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Literature summary for 3.4.24.B14 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)

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

Inhibitors

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

KM Value [mM]

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

Localization

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

Organism

Organism UniProt Comment Textmining
Rattus norvegicus P0C1T0
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
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)

Purification (Comment) Organism
-
Rattus norvegicus

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-methoxysuccinyl-Gly-Leu-Phe-Met-7-amido-4-methylcoumarin + H2O
-
Rattus norvegicus 3-methoxysuccinyl-Gly-Leu + Phe-Met-7-amido-4-methylcoumarin
-
?
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
-
?
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg + H2O i.e. bradykinin Rattus norvegicus Arg-Pro-Pro-Gly-Phe-Ser-Pro + Phe-Arg
-
?
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
-
?
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
-
?
Asp-Tyr-Met-Gly-Trp-Met + H2O i.e. cholecystokinin-(1-6) Rattus norvegicus Asp-Tyr-Met-Gly + Trp-Met
-
?
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
-
?
Gly-Gly-Phe-Met + H2O i.e. Des-[Tyr1, Met5]enkephalin Rattus norvegicus Gly-Gly + Phe-Met
-
?
Gly-Trp-Met-Asp-Phe-NH2 + H2O i.e. cholecystokinin-(4-8) Rattus norvegicus Gly + Trp-Met-Asp-Phe-NH2
-
?
gonadotropin-releasing hormone + H2O cleavage site: pEHWSYG-/-LRPG-NH2 Rattus norvegicus ?
-
?
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 ?
-
?
Phe-Gly-Leu-Met-NH2 + H2O i.e. substance P(8-11) Rattus norvegicus Phe-Gly + Leu-Met-NH2
-
?
Phe-Phe-Gly-Leu-Met-NH2 + H2O i.e. substance P(7-11) Rattus norvegicus Phe-Phe-Gly + Leu-Met-NH2
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
-
Rattus norvegicus succinyl-Ala-Ala + Phe-7-amido-4-methylcoumarin
-
?
succinyl-Ala-Ala-Val-7-amido-4-methylcoumarin + H2O
-
Rattus norvegicus succinyl-Ala-Ala + Val-7-amido-4-methylcoumarin
-
?
Tyr-Gly-Ala-Phe-Met + H2O i.e. [L-Ala3,Met5]enkephalin Rattus norvegicus Tyr-Gly-Ala + Phe-Met
-
?
Tyr-Gly-Gly-Phe-Leu + H2O i.e. [Leu5]enkephalin Rattus norvegicus Tyr-Gly-Gly + Phe-Leu
-
?
Tyr-Gly-Gly-Phe-Leu-NH2 + H2O i.e. [Leu5]enkephalin-NH2 Rattus norvegicus Tyr-Gly-Gly + Phe-Leu-NH2
-
?
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
-
?
Tyr-Gly-Gly-Phe-Met-NH2 + H2O i.e. [Met5]enkephalin-NH2 Rattus norvegicus Tyr-Gly-Gly + Phe-Met-NH2
-
?

Synonyms

Synonyms Comment Organism
NEP2
-
Rattus norvegicus
neprilysin 2
-
Rattus norvegicus

Turnover Number [1/s]

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

Ki Value [mM]

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