3.4.24.63: meprin B
This is an abbreviated version!
For detailed information about meprin B, go to the full flat file.
Word Map on EC 3.4.24.63
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3.4.24.63
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alzheimer
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amyloid
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abeta
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gamma-secretase
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beta-amyloid
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plaque
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amyloid-beta
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beta-site
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amyloidogenic
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alpha-secretase
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aspartyl
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cerebral
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presenilins
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senile
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neurodegenerative
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bace-1
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swedish
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sappalpha
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neuropathology
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tau
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neurotoxic
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app-cleaving
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neuroblastoma
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beta-peptide
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ectodomains
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dementia
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protein-cleaving
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medicine
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nicastrin
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drug development
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amyloidogenesis
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tangles
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isostere
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memapsin
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peptidomimetic
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abeta1-40
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appswe
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ad-like
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hydroxyethylene
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neurofibrillary
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adam10
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beta-protein
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ad-associated
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endoproteolytic
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insulin-degrading
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non-amyloidogenic
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betaapp
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neprilysin
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pharmacology
- 3.4.24.63
- alzheimer
-
amyloid
- abeta
- gamma-secretase
- beta-amyloid
- plaque
- amyloid-beta
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beta-site
-
amyloidogenic
- alpha-secretase
-
aspartyl
- cerebral
-
presenilins
-
senile
- neurodegenerative
- bace-1
-
swedish
-
sappalpha
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neuropathology
- tau
-
neurotoxic
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app-cleaving
- neuroblastoma
- beta-peptide
- ectodomains
- dementia
-
protein-cleaving
- medicine
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nicastrin
- drug development
-
amyloidogenesis
-
tangles
-
isostere
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memapsin
-
peptidomimetic
- abeta1-40
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appswe
-
ad-like
-
hydroxyethylene
-
neurofibrillary
- adam10
- beta-protein
-
ad-associated
-
endoproteolytic
-
insulin-degrading
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non-amyloidogenic
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betaapp
- neprilysin
- pharmacology
Reaction
Hydrolysis of proteins, including azocasein, and peptides. Hydrolysis of -His5-/-Leu-, -Leu6-/-Cys-, -Ala14-/-Leu- and -Cys19-/-Gly- bonds in insulin B chain =
Synonyms
beta-secretase, cell surface sheddase, h-meprin beta, MEP1B, mephrin beta, meprin A subunit beta, Meprin b, meprin B metalloprotease, meprin beta, meprin beta metalloproteinase, meprin metalloprotease, meprin metalloproteinase, meprin metalloproteinase beta, meprin-beta, meprinbeta, metalloprotease meprin, metalloprotease meprin B, metalloprotease meprin beta, metalloproteinase meprin beta, Mmepb, More, mouse meprin beta, procollagen proteinase, Rmepb
ECTree
3.4.24.63 meprin BAdvanced search results
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results (Substrates Products
Substrates Products on EC 3.4.24.63 - meprin B
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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-YVADAPK-(K-epsilon-DNP)-NH2 + H2O
?
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-
-
?
(7-methyloxycoumarin-4-yl)acetyl-EDEDED-(K-epsilon-2,4-dinitrophenyl) + H2O
?
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-
-
?
(7-methyloxycoumarin-4-yl)acetyl-EDEDED-NH2-(2,4-dinitrophenyl) + H2O
?
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-
-
?
2-aminobenzoyl-MGWMDEIDK(2,4-dinitrophenyl)SG + H2O
2-aminobenzoyl-MGWM + DEIDK(2,4-dinitrophenyl)SG
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-
-
?
Abz-VKMDAE-EDDnp + H2O
?
wild-type beta-site fluorogenic substrate sequence
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-
?
Abz-VNLDAE-EDDnp + H2O
?
