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 |
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 |
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 |
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 | - |
- |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
3.4.24.B14 | Rattus norvegicus | P0C1T0 | - |
- |
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 |
EC Number | Purification (Comment) | Organism |
---|---|---|
3.4.24.B14 | - |
Rattus norvegicus |
EC Number | Source Tissue | Comment | Organism | Textmining |
---|---|---|---|---|
3.4.24.B14 | brain | - |
Rattus norvegicus | - |
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 | - |
? |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
3.4.24.B14 | NEP2 | - |
Rattus norvegicus |
3.4.24.B14 | neprilysin 2 | - |
Rattus norvegicus |
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 |
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 |