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Information on EC 3.4.24.11 - neprilysin
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Word Map
- 3.4.24.11
- angiotensin
-
natriuretic
- alzheimer
-
angiotensin-converting
- phosphoramidon
- atrial
-
amyloid
- thiorphan
- cardiovascular
- hypertension
- bradykinin
- neuropeptides
- aminopeptidase
-
ejection
- airway
- anp
- ventricular
-
blocker
- captopril
- endothelins
-
opioids
- metallopeptidase
- tachykinins
-
renin-angiotensin
- hf
- valsartan
- enalapril
-
renin-angiotensin-aldosterone
- neurokinin
-
vasoactive
-
endothelin-converting
-
hfref
- naloxone
-
insulin-degrading
- bestatin
- kinin
-
diuretic
-
3.4.15.1
-
lily
-
aceis
- met-enkephalin
-
bronchoconstriction
- angioedema
- amastatin
-
angiotensin-1-7
-
kininase
- lisinopril
-
nt-probnp
- medicine
-
bronchoconstrictors
- pharmacology
- analysis
- molecular biology
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angiotensin-receptor
The enzyme appears in viruses and cellular organisms
Reaction Schemes
preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'
Synonyms
neprilysin, neutral endopeptidase, enkephalinase, calla, endopeptidase-24.11, neutral endopeptidase 24.11, common acute lymphoblastic leukemia antigen, nep 24.11, nep/cd10, abeta-degrading enzyme, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
antigen, CALLA (common acute lymphoblastic leukemia-associated)
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CALLA
CALLA (common acute lymphoblastic leukemia-associated) antigens
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CALLA antigen
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CALLA glycoproteins
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CD10
common acute lymphoblastic leukemia antigen
common acute lymphoblastic leukemia-associated antigens
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Common acute lymphocytic leukemia antigen
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Endopeptidase-2
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-
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endopeptidase-24.11
enkephalinase
glycoprotein, CALLA
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kidney-brush-border neutral endopeptidase
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kidney-brush-border neutral peptidase
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kidney-brush-border neutral proteinase
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membrane metalloendopeptidase
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NEP
NEP, enkephalinase, neutrophil cluster-differentiation antigen 10, common acute lymphoblastic leukemia antigen
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neprilysin
neprilysin 4
Q9I7I4
two isoforms exist due to different splice-variants: larger isoform A is expressed as a membrane bound protein and isoform B lacking the N-terminal cytosolic and transmembrane region is expressed as a soluble protein
neutral endopeptidase
neutral endopeptidase 24.11
neutral metallendopeptidase
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peptidase, endo-
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-
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peptidase, membrane metalloendo-
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skin fibroblast elastase
CALLA
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CD10
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endopeptidase-24.11
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enkephalinase
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NEP
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-
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NEP
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neutral endopeptidase
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neutral endopeptidase 24.11
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
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-
endopeptidase
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hydrolysis of peptide bond
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peptides, endopeptidase
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CAS REGISTRY NUMBER
COMMENTARY
82707-54-8
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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
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl) + H2O
?
a bradykinin-based peptide substrate QFS
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl) + H2O
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala + Phe-Lys-(2,4-dinitrophenyl)
bradykinin-based quenched fluorescent substrate assay
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-
?
