin + H2O
endothelin + ?
show the reaction diagram
-
-
-
?
preproendothelin-1 + H2O
endothelin-1 + ?
show the reaction diagram
-
-
-
-
?
proendothelin-1 + H2O
endothelin + ?
show the reaction diagram
A7LFV6
activation
-
-
?
Substance P + H2O
?
show the reaction diagram
-
-
-
-
?
calcitonin gene-related peptide + H2O
?
show the reaction diagram
-
degradation, co-internalization with ECE-1 into early endosomes, calcitonin gene-related peptide degradation promotes CLR/RAMP1 recycling and beta-arrestin2 redistribution into the cytosol, ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/RAMP1 recycling and resensitization, whereas ECE-1 overexpression has the opposite effect, mechanism, overview
-
-
?
additional information
?
-
-
endothelin-converting enzyme function as vasopeptidase
-
-
-
additional information
?
-
-
isoforms of endothelin-converting enzyme-1, ECE-1a-d, are present in early endosomes, where they degrade neuropeptides and regulate post-endocytic sorting of receptors, ECE-1 does not regulate either the resensitization of receptors for peptides that are not ECE-1 substrates, e.g. angiotensin II, or the recycling of the bradykinin B2 receptor, which transiently interacts with beta-arrestins
-
-
-
additional information
?
-
-
the enzyme catalyzes the final step in endothelin processing
-
-
-
additional information
?
-
-
the enzyme is involved in chalizia, a granulomatous lesions of the eyelid
-
-
-
additional information
?
-
-
the enzyme plays a crucial role in the regulation of vascular tone and endothelial function
-
-
-
additional information
?
-
-
ECE-1 and endosomal acidification regulate the duration of substance P-induced ERK2 activation
-
-
-
additional information
?
-
-
endothelin-converting enzyme-1 degrades substance P in early endosomes of epithelial cells and neurons to destabilize the endosomal mitogen-activated protein kinase signalosome and terminate signaling
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
metalloprotease
Zinc
-
zinc metalloproteinase, zinc-binding domain
Zn2+
-
zinc-dependent
Zn2+
-
ECE-1 belongs to the neprilysin family of zinc metallopeptidases
Zn2+
-
ECE-1 is a type II membrane zinc metalloprotease
Zn2+
P42892
binding site is located in the C-terminal domain and is close to the inner surface of the protein, coordinated in an approximately tetrahedral geometry, involving the side chains of the residues His607, His611, and Glu667
Zn2+
-
ECE-1 is a zinc metallopeptidase
Mg2+
-
-
additional information
-
neutral metalloendopeptidase
additional information
-
metalloenzyme
additional information
-
ECE-1 is a membrane-bound metalloprotease
additional information
-
ECE-1 is a metallo-endopeptidase
additional information
-
metalloendopeptidase
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R,3R,4R,5R)-(2S)-(4-[2-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)ethyl]-3-isobutyl-5-phosphonopyrrolidine-2-carbonyl-amino)-3-(1H-indol-3-yl)propionic acid
-
0.01 mM, 91% inhibition of enzyme activity
(2R,4S,5R,6R)-(2S)-(5-[2-(1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-yl)ethyl]-4-isobutyl-6-phosphonopiperidine-2-carbonyl-amino)-3-(1H-indol-3-yl)propionic acid
-
0.01 mM, 98% inhibition of enzyme activity
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino) 1H-Indole-3-propanoic acid
-
-
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-(4-hydroxy-phenyl) propanoic acid
-
-
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino) 1H-indole-3-propanoic acid
-
-
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-(4-hydroxy-phenyl) propanoic acid
-
-
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-phenyl propanoic acid
-
-
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-phenyl propanoic acid
-
-
(2S)-2-([3-(1,1'-biphenyl)-2-([hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)phosphinyl]methyl)-1-oxopropyl]-amino) 1H-indole-3-propanoic acid
-
-
(2S)-2-([3-(3'-[1,1'-biphenyl]-4''-yl-4',5'-dihydro-5'-isoxazolyl)-2-([hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)-phosphinyl]methyl)-1-oxopropyl]amino) 1H-indole-3-propanoic acid
-
-
(2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-mercaptopyrrolidine-1-carboxylic acid isopropyl ester
-
IC50: 0.00109 mM
(2S,4R)-2-[2-[[4-mercapto-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carbonyl]methylamino]acetylamino]-benzoic acid methyl ester
-
IC50: 0.01089 mM
(2S,4R)-4-acetylsulfanyl-2-(2,4,5-trifluorobenzyloxymethyl)pyrrolidine-1-carboxylic acid 2,3-dihydrobenzo-[1,4]dioxin-5-yl ester
-
IC50: 0.0000765 mM
(2S,4R)-4-acetylsulfanyl-2-(2,4,5-trifluorobenzyloxymethyl)pyrrolidine-1-carboxylic acid 2-methoxycarbonylphenylester
-
IC50: 0.0000215 mM
(2S,4R)-4-mercapto-1-(naphthalene-2-sulfonyl)pyrrolidine-2-carboxylic acid N-methyl-N-(4-methylphenylsulfonyl)hydrazide
-
IC50: 0.00253 mM
(2S,4R)-4-mercapto-2-(2,4,5-trifluorobenzyloxymethyl)-pyrrolidine-1-carboxylic acid 2,3-dihydrobenzo[1,4]-dioxin-5-yl ester
-
IC50: 0.000137 mM
(2S,4R)-4-mercapto-2-(2,4,5-trifluorobenzyloxymethyl)-pyrrolidine-1-carboxylic acid 2-ethoxycarbonylphenylester
-
IC50: 0.000067 mM
(2S,4R)-5-[(2,5-difluorobenzylamino)methyl]-1-(5-propylpyrimidin-2-yl)pyrrolidine-3-thiol
-
IC50: 0.0000729 mM
(3R,5S)-1-(5-propylpyrimidin-2-yl)-5-(2,4,5-trifluorobenzyloxymethyl)pyrrolidine-3-thiol trifluoroacetate
-
IC50: 0.0000198 mM
(R,R)-5-[(2,4-difluorophenyl)-2-(3,3,3-trifluoro-2-methoxy-2-phenylpropionyl)amino]pent-4-ynoic acid methyl ester
-
-
(R,S)-5-[(2,4-difluorophenyl)-2-(3,3,3-trifluoro-2-methoxy-2-phenylpropionyl)amino]pent-4-ynoic acid methyl ester
-
-
(S)-2-amino-5-(2,4-difluorophenyl)pent-4-ynoic acid methyl ester
-
-
(S)-2-[(tert-butoxycarbonyl)amino]-5-(2,4-difluorophenyl)pent-4-ynoic acid
-
-
(S)-2-[(tert-butoxycarbonyl)amino]-5-(2,4-difluorophenyl)pent-4-ynoic acid methyl ester
-
-
(S)-2-[(tert-butoxycarbonyl)amino]pent-4-ynoic acid
-
-
(S)-3-[5-[1-amino-4-(2-methoxyphenyl)but-3-ynyl]tetrazol-1-yl]propionitrile
-
-
