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Information on EC 3.4.24.18 - meprin A and Organism(s) Rattus norvegicus and UniProt Accession Q64230
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3.4.24.18 meprin ASpecify your search results
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- 3.4.24.18
-
3.4.24.11
- enkephalinase
- metalloendopeptidase
- atrial
- phosphoramidon
-
natriuretic
- enkephalin
- thiorphan
-
angiotensin-converting
- angiotensin
- astacins
- metalloproteases
-
brush
- bradykinin
-
3.4.15.1
- captopril
- neprilysin
- metallopeptidases
- anp
- aminopeptidases
- acetorphan
-
math
- endopeptidases
-
brush-border
- microvillar
- actinonin
- calla
- bestatin
- amastatin
- azocasein
-
phosphoramidon-sensitive
- sheddase
-
dipeptidylaminopeptidase
-
metzincins
- pharmacology
- neurokinins
-
astacin-like
-
met5enkephalin
-
depressor
- medicine
- tachykinins
- neurotensin
- leu-enkephalin
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Hydrolysis of protein and peptide substrates preferentially on carboxyl side of hydrophobic residues
Synonyms
meprin, meprin a, mep1a, meprin alpha, meprin beta, meprin-a, meprin-alpha, endopeptidase-2, pph alpha, mouse meprin alpha, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
E-24.18
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-
-
-
Endopeptidase-2
-
-
-
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Meprin
-
-
-
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Meprin-a
-
-
-
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N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase
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-
-
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PABA peptide hydrolase
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-
-
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PABA-peptide hydrolase
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-
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PPH
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-
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PPH alpha
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-
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PPH beta
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-
-
-
additional information
-
meprin A from mouse, endopeptidase-2 from rat and PPH from human are closely related enzymes of the astacin family
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
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hydrolysis of arylamide bond
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-
-
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CAS REGISTRY NUMBER
COMMENTARY
148938-24-3
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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
pro-interleukin 1beta + H2O
interleukin 1beta + H2O
cleavage at the H115-D116 bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin beta site. Both oligomeric meprin A and recombinant meprin alpha are capable of cleaving
the biological activity of the pro-interleukin-1beta cleaved product produced by meprin A, is 3fold higher to that of the interleukin-1beta product produced by meprin b or caspase-1
-
?
2-aminobenzoic acid-RPPGFSPFRK(2,4-dinitrophenyl)G-OH + H2O
?
-
-
-
?
angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
?
Luliberin + H2O
?
-
i.e. luteinizing-hormone releasing hormone, preferred cleavage site: Trp3-Ser4, other sites are Ser4-Tyr5 and Tyr5-Gly6
-
-
?
neurotensin + H2O
?
-
i.e. pyro-Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, mouse, rat, cleavage sites: Glu-Asn, Asn-Lys
-
-
?
angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
-
poor substrate
-
-
?
angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
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cleavage site: Tyr-Ile
-
-
?
angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
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i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
?
angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
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poor substrate
-
?
angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
?
angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
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i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
?
azocasein + H2O
fragments of azocasein
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
?
azocasein + H2O
fragments of azocasein
-
better substrate for mouse enzyme than for rat enzyme
-
-
?
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
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one cleavage site: Phe-Ser (major cleavage site)
-
-
?
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
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one cleavage site: Phe-Ser
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-
?
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
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minor cleavage site: Gly-Phe
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-
?
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
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I125-iodinated
-
-
?
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
-
-
?
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
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7 major and 3 minor sites
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-
?
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
-
-
-
-
?
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
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i.e. PABA-peptide, rat, human, arylamidolysis
-
-
?
Substance P + H2O
Hydrolyzed substance P
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cleavage sites: Glu6-Phe7, Phe7-Phe8, Phe8-Gly9
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-
?
additional information
?
-
-
hydrolysis occurs on carboxy side of aromatic residues
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-
?
additional information
?
-
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insulin, [Arg8]-vasopressin, cytochrome c, ovalbumin, serum albumin
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-
?
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
?
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
additional information
?
