3.4.24.11: neprilysin

This is an abbreviated version!
For detailed information about neprilysin, go to the full flat file.

Reaction

preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1' =

Synonyms

Abeta-degrading enzyme, acute lymphoblastic leukemia antigen, antigen, CALLA (common acute lymphoblastic leukemia-associated), atriopeptidase, CALLA, CALLA (common acute lymphoblastic leukemia-associated) antigens, CALLA antigen, CALLA glycoproteins, CD10, CD10/neutral endopeptidase, CD10/neutral endopeptidase 24.11, common acute lymphoblastic leukemia antigen, common acute lymphoblastic leukemia-associated antigens, Common acute lymphocytic leukemia antigen, endopeptidase CD10, Endopeptidase-2, endopeptidase-24.11, enkephalinase, EP24.11, glycoprotein, CALLA, kidney-brush-border neutral endopeptidase, kidney-brush-border neutral peptidase, kidney-brush-border neutral proteinase, membrane metallo-endopeptidase, membrane metalloendopeptidase, MME, NEP, NEP 24.11, NEP, enkephalinase, neutrophil cluster-differentiation antigen 10, common acute lymphoblastic leukemia antigen, NEP-1, NEP/CD10, NEP2, NEP4A, NEP4B, neprilypsin, neprilysin, neprilysin 4, neutral endopeptidase, neutral endopeptidase 24.11, neutral endopeptidase 24.11/CD10, neutral metallendopeptidase, NL-1, peptidase, endo-, peptidase, membrane metalloendo-, SEP, skin fibroblast elastase

ECTree

     3 Hydrolases

         3.4 Acting on peptide bonds (peptidases)

             3.4.24 Metalloendopeptidases

                3.4.24.11 neprilysin

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Results	in table
8	Activating Compound
1426	AA Sequence
16	Application
1	CAS Registry Number
30	Cloned(Commentary)
5	Crystallization (Commentary)
5034	Disease/ Diagnostics
8	Expression
54	General Information
122	IC50 Value
302	Inhibitors
20	kcat/KM [mM/s]
18	Ki Value [mM]
162	KM Value [mM]
41	Localization
26	Metals/Ions
18	Molecular Weight [Da]
67	Natural Substrates/ Products (Substrates)
174	Organism
25	PDB ID
32	pH Optimum
8	pH Range
14	Posttranslational Modification
50	Protein Variants
18	Purification (Commentary)
1	Reaction
6	Reaction Type
173	Reference
229	Source Tissue
9	Specific Activity [micromol/min/mg]
446	Substrates and Products (Substrate)
9	Subunits
145	Synonyms
17	Temperature Optimum [°C]
1	Temperature Stability [°C]
77	Turnover Number [1/s]

Application

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Application on EC 3.4.24.11 - neprilysin

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APPLICATION

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

analysis

Homo sapiens

P08473

the synthetic fluorogenic peptide substrate qf-Abeta(12-16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM can be detected at peptide concentration of 0.002 mM. It can be used for high-throughput screening of compounds that upregulate NEP

755120

medicine

13 entries

molecular biology

Homo sapiens

-

the established assay is extremely sensitive to neprilysin, but insensitive, or much less sensitive, to other Abeta-degrading enzymes. As low as 0.1 nM of neprilysin can be detected

718018

pharmacology

Rattus norvegicus

-

inhibitor thiorphan might be effective for reducing elevated A-type natriuretic peptide levels in sepsis. Plasma and lung A-type natriuretic peptide levels in rats treated with lipopolysaccharide are significantly higher than those in the control group, but are significantly decreased by thiorphan administration. Natriuretic peptide receptor-A mRNA levels do not differ significantly among the groups. Natriuretic peptide receptor-C mRNA levels in animals treated with lipopolysaccharide plus thiorphan group are significantly higher than those in the other groups

701256

medicine

Mus musculus

-

neprilysin can reduce the size and number of Abeta deposits in a transgenic mouse model. Neprilysin gene transfer therapy or other methods to increase endogenous neprilysin activity have the potential to prevent the accumulation of the amyloid Abeta peptide and as such may be able to prevent or delay the onset of Alzheimer#s disease