(S)-5-(2,4-difluorophenyl)-2-[[(dimethoxyphosphoryl)methyl]amino]pent-4-ynoic acid
-
-
(S)-5-(2,4-difluorophenyl)-2-[[(dimethoxyphosphoryl)methyl]amino]pent-4-ynoic acid methyl ester
-
-
(S)-[1-[(2-cyanoethyl)-1-H-tetrazol-5-yl]-4-(2-methoxyphenyl)but-3-ynyl]carbamic acid tert-butyl ester
-
-
(S)-[1-[(2-cyanoethyl)carbamoyl]-4-(2-methoxyphenyl)but-3-ynyl]carbamic acid tert-butyl ester
-
-
(S)-[1-[(2-cyanoethyl)carbamoyl]but-3-ynyl]carbamic acid tert-butyl ester
-
-
(S)-[[1-[[(2-biphenyl-4-ylethyl)-carbamoyl]-4-(2-fluorophenyl)but-3-ynyl]amino]methyl]phosphonic acid
-
-
(S)-[[[1-[1-(2-cyanoethyl)-1-H-tetrazol-5-yl]-4-(2-methoxyphenyl)but-3-ynyl]amino]methyl] phosphonic acid diphenyl ester
-
-
(S)-[[[[4-(2-methoxyphenyl)-1-H-tetrazol-5-yl]but-3-ynyl]amino]methyl] phosphonic acid
-
-
(S)-[[[[4-(2-methoxyphenyl)-1-H-tetrazol-5-yl]but-3-ynyl]amino]methyl] phosphonic acid diphenyl ester
-
-
(S,S)-2-[5-(2,4-difluorophenyl)-2-[[(dimethoxyphosphoryl)methyl]amino]pent-4-ynoyl]-4-methylpentanoic acid methyl ester
-
-
(S,S)-2-[[2-amino-5-(2-chlorophenyl)pent-4-ynoyl]amino]-4-methylpentanoic acid methyl ester
-
-
(S,S)-2-[[2-[(tert-butoxycarbonyl)amino]-5-(2-chlorophenyl)pent-4-ynoyl]-amino]-4-methylpentanoic acid methyl ester
-
-
(S,S)-2-[[2-[(tert-butoxycarbonyl)amino]pent-4-ynoyl]-amino]-4-methylpentanoic acid methyl ester
-
-
(S,S)-2-[[5-(2,4-difluorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino]-4-methylpentanoic acid
-
-
(S,S)-2-[[5-(2-chlorophenyl)-2-[(phosphonomethyl)amino]pent-4-ynoyl]amino]-4-methylpentanoic acid
-
-
(S,S)-2-[[5-(2-chlorophenyl)-2-[[(dimethoxyphosphoryl)-methyl]amino]pent-4-ynoyl]amino]-4-methylpentanoic acid methyl ester
-
-
(S,S)-2-[[5-(2-fluorophenyl)-2-[(phosphonomethyl)-amino]pent-4-ynoyl]amino]-4-methyl pentanoic acid
-
-
(S,S)-2-[[5-(3-fluorophenyl)-2-[(phosphonomethyl)-amino]pent-4-ynoyl]amino]-4-methyl pentanoic acid
-
-
(S,S)-5-phenyl-2-[(3,3,3-trifluoro-2-methoxy-2-phenylpropionyl)amino]pent-4-ynoic acid (2-cyanoethyl)amide
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
1 mM, inhibition of ECE-1 activity
1-(2,6-difluorobenzyl)-5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00065 mM
1-(2-fluorobenzyl)-5-[[(1-methylcyclopentyl)acetyl]amino]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00012 mM
1-(cyclohexylmethyl)-5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00086 mM
2-[(tert-butoxycarbonyl)amino]-5-(2,4-difluorophenyl)pent-4-ynoic acid methyl ester
-
-
4-chloro-N-(((4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl)amino)carbonyl)benzenesulfonamide
-
-
4-chloro-N-[(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl)amino]carbonyl benzenesulfonamide
-
-
-
4-[([5-[(2,2-dimethylpropyl)carbamoyl]-1-(2-fluorobenzyl)-1H-indol-2-yl]carbonyl)amino]benzoic acid
-
IC50: 0.00039 mM
5-[(3,3-dimethylbutanethioyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00066 mM
5-[(3,3-dimethylbutanoyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00022 mM
5-[(3,3-dimethylbutanoyl)amino]-1-(2-methylbenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.003 mM
5-[(3,3-dimethylbutanoyl)amino]-1-[(2-methyl-1,3-thiazol-4-yl)methyl]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0022 mM
5-[(3,3-dimethylbutanoyl)amino]-N,1-diphenyl-1H-indole-2-carboxamide
-
IC50: 0.0059 mM
5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1-(2-phenylethyl)-1H-indole-2-carboxamide
-
IC50: 0.0051 mM
5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1-[2-(trifluoromethyl)benzyl]-1H-indole-2-carboxamide
-
IC50: 0.00017 mM
5-[(4,4-dimethylpentanoyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00074 mM
5-[(bicyclo[2.2.1]hept-2-ylacetyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0003 mM
5-[(cyclopentylacetyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0064 mM
5-[([5-[(2,2-dimethylpropyl)carbamoyl]-1-(2-fluorobenzyl)-1H-indol-2-yl]carbonyl)amino]pyridine-3-carboxylic acid
-
IC50: 0.074 mM
5-[[(2,2-dimethylpropyl)sulfonyl]amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0067 mM
benzoylsulfanyl-2-(2,4,5-trifluorobenzyloxymethyl)-pyrrolidine-1-carboxylic acid 2,3-dihydrobenzo[1,4]-dioxin-5-yl ester
-
IC50: 0.0004805 mM
CGS 26303
-
-
CGS 26303
-
synthetic inhibitor, ECE-1/NEP inhibitor
CGS 26393
-
slight inhibition
CGS 26582
-
synthetic inhibitor, ECE/NEP/ACE inhibitor
CGS 34043
-
synthetic inhibitor, ECE-1/NEP inhibitor
CGS 34226
-
synthetic inhibitor, ECE-1/NEP inhibitor
CGS 35066
-
-
CGS 35066
-
synthetic inhibitor, selective ECE-1 inhibitor
CGS 35066
-
-
CGS 35339
-
-
CGS 35601
-
synthetic inhibitor, ECE/NEP/ACE inhibitor
CGS-26303
-
specific, complete inhibition at 0.025 mM
CGS-35066
-
a selective ECE-1 inhibitor, mimicks the effects of CGS-26303
Co3+-ATCUN complex
-
-
-
cyclohexyl-2-[[5-(2,4-difluorophenyl)-2-[(phosphonomethyl)-amino]pent-4-ynoyl]amino]propionic acid
-
-
ECEi
-
addition of an ECE-1 specific inhibitor (ECEi) to PC-3 cells reduces phosphorylation of focal adhesion kinase
-
EDTA
-
0.03 mM, Zn2+ restores, Cu2+, Co2+, Mn2+ or Fe2+ partially restores, not Ca2+ or Mg2+
FR-901533
-
-
FR9015133
-
specific ECE-1 inhibitor, in vitro not in vivo
-
L-tryptophan, N-[[1-[[(2S)-2-(acetylthio)-4-methyl-1 oxopentyl]amino]cyclopentyl]-carbonyl]-methyl ester
-
CGS 37808, at an oral dose of 10 mgEq per kg, CGS 37808 produced 71% and 67% inhibition of the big ET-1 pressor response at 30 and 120 min, respectively
N-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)-1H-indole-5-carboxamide
-
IC50: 0.01 mM
N-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-2-[(phenylamino)methyl]-1H-indole-5-carboxamide
-
IC50: 0.01 mM
N-(2-benzyl-3-[[(1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl](hydroxy)phosphoryl]propanoyl)-L-tryptophan
-
-
N-(3-{[(1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl}-2-{[3-(biphenyl-4-yl)-4,5-dihydro-1,2-oxazol-5-yl]methyl}propanoyl)-L-tryptophan
-
-
N-(alpha-L-rhamnopyranosyl-oxyhydroxy-phosphinyl)-L-Leu-L-Trp
P42892
mechanism of inhibitor binding analysed (cocrystallization)