2 KFRRQRPRLSHKGPMPF + 2 H2O
KFRRQRPR + LSHKGPMPF + KFRRQRPRL + SHKGPMPF
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-
-
ir
2 LVQPRGSRNGPGPWQGGRRKFRRQRPRLSHKGPMPF + 2 H2O
LVQPRGSRNGPGPWQGGRRKFRRQRPRL + SHKGPMPF + LVQPRGSRNGPGPWQGGRRKFRRQRPR + LSHKGPMPF
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-
-
ir
2 pGlu-RPRLSHKGPMPF + 2 H2O
pGlu-RPRL + pGlu-RPR + SHKGPMPF + LSHKGPMPF
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ir
2-aminobenzoyl-ARFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-AR + FK-2,4-dinitrophenyl ester
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-
-
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ir
2-aminobenzoyl-DRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-DR + FK-2,4-dinitrophenyl ester
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-
-
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ir
2-aminobenzoyl-FRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-FR + FK-2,4-dinitrophenyl ester
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-
-
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ir
2-aminobenzoyl-HRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-HR + FK-2,4-dinitrophenyl ester
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-
-
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ir
2-aminobenzoyl-IRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-IR + FK-2,4-dinitrophenyl ester
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-
-
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ir
2-aminobenzoyl-KRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-KR + FK-2,4-dinitrophenyl ester
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-
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ir
2-aminobenzoyl-LRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-LR + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-NRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-NR + FK-2,4-dinitrophenyl ester
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-
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ir
2-aminobenzoyl-RAFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RA + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RDFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RD + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-REFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RE + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-rGF-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Phe-N-(2,4-dinitrophenyl)ethylenediamine
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ir
2-aminobenzoyl-RGFK(Dnp)-OH + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl amide
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ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
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-
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ir
2-aminobenzoyl-rGL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Leu-N-(2,4dinitrophenyl)ethylenediamine
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-
-
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ir
2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Val-N-(2,4-dinitrophenyl)ethylenediamine
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ir
2-aminobenzoyl-RHFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RH + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RKFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RK + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RNFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RN + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RPFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RP + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RQFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RQ + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl amide
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ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-rRL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Arg + Leu-N-(2,4-dinitrophenyl)ethylenediamine
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ir
2-aminobenzoyl-RSFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RS + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-rSL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Ser + Leu-N-(2,4-dinitrophenyl)ethylenediamine
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ir
2-aminobenzoyl-RTFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RT + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-SRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-SR + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-TRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-TR + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-VRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-VR + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-WRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-WR + FK-2,4-dinitrophenyl ester
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ir
2-aminobenzoyl-YRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-YR + FK-2,4-dinitrophenyl ester
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ir
amyloid beta peptide Abeta42 + H2O
?
-
the peptide primarily undergoes degradation by NEP in vivo in the brain
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-
?
amyloid beta peptide1-40 + H2O
amyloid beta peptide Asp1-Lys16 + amyloid beta peptide Asp1-Leu17 + amyloid beta peptide Asp1-Phe19
the wild-type enzyme cleaves Ab1-40 predominantly at Lys16-Leu17, Leu17-Val18 and Phe19-Phe20. The mutant G399V/G714K cleaves preferentially at Phe20-Ala21
main cleavage fragments after 60 min with the wild-type enzyme. After 360 min these fragments are degraded further, accompanied by the appearance of Val12-Leu17 and Tyr10-Leu17 fragments
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?
amyloid beta(1-40) mutant A21G + H2O
?
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Flemish variant of amyloid beta. Decreased degradation by neprilysin compared to either wild-type peptide or the other mutant peptides
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?
amyloid-beta(1-7)AAC + H2O
?
a synthetic peptide, design and synthesis of a quenched fluorogenic peptide substrate qf-Abeta(1-7)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus
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?
amyloid-beta(12-16)AAC + H2O
?
a synthetic peptide, design and synthesis of a quenched fluorogenic peptide substrate qf-Abeta(12-16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emits strong fluorescence upon cleavage. 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
-
-
?
benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
benzoyl-Gly-Gly-Arg + L-Leu-2-naphthylamide
-
-
-
-
?
glutaryl-Ala-Ala-Phe-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-2-naphthylamide
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-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly + Phe-2-naphthylamide
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-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly-Phe + 2-naphthylamine
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-
-
?
hippuryl-Arg-Arg-Ala-2-naphthylamide + H2O
hippuryl-Arg-Arg + Ala-2-naphthylamide
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-
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?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
leucine5-enkephalin + H2O
?
Tyr-Gly-Gly-Phe-Leu is cleaved at the Gly-Phe bond by the wild-type enzyme
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-
?
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide + H2O
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-L-phenylalanine + 4-methoxy-2-naphthylamine
-
-
-
?
N-benzyloxycarbonyl-Gly-Gly-Leu 2-naphthylamide + H2O
N-benzyloxycarbonyl-Gly-Gly + L-leucine 2-naphthylamide
-
-
-
?
N-benzyoxycarbonyl-Gly-Gly-Leu-2-naphthylamide + H2O
N-benzyoxycarbonyl-Gly-Gly + L-Leu-2-naphthylamide
-
-
-
-
?
N-formyl-L-Met-Leu-Phe + H2O
?
-
the enzyme may play an important role in modulating chemotactic response by cleavage of the chemotactic substance N-formyl-Met-Leu-Phe
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Ala-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Phe-2-naphthylamide
-
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-
?
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Gly-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
neuropeptide Y + H2O
truncated neuropeptide Y + C-terminal fragments of neuropeptide Y
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neuropeptide Y 21-36 and 31-36 are the most abundant fragments generated in vivo
-
?
pulmonary vasodilative vasoactive intestinal peptide + H2O
?
rapid inactivation
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-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2