669913

medicine

Homo sapiens

-

CD10, i.e. beta-secretase, expression is detected in 62.2% of prostate cancer samples and occurs preferentially in higher Gleason pattern. CD10 expression positively correlates with adverse tumor features such as elevated preoperative prostate-specific antigen, higher Gleason score, and advanced stage. Prostate-specific antigen recurrence is significantly associated with the staining pattern of CD10 expression. Outcome significantly declines from negative over membranous, membranous-cytoplasmic, to exclusively cytoplasmatic CD10 expression. In multivariate analysis, CD10 expression is an independent predictor for prostate-specific antigen failure

697378

medicine

Homo sapiens

-

expression of neprilysin on the surface of leukocytes in mouse model of Alzheimer's disease reduces soluble brain amyloid beta peptide levels by
30% and lowers the accumulation of amyloid beta peptides by 50-60% when transplantation is performed at both young and early adult age. Peripheral neprilysin expression reduces amyloid-dependent performance deficits as measured by the Morris water maze test. Neprilysin expression results in the catabolism of amyloid beta to small, innocuous peptide fragments

699683

medicine

Rattus norvegicus

-

impaired cardiopulmonary vagal reflex control of heart rate is a feature of normal aging, and this deficit may be ameliorated by either atrium natriuretic peptide infusion or chronic neutral endopeptidase inhibition

698207

medicine

Homo sapiens

-

in the Flemish variant of amyloid beta, resistance to degradation by nepriylsin may underlie the pathogenicity associated with the A21G mutantion in amyloid beta

700415

medicine

Homo sapiens

-

overexpression neprilysin at low levels in transgenic mouse affects primarily the levels of neuropeptide Y compared with other neuropeptides. Neprilysin cleaves neuropeptide Y in C-terminal fragments, whereas silcencing neprilysin reduces neuropeptide Y processing. Infusion of the most abundant neuropeptide Y fragments 21-36 and 31-36 into the brain of amyloid precursor protein transgenic mice ameliorates the neurodegenerative pathology in this model. The amidated neuropeptide Y fragments protect human neuronal cultures from the neurotoxic effects of amyloid beta

699693

medicine

Homo sapiens

-

overexpression of human neprilysin for 4 months in young amyloid precursor protein//DeltaPS1 double-transgenic mice results in reduction in amyloid beta peptide levels, attenuation of amyloid load, oxidative stress, and inflammation, and improved spatial orientation. The overall reduction in amyloidosis and associated pathogenetic changes in the brain results in decreased memory impairment by about 50%

695449

medicine

Homo sapiens

-

sustained expression of a lentiviral vector carrying the neprilysin gene in amyloid precursor protein transgenic mice for up to 6 months lowers not only the amyloid plaque load but also reduces the levels of intracellular amyloid beta immunoreactivity. This is associated with improved behavioral performance in the water maze test and ameliorates the dendritic and synaptic pathology in the amyloid precursor protein transgenic mice

696994

medicine

Homo sapiens

P08473

engineered neprilysin can be a therapeutic for Alzheimer's disease due to its ability to degrade the peptide amyloid beta

735116

medicine

Homo sapiens

P08473

since accumulation of neurotoxic amyloid beta peptide aggregates in the brain appears to be a causative agent in the pathophysiology of Alzheimer's disease, increased clearance of amyloid beta peptide resulting from overexpression of the enzyme exhibits therapeutic potential for Alzheimer's disease

734365

medicine

Homo sapiens

P08473

the enzyme is a potential therapeutic source for degradation of deposited amyloid beta in Alzheimer's disease

733595

medicine

Homo sapiens

P08473

NEP is a target for Entresto used in treatment of heart failure

753262

medicine

Homo sapiens

P08473

upregulation of neprilysin (NEP) to reduce amyloid-beta (Abeta) accumulation in the brain is a promising strategy for the prevention of Alzheimer's disease (AD)

755120