Swedish mutant beta-site fluorogenic substrate sequence
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-
?
alpha-secretase + H2O
?
meprin beta-mediated activation of the alpha-secretase
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-
?
amyloid precursor protein + H2O
amyloid beta peptides
meprin beta initially sheds amyloid precursor protein, releasing different amyloid beta species with several cleavage sites identical with or proximal to the known beta-secretase cleavage site
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-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
amyloid precursor protein APP751 + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
recombinant human substrate, coexpressed with the enzyme in HEK-293T cells, or exogenous soluble meprin beta incubated with APP751 stably overexpressing 7WD10 cells, is able to produce amyloid precursor fragment N-APP20
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-
?
Boc-CCK8NH2 + H2O
N-tert-butyloxycarbonyl-L-Asp-L-Tyr-L-Met-Gly-L-Trp-L-Met + L-Asp-L-Phe
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peptide of the gastrointestinal tract
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?
CCK8NH2 + H2O
L-Asp-L-Tyr-L-Met-Gly-L-Trp-L-Met + L-Asp-L-Phe
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peptide of the gastrointestinal tract
-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
gastri-releasing peptide-(14-27) + H2O
?
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peptide of the gastrointestinal tract
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?
interleukin-1beta precursor + H2O
interleukin-1beta + interleukin-1beta propeptide
proteolytic cleavage to a biologically active form
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-
?
KKGYVADAP-7-amido-4-methylcoumarin + H2O
KKGYVA + DAP-7-amido-4-methylcoumarin
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-
-
?
lymphoepithelial Kazal-type-related inhibitor + H2O
?
a serine protease inhibitor
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-
?
protein kinase A + H2O
?
the enzyme cleaves at defined sites, isoform-specific interactions between the catalytic subunit of PKA (PKA C) and meprins, overview
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-
?
protein kinase A catalytic subunit Calpha + H2O
?
the enzyme cleaves at defined sites, cytosolic-enriched kidney proteins from meprin alphabeta double knockout mice, and purified forms of recombinant mouse PKA Calpha, Cbeta1, and Cbeta2, are incubated with activated forms of either homomeric meprinA, EC 3.4.24.18, or meprin B, product analysis by mass spectrometry, overview. Meprin B cleaves all three PKA C isoforms
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-
?
protein kinase A catalytic subunit Cbeta1 + H2O
?
the enzyme cleaves at defined sites, cytosolic-enriched kidney proteins from meprin alphabeta double knockout mice, and purified forms of recombinant mouse PKA Calpha, Cbeta1, and Cbeta2, are incubated with activated forms of either homomeric meprinA, EC 3.4.24.18, or meprin B, product overview. Meprin B cleaves all three PKA C isoforms
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-
?
protein kinase A catalytic subunit Cbeta2 + H2O
?
the enzyme cleaves at defined sites, cytosolic-enriched kidney proteins from meprin alphabeta double knockout mice, and purified forms of recombinant mouse PKA Calpha, Cbeta1, and Cbeta2, are incubated with activated forms of either homomeric meprinA, EC 3.4.24.18, or meprin B, product overview. Meprin B cleaves all three PKA C isoforms
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-
?
sCCK8NH2 + H2O
L-Asp-L-Tyr(SO3)-L-Met-Gly-L-Trp-L-Met + L-Asp-L-Phe
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peptide of the gastrointestinal tract
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?
tenascin-C + H2O
tenascin-C peptide fragments
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mapping of proteolytic fragments generated by meprinbeta from the chicken tenascin-C and the human recombinant 250 kDa TN-C variant. In chicken tenascin-C, meprinbeta processes all three major splicing variants by removal of 10 kDa N-terminal and 38 kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern exists for large human tenascin-C variant where two N-terminal peptides of 10 and 15 kDa and two C-terminal fragments of 40 and 55 kDa are removed from the intact subunit. N-terminal sequencing reveals the exact amino acid positions of cleavage sites. In both chicken and human tenascin-C N-terminal cleavages occur just before and/or after the heptad repeats involved in subunit oligomerization. In the human protein, an additional cleavage site is identified in the alternative fibronectin type III repeat, and a unique cleavage by meprinbeta is located to the 7th constant fibronectin type III repeat in both chicken and human tenascin-C, cleavage at this site removes the C-terminal domain involved in its anti-adhesive activity
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?
