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Literature summary for 3.4.24.63 extracted from
- Regulation of the alternative beta-secretase meprin beta by ADAM-mediated shedding (2019), Cell. Mol. Life Sci., 76, 3193-3206 .
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | the pro-enzyme is activated by proteoltyic cleavage of a propeptide | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene MEP1B | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | meprin beta silencing by nanoparticle-based application of meprin beta specific siRNA | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | 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 | Homo sapiens | |
| additional information | 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 | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cell surface | - |
Homo sapiens | 9986 | - |
| cell surface | - |
Mus musculus | 9986 | - |
| membrane | - |
Homo sapiens | 16020 | - |
| membrane | - |
Mus musculus | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | a zinc-dependent metalloprotease | Homo sapiens |  |
| 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 | Homo sapiens | APP, cleavage mechanism by meprin beta, overview | ? | - |
? | |
| amyloid precursor protein + H2O | Mus musculus | APP, cleavage mechanism by meprin beta, overview | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q16820 | - |
- |
| Mus musculus | Q61847 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | proteolytic activation and shedding of meprin beta are mutually exclusive events. Cleavage of the pro-peptide completely blocks shedding by ADAM10/17 | Mus musculus |
| proteolytic modification | proteolytic activation and shedding of meprin beta are mutually exclusive events. Cleavage of the pro-peptide completely blocks shedding of meprin beta by ADAM10 and ADAM17. The anti-amyloidogenic alpha-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a direct competitor for APP at the cell surface, but also a sheddase of inactive pro-meprin beta. Shedding of meprin beta by ADAM10/17 is completely abolished upon its activation by matrilysin-2 (MT-2, 3.4.24.23) at the cell surface. Only the proform of meprin beta can be shed. Meprin beta requires activation by tryptic proteases | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Homo sapiens | - |
| brain | meprin beta co-fractionates with APP and PS1 in the same high molecular weight fraction in wild-type mouse brains, and this fraction is responsible for the majority of Abeta generation | Mus musculus | - |
| lung | lung fibrosis | Homo sapiens | - |
| lung | lung fibrosis | Mus musculus | - |
| skin | - |
Homo sapiens | - |
| skin | - |
Mus musculus | - |
| small intestine | - |
Homo sapiens | - |
| small intestine | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| amyloid precursor protein + H2O | APP, cleavage mechanism by meprin beta, overview | Homo sapiens | ? | - |
? | |
| