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EC Tree
The taxonomic range for the selected organisms is: Rattus norvegicus The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Hydrolysis of the -Trp21-/-Val- bond in big endothelin to form endothelin 1
Synonyms
ece-1, endothelin-converting enzyme, endothelin converting enzyme, endothelin-converting enzyme-1, ece-1b, endothelin converting enzyme-1, hece-1, et converting enzyme, endothelin-converting enzyme 1, endothelin-converting enzyme 1 (ece-1),
more
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endothelin-converting enzyme-1
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Endothelin-converting enzyme
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endothelin-converting enzyme 1 (ECE-1)
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endothelin-converting enzyme-1
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ECE-1
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hydrolysis of peptide bond
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big endothelin + H2O
endothelin-1 + ?
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-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
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-
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?
amyloid-beta peptide + H2O
?
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degradation
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-
?
big endothelin + H2O
endothelin-1 + ?
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-
-
-
?
Big endothelin 1 + H2O
?
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key enzyme in endothelin production, generates potent vasoconstrictor endothelin from its inactive precursor
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-
?
big endothelin-1 + H2O
endothelin-1 + ?
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-
-
-
?
big endothelin-2 + H2O
?
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-
-
-
?
big endothelin-3 + H2O
endothelin-3 + ?
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-
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?
Human big endothelin 1 + H2O
Endothelin 1 + big endothelin 1(21-38)
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best substrate
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-
?
Human big endothelin 2 + H2O
?
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hydrolysis at 25% the rate of big endothelin1
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?
Human big endothelin 3 + H2O
?
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hydrolysis at 50% the rate of big endothelin1
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?
preproendothelin-1 + H2O
endothelin-1 + ?
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?
additional information
?
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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
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?
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big endothelin + H2O
endothelin-1 + ?
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?
big endothelin-1 + H2O
endothelin-1 + ?
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?
amyloid-beta peptide + H2O
?
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degradation
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?
big endothelin + H2O
endothelin-1 + ?
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-
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-
?
Big endothelin 1 + H2O
?
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key enzyme in endothelin production, generates potent vasoconstrictor endothelin from its inactive precursor
-
-
?
big endothelin-1 + H2O
endothelin-1 + ?
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?
preproendothelin-1 + H2O
endothelin-1 + ?
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?
additional information
?
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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
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?
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Zinc
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zinc metalloproteinase, zinc-binding domain
additional information
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neutral metalloendopeptidase
Zn2+
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4-chloro-N-(((4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl)amino)carbonyl)benzenesulfonamide
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RO 67-7447
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synthetic inhibitor, selective ECE-1 inhibitor
SM-19712
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a specific ECE-1 inhibitor. SM-191712 causes sustained ERK2 activation in cytosolic and nuclear fractions after substance P removal
additional information
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no inhibition by thiorphan, captopril
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additional information
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no inhibition by thiorphan, captopril
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additional information
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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
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additional information
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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
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additional information
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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
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0.0002
Big endothelin-1
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0.00046
big endothelin-2
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0.00027
big endothelin-3
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0.0000012
RO 67-7447
Rattus norvegicus
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6.5 - 7.2
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active in a narrow range
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UniProt
brenda
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brenda
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brenda
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brenda
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brenda
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brenda
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analysis of the levels of ECE-1 expression and distribution under normal and pathologic conditions of Alzheimer disease, overview
brenda
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ECE-1 promotes re-sensitization of SP-induced inflammation
brenda
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vascular
brenda
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brenda
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lung enzyme is similar to that of endothelial cells
brenda
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dorsal skin, ECE-1 promotes re-sensitization of SP-induced inflammation
brenda
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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
brenda
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ECE-1 promotes re-sensitization of SP-induced inflammation
brenda
additional information
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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
brenda
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brenda
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medulla and cortex, expression analysis after enzyme induction, overview
brenda
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brenda
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brenda
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brenda
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brenda
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brenda
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malfunction
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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
metabolism
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regulation of neuropeptide signaling at the cell surface involving ECE-1, detailed overview
physiological function
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ECE-1 regulates the duration and subcellular location of substance P-induced, beta-arrestin-dependent ERK activation, overview
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ECE1_RAT
762
1
86126
Swiss-Prot
Secretory Pathway (Reliability: 5 )
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130000
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1 * 130000, SDS-PAGE
170000 - 190000
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rat, FPLC gel filtration
85520
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rat, deduced from nucleotide sequence
86000
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1 * 86000, deglycosylated enzyme, SDS-PAGE
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monomer
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1 * 130000, SDS-PAGE
monomer
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1 * 86000, deglycosylated enzyme, SDS-PAGE
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glycoprotein
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highly glycosylated with 10 possible N-linked glycosylated sites
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cyclosporine A intensifies renal enzyme expression. The enzyme is upregulated by hypoxia via hypoxia-inducible factor
enzyme expression is significantly increased in the placenta and its implantation site of pregnant hyperinsulinemic rats. In the kidney and heart, protein expression is increased by 230 and 220%, respectively, while its level in the liver is similar in normal and hyperinsulinemic rats
the mRNA expression of isoforms ECE-1a and -b is upregulated in biliary cirrhosis and in CCl4-injured livers, whereas isoform ECE-1c mRNA remains unchanged. Enzyme activity is increased after bile duct occlusion and peaks at 12 h after acute CCl4-intoxication
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Takahashi, M.; Matsushita, Y.; Iijima, Y.; Tanzawa, K.