N-(alpha-rhamnopyranosyloxyhydroxyphosphinyl)-Leu-Trp
-
phosphoramidon, synthetic inhibitor, ECE-1/NEP inhibitor
N-[3-{[(1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl}-2-(biphenyl-4-ylmethyl)propanoyl]-L-tryptophan
-
-
N-{(2S)-3-{[(1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl}-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propanoyl}-L-tryptophan
-
-
N2-(4-carbamoylphenyl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00022 mM
N2-(5-aminopyridin-2-yl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.0012 mM
N2-(6-aminopyridin-3-yl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00017 mM
N2-(6-chloropyridin-3-yl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00044 mM
N2-[4-(dimethylcarbamoyl)phenyl]-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00021 mM
N2-[4-[(butylsulfonyl)amino]phenyl]-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.0002 mM
N2-[6-(acetylamino)pyridin-3-yl]-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00013 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-(3-[[4-(methylsulfamoyl)phenyl]carbamoyl]phenyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00015 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-1,3,4-thiadiazol-2-yl-1H-indole-2,5-dicarboxamide
-
IC50: 0.0023 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-1H-pyrazol-3-yl-1H-indole-2,5-dicarboxamide
-
IC50: 0.01 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-phenyl-1H-indole-2,5-dicarboxamide
-
IC50: 0.007 mM; IC50: 0.01 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-pyridin-3-yl-1H-indole-2,5-dicarboxamide
-
IC50: 0.00085 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-[3-[(4-sulfamoylphenyl)carbamoyl]phenyl]-1H-indole-2,5-dicarboxamide
-
IC50: 0.000039 mM
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-[5-[(4-methylpiperazin-1-yl)carbonyl]pyridin-3-yl]-1H-indole-2,5-dicarboxamide
-
IC50: 0.09 mM
PD 069185
-
-
PD-069185
-
-
PD069185
-
a more selective ECE inhibitor
phosphoramidon
-
-
phosphoramidon
-
0.1 mM, in vivo and in vitro
phosphoramidon
-
-
phosphoramidon
-
0.1 M, 35% inhibition of ECE-1 activity
phosphoramidon
-
complete inhibition at 0.1 mM
phosphoramidon
-
a metalloproteinase inhibitor
RO 67-7447
-
i.e. (2S,4R)-4-mercapto-2-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidine-1-carboxylic acid 2-methoxycarbonyl-phenyl ester, a selective ECE-1 inhibitor
RO 67-7447
-
synthetic inhibitor, selective ECE-1 inhibitor
RXPA380
-
-
SCH 54470
-
synthetic inhibitor, ECE/NEP/ACE inhibitor
SCH-54,470
-
-
SLV-306
-
KC-12792, synthetic inhibitor, ECE-1/NEP inhibitor, clinical trial for treatment of arterial hypertension and heart failure in human
SM-19712
-
a specific ECE-1 inhibitor
SM-19712
-
synthetic inhibitor, selective ECE-1 inhibitor
SM-19712
-
a specific ECE-1 inhibitor. SM-191712 causes sustained ERK2 activation in cytosolic and nuclear fractions after substance P removal
SM-19712
-
ECE-1 inhibitor prevents endosomal substance P degardation. Thus, neurokinin 1 receptor (NK1R) recycling is suppressed by more than 50%
specific ECE-1 inhibitor
-
in the presence of 0.001 M ECE-1 inhibitor, cell number was effectively reduced to ~70% of control
-
thiorphan
-
50% inhibition of native ECE-1, 70% inhibition of solECE-1
thiorphan
-
1 mM, inhibition of ECE-1 activity
thiorphan
-
-
WS-79089B
-
natural inhibitor, selective ECE-1 inhibitor
WS75624A
-
natural inhibitor, selective ECE-1 inhibitor
WS79089A
-
natural inhibitor, selective ECE-1 inhibitor
WS79089C
-
natural inhibitor, selective ECE-1 inhibitor
[KGHK-Cu]+
-
-
-
[Lys-Gly-His-Lys-Co(NH3)2]2+
-
metallopeptide
[Lys-Gly-His-Lys-Cu]+
-
metallopeptide, IC50: 0.0049 mM under hydrolytic condtions
L-tryptophan, N-[[1-[[(2S)-2-mercapto-4-methyl-1-oxopentyl]amino]-cyclopentyl]carbonyl]
-
CGS 35601, IC50: 55 nM
additional information
-
no inhibition by thiorphan, captopril
-
additional information
-
leupeptin, chymostatin, pepstatin A, E-64, p-chloromercuriphenylsulfonic acid, N-ethylmaleimide or 4-amidinophenylmethyl sulfonylfluoride; no inhibition by thiorphan, captopril
-
additional information
-
little or no inhibition with captopril
-
additional information
-
not inhibited by thiorphan and captopril
-
additional information
-
enzyme activity unaffected by thiorphan
-
additional information
-
acidification to pH 6.4 inhibits plasma membrane ECE activity
-
additional information
-
neither exogenously added ET-1 nor the blockade of the receptors with bosentan modifies ECE-1 protein, overview
-
additional information
-
prevention of acidification of endosomes using bafilomycin A1 inhibits the degradation of internalized somatostatin-14
-
additional information
-
carbachol and phorbol 12-myristate 13-acetate reduce enzyme expression in neuroblastoma NB7 cells, only isozyme ECE-1c remains detectable, overview
-
additional information
-
expression of ECE-1 is significantly reduced in the cortex of adult rats after 15 mins of global ischemia, and is also significantly reduced in the striatum of rats subjected to prenatal hypoxia
-
additional information
-
RNAi-induced knockdown of ECE-1 reduces ECE-1 mRNA and protein levels leading to 80% to 90% inhibition of endothelin-1 secretion by the ovarian carcinoma cells, analysation of cell's behaviour and effect on the cancer
-
additional information
-
ECE-1 inhibition causes endosomal retention of the substance P neurokinin 1 receptor, beta-arrestins, and Src, resulting in markedly sustained ERK2 activation in the cytosol and nucleus. ECE-1 inhibition also enhances substance P-induced expression and phosphorylation of the nuclear death receptor Nur77, resulting in cell death
-
additional information
-
phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1, while sparing neprilysin, inhibitors, overview
-
additional information
-
no inhibition by thiorphan and captopril
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
captopril
-
solECE, activity 106.9%
chymostatin
-
-
pepstatin A
