BRENDA - Enzyme Database
show all sequences of 3.4.24.B14

Amyloid-beta and Alzheimers disease: the role of neprilysin-2 in amyloid-beta clearance

Marr, R.A.; Hafez, D.M.; Front. Aging Neurosci. 6, 187 (2014)

Data extracted from this reference:

Inhibitors
Inhibitors
Commentary
Organism
Structure
phosphoramidon
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
Mus musculus
phosphoramidon
-
Homo sapiens
thiorphan
-
Homo sapiens
thiorphan
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
Mus musculus
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
cell surface
human neprilysin-2-beta is either localized to the extracellular surface or secreted
Homo sapiens
9986
-
extracellular
human neprilysin-2-beta is either localized to the extracellular surface or secreted
Homo sapiens
-
-
extracellular
due to alternative splicing, murine NEP2 can exist in a membrane-bound form (mNEP2-alpha) or a secreted form (mNEP2-beta)
Mus musculus
-
-
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
-
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
-
-
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
gonadotropin-releasing hormone + H2O
Homo sapiens
-
?
-
-
?
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
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q495T6
-
-
Mus musculus
Q9JLI3
-
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
blood
peripheral
Homo sapiens
-
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
-
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
-
brain stem
high enzyme level
Mus musculus
-
hypothalamus
high enzyme level
Mus musculus
-
pituitary gland
high enzyme level
Mus musculus
-
testis
-
Homo sapiens
-
testis
-
Mus musculus
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
gonadotropin-releasing hormone + H2O
-
733906
Homo sapiens
?
-
-
-
?
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
733906
Mus musculus
?
-
-
-
-
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
733906
Homo sapiens
?
-
-
-
-
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
733906
Mus musculus
?
-
-
-
-
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
phosphoramidon
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
Mus musculus
phosphoramidon
-
Homo sapiens
thiorphan
-
Homo sapiens
thiorphan
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
Mus musculus
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
cell surface
human neprilysin-2-beta is either localized to the extracellular surface or secreted
Homo sapiens
9986
-
extracellular
human neprilysin-2-beta is either localized to the extracellular surface or secreted
Homo sapiens
-
-
extracellular
due to alternative splicing, murine NEP2 can exist in a membrane-bound form (mNEP2-alpha) or a secreted form (mNEP2-beta)
Mus musculus
-
-
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
-
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
-
-
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
gonadotropin-releasing hormone + H2O
Homo sapiens
-
?
-
-
?
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
?
-
-
-
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
blood
peripheral
Homo sapiens
-
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
-
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
-
brain stem
high enzyme level
Mus musculus
-
hypothalamus
high enzyme level
Mus musculus
-
pituitary gland
high enzyme level
Mus musculus
-
testis
-
Homo sapiens
-
testis
-
Mus musculus
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
gonadotropin-releasing hormone + H2O
-
733906
Homo sapiens
?
-
-
-
?
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
733906
Mus musculus
?
-
-
-
-
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
733906
Homo sapiens
?
-
-
-
-
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
733906
Mus musculus
?
-
-
-
-
Expression
Organism
Commentary
Expression
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
General Information
Commentary
Organism
evolution
neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin
Homo sapiens
evolution
neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin
Mus musculus
malfunction
reduced enzyme activity in association with mild-cognitive impaired subjects and Alzheimer's disease subjects regardless of sex
Homo sapiens
malfunction
NEP2 knockout mice show reduced sperm function
Mus musculus
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
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
additional information
enzyme splice variants and their involvement in amyloid beta peptide cleavage, overview
Homo sapiens
additional information
enzyme splice variants and their involvement in amloid beta peptide cleavage, overview
Mus musculus
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
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
General Information (protein specific)
General Information
Commentary
Organism
evolution
neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin
Homo sapiens
evolution
neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin
Mus musculus
malfunction
reduced enzyme activity in association with mild-cognitive impaired subjects and Alzheimer's disease subjects regardless of sex
Homo sapiens
malfunction
NEP2 knockout mice show reduced sperm function
Mus musculus
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
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
additional information
enzyme splice variants and their involvement in amyloid beta peptide cleavage, overview
Homo sapiens
additional information
enzyme splice variants and their involvement in amloid beta peptide cleavage, overview
Mus musculus
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
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
Expression (protein specific)
Organism
Commentary
Expression
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
Other publictions for EC 3.4.24.B14
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [C]
Temperature Range [C]
Temperature Stability [C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [C] (protein specific)
Temperature Range [C] (protein specific)
Temperature Stability [C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
733906
Marr
Amyloid-beta and Alzheimers di ...
Homo sapiens, Mus musculus
Front. Aging Neurosci.
6
187
2014
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1
10
10
1
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735280
Takamatsu
Degradation of amyloid beta by ...
Homo sapiens
Stem Cell Res.
13
442-453
2014
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717700
Huang
Altered NEP2 Expression and Ac ...
Homo sapiens
J. Alzheimers Dis.
28
433-441
2012
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1
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1
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717067
Hafez
Neprilysin-2 is an important b ...
Mus musculus
Am. J. Pathol.
178
306-312
2011
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1
1
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694555
Bland
Locomotor and geotactic behavi ...
Drosophila melanogaster
Peptides
30
571-574
2009
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681904
Oh-Hashi
Biosynthesis, processing, traf ...
Mus musculus
Mol. Cell. Biochem.
313
103-111
2008
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692350
Whyteside
Human neprilysin-2 (NEP2) and ...
Homo sapiens
FEBS Lett.
582
2382-2386
2008
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682251
Bland
Expression of NEP2, a soluble ...
Drosophila melanogaster, Drosophila melanogaster OregonR
Peptides
28
127-135
2007
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12
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667419
Voisin
The ultimate tryptophan residu ...
Rattus norvegicus
Biochem. Biophys. Res. Commun.
335
356-360
2005
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667494
Thomas
Drosophila melanogaster NEP2 i ...
Drosophila melanogaster
Biochem. J.
386
357-366
2005
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669280
Voisin
A three-dimensional model of t ...
Rattus norvegicus
J. Biol. Chem.
279
46172-46181
2004
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11
6
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670239
Carpentier
Reduced fertility in male mice ...
Mus musculus
Mol. Cell. Biol.
24
4428-4437
2004
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395498
Boeckmann
The SWISS-PROT protein knowled ...
Mus musculus
Nucleic Acids Res.
31
365-370
2003
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690798
Rose
Cell-specific activity of nepr ...
Rattus norvegicus
Biochem. J.
363
697-705
2002
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1
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20
6
2
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23
6
2
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20
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19
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690691
Ouimet
Neprilysin II: A putative nove ...
Rattus norvegicus
Biochem. Biophys. Res. Commun.
271
565-570
2000
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Ikeda
Molecular identification and c ...
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32469-32477
1999
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