EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
3.4.24.11 | phosphoramidon | - |
Homo sapiens | |
3.4.24.11 | phosphoramidon | the inhibitor induces a dramatic increase in amyloid-beta peptide levels | Mus musculus | |
3.4.24.11 | phosphoramidon | the inhibitor induces a dramatic increase in amyloid-beta peptide levels | Rattus norvegicus | |
3.4.24.11 | thiorphan | - |
Homo sapiens | |
3.4.24.11 | thiorphan | the inhibitor induces a dramatic increase in amyloid-beta peptide levels | Mus musculus | |
3.4.24.11 | thiorphan | the inhibitor induces a dramatic increase in amyloid-beta peptide levels | Rattus norvegicus | |
3.4.24.B14 | phosphoramidon | - |
Homo sapiens | |
3.4.24.B14 | phosphoramidon | the inhibitor induces a dramatic increase in amyloid-beta peptide levels | Mus musculus | |
3.4.24.B14 | thiorphan | - |
Homo sapiens | |
3.4.24.B14 | thiorphan | the inhibitor induces a dramatic increase in amyloid-beta peptide levels | Mus musculus |
EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|---|
3.4.24.B14 | cell surface | human neprilysin-2-beta is either localized to the extracellular surface or secreted | Homo sapiens | 9986 | - |
3.4.24.B14 | extracellular | due to alternative splicing, murine NEP2 can exist in a membrane-bound form (mNEP2-alpha) or a secreted form (mNEP2-beta) | Mus musculus | - |
- |
3.4.24.B14 | extracellular | human neprilysin-2-beta is either localized to the extracellular surface or secreted | Homo sapiens | - |
- |
3.4.24.B14 | membrane | due to alternative splicing, murine NEP2 can exist in a membrane-bound form (mNEP2-alpha) or a secreted form (mNEP2-beta) | Mus musculus | 16020 | - |
3.4.24.B14 | additional information | alternative splicing acts on the human form of neprilysin-2 creating several isoforms. Isoform hNEP2-gamma does not show secreted amyloid beta peptide-degrading activity or activity at the cell surface | Homo sapiens | - |
- |
EC Number | Metals/Ions | Comment | Organism | Structure |
---|---|---|---|---|
3.4.24.11 | Zn2+ | neprilysin is a zinc metalloendopeptidase | Rattus norvegicus | |
3.4.24.11 | Zn2+ | neprilysin is a zinc metalloendopeptidase | Homo sapiens | |
3.4.24.11 | Zn2+ | neprilysin is a zinc metalloendopeptidase | Mus musculus |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
3.4.24.11 | amyloid beta peptide Abeta42 + H2O | Rattus norvegicus | the peptide primarily undergoes degradation by NEP in vivo in the brain | ? | - |
? | |
3.4.24.B14 | gonadotropin-releasing hormone + H2O | Homo sapiens | - |
? | - |
? | |
3.4.24.B14 | additional information | Mus musculus | in vivo in cells membrane-bound isoforms mNEP2-alpha and mNEP2-beta have similar activity against amyloid beta peptide Ab40 and Ab42 compared to neprilysin, EC 3.4.24.11 | ? | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
3.4.24.11 | Homo sapiens | P08473 | - |
- |
3.4.24.11 | Mus musculus | Q61391 | - |
- |
3.4.24.11 | Rattus norvegicus | - |
- |
- |
3.4.24.B14 | Homo sapiens | Q495T6 | - |
- |
3.4.24.B14 | Mus musculus | Q9JLI3 | - |
- |
EC Number | Source Tissue | Comment | Organism | Textmining |
---|---|---|---|---|
3.4.24.11 | brain | - |
Rattus norvegicus | - |
3.4.24.11 | brain | - |
Homo sapiens | - |
3.4.24.11 | brain | - |
Mus musculus | - |
3.4.24.B14 | blood | peripheral | Homo sapiens | - |
3.4.24.B14 | brain | while NEP2 is expressed at variable levels in most brain regions, it is most highly expressed in the brain stem, hypothalamus and pituitary | Mus musculus | - |
3.4.24.B14 | brain | while NEP2 is expressed at variable levels in most brain regions. Levels of neprilysin-2 mRNA in those with Alzheimer's disease are not different from non-impaired controls | Homo sapiens | - |
3.4.24.B14 | brain stem | high enzyme level | Mus musculus | - |
3.4.24.B14 | hypothalamus | high enzyme level | Mus musculus | - |
3.4.24.B14 | pituitary gland | high enzyme level | Mus musculus | - |
3.4.24.B14 | testis | - |
Mus musculus | - |
3.4.24.B14 | testis | - |
Homo sapiens | - |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
3.4.24.11 | amyloid beta peptide Abeta42 + H2O | the peptide primarily undergoes degradation by NEP in vivo in the brain | Rattus norvegicus | ? | - |
? | |
3.4.24.11 | additional information | human neprilysin-2 has a more restricted substrate specificity compared to human neprilysin with less activity against several vasoactive peptides | Homo sapiens | ? | - |
? | |
3.4.24.B14 | gonadotropin-releasing hormone + H2O | - |
Homo sapiens | ? | - |
? | |
3.4.24.B14 | additional information | in vivo in cells membrane-bound isoforms mNEP2-alpha and mNEP2-beta have similar activity against amyloid beta peptide Ab40 and Ab42 compared to neprilysin, EC 3.4.24.11 | Mus musculus | ? | - |
? | |
3.4.24.B14 | additional information | human neprilysin-2 has a more restricted substrate specificity compared to human neprilysin, EC 3.4.24.11, with less activity against several vasoactive peptides | Homo sapiens | ? | - |