-
-
the enzyme is capable of hydrolyzing and processing a large number of substrates, including extracellular matrix proteins, cytokines, adherens junction proteins, hormones, bioactive peptides, and cell surface proteins
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Calcium
Zinc
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
verapamil
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verapamil at 1 mg/kg, i.v. can efficiently prevent the ischemic acute kidney injury in female rats, as well as male rats
actinonin
-
pre-ischemic treatment with actinonin at 10 or 30 mg/kg, i.v. dose-ependently attenuates the ischemia/reperfusion-induced renal injury in male rats, but fails to improve the renal injury in female rats
additional information
-
L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (i.e. E-64)
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no activation by organomercurials or trypsin treatment
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
tissue distribution (immuno-peroxidase staining), not in brain or spinal cord
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
brush-border membranes of proximal tubules and intestines
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cell surface metalloproteinase, alphabeta-heterodimers firmly attached to brush border membrane, alpha2-homodimers only associated with membrane
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beta subunits are type I integral membrane proteins and alpha subunits are disulfide linked to or non-covalently associated with membrane-anchored meprin beta subunits
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meprin A, is a membrane-associated neutral metalloendoprotease. Importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme encoded by Rmepa belongs to the BTP cluster of the astacin enzyme family. Structure-activity relationship of astacin metalloproteases, EDTA is used to dock into the active site cleft of the astacins to know the interaction network and to identify the important residues for binding, comparative three-dimensional structure homology modeling and docking study, and potential binding site, detailed overview
evolution
-
meprin A, is a membrane-associated neutral metalloendoprotease that belongs to the astacin family of zinc endopeptidases
malfunction
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altered localization and shedding of meprin A in places other than the apical membranes may be deleterious in vivo in acute tubular injury. Importance of a sheddase involved in the release of membrane-associated meprin A under pathological conditions
metabolism
-
following ischemia-reperfusion- and cisplatin-induced acute kidney injury, meprin A is redistributed toward the basolateral plasma membrane, and the cleaved form of meprin A is excreted in the urine
additional information
the hydrogen bonding residues of the enzyme are Ser131, Glu157, His166, Ser169, and Tyr195, comparative three-dimensional structure homology modeling (template crystal structure PDB ID 4GWN) and docking study, and potential binding site, detailed overview
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). MEP1A_RAT
748
1
85123
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
148000
-
homooligomeric isoform, active, dimer, MALDI-TOF mass spectroscopy
152000
-
heterooligomeric isoform, active, dimer, MALDI-TOF mass spectroscopy
156000
-
homooligomeric isoform, latent, dimer, MALDI-TOF mass spectroscopy
166000
-
heterooligomeric isoform, latent, dimer, MALDI-TOF mass spectroscopy
69000
-
x * 69000 + x * 79000, mouse, deglycosylated alpha and beta-subunit, SDS-PAGE in the presence of 2-mercaptoethanol
74300
-
homooligomeric isoform, active, monomer, MALDI-TOF mass spectroscopy
77700
-
homooligomeric isoform, latent, monomer, MALDI-TOF mass spectroscopy
79000
-
x * 69000 + x * 79000, mouse, deglycosylated alpha and beta-subunit, SDS-PAGE in the presence of 2-mercaptoethanol
86000
-
x * 86000, mouse, performic acid oxidized enzyme, sedimentation equilibrium centrifugation with 4 M guanidine-HCl
90000
additional information
-
amino acid sequence, domain structure and tertiary structure deduced from cDNAs
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oligomer
tetramer
additional information
oligomer
-
x * 69000 + x * 79000, mouse, deglycosylated alpha and beta-subunit, SDS-PAGE in the presence of 2-mercaptoethanol
oligomer
-
x * 86000, mouse, performic acid oxidized enzyme, sedimentation equilibrium centrifugation with 4 M guanidine-HCl
tetramer
-
disulfide-bridged dimers (alpha2 or alphabeta) aggregate non-covalently to form higher MW complexes, predominantly tetramers
additional information
-
the mouse enzyme is composed of disulfide linked dimers associating non-covalently to form tetramers and sometimes higher order oligomers
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
homooligomeric meprin A produced by transfecting cells with alpha or beta cDNA
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
animals treated with streptozocin, representing a model of type 1 diabetes mellitus, show inverse relationship between renal enzyme content and the severity of the renal injury
pharmacology
-
ischemic acute kidney injury was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. At 24 h after reperfusion, renal function and histology of both males and females showed significant deterioration. The degrees of renal dysfunction and histological damage are much more severe in males than in females. Pre-ischemic treatment with actinonin at 10 or 30 mg/kg i.v., dose-ependently attenuats the ischemia/reperfusion-induced renal injury in male rats, but fails to improve the renal injury in female rats. Verapamil at 1 mg/kg i.v., can efficiently prevent the ischemic acute kidney injury in female rats, as well as male rats
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Stephenson, S.L.; Kenny, A.J.