Tyr-Leu-Val-Cys(SO3-)-Gly-Glu-Arg-Gly + H2O
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synthetic octapeptide, derived from insulin B-chain
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-
?
actin + H2O
?
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villin and actin bind to the cytoplasmic tail of meprin beta
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-
?
actin + H2O
?
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villin and actin bind to the cytoplasmic tail of meprin beta
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-
?
ADAM10 + H2O
?
i.e. a disintegrin and metalloproteinase 10, reombinant C-terminally Myc-tagged substrate, recombinant N-terminally Strep-tagged meprin beta cleaves the ADAM10 prodomain at amino acids Gln198/Glu199 and Glu199/Glu200
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-
?
ADAM17 + H2O
?
i.e. a disintegrin and metalloproteinase 17, reombinant C-terminally Myc-tagged substrate
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-
?
ADAM9 + H2O
?
i.e. a disintegrin and metalloproteinase 9, reombinant C-terminally Myc-tagged substrate, recombinant N-terminally Strep-tagged meprin beta cleaves the ADAM9 prodomain at amino acids Gly189/Asp190 and Glu191/Glu192
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-
?
amyloid precursor protein + H2O
?
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APP Is Processed by meprin beta in Vivo
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-
?
amyloid precursor protein + H2O
?
meprin beta cleaves amyloid precursor protein at the beta-secretase site, giving rise to amyloidogenic peptides
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-
?
amyloid precursor protein + H2O
?
recombinant soluble human APP695, cleavage at the beta-secretase site
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-
?
amyloid precursor protein + H2O
?
APP, cleavage mechanism by meprin beta, overview
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-
?
amyloid precursor protein + H2O
?
APP, the precursor protein is cleaved by meprin beta in distinct ways, either at the beta-secretase site resulting in increased levels of amyloid beta (Abeta) peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The N-terminal 11 kDa and 20 kDa peptide fragments represent physiological cleavage products
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-
?
amyloid precursor protein + H2O
?
APP, cleavage mechanism by meprin beta, overview. Generation of truncated Abeta2-x peptides
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-
?
amyloid precursor protein + H2O
?
APP, the precursor protein is cleaved by meprin beta in distinct ways, either at the beta-secretase site resulting in increased levels of amyloid beta (Abeta) peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments
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-
?
amyloid precursor protein + H2O
?
APP, cleavage mechanism by meprin beta, overview
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-
?
amyloid precursor protein + H2O
?
metalloprotease meprin beta cleaves amyloid precursor protein (APP) predominantly generating N-terminally truncated Abeta2-x variants
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?
amyloid precursor protein + H2O
?
metalloprotease meprin beta cleaves amyloid precursor protein (APP) predominantly generating N-terminally truncated Abeta2-x variants
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-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
meprin beta can also process amyloid precursor protein in a manner reminiscent of beta-secretase, identification of cleavage sites of meprin beta in the amyloid beta sequence of the wild-type and Swedish mutant of amyloid precursor protein at positions p1 and p2, thereby generating amyloid beta variants starting at the first or second amino acid residue, mass spectrometry analysis, overview
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-
?
amyloid precursor protein + H2O
amyloid precursor protein N-terminal fragments + amyloid beta protein
catalytic properties and cleavage sites of meprin beta within different amyloid precursor protein peptides, overview
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-
?
azocasein + H2O
?
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mouse enzyme: poor substrate unless activated by trypsin treatment (i.e. latent azocaseinase activity)
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?
azocasein + H2O
?
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mouse enzyme: poor substrate unless activated by trypsin treatment (i.e. latent azocaseinase activity)
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-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
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-
?
fibrillar procollagen type I + H2O
fibrillar collagen type I + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III. Cleavage sites are at positions YYRA1218-/-1219DDAN and VRDR1227/-1228DLEV for the alpha1(I) chain, and additionally GGGY1108-/-1109DFGY for alpha2(I). For the N-terminal propeptide SYGY166-/-167DEKS (alpha1(I)) and AAQY81-/-82DGKG (alpha2(I)) are identified as meprin cleavage sites
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-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
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-
?
fibrillar procollagen type III + H2O
fibrillar collagen type III + fibrillar collagen type I propeptide
the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III
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-
?
