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Literature summary extracted from

  • Marr, R.A.; Hafez, D.M.
    Amyloid-beta and Alzheimers disease: the role of neprilysin-2 in amyloid-beta clearance (2014), Front. Aging Neurosci., 6, 187.
    View publication on PubMedView publication on EuropePMC

Inhibitors

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

Localization

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
-
-

Metals/Ions

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

Natural Substrates/ Products (Substrates)

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 ?
-
?

Organism

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
-
-

Source Tissue

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
-

Substrates and Products (Substrate)

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 ?
-
?

Synonyms

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

Expression

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

General 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