-
-
PMSF
-
-
E-64
-
-
additional information
-
the peptidase inhibitor CGS-26303, bigendothelin-1, and phosphoramidon, though not thiorphan, a neutral endopeptidase inhibitor, increase endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1, CGS-26303 and big endothelin increase ECE-1 promoter activity, the stimulation is abolished by cycloheximide, overview
-
additional information
A7LFV6
enzyme expression is twofold increased during transfer from seawater to freshwater, and sixfold during transfer from freshwater to seawater, while chronic exposure to fresh- or seawater has no effet on the enzyme, overview
-
additional information
-
diabetes and radiocontrast media increase medullary, but not cortical endothelin converting enzyme-1 content in the kidney, in vivo, the induction of diabetes or the administration of contrast media rises the enzyme activity 4-5fold, but 15fold when diabetic rats are given contrast media, the in vitro activity is increased 3-4fold, overview
-
additional information
-
protein kinase C epsilon, PKCepsilon, stimulates ECE-1 activity, overview
-
additional information
-
protein kinase C epsilon, PKCepsilon, stimulates the amyloid-beta peptide degradation by ECE-1 in transgenic mice, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0046
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-2,4-dinitrophenyl-OH
-
pH not specified in the publication, temperature not specified in the publication
0.0002
Big endothelin-1
-
-
0.0027
Big endothelin-1
-
pH 6.8, 37C, ECE-1a
0.00465
Big endothelin-1
-
pH 6.4, 37C, solECE-1
0.00751
Big endothelin-1
-
pH 6.4, 37C, ECE-1a
0.0082
Big endothelin-1
-
pH 6.8, 37C, solECE-1a
0.01987
Big endothelin-1
-
pH 7.1, 37C, ECE-1a
0.04831
Big endothelin-1
-
pH 7.1, 37C, solECE-1a
0.00046
big endothelin-2
-
-
0.00014
big endothelin-3
-
pH 7.0, 37C
0.00027
big endothelin-3
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00528
Big endothelin-1
-
pH 6.4, 37C, ECE-1a
0.097
Big endothelin-1
-
pH 6.4, 37C, solECE-1
0.112
Big endothelin-1
-
pH 6.8, 37C, ECE-1a
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000008
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino) 1H-Indole-3-propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000014
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-(4-hydroxy-phenyl) propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000026
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino) 1H-indole-3-propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000275
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]-amino)ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-(4-hydroxy-phenyl) propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0000077
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)phosphinyl]-(2R)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-phenyl propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00024
(2S)-2-((3-[hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl)amino)-3-phenyl propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.01
(2S)-2-([3-(1,1'-biphenyl)-2-([hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)phosphinyl]methyl)-1-oxopropyl]-amino) 1H-indole-3-propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.01
(2S)-2-([3-(3'-[1,1'-biphenyl]-4''-yl-4',5'-dihydro-5'-isoxazolyl)-2-([hydroxyl(2-phenyl-(1R)-1-([(benzyloxy)carbonyl]amino)ethyl)-phosphinyl]methyl)-1-oxopropyl]amino) 1H-indole-3-propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.000022
CGS 35066
-
pH not specified in the publication, temperature not specified in the publication
0.0012
N-(2-benzyl-3-[[(1R)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl](hydroxy)phosphoryl]propanoyl)-L-tryptophan
-
pH not specified in the publication, temperature not specified in the publication
0.00091
N-(3-{[(1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl}-2-{[3-(biphenyl-4-yl)-4,5-dihydro-1,2-oxazol-5-yl]methyl}propanoyl)-L-tryptophan
-
pH not specified in the publication, temperature not specified in the publication
0.0021
N-[3-{[(1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl}-2-(biphenyl-4-ylmethyl)propanoyl]-L-tryptophan
-
pH not specified in the publication, temperature not specified in the publication
0.005
N-{(2S)-3-{[(1R)-1-{[(benzyloxy)carbonyl]amino}-2-phenylethyl](hydroxy)phosphoryl}-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propanoyl}-L-tryptophan
-
pH not specified in the publication, temperature not specified in the publication
0.0012
phosphoramidon
-
pH not specified in the publication, temperature not specified in the publication
0.05
RXPA380
-
pH not specified in the publication, temperature not specified in the publication
0.00008
SCH-54,470
-
pH not specified in the publication, temperature not specified in the publication
0.00207
[KGHK-Cu]+
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00109
(2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-mercaptopyrrolidine-1-carboxylic acid isopropyl ester
-
IC50: 0.00109 mM
0.01089
(2S,4R)-2-[2-[[4-mercapto-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carbonyl]methylamino]acetylamino]-benzoic acid methyl ester
-
IC50: 0.01089 mM
0.0000765
(2S,4R)-4-acetylsulfanyl-2-(2,4,5-trifluorobenzyloxymethyl)pyrrolidine-1-carboxylic acid 2,3-dihydrobenzo-[1,4]dioxin-5-yl ester
-
IC50: 0.0000765 mM
0.0000215
(2S,4R)-4-acetylsulfanyl-2-(2,4,5-trifluorobenzyloxymethyl)pyrrolidine-1-carboxylic acid 2-methoxycarbonylphenylester
-
IC50: 0.0000215 mM
0.00253
(2S,4R)-4-mercapto-1-(naphthalene-2-sulfonyl)pyrrolidine-2-carboxylic acid N-methyl-N-(4-methylphenylsulfonyl)hydrazide
-
IC50: 0.00253 mM
0.000137
(2S,4R)-4-mercapto-2-(2,4,5-trifluorobenzyloxymethyl)-pyrrolidine-1-carboxylic acid 2,3-dihydrobenzo[1,4]-dioxin-5-yl ester
-
IC50: 0.000137 mM
0.000067
(2S,4R)-4-mercapto-2-(2,4,5-trifluorobenzyloxymethyl)-pyrrolidine-1-carboxylic acid 2-ethoxycarbonylphenylester
-
IC50: 0.000067 mM
0.0000729