The metabolism of neuropeptides. Hydrolysis of peptides by the phosphoramidon-insensitive rat kidney enzyme endopeptidase-2 and by rat microvillar membranes
Biochem. J.
255
45-51
1988
Rattus norvegicus
Barnes, K.; Ingram, J.; Kenny, A.J.
Proteins of the kidney microvillar membrane. Structural and immunochemical properties of rat endopeptidase-2 and its immunohistochemical localization in tissues of rat and mouse
Biochem. J.
264
335-346
1989
Mus musculus, Rattus norvegicus
Johnson, G.D.; Hersh, L.B.
Cloning a rat meprin cDNA reveals the enzyme is a heterodimer [published erratum appears in J Biol Chem 1993 Aug 15;268(23):17647]
J. Biol. Chem.
267
13505-13512
1992
Rattus norvegicus
Marchand, P.; Tang, J.; Bond, J.S.
Membrane association and oligomeric organization of the alpha and beta subunits of mouse meprin A
J. Biol. Chem.
269
15388-15393
1994
Mus musculus, Rattus norvegicus
Kaushal, G.P.; Walker, P.D.; Shah, S.V.
An old enzyme with a new function: purification and characterization of a distinct matrix-degrading metalloproteinase in rat kidney cortex and its identification as meprin
J. Cell Biol.
126
1319-1327
1994
Rattus norvegicus
Marchand, P.; Tang, J.; Johnson, G.D.; Bond, J.S.
COOH-Terminal proteolytic processing of secreted and membrane forms of the alpha subunit of the metalloprotease meprin A. Requirement of the I domain for processing in the endoplasmic reticulum
J. Biol. Chem.
270
5449-5456
1995
Mus musculus, Rattus norvegicus
Wolz, R.L.; Bond, J.S.
Meprins A and B
Methods Enzymol.
248
325-345
1995
Homo sapiens, Mus musculus, Rattus norvegicus, Homo sapiens PPH
Bertenshaw, G.P.; Villa, J.P.; Hengst, J.A.; Bond, J.S.
Probing the active sites and mechanisms of rat metalloproteases meprin A and B
Biol. Chem.
383
1175-1183
2002
Rattus norvegicus
Bertenshaw, G.P.; Norcum, M.T.; Bond, J.S.
Structure of homo- and hetero-oligomeric meprin metalloproteases
J. Biol. Chem.
278
2522-2532
2003
Rattus norvegicus
Mathew, R.; Futterweit, S.; Valderrama, E.; Tarectecan, A.A.; Bylander, J.E.; Bond, J.S.; Trachtman, H.
Meprin-alpha in chronic diabetic nephropathy: interaction with the renin-angiotensin axis
Am. J. Physiol. Renal Physiol.
289
F911-F921
2005
Mus musculus, Rattus norvegicus
Herzog, C.; Haun, R.S.; Kaushal, V.; Mayeux, P.R.; Shah, S.V.; Kaushal, G.P.
Meprin A and meprin alpha generate biologically functional IL-1beta from pro-IL-1beta
Biochem. Biophys. Res. Commun.
379
904-908
2009
Mus musculus, Rattus norvegicus (Q64230)
Takayama, J.; Takaoka, M.; Yamamoto, S.; Nohara, A.; Ohkita, M.; Matsumura, Y.
Actinonin, a meprin inhibitor, protects ischemic acute kidney injury in male but not in female rats
Eur. J. Pharmacol.
581
157-163
2008
Rattus norvegicus
Kaushal, G.P.; Haun, R.S.; Herzog, C.; Shah, S.V.
Meprin A metalloproteinase and its role in acute kidney injury
Am. J. Physiol. Renal Physiol.
304
F1150-F1158
2013
Homo sapiens, Mus musculus, Rattus norvegicus, Mus musculus C57BL/6N
Chaudhuri, A.; Chakraborty, S.
Structure-activity relationship of astacin metalloproteases A comparative study using EDTA
Curr. Enzyme Inhib.
14
131-140
2018
Mus musculus (P28825), Rattus norvegicus (Q64230)
-
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