Purification and characterization of endothelin-converting enzyme from rat lung
J. Biol. Chem.
268
21394-21398
1993
Rattus norvegicus
brenda
Shimada, K.; Takahashi, M.; Tanzawa, K.
Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells
J. Biol. Chem.
269
18275-18278
1994
Rattus norvegicus
brenda
Fisk, L.; Nalivaeva, N.N.; Turner, A.J.
Regulation of endothelin-converting enzyme-1 expression in human neuroblastoma cells
Exp. Biol. Med.
231
1048-1053
2006
Homo sapiens, Rattus norvegicus
brenda
Khamaisi, M.; Raz, I.; Shilo, V.; Shina, A.; Rosenberger, C.; Dahan, R.; Abassi, Z.; Meidan, R.; Lecht, S.; Heyman, S.N.
Diabetes and radiocontrast media increase endothelin converting enzyme-1 in the kidney
Kidney Int.
74
91-100
2008
Rattus norvegicus
brenda
Khimji, A.K.; Shao, R.; Rockey, D.C.
Divergent transforming growth factor-beta signaling in hepatic stellate cells after liver injury: functional effects on ECE-1 regulation
Am. J. Pathol.
173
716-727
2008
Rattus norvegicus
brenda
Cattaruzza, F.; Cottrell, G.S.; Vaksman, N.; Bunnett, N.W.
Endothelin-converting enzyme 1 promotes re-sensitization of neurokinin 1 receptor-dependent neurogenic inflammation
Br. J. Pharmacol.
156
730-739
2009
Homo sapiens, Rattus norvegicus
brenda
Cerdeira, A.S.; Bras-Silva, C.; Leite-Moreira, A.F.
Endothelin-converting enzyme inhibitors: their application in cardiovascular diseases
Rev. Port. Cardiol.
27
385-408
2008
Bos taurus, Homo sapiens, Rattus norvegicus, Sus scrofa, Cavia sp.
brenda
Cottrell, G.S.; Padilla, B.E.; Amadesi, S.; Poole, D.P.; Murphy, J.E.; Hardt, M.; Roosterman, D.; Steinhoff, M.; Bunnett, N.W.
Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling
J. Biol. Chem.
284
22411-22425
2009
Homo sapiens, Mus musculus, Rattus norvegicus
brenda
Khamaisi, M.; Skarzinski, G.; Mekler, J.; Zreik, F.; Damouni, R.; Ariel, I.; Bursztyn, M.
Hyperinsulinemia increases placenta endothelin-converting enzyme-1 expression in trophoblasts
Am. J. Hypertens.
25
109-114
2012
Rattus norvegicus (P42893)
brenda
Heyman, S.N.; Abassi, Z.; Rosenberger, C.; Yaseen, H.; Skarjinski, G.; Shina, A.; Mathia, S.; Krits, N.; Khamaisi, M.
Cyclosporine A induces endothelin-converting enzyme-1 Studies invivo and invitro
Acta Physiol. (Oxf.)
223
e13033
2018
Rattus norvegicus (P42893)
brenda
Cho, T.J.; Kim, H.J.; Cho, J.
Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
Anim. Cells Sys.
23
170-175
2019
Rattus norvegicus (P42893)
brenda