(2S,4R)-5-[(2,5-difluorobenzylamino)methyl]-1-(5-propylpyrimidin-2-yl)pyrrolidine-3-thiol
-
IC50: 0.0000729 mM
0.0000198
(3R,5S)-1-(5-propylpyrimidin-2-yl)-5-(2,4,5-trifluorobenzyloxymethyl)pyrrolidine-3-thiol trifluoroacetate
-
IC50: 0.0000198 mM
0.00065
1-(2,6-difluorobenzyl)-5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00065 mM
0.00012
1-(2-fluorobenzyl)-5-[[(1-methylcyclopentyl)acetyl]amino]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00012 mM
0.00086
1-(cyclohexylmethyl)-5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00086 mM
0.00039
4-[([5-[(2,2-dimethylpropyl)carbamoyl]-1-(2-fluorobenzyl)-1H-indol-2-yl]carbonyl)amino]benzoic acid
-
IC50: 0.00039 mM
0.00066
5-[(3,3-dimethylbutanethioyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00066 mM
0.00022
5-[(3,3-dimethylbutanoyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00022 mM
0.003
5-[(3,3-dimethylbutanoyl)amino]-1-(2-methylbenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.003 mM
0.0022
5-[(3,3-dimethylbutanoyl)amino]-1-[(2-methyl-1,3-thiazol-4-yl)methyl]-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0022 mM
0.0059
5-[(3,3-dimethylbutanoyl)amino]-N,1-diphenyl-1H-indole-2-carboxamide
-
IC50: 0.0059 mM
0.0051
5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1-(2-phenylethyl)-1H-indole-2-carboxamide
-
IC50: 0.0051 mM
0.00017
5-[(3,3-dimethylbutanoyl)amino]-N-phenyl-1-[2-(trifluoromethyl)benzyl]-1H-indole-2-carboxamide
-
IC50: 0.00017 mM
0.00074
5-[(4,4-dimethylpentanoyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.00074 mM
0.0003
5-[(bicyclo[2.2.1]hept-2-ylacetyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0003 mM
0.0064
5-[(cyclopentylacetyl)amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0064 mM
0.074
5-[([5-[(2,2-dimethylpropyl)carbamoyl]-1-(2-fluorobenzyl)-1H-indol-2-yl]carbonyl)amino]pyridine-3-carboxylic acid
-
IC50: 0.074 mM
0.0067
5-[[(2,2-dimethylpropyl)sulfonyl]amino]-1-(2-fluorobenzyl)-N-phenyl-1H-indole-2-carboxamide
-
IC50: 0.0067 mM
0.0004805
benzoylsulfanyl-2-(2,4,5-trifluorobenzyloxymethyl)-pyrrolidine-1-carboxylic acid 2,3-dihydrobenzo[1,4]-dioxin-5-yl ester
-
IC50: 0.0004805 mM
0.000017
CGS 26303
-
optimized form of inhibitor, human recombinant ECE-1 overexpressed in CHO cells
0.0011
CGS 26303
-
long-active in vivo
0.00062
CGS 26582
-
-
0.0000058
CGS 34043
-
human recombinant ECE-1 overexpressed in CHO cells
0.000011
CGS 34226
-
human recombinant ECE-1 overexpressed in CHO cells
0.000022
CGS 35066
-
COS-1 cell membrane with overexpression of human ECE-1
0.000055
CGS 35601
-
-
0.000055
L-tryptophan, N-[[1-[[(2S)-2-mercapto-4-methyl-1-oxopentyl]amino]-cyclopentyl]carbonyl]
-
CGS 35601, IC50: 55 nM
0.01
N-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)-1H-indole-5-carboxamide
-
IC50: 0.01 mM
0.01
N-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-2-[(phenylamino)methyl]-1H-indole-5-carboxamide
-
IC50: 0.01 mM
0.0035
N-(alpha-rhamnopyranosyloxyhydroxyphosphinyl)-Leu-Trp
-
potency varies with pH of medium
0.00022
N2-(4-carbamoylphenyl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00022 mM
0.0012
N2-(5-aminopyridin-2-yl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.0012 mM
0.00017
N2-(6-aminopyridin-3-yl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00017 mM
0.00044
N2-(6-chloropyridin-3-yl)-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00044 mM
0.00021
N2-[4-(dimethylcarbamoyl)phenyl]-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00021 mM
0.0002
N2-[4-[(butylsulfonyl)amino]phenyl]-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.0002 mM
0.00013
N2-[6-(acetylamino)pyridin-3-yl]-N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00013 mM
0.00015
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-(3-[[4-(methylsulfamoyl)phenyl]carbamoyl]phenyl)-1H-indole-2,5-dicarboxamide
-
IC50: 0.00015 mM
0.0023
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-1,3,4-thiadiazol-2-yl-1H-indole-2,5-dicarboxamide
-
IC50: 0.0023 mM
0.01
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-1H-pyrazol-3-yl-1H-indole-2,5-dicarboxamide
-
IC50: 0.01 mM
0.007
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-phenyl-1H-indole-2,5-dicarboxamide
-
IC50: 0.007 mM
0.01
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-phenyl-1H-indole-2,5-dicarboxamide
-
IC50: 0.01 mM
0.00085
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-pyridin-3-yl-1H-indole-2,5-dicarboxamide
-
IC50: 0.00085 mM
0.000039
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-[3-[(4-sulfamoylphenyl)carbamoyl]phenyl]-1H-indole-2,5-dicarboxamide
-
IC50: 0.000039 mM
0.09
N5-(2,2-dimethylpropyl)-1-(2-fluorobenzyl)-N2-[5-[(4-methylpiperazin-1-yl)carbonyl]pyridin-3-yl]-1H-indole-2,5-dicarboxamide
-
IC50: 0.09 mM
0.0000012
RO 67-7447
-
-
0.00008
SCH 54470
-
-
0.000042
SM-19712
-
in vitro result, in vivo potency is lower than expected compared to in vitro result
0.00014
WS-79089B
-
-
0.00073
WS79089A
-
-
0.00342
WS79089C
-
-
0.0049
[Lys-Gly-His-Lys-Cu]+
-
metallopeptide, IC50: 0.0049 mM under hydrolytic condtions
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0001799
-
recombinant enzyme
0.00127
-
-
additional information
-
-
additional information
-
-
additional information
-
RNAi experiment: premature delivery in mouse can be controlled by hydrodynamic transfection with ECE-1 RNAi
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
ECE-1 degrades Ucn1 and CRF at endosomal (pH 5.5)
6.1 - 6.4
-
solECE-1
6.6 - 6.8
-
-
6.6
-
-
6.7 - 6.9
-
ECE-1
6.8
-
-
7.4
-
assay at
7.4
-
ECE-1 degrades Ucn1 at both extracellular (pH 7.4)
7.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 6.8
-
solECE-1 half-maximal activity at pH 5.7 and pH 6.7
5.7 - 7.3
-
native ECE-1, half-maximal activity at pH 6.2 and pH 7.0
5.8 - 7.8
-
about half-maximal activity at pH 5.8 and 7.8
6.5 - 7.2
-
active in a narrow range
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
