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Information on EC 3.4.24.B14 - neprilysin-2 and Organism(s) Homo sapiens and UniProt Accession Q495T6
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3.4.24.B14 neprilysin-2Specify your search results
Word Map
- 3.4.24.B14
- neprilysins
- alzheimer
- endopeptidases
-
amyloid
- thiorphan
- phosphoramidon
- metalloproteases
- neuropeptides
-
3.4.24.11
-
zinc-dependent
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
mmel1, neprilysin-2, neprilysin 2, mmel2, neplp, nl1 protein, nep-like endopeptidase, membrane metallo-endopeptidase-like protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
NEP2
NEP2
NEP2 exists as two alternatively spliced isoforms, NEP2 and NEP2DELTA
CAS REGISTRY NUMBER
COMMENTARY
252986-92-8
-
82707-54-8
not distinguished from EC 3.4.24.11
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
neprilysin-2 shows a much restriceted substrate specificity compared to neprilysin
-
-
?
additional information
?
-
-
neprilysin-2 shows a much restriceted substrate specificity compared to neprilysin
-
-
?
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
fasidotrilat
fasidotrilat interacts with the Arg661 of hNEP-2 with more consistent bidentate hydrogen bonding and with weaker His658 with monodentate hydrogen bonding. The extended conformation of the inhibitor in the hNEP2 pocket might be the reason for its weak interactions
phosphoramidon
approximately 8-fold more potent against neprilysin (EC 3.4.24.11) than neprilysin-2
thiorphan
far more potent against neprilysin (EC 3.4.24.11) than neprilysin-2
additional information
molecular docking studies, overview. For substrate and inhibitor binding, Arg661 and Zn694 are identified as the most conserved residues
-
additional information
-
molecular docking studies, overview. For substrate and inhibitor binding, Arg661 and Zn694 are identified as the most conserved residues
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
NEP2 expression is measured in non-impaired, mild cognitive impaired, and clinical Alzheimer's disease human brain tissue from two Alzheimer's disease -susceptible and two resistant regions. NEP2 and NEP mRNA expression is altered in mild cognitive impaired subjects relative to non-impaired subjects in Alzheimer's disease -susceptible regions. NEP2 enzymatic activity is lowered in association with mild cognitive impaired and Alzheimer's disease and is positively associated with cognitive function, independent of diagnostic category
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
human neprilysin-2-beta is either localized to the extracellular surface or secreted
additional information
human neprilysin-2-beta is either localized to the extracellular surface or secreted
-
NEP2 exists as a membrane-bound and soluble enzyme, isoform NEP2DELTA exists as two membrane-bound glycoforms glycoforms, localised to the ER and plasma membrane
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
-
additional information
neprilysin-2 has two alternatively spliced forms, a membrane-bound and soluble-secreted variant
-
additional information
-
neprilysin-2 has two alternatively spliced forms, a membrane-bound and soluble-secreted variant
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
reduced enzyme activity in association with mild-cognitive impaired subjects and Alzheimer's disease subjects regardless of sex
metabolism
physiological function
additional information
evolution
neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin
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
metabolism
neprilysin-2 (NEP2) in the central nervous system controls Alzheimer's protein (amyloid-beta) deposition, and prevents its occurrence, while in the peripheral system, its closest homologue, neutral endopeptidase neprilysin (NEP, EC 3.4.24.11), regulates hypertension and heart related diseases
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
physiological function
neprilysin-2 (NEP2) in the central nervous system controls Alzheimer's protein (amyloid-beta) deposition, and prevents its occurrence
additional information
enzyme splice variants and their involvement in amyloid beta peptide cleavage, overview
additional information
molecular dynamics (MD) simulations of NEP-2 and modelling, overview. For substrate and inhibitor binding, Arg661 and Zn694 are identified as the most conserved residues
additional information
-
molecular dynamics (MD) simulations of NEP-2 and modelling, overview. For substrate and inhibitor binding, Arg661 and Zn694 are identified as the most conserved residues
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
isoform NEP2DELTA exists as two membrane-bound glycoforms glycoforms, localised to the ER and plasma membrane
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
neprilysin-2 expression in human induced pluripotent stem (iPS) cell-derived macrophage-like cells which leads to secretion of the enzyme, to reduced level of soluble amyloid beta oligomer in the culture medium, and to alleviated neurotoxicity of amyloid beta. Intracerebrally administration of the iPS-ML/NEP2 cells to 5XFAD mice leading to significant reduction in the level of amyloid beta in the brain interstitial fluid. 5XFAD mice harbor three mutations in the amyloid precursor protein (APP) gene and two in the presenilin-1 (PS1) gene and are a mouse model of Alzheimer's disease
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
NEP2 expression is measured in non-impaired, mild cognitive impaired, and clinical Alzheimer's disease human brain tissue from two Alzheimer's disease -susceptible and two resistant regions. NEP2 and NEP mRNA expression is altered in mild cognitive impaired subjects relative to non-impaired subjects in Alzheimer's disease -susceptible regions. NEP2 enzymatic activity is lowered in association with mild cognitive impaired and Alzheimer's disease and is positively associated with cognitive function, independent of diagnostic category
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
altered NEP2 expression in mild cognitive impaired patients may potentially serve as preclinical markers for Alzheimer's disease and reduced NEP2 activity may be associated with the development of Alzheimer's disease
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Whyteside, A.R.; Turner, A.J.
Human neprilysin-2 (NEP2) and NEP display distinct subcellular localisations and substrate preferences
FEBS Lett.
582
2382-2386
2008
Homo sapiens (Q495T6), Homo sapiens
Huang, J.Y.; Hafez, D.M.; James, B.D.; Bennett, D.A.; Marr, R.A.
Altered NEP2 Expression and Activity in Mild Cognitive Impairment and Alzheimers Disease
J. Alzheimers Dis.
28
433-441
2012
Homo sapiens
Marr, R.A.; Hafez, D.M.
Amyloid-beta and Alzheimers disease: the role of neprilysin-2 in amyloid-beta clearance
Front. Aging Neurosci.
6
187
2014
Homo sapiens (Q495T6), Mus musculus (Q9JLI3)
Takamatsu, K.; Ikeda, T.; Haruta, M.; Matsumura, K.; Ogi, Y.; Nakagata, N.; Uchino, M.; Ando, Y.; Nishimura, Y.; Senju, S.
Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing neprilysin-2
Stem Cell Res.
13
442-453
2014
Homo sapiens (Q495T6), Homo sapiens
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