Insulin B-chain + H2O
?
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4 cleavage sites (2 major and 2 minor): His5-Leu6, Leu6-Cys(SO3-)7, Ala14-Leu15, Cys(SO3-)19-Gly20
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-
?
interleukin-6 + H2O
?
recombinant human substrate expressed in eukaryotic B9 cell line, inactivation. Human meprin B cleaves 35% and 65% of human interleukin-6 of about 22 kDa to a smaller product of about 21 kDa within 30 min and 2 h, respectively
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-
?
interleukin-6 + H2O
?
recombinant human substrate expressed in Escherichia coli, inactivation
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-
?
interleukin-6 + H2O
?
recombinant murine substrate expressed in Escherichia coli, inactivation. Rat meprin B cleaves 65% murine interleukin-6 of about 22 kDa to a smaller product of about 21 kDa within 30 min
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-
?
N-Benzoyl-Tyr 4-aminobenzoate + H2O
?
-
rat or human enzyme, cleaves arylamide bond
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-
?
N-Benzoyl-Tyr 4-aminobenzoate + H2O
?
-
rat or human enzyme, cleaves arylamide bond
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-
?
osteosarcoma-9 + H2O
?
OS-9, purified recombinant human osteosarcoma-9 protein, specific degradation by meprin beta
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-
?
osteosarcoma-9 + H2O
?
OS-9, specific degradation by meprin beta
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-
?
osteosarcoma-9 + H2O
?
OS-9, purified recombinant human osteosarcoma-9 protein, specific degradation by meprin beta
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-
?
pro-collagen I + H2O
collagen I + collagen I propeptide
cleavage of the C-terminal pro-domain
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-
?
procollagen I + H2O
collagen I + propeptide of collagen III
meprin beta removes both the C- and N-propeptides of type I procollagen, subsequently releasing fibril-forming mature collagen molecules. The C-terminal cleavage sites in the proalpha1(I) chain generated by the enzyme is identified as Ala1218/Asp1219, identical to the BMP-1 cleavage site, and also Arg1227/Asp1228, nine residues C-terminal to the BMP-1 cleavage site
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-
?
procollagen I + H2O
collagen I + propeptide of collagen III
recombinant human substrate, generation of mature collagen molecules that spontaneously assemble into collagen fibrils
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?
Reelin + H2O
?
Reelin is a secreted glycoprotein whose function is regulated by proteolysis
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?
Reelin + H2O
?
cleavage between Ala2688 and Asp2689, the specific cleavage site of Reelin called C-t is located approximately between the sixth and seventh Reelin repeat
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?
tenascin-C + H2O
?
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specific processing by meprinbeta, cleavage mechanism, overview. Meprinbeta-digested human tenascin-C is not able to interfere with fibronectin-mediated cell spreading, confirming cleavage in the anti-adhesive domain. Meprinbeta processing of human tenascin-C neutralizes its inhibitory effect on fibronectin-mediated cell spreading
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?
villin + H2O
?
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villin and actin bind to the cytoplasmic tail of meprin beta
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?
villin + H2O
?
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villin and actin bind to the cytoplasmic tail of meprin beta
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?
additional information
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residues of the alpha1 subunit involved in the active site are Asp61 and Arg150, catalytic domain structure, overview
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?
additional information
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residues of the alpha1 subunit involved in the active site are Asp61 and Arg150, catalytic domain structure, overview
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?
additional information
?
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residues of the alpha1 subunit involved in the active site are Asp61 and Arg150, catalytic domain structure, overview
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?
additional information
?
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residues of the alpha1 subunit involved in the active site are Asp61 and Arg150, catalytic domain structure, overview
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?
additional information
?
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residues of the alpha2 subunit involved in the active site are Glu80 and Lys122, catalytic domain structure, overview
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?
additional information
?