determination of enzyme expression by immunohistochemical analysis on atherosclerotic and nonatherosclerotic vascular tissue using a combination of ECE-1 isoform-specific antibodies, distinct expression patterns for ECE-1a and ECE-1c, overview
Manually annotated by BRENDA team
-
increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
-
Manually annotated by BRENDA team
-
treatment with oxidized-low density lipoproteins results in increased ECE-1 protein content, mRNA expression and promotor activity
Manually annotated by BRENDA team
-
lower expression of ECE-1
Manually annotated by BRENDA team
-
analysis of the levels of ECE-1 expression and distribution under normal and pathologic conditions of Alzheimer disease, overview
Manually annotated by BRENDA team
-
PKCepsilon regulates the expression of ECE-1 in the brain
Manually annotated by BRENDA team
-
expression analysis of ECE-1 in the temporal cortex of patients with Alzheimer's disease, vascular dementia, and controls, overview. ECE-1 occurs in vascular endothelial cells. ECE-1 mRNA or protein levels, of either full-length ECE-1 or soluble spliced variant, ECE-1sv, in Alzheimer's disease or vascular dementia show no differences compared to controls
Manually annotated by BRENDA team
-
ECE-1 overexpression, immunohistochemic ECE-1 expression analysis of 600 different samples, the expression of ECE-1 is correlated to VEGF expression, overview
Manually annotated by BRENDA team
-
cerebellar, lower expression of ECE-1
Manually annotated by BRENDA team
-
ECE-1 expression in Alzheimer's disease brain shows no significant difference compared with age-matched controls
Manually annotated by BRENDA team
-
from healthy persons and from patients with Crohn's disease, enzyme expression anaylsis in different samples, healthy tissue shows enzyme expression mainly in the muscular layer and the vasculature, while in Crohn'sdisease colonic tissue, the enzyme is found at inflammatory sites and fibrotic tissue, overview
Manually annotated by BRENDA team
-
expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
expression of isozymes ECE-1a-d
Manually annotated by BRENDA team
-
ECE-1 promotes re-sensitization of SP-induced inflammation
Manually annotated by BRENDA team
-
enzyme distribution in the endometrium during different developmental phases, the enzyme expression varies during the menstrual cycle, epithelial cell, overview
Manually annotated by BRENDA team
-
ECE-1 is very abundant
Manually annotated by BRENDA team
-
endometrial, primary cell culture
Manually annotated by BRENDA team
-
enzyme expression in chalizia in meibomian adenomers, conjunctival epithelium, tarsal mucous glands, and in inflammatory cells, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
quantitative immunohistochemic analysis of enzyme distribution in autopsy specimen of post-percutaneous coronary intervention, PCI, sites and restenotic sites, the enzyme is detectable in the first 3 months after PCI, overview
Manually annotated by BRENDA team
-
no increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
no increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
-
Manually annotated by BRENDA team
-
medulla and cortex, expression analysis after enzyme induction, overview
Manually annotated by BRENDA team
-
increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
-
Manually annotated by BRENDA team
-
expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
lung enzyme is similar to that of endothelial cells
Manually annotated by BRENDA team
-
increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
increased ECE-1 protein content (immunohistochemistry, immunoblot) and mRNA expression (Northern blot) in apolipoprotein E-deficient mouse
-
Manually annotated by BRENDA team
-
from blood, determination of enzyme expression by immunohistochemical analysis using a combination of ECE-1 isoform-specific antibodies, expression of isozymes ECE-1a and ECE-1c
Manually annotated by BRENDA team
-
ECE-1 occurs in neurons in the cerebral cortex, hippocampus, amygdala, basal forebrain nuclei, diencephalon, brain stem and cerebellar hemisphere, ECE-2
Manually annotated by BRENDA team
-
myenteric neuron
Manually annotated by BRENDA team
-
expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
increased ECE-1 content in hypercholesterolemic patients
Manually annotated by BRENDA team
-
elevated ECE-1 expression level when developing lipopolysaccharide-induced premature delivery (Western blot)
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
elevated ECE-1 expression level when developing lipopolysaccharide-induced premature delivery (Western blot)
-
Manually annotated by BRENDA team
-
expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
primary cells derived from malignant tissue from radical prostatectomies, expression and localization of the ECE-1 isozymes, overview, upregulation of the isozyme ECE-1c
Manually annotated by BRENDA team
-
primary cells derived from benign tissue from radical prostatectomies, expression and localization of the ECE-1 isozymes, overview
Manually annotated by BRENDA team
-
hippocampal and neocortical
Manually annotated by BRENDA team
-
lower expression of ECE-1
Manually annotated by BRENDA team
-
dorsal skin, ECE-1 promotes re-sensitization of SP-induced inflammation
Manually annotated by BRENDA team
-
aortic, determination of enzyme expression by immunohistochemical analysis using a combination of ECE-1 isoform-specific antibodies, expression of isozyme ECE-1a
Manually annotated by BRENDA team
-
ECE-1 protein level in stellate cell from bile duct ligation-injured liver is increased twofold compared to those in normal stellate cell, ECE-1 protein is also up-regulated in cell from CCl4-injured liver and culture-activated stellate cell. Exposure of stellate cell from injured livers to TGF-betaincreases ECE-1 expression
Manually annotated by BRENDA team
-
ECE-1 is secreted to the medium, ECE-1 shedding from the surface of endothelial cells
Manually annotated by BRENDA team
-
primary, expression of isozymes ECE-1a-d
