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Literature summary extracted from

  • Rose, C.; Voisin, S.; Gros, C.; Schwartz, J.C.; Ouimet, T.
    Cell-specific activity of neprilysin 2 isoforms and enzymic specificity compared with neprilysin (2002), Biochem. J., 363, 697-705.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.24.B14 expression of two alternatively spliced isoforms of NEP2 in Chinese hamster ovary and AtT20 cells Rattus norvegicus

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.24.B14 Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2
-
Rattus norvegicus
3.4.24.B14 Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
Rattus norvegicus
3.4.24.B14 Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu
-
Rattus norvegicus
3.4.24.B14 Asp-Tyr(sulfated)-Met-Gly-Trp-Met-Asp-Phe-NH2
-
Rattus norvegicus
3.4.24.B14 Asp-Tyr-Met-Gly-Trp-Met
-
Rattus norvegicus
3.4.24.B14 Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2
-
Rattus norvegicus
3.4.24.B14 EDTA 1 mM, complete inhibition Rattus norvegicus
3.4.24.B14 fasidotrilat
-
Rattus norvegicus
3.4.24.B14 Gly-Gly-Phe-Met
-
Rattus norvegicus
3.4.24.B14 gonadotropin-releasing hormone
-
Rattus norvegicus
3.4.24.B14 omapatrilat
-
Rattus norvegicus
3.4.24.B14 Phe-Phe-Gly-Leu-Met-NH2
-
Rattus norvegicus
3.4.24.B14 phosphoramidon
-
Rattus norvegicus
3.4.24.B14 thiorphan
-
Rattus norvegicus
3.4.24.B14 Trp-Met-Asp-Phe-NH2
-
Rattus norvegicus
3.4.24.B14 Tyr-Gly-Ala-Phe-Met
-
Rattus norvegicus
3.4.24.B14 Tyr-Gly-Gly-Phe-Leu
-
Rattus norvegicus
3.4.24.B14 Tyr-Gly-Gly-Phe-Leu-NH2
-
Rattus norvegicus
3.4.24.B14 Tyr-Gly-Gly-Phe-Met
-
Rattus norvegicus
3.4.24.B14 Tyr-Gly-Gly-Phe-Met-NH2
-
Rattus norvegicus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.4.24.B14 0.023
-
3-methoxysuccinyl-Gly-Leu-Phe-Met-7-amido-4-methylcoumarin 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.027
-
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.035
-
3-methoxysuccinyl-Gly-Leu-Phe-Met-7-amido-4-methylcoumarin 37°C, secreted soluble form of NEP2 Rattus norvegicus
3.4.24.B14 0.04
-
succinyl-Ala-Ala-Val-7-amido-4-methylcoumarin 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.05
-
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin 37°C, secreted soluble form of NEP2 Rattus norvegicus
3.4.24.B14 0.1
-
succinyl-Ala-Ala-Val-7-amido-4-methylcoumarin 37°C, secreted soluble form of NEP2 Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.24.B14 membrane NEP2(m), membrane-bound form of NEP2 Rattus norvegicus 16020
-
3.4.24.B14 soluble NEP2(s), secreted soluble form of NEP2 Rattus norvegicus
-
-

Organism

EC Number Organism UniProt Comment Textmining
3.4.24.B14 Rattus norvegicus P0C1T0
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
3.4.24.B14 glycoprotein when expressed in Chinese hamster ovary and AtT20 cells, both isoforms are type II glycoproteins inserted in the endoplasmic reticulum as inactive precursors Rattus norvegicus

Purification (Commentary)

