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Literature summary for 3.4.24.63 extracted from

  • Schoenherr, C.; Bien, J.; Isbert, S.; Wichert, R.; Prox, J.; Altmeppen, H.; Kumar, S.; Walter, J.; Lichtenthaler, S.F.; Weggen, S.; Glatzel, M.; Becker-Pauly, C.; Pietrzik, C.U.
    Generation of aggregation prone N-terminally truncated amyloid beta peptides by meprin beta depends on the sequence specificity at the cleavage site (2016), Mol. Neurodegener., 11, 19 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene Mep1B, transient overexpression of meprin beta in MEF cells, cell surface localization Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of meprin beta knockout mice. Knockout of meprin beta leads to increased sAPPalpha secretion in cortical neurons. Decrease of Abeta2-40 and increase of mature APP in primary neurons of meprin beta knockout mice Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface
-
Mus musculus 9986
-
membrane
-
Mus musculus 16020
-

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ a zinc-dependent metalloprotease Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amyloid precursor protein + H2O Mus musculus metalloprotease meprin beta cleaves amyloid precursor protein (APP) predominantly generating N-terminally truncated Abeta2-x variants ?
-
?
amyloid precursor protein + H2O Mus musculus C57BL/6 metalloprotease meprin beta cleaves amyloid precursor protein (APP) predominantly generating N-terminally truncated Abeta2-x variants ?
-
?
additional information Mus musculus meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe) ?
-
?
additional information Mus musculus C57BL/6 meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe) ?
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q61847
-
-
Mus musculus C57BL/6 Q61847
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Mus musculus
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neuron cortical Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amyloid precursor protein + H2O metalloprotease meprin beta cleaves amyloid precursor protein (APP) predominantly generating N-terminally truncated Abeta2-x variants Mus musculus ?
-
?
amyloid precursor protein + H2O metalloprotease meprin beta cleaves amyloid precursor protein (APP) predominantly generating N-terminally truncated Abeta2-x variants Mus musculus C57BL/6 ?
-
?
additional information meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe) Mus musculus ?
-
?
additional information 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 Mus musculus ?
-
?
additional information meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe) Mus musculus C57BL/6 ?
-
?
additional information 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 Mus musculus C57BL/6 ?
-
?

Synonyms

Synonyms Comment Organism
meprin beta
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Mus musculus

General Information

General Information Comment Organism
malfunction knockout of meprin beta leads to increased sAPPalpha secretion in cortical neurons. BACE-1 activity is not increased by meprin beta preincubation. Decrease of Abeta2-40 and increase of mature APP in primary neurons of meprin beta knockout mice Mus musculus
metabolism BACE-1 acts as the major beta-secretase in vivo generating most of the amyloid beta (Abeta) peptides at position 1, while meprin beta may act as an alternative enzyme responsible for the release of small amounts of N-terminally truncated Abeta species. APP and meprin beta co-localize in the late secretory pathway or at the cell membrane. The aggregation of N-terminally truncated Abeta2-40 peptide is significantly different from that of the non-truncated wt Abeta1-40 peptide. In particular, the Abeta2-40 species aggregate faster and reached a higher aggregation state than Abeta1-40 peptide Mus musculus
physiological function metalloprotease meprin beta cleaves the Alzheimer's disease (AD) relevant amyloid precursor protein (APP) as a beta-secretase reminiscent of BACE-1, but predominantly generating N-terminally truncated Abeta2-x variants. Generation of aggregation prone N-terminally truncated amyloid beta peptides by meprin beta depends on the sequence specificity at the cleavage site. The N-terminally truncated Abeta2-40 variant shows increased aggregation propensity compared to Abeta1-40 and acts even as a seed for Abeta1-40 aggregation. Meprin beta cleavage of APP occurs prior to the endocytic compartments, as diminished APP endocytosis has no influence on meprin beta mediated Abeta generation. Mechanism, overview. Cellular interaction between meprin beta and APP occurs prior to endocytosis. The C-terminal motif NPxY (APPDELTANPxY) of APP is critical for proper endocytosis. Meprin beta generated Abeta2-40 promotes and seeds aggregation of Abeta peptides Mus musculus