Manually annotated by BRENDA team
-
i.e. HUVECs, high levels of endogenous ECE
Manually annotated by BRENDA team
-
ECE-1 promotes re-sensitization of SP-induced inflammation
Manually annotated by BRENDA team
-
elevated ECE-1 expression level when developing lipopolysaccharide-induced premature delivery (Western blot)
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
elevated ECE-1 expression level when developing lipopolysaccharide-induced premature delivery (Western blot)
-
Manually annotated by BRENDA team
additional information
-
tissue distribution of mRNA
Manually annotated by BRENDA team
additional information
A7LFV6
ECE1 is ubiquitously expressed in killifish
Manually annotated by BRENDA team
additional information
-
expression of ECE-1 is significantly reduced in the cortex of adult rats after 15 mins of global ischemia, and is also significantly reduced in the striatum of rats subjected to prenatal hypoxia
Manually annotated by BRENDA team
additional information
-
isozyme expression and distribution analysis, overview
Manually annotated by BRENDA team
additional information
-
ECE-1 immunohistochemic analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
ECE-1 shedding from the surface of endothelial cells
Manually annotated by BRENDA team
-
isozyme ECE-1b
Manually annotated by BRENDA team
-
early endosomes from sequestration of recombinant somatostatin receptor subtype 2A, sst2A, in HEK-293 cells after induction by somatostatin-14 or octreotide, co-localization od ECE-1 and sst2A, overview
Manually annotated by BRENDA team
-
isozymes ECE-1a and ECE-1c
Manually annotated by BRENDA team
-
isozyme ECE-1b
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
anchored to the plasma membrane
Manually annotated by BRENDA team
-
ECE-1 is a membrane-bound metalloprotease
Manually annotated by BRENDA team
-
ECE-1 is a type II membrane protease
Manually annotated by BRENDA team
-
ECE-1 is a type II membrane protein
Manually annotated by BRENDA team
-
ECE-1 is a type II membrane zinc metalloprotease
Manually annotated by BRENDA team
-
ECEs are type II integral membrane-bound proteases
Manually annotated by BRENDA team
-
ECE-1a but not ECE-1b co-localizes with nuclear membrane markers
Manually annotated by BRENDA team
-
isozyme ECE-1a co-localizes with nucleolin
Manually annotated by BRENDA team
-
isozymes ECE-1a and ECE-1c
Manually annotated by BRENDA team
additional information
-
expression and localization of ECE-1 isozymes in symptomatic atherosclerotic disease and saphenous vein, overview
-
Manually annotated by BRENDA team
additional information
-
maintenance of cells in high glucose at 25 mM promotes relocalization of ECE-1a from the membrane to the intracellular compartment, mechanism, overview, phosphorylation might play an important role in the regulation of intracellular trafficking of ECE-1 subisoforms
-
Manually annotated by BRENDA team
additional information
-
the isozymes contain a signal peptide
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
78000
P42892
crystallization, 680 residues of monomeric enzyme (extracellular domain, residues 90-770)
699564
85520
-
rat, deduced from nucleotide sequence
31469
85610
-
bovine, deduced from nucleotide sequence
31470
140000
-
SDS-PAGE
651242
170000 - 190000
-
rat, FPLC gel filtration
31468
232000
-
gel filtration
649414
250000 - 300000
-
gel filtration
651235
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
-
dimer
-
2 * 110000, SDS-PAGE, 2 * 107600, MALDI
dimer
-
2 * 110000-140000, gel filtration, 2 * 115000, isoenzyme sECE, gel filtration
homodimer
P42892
forms in vivo, intra-molecular disulfide bond formed by C428, here crystallisation of monomeric mutant (extracellular domain, residues 90-770)
monomer
-
1 * 86000, rat, deglycosylated enzyme, SDS-PAGE
monomer
-
1 * 126000, SDS-PAGE
monomer
-
1 * 130000, rat, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
-
phosphoprotein
-
the isozymes contain a different number of putative phosphorylation sites for protein kinase C and protein kinase A in the amino-terminal region, stimulation of phosphorylation by phorbol myristate acetate, inhibition by calphostin C, phosphorylation might play an important role in the regulation of intracellular trafficking of ECE-1 subisoforms
glycoprotein
-
highly glycosylated with 10 possible N-linked glycosylated sites
glycoprotein
-
isozyme ECE-1d and ECE-1e are deglycosylated by PNGase F, the truncated variant ECE-1sv, lacking the signal peptide, is not glycosylated
additional information
P42892
intra-molecular disulfide bond formed by C428 (homodimer)
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cocrystallization of C428S mutant of monomeric form (extracellular domain, residues 90-770) with inhibitor N-(alpha-L-rhamnopyranosyl-oxyhydroxy-phosphinyl)-L-Leu-L-Trp
P42892
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
to near homogeneity
-
cell rupture by lysozyme and continuous cell disrupter, washing of insoluble pellet
P42892
Sepharose 4B column affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
bovine; expressed in Chinese hamster ovary CHO-K1 cells
-
DNA and amino acid sequence determination and anaylsis, phylogenetic analysis
A7LFV6
COS-1 cell membrane with overexpression of human ECE-1
-
DNA and amino acid sequence determination and anaylsis, genotyping, the ECE encoding gene shows several single nucleotide polymorphisms, overview
-
ECE-1 is endogenously expressed in HMEC-1 cells (RT-PCR, immunofluorescence)
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ECE-1 mRNA level is 42% lower in stenotic valves
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expressed in Chinese hamster ovary cells
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expression of ECE-1 is significantly higher in the solid tumors compared with effusions
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extracellular domain of monomeric human ECE-1 (C428S) mutant (Q90-W770) is amplified by PCR and produced recombinantly in Escherichia coli (inclusion bodies)