EC Number Purification (Comment) Organism
3.4.24.B14
-
Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.4.24.B14 brain
-
Rattus norvegicus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.24.B14 3-methoxysuccinyl-Gly-Leu-Phe-Met-7-amido-4-methylcoumarin + H2O
-
Rattus norvegicus 3-methoxysuccinyl-Gly-Leu + Phe-Met-7-amido-4-methylcoumarin
-
?
3.4.24.B14 Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O i.e. substance P(1-11), Arg-Pro-Lys-Pro-Gln-Gln-/-Phe-Phe-Gly-/-Leu-Met-NH2. Hydrolysis of substance P and derivatives occurs predominantly at the Gly9-/-Leu10 bond in the case of neprilysin and neprilysin 2. In addition neprilysin 2 cleaves at the Gln6-Phe7 bond Rattus norvegicus Arg-Pro-Lys-Pro-Gln-Gln + Phe-Phe-Gly + Leu-Met-NH2
-
?
3.4.24.B14 Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O i.e. bradykinin Rattus norvegicus Arg-Pro-Pro-Gly-Phe-Ser-Pro + Phe-Arg
-
?
3.4.24.B14 Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu + H2O i.e. angiotensin Rattus norvegicus Asp-Arg-Val-Tyr-Ile-His-Pro + Phe-His-Leu
-
?
3.4.24.B14 Asp-Tyr(sulfated)-Met-Gly-Trp-Met-Asp-Phe-NH2 + H2O i.e. cholecystokinin-8(sulfated). In cholecystokinins and derivatives, clear differences between neprilysin (EC 3.4.24.11) and neprilysin 2 can be observed: NEP2 does not attack the Asp7-/-Phe8-NH2 bond, a preferential cleavage site for neprilysin (EC 3.4.24.11, NEP) but cleaves the Gly4-/-Trp5 amide bond Rattus norvegicus Asp-Tyr(sulfated)-Met-Gly + Trp-Met-Asp-Phe-NH2
-
?
3.4.24.B14 Asp-Tyr-Met-Gly-Trp-Met + H2O i.e. cholecystokinin-(1-6) Rattus norvegicus Asp-Tyr-Met-Gly + Trp-Met
-
?
3.4.24.B14 Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 + H2O i.e. cholecystokinin-8(non-sulfated) Rattus norvegicus Asp-Tyr-Met-Gly + Trp-Met-Asp-Phe-NH2
-
?
3.4.24.B14 Gly-Gly-Phe-Met + H2O i.e. Des-[Tyr1, Met5]enkephalin Rattus norvegicus Gly-Gly + Phe-Met
-
?
3.4.24.B14 Gly-Trp-Met-Asp-Phe-NH2 + H2O i.e. cholecystokinin-(4-8) Rattus norvegicus Gly + Trp-Met-Asp-Phe-NH2
-
?
3.4.24.B14 gonadotropin-releasing hormone + H2O cleavage site: pEHWSYG-/-LRPG-NH2 Rattus norvegicus ?
-
?
3.4.24.B14 additional information the following synthetic substrates are not hydrolysed by either isoform of NEP2: succinyl-Gly-Pro-7-amido-4-methylcoumarin, 3-methoxysuccinyl-Ala-Ala-Pro-Met-7-amido-4-methylcoumarin, 3-methoxysuccinyl-ASp-Tyr-Met-7-amido-4-methylcoumarin, benzyloxycarbony-Arg-7-amido-4-methylcoumarin, tert-butyloxycarbonyl-Val-Gly-Arg-7-amido-4-methylcoumarin, benzyloxycarbonyl-Arg-7-amido-4-methylcoumarin, tert-butyloxycarbonyl-Arg-Val-Arg-Arg-7-amido-4-methylcoumarin and tert-butyloxycarbonyl-Gly-Pro-Arg-7-amido-4-methylcoumarin Rattus norvegicus ?
-
?
3.4.24.B14 Phe-Gly-Leu-Met-NH2 + H2O i.e. substance P(8-11) Rattus norvegicus Phe-Gly + Leu-Met-NH2
-
?
3.4.24.B14 Phe-Phe-Gly-Leu-Met-NH2 + H2O i.e. substance P(7-11) Rattus norvegicus Phe-Phe-Gly + Leu-Met-NH2
-
?
3.4.24.B14 succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
-
Rattus norvegicus succinyl-Ala-Ala + Phe-7-amido-4-methylcoumarin
-
?
3.4.24.B14 succinyl-Ala-Ala-Val-7-amido-4-methylcoumarin + H2O
-
Rattus norvegicus succinyl-Ala-Ala + Val-7-amido-4-methylcoumarin
-
?
3.4.24.B14 Tyr-Gly-Ala-Phe-Met + H2O i.e. [L-Ala3,Met5]enkephalin Rattus norvegicus Tyr-Gly-Ala + Phe-Met
-
?
3.4.24.B14 Tyr-Gly-Gly-Phe-Leu + H2O i.e. [Leu5]enkephalin Rattus norvegicus Tyr-Gly-Gly + Phe-Leu
-
?
3.4.24.B14 Tyr-Gly-Gly-Phe-Leu-NH2 + H2O i.e. [Leu5]enkephalin-NH2 Rattus norvegicus Tyr-Gly-Gly + Phe-Leu-NH2
-
?
3.4.24.B14 Tyr-Gly-Gly-Phe-Met + H2O i.e. [Met5]enkephalin. Regarding enkephalins and related opioid peptides, neprilysin (EC 3.4.24.11, NEP) and neprilysin 2 (NEP2) cleave the same Gly-/-Phe bond in all susceptible peptides, and hydrolysis by NEP2 and NEP is strongly reduced when the C-terminal carboxylate is amidated. Differences are: Ala instead of Gly in P1 significantly enhances hydrolysis by NEP2 but not NEP, whereas Leu instead of Met in P2' has an opposite influence (whereas affinity is enhanced) on NEP2. In contrast, neither affinity nor hydrolysis was significantly affected by the latter change in the case of NEP (EC 3.4.24.11) Rattus norvegicus Tyr-Gly-Gly + Phe-Met
-
?
3.4.24.B14 Tyr-Gly-Gly-Phe-Met-NH2 + H2O i.e. [Met5]enkephalin-NH2 Rattus norvegicus Tyr-Gly-Gly + Phe-Met-NH2
-
?