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residues of the alpha2 subunit involved in the active site are Glu80 and Lys122, catalytic domain structure, overview
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?
additional information
?
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residues of the alpha2 subunit involved in the active site are Glu80 and Lys122, catalytic domain structure, overview
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?
additional information
?
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residues of the alpha2 subunit involved in the active site are Glu80 and Lys122, catalytic domain structure, overview
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?
additional information
?
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the residue of the beta subunit involved in the active site is Lys123, catalytic domain structure, overview
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?
additional information
?
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the residue of the beta subunit involved in the active site is Lys123, catalytic domain structure, overview
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?
additional information
?
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the residue of the beta subunit involved in the active site is Lys123, catalytic domain structure, overview
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?
additional information
?
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the residue of the beta subunit involved in the active site is Lys123, catalytic domain structure, overview
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?
additional information
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meprin B may play an important role in activation of the proinflammatory cytokine in various pathophysiological conditions
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?
additional information
?
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whereas the expression of meprinbeta and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibit many meprinbeta-positive leukocytes in regions where tenascin-C is strongly induced. At least under pathological conditions, meprinbeta might attack specific functional sites in tenascin-C that are important for its oligomerization and anti-adhesive activity
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?
additional information
?
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meprin interacts with epithelial Na+ channel (ENaC)
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?
additional information
?
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sheddase mechanism of meprin beta, overview
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?
additional information
?
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meprin beta preferentially cleaves substrates with acidic amino acids in P1'-position
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?
additional information
?
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comparison of cleavage sites of BACE-1 (EC 3.4.23.46) and meprin beta on APP wild-type and APPswe isoform. The protective A673T mutation in amyloid precursor protein (APP) results in reduced Abeta levels in patients, also prevents from meprin beta cleavage at position p2. Alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
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?
additional information
?
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comparison of cleavage sites of BACE-1 (EC 3.4.23.46) and meprin beta on APP wild-type and APPswe isoform. The protective A673T mutation in amyloid precursor protein (APP) results in reduced Abeta levels in patients, also prevents from meprin beta cleavage at position p2. Alterations of the amino acid composition close to the beta-secretase cleavage site may inhibit meprin beta activity on the generation of N-terminal truncated Abeta peptides
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?
additional information
?
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specific N-terminal processing of ADAM9, 10, and 17 by meprin beta and identification of cleavage sites within their prodomains. Direct interaction of meprin beta and ADAM proteases. Meprin beta specifically cleaves ADAM9, 10, and 17 N-terminal of the furin cleavage site
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?
additional information
?
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the cleavage of a meprin beta substrate leads to generation of the prolyl tripeptidyl aminopeptidase (PtP, EC 3.4.14.12) substrate, and the activity of PtP results in release of a chromophore or fluorophore, coupled assay method evaluation, overview
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?
additional information
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meprin beta is likely to contribute to leukocyte transmigration events important to intestinal immune responses
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?
additional information
?
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the alpha/beta isoform is deleterious in case of ischemia-reperfusion, overview
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?
additional information
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meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe)
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?
additional information
?
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APP A673T mutant is less prone to cleavage by meprin beta. But, in contrast to BACE-1, meprin beta exhibits the same increased affinity for APPwt peptides and those carrying the Swedish mutation (K670N/M671L) in vitro. The amino acid composition around the beta-site in APP affects meprin beta cleavage preference
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?
additional information
?
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specific N-terminal processing of ADAM9, 10, and 17 by meprin beta
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?
additional information
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Mus musculus C57/BL6N
specific N-terminal processing of ADAM9, 10, and 17 by meprin beta
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?
additional information
?
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meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe)
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?
additional information
?
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APP A673T mutant is less prone to cleavage by meprin beta. But, in contrast to BACE-1, meprin beta exhibits the same increased affinity for APPwt peptides and those carrying the Swedish mutation (K670N/M671L) in vitro. The amino acid composition around the beta-site in APP affects meprin beta cleavage preference
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?
additional information
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no substrates are glutaryl-Ala-Ala-Phe 4-methoxynaphthalamine 2-amide
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?