P42892
gene ECE-1b , the ECE-1 gene is located on chromosome 1, 1p36, genotyping
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GFP-tagged ECE-1 overexpression in HEK-293 cells
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isozyme genetic structure, overview, expression of wild-type isozyme ECE-1d and of truncated variant ECE-1sv lacking the signal peptide, expression analysis of isozymes and splicing variants, overview
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overexpression of GFP-tagged isozymes in HEK cell endosomes, subcellular localization, overview
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sECE, constructed by fusing the cleavable signal peptide of pro-opiomelanocortin in frame to complete extracellular domain of ECE-1, expressed in CHO cells
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solECE-1 constructed by fusing the cleavable N-terminalsignal sequence of human alkaline phosphatase in frame with the entire extracellular domain of ECE-1, transfected into CHO-K1 cells
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generation of apolipoprotein E-deficient mouse from strain C57BL/6J
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expressed in COS-cells; rat
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COS-1 cell membrane with overexpression of human ECE-1
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
nitric oxide decreases the expression of ECE-1 through a cGMP/PKG-dependent regulatory mechanism at the post-transcriptional level via the 3'-UTR of the ECE-1 gene
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siRNA-mediated knockdown of ECE-1 results in a significant reduction in FAK phosphorylation
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transient ECE-1 overexpression in PNT1-a cells increases FAK phosphorylation
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C428S
P42892
mutant of monomeric form
K198N
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naturally occuring polymorphism, the mutant shows impaired function
additional information
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ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/RAMP1 recycling and resensitization, whereas ECE-1 overexpression has the opposite effect, overview
additional information
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increased ECE activity in PKCepsilon-transfected EA.hy926 cells
additional information
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the ECE encoding gene shows polymorphisms, genotyping, overview
additional information
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ECE-1 overexpression attenuates ERK2 activation
additional information
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overexpression of ECE-1a or 1b in CHO cells results in a 75-90% reduction in Abeta1-40 and a 45-60% reduction in Abeta1-42, completely abolished by treatment with phosphoramidon
additional information
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the C338A polymorphism, that is located in the ECE-1 gene promoter, occurs in gene ECE-1b in carotid atherosclerosis, genotyping of a Chinese population, carotid atherosclerosis patients and healthy subjects, overview
additional information
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construction of transgenic mice overexpressing human amyloid-beta peptide and protein kinase C epsilon, overview, increased ECE activity in PKCepsilon-transfected EA.hy926 cells
additional information
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dual neprilysin/ECE knock-out mice show additive effects on amyloid-beta peptide accumulation, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
inclusion bodies solubilized in Tris-HCl, urea, beta-mercaptoethanol, dithiotreithol, glutathione, glycine
P42892
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
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ECE-1 is a potential target for the treatment of Alzheimers disease based on its role in amyloid-beta peptide degradation
drug development
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ECE-1 silencing (RNAi) may be a promising ovarian carcinoma anticancer therapy
drug development
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Inhibition of endothelin-1 production by ECE-1 is a promising target for the treatment of cardiovascular disease, but lack of substrate specifity is disadvantageous since inhibition of ECE-1 has impact on other pathways too
drug development
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mixed ACE/ECE-1 inhibitor may lead to vasopeptide inhibitors that can reduce the levels of angiotensin-II and endothelin-1, without interfering with bradykinin cleavage
medicine
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design of new potent and selective inhibitors might eventually lead to drugs against hypertension
medicine
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elevated plasma levels of endothelin-1 found in several diseases like asthma, hypertension, cerebral vacospasm, congestive heart failure and chronic and acute renal failure, blockade of the ET-1 system could have therapeutic utility
medicine
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analysis of effect of various ECE inhibitors in myocardial infarction, pulmonary hypertension, arterial hypertension. Overview is given on human studies
drug development
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the enzyme is a target for drug design in cardiovascular disease
medicine
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ECE-1 is a potential target for RNAi in order to prevent premature delivery
medicine
Mus musculus C57BL/6
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ECE-1 is a potential target for RNAi in order to prevent premature delivery
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