Cloned (Comment) | Organism |
---|---|
gene Mep1B, transient overexpression of meprin beta in MEF cells, cell surface localization | Mus musculus |
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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cell surface | - |
Mus musculus | 9986 | - |
membrane | - |
Mus musculus | 16020 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | a zinc-dependent metalloprotease | Mus musculus |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | Q61847 | - |
- |
Mus musculus C57BL/6 | Q61847 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Mus musculus | - |
neuron | cortical | Mus musculus | - |
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 | Comment | Organism |
---|---|---|
meprin beta | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Mus musculus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Mus musculus |
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 |