? | |
3.4.24.B14 | additional information | in vitro membrane-bound isoform mNEP2-alpha has slower and weaker amyloid beta peptide Ab40 degrading properties when compared to neprilysin, EC 3.4.24.11, and shows little to no effect on amyloid beta peptide Ab42. Membrane-bound isozymes mNEP2-beta and gamma have nearly undetectable activity against amyloid beta peptide | Mus musculus | ? | - |
? |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
3.4.24.11 | NEP | - |
Rattus norvegicus |
3.4.24.11 | NEP | - |
Homo sapiens |
3.4.24.11 | NEP | - |
Mus musculus |
3.4.24.B14 | membrane-bound metalloendopeptidase-like enzyme 1 | - |
Homo sapiens |
3.4.24.B14 | membrane-bound metalloendopeptidase-like enzyme 2 | - |
Homo sapiens |
3.4.24.B14 | MMEL1 | - |
Homo sapiens |
3.4.24.B14 | MMEL2 | - |
Homo sapiens |
3.4.24.B14 | NEP-like endopeptidase | - |
Mus musculus |
3.4.24.B14 | NEP-like endopeptidase | - |
Homo sapiens |
3.4.24.B14 | NEP2 | - |
Mus musculus |
3.4.24.B14 | NEP2 | - |
Homo sapiens |
3.4.24.B14 | NEPLP | - |
Mus musculus |
3.4.24.B14 | neprilysin-2 | - |
Mus musculus |
3.4.24.B14 | neprilysin-2 | - |
Homo sapiens |
3.4.24.B14 | neprilysin-like protein | - |
Mus musculus |
3.4.24.B14 | Nl1 | - |
Mus musculus |
3.4.24.B14 | SEP | - |
Mus musculus |
3.4.24.B14 | soluble-secreted endopeptidase | - |
Mus musculus |
EC Number | Organism | Comment | Expression |
---|---|---|---|
3.4.24.B14 | Homo sapiens | the altered enzyme expression has a sexually dimorphic change, with mild-cognitive impaired males having significantly elevated NEP2 mRNA levels compared to non-impaired males in the mid-temporal and mid-frontal gyri | additional information |
EC Number | General Information | Comment | Organism |
---|---|---|---|
3.4.24.11 | evolution | neprilysin is a zinc metalloendopeptidase belonging to the M13 family | Rattus norvegicus |
3.4.24.11 | evolution | neprilysin is a zinc metalloendopeptidase belonging to the M13 family | Homo sapiens |
3.4.24.11 | evolution | neprilysin is a zinc metalloendopeptidase belonging to the M13 family | Mus musculus |
3.4.24.11 | malfunction | application of inhibitors to NEP in mouse brain produced dramatic elevations of endogenous amyloid beta peptide resulting in plaque deposition. But enzyme knockout mice show only a moderate increase in amyloid beta levels that are far from the levels needed to induce plaque deposition. This modest increase in amyloid beta peptide raises the possibility of alternative amyloid beta degrading-enzymes that are likewise sensitive to NEP-inhibitors | Mus musculus |
3.4.24.11 | malfunction | application of inhibitors to NEP in rat brain produced dramatic elevations of endogenous amyloid beta peptide resulting in plaque deposition | Rattus norvegicus |
3.4.24.11 | metabolism | neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP) to control amyloid-beta peptide levels in the brain | Rattus norvegicus |
3.4.24.11 | metabolism | neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP) to control amyloid-beta peptide levels in the brain | Homo sapiens |
3.4.24.11 | metabolism | neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP) to control amyloid-beta peptide levels in the brain | Mus musculus |
3.4.24.B14 | evolution | neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin | Mus musculus |
3.4.24.B14 | evolution | neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin | Homo sapiens |
3.4.24.B14 | malfunction | NEP2 knockout mice show reduced sperm function | Mus musculus |
3.4.24.B14 | malfunction | reduced enzyme activity in association with mild-cognitive impaired subjects and Alzheimer's disease subjects regardless of sex | Homo sapiens |
3.4.24.B14 | metabolism | neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP, EC 3.4.24.11) to control amyloid-beta peptide levels in the brain | Mus musculus |
3.4.24.B14 | metabolism | neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP, EC 3.4.24.11) to control amyloid-beta peptide levels in the brain | Homo sapiens |
3.4.24.B14 | additional information | enzyme splice variants and their involvement in amloid beta peptide cleavage, overview | Mus musculus |
3.4.24.B14 | additional information | enzyme splice variants and their involvement in amyloid beta peptide cleavage, overview | Homo sapiens |
3.4.24.B14 | physiological function | NEP-like proteases, e.g. neprilysin-2, are important because of their potential involvement in the spike in amyloid beta peptide levels posttreatment with NEP inhibitors. Neprilysin-2 has importance in amyloid peptide regulation | Mus musculus |
3.4.24.B14 | physiological function | NEP-like proteases, e.g. neprilysin-2, are important because of their potential involvement in the spike in amyloid beta peptide levels posttreatment with NEP inhibitors. The enzyme might play a role in the metabolism of neuropeptides of the hypothalamo-pituitary axis | Homo sapiens |