Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.4.24.B14 - neprilysin-2 and Organism(s) Mus musculus and UniProt Accession Q9JLI3

for references in articles please use BRENDA:EC3.4.24.B14
preliminary BRENDA-supplied EC number
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.24 Metalloendopeptidases
                3.4.24.B14 neprilysin-2
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Mus musculus
UNIPROT: Q9JLI3
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
proteolytic degradation of proteins
Synonyms
mmel1, neprilysin-2, neprilysin 2, mmel2, neplp, nl1 protein, nep-like endopeptidase, membrane metallo-endopeptidase-like protein, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
M13.008
Merops-ID
NEP-like endopeptidase
-
neprilysin-2
-
neprilysin-like protein
-
soluble-secreted endopeptidase
-
NEP2
-
-
neprilysin 2
-
-
neprilysin-2
-
-
NL-1
-
-
NL1 protein
-
-
additional information
may be identical with neprilysin EC 3.4.24.11
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
CAS REGISTRY NUMBER
COMMENTARY hide
252986-92-8
-
82707-54-8
not distinguished from EC 3.4.24.11
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
angiotensin I + H2O
?
show the reaction diagram
-
-
?
atrial natriuretic peptide + H2O
?
show the reaction diagram
-
-
?
bradykinin + H2O
?
show the reaction diagram
-
-
?
endothelin-1 + H2O
?
show the reaction diagram
-
-
?
protein + H2O
peptides
show the reaction diagram
Substance P + H2O
?
show the reaction diagram
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
succinyl-Ala-Ala + Phe-7-amido-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
protein + H2O
peptides
show the reaction diagram
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
zinc-metalloprotease
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
inhibition of the soluble isozyme SEP
phosphoramidon
thiorphan
calcium ionophore A23187
-
0.001 mM
forskolin
-
0.01 mM
thapsigargin
-
0.0001 mM
tunicamycin
-
inhibition of N-glycosylation by tunicamycin reduces the enzymatic activity of extracellular NEP2 to about 50% and the molecular size of intracellular NEP2
additional information
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
sharp pH-dependence
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
isozymes SEP and SEPDELTA
Manually annotated by BRENDA team
high enzyme level
Manually annotated by BRENDA team
isozymes SEP and SEPDELTA
Manually annotated by BRENDA team
high enzyme level
Manually annotated by BRENDA team
isozymes SEP and SEPDELTA
Manually annotated by BRENDA team
isozymes SEP and SEPDELTA
Manually annotated by BRENDA team
isozymes SEP and SEPDELTA
Manually annotated by BRENDA team
isozymes SEP and SEPDELTA
Manually annotated by BRENDA team
isozyme SEP
Manually annotated by BRENDA team
high enzyme level
Manually annotated by BRENDA team
-
the NL1 protein in mice is related to the sperm function and modulates the processes of fertilization and early embryonic development in vivo
Manually annotated by BRENDA team
additional information
in most cases isozyme SEPDELTA shows higher expression rates than isozyme SEP
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
neprilysin-2 is also a zinc metalloendopeptidase belonging to the same M13 family as neprilysin
malfunction
NEP2 knockout mice show reduced sperm function
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
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
malfunction
-
mice deficient for the NEP2 gene show significant elevations in total amyloid-beta peptide species in the hippocampus and brainstem/diencephalon (1.5fold). Increases in amyloid-beta peptide accumulation are more dramatic in NEP2 knockout mice crossbred with APP transgenic mice. In NEP/NEP2 double-knockout mice, amyloid-beta peptide levels are marginally increased (1.5 to 2fold), compared with NEP-/-/NEP2+/+ controls. Treatment of these double-knockout mice with phosphoramidon results in elevations of amyloid-beta peptide, suggesting that yet other NEP-like amyloid-beta peptide -degrading endopeptidases are contributing to amyloid-beta peptide catabolism
additional information
enzyme splice variants and their involvement in amloid beta peptide cleavage, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MMEL1_MOUSE
765
1
88700
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
x * 110000, membrane-bound isozymes SEP and SEPDELTA, SDS-PAGE, x * 126000, soluble isozyme SEP, SDS-PAGE
126000
x * 110000, membrane-bound isozymes SEP and SEPDELTA, SDS-PAGE, x * 126000, soluble isozyme SEP, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 110000, membrane-bound isozymes SEP and SEPDELTA, SDS-PAGE, x * 126000, soluble isozyme SEP, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
soluble isozyme SEP, and membrane-bound isozyme SEP and SEPDELTA
glycoprotein
-
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
isozymes SEP and SEPDELTA, DNA determination and analysis, transient expression of both isoforms in CHO cells
expressed in HEK293 cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Mus musculus (Q9JLI3)
Manually annotated by BRENDA team
Ikeda, K.; Emoto, N.; Raharjo, S.B.; Nurhantari, Y.; Saiki, K.; Yokoyama, M.; Matsuo, M.
Molecular identification and characterization of novel membrane-bound metalloprotease, the soluble secreted form of which hydrolyzes a variety of vasoactive peptides
J. Biol. Chem.
274
32469-32477
1999
Mus musculus (Q9JLI3)
Manually annotated by BRENDA team
Carpentier, M.; Guillemette, C.; Bailey, J.L.; Boileau, G.; Jeannotte, L.; DesGroseillers, L.; Charron, J.
Reduced fertility in male mice deficient in the zinc metallopeptidase NL1
Mol. Cell. Biol.
24
4428-4437
2004
Mus musculus
Manually annotated by BRENDA team
Oh-Hashi, K.; Ohkubo, K.; Shizu, K.; Fukuda, H.; Hirata, Y.; Kiuchi, K.
Biosynthesis, processing, trafficking, and enzymatic activity of mouse neprilysin 2
Mol. Cell. Biochem.
313
103-111
2008
Mus musculus
Manually annotated by BRENDA team
Hafez, D.; Huang, J.Y.; Huynh, A.M.; Valtierra, S.; Rockenstein, E.; Bruno, A.M.; Lu, B.; DesGroseillers, L.; Masliah, E.; Marr, R.A.
Neprilysin-2 is an important beta-amyloid degrading enzyme
Am. J. Pathol.
178
306-312
2011
Mus musculus
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team