Synonyms

EC Number Synonyms Comment Organism
3.4.24.B14 NEP2
-
Rattus norvegicus
3.4.24.B14 neprilysin 2
-
Rattus norvegicus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.4.24.B14 0.33
-
Tyr-Gly-Gly-Phe-Met-NH2 37°C Rattus norvegicus
3.4.24.B14 0.33
-
Tyr-Gly-Gly-Phe-Leu-NH2 37°C Rattus norvegicus
3.4.24.B14 2.5
-
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg 37°C Rattus norvegicus
3.4.24.B14 2.7
-
Tyr-Gly-Gly-Phe-Leu 37°C Rattus norvegicus
3.4.24.B14 3
-
Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu 37°C Rattus norvegicus
3.4.24.B14 4
-
Gly-Trp-Met-Asp-Phe-NH2 37°C Rattus norvegicus
3.4.24.B14 6
-
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 37°C Rattus norvegicus
3.4.24.B14 6.17
-
Asp-Tyr(sulfated)-Met-Gly-Trp-Met-Asp-Phe-NH2 37°C Rattus norvegicus
3.4.24.B14 8.5
-
gonadotropin-releasing hormone 37°C Rattus norvegicus
3.4.24.B14 8.5
-
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin 37°C Rattus norvegicus
3.4.24.B14 8.5
-
Gly-Gly-Phe-Met 37°C Rattus norvegicus
3.4.24.B14 9
-
Tyr-Gly-Gly-Phe-Met 37°C Rattus norvegicus
3.4.24.B14 11.5
-
3-methoxysuccinyl-Gly-Leu-Phe-Met-7-amido-4-methylcoumarin 37°C Rattus norvegicus
3.4.24.B14 13.17
-
Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 37°C Rattus norvegicus
3.4.24.B14 13.8
-
succinyl-Ala-Ala-Val-7-amido-4-methylcoumarin 37°C Rattus norvegicus
3.4.24.B14 22.83
-
Phe-Gly-Leu-Met-NH2 37°C Rattus norvegicus
3.4.24.B14 34.5
-
Asp-Tyr-Met-Gly-Trp-Met 37°C Rattus norvegicus
3.4.24.B14 41.7
-
Tyr-Gly-Ala-Phe-Met 37°C Rattus norvegicus
3.4.24.B14 50
-
Phe-Phe-Gly-Leu-Met-NH2 37°C Rattus norvegicus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
3.4.24.B14 0.0000008
-
phosphoramidon 37°C, secreted soluble form of NEP2 Rattus norvegicus
3.4.24.B14 0.000002
-
phosphoramidon 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.000008
-
omapatrilat 37°C, secreted soluble form of NEP2 Rattus norvegicus
3.4.24.B14 0.000016
-
fasidotrilat 37°C, secreted soluble form of NEP2 Rattus norvegicus
3.4.24.B14 0.000017
-
omapatrilat 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.000019
-
fasidotrilat 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.00012
-
thiorphan 37°C, secreted soluble form of NEP2 Rattus norvegicus
3.4.24.B14 0.00025
-
thiorphan 37°C, membrane-bound form of NEP2 Rattus norvegicus
3.4.24.B14 0.002
-
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg 37°C Rattus norvegicus
3.4.24.B14 0.0035
-
Tyr-Gly-Gly-Phe-Leu 37°C Rattus norvegicus
3.4.24.B14 0.004
-
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2
-
Rattus norvegicus
3.4.24.B14 0.006
-
Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu 37°C Rattus norvegicus
3.4.24.B14 0.01
-
Tyr-Gly-Gly-Phe-Met 37°C Rattus norvegicus
3.4.24.B14 0.014
-
Gly-Gly-Phe-Met 37°C Rattus norvegicus
3.4.24.B14 0.018
-
gonadotropin-releasing hormone 37°C Rattus norvegicus
3.4.24.B14 0.018
-
Asp-Tyr-Met-Gly-Trp-Met 37°C Rattus norvegicus
3.4.24.B14 0.021
-
Tyr-Gly-Gly-Phe-Leu-NH2 37°C Rattus norvegicus
3.4.24.B14 0.021
-
Asp-Tyr(sulfated)-Met-Gly-Trp-Met-Asp-Phe-NH2 37°C Rattus norvegicus
3.4.24.B14 0.025
-
Tyr-Gly-Gly-Phe-Met-NH2 37°C Rattus norvegicus
3.4.24.B14 0.03
-
Tyr-Gly-Ala-Phe-Met 37°C Rattus norvegicus
3.4.24.B14 0.039
-
Trp-Met-Asp-Phe-NH2 37°C Rattus norvegicus
3.4.24.B14 0.05
-
Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2 37°C Rattus norvegicus
3.4.24.B14 0.09
-
Phe-Phe-Gly-Leu-Met-NH2
-
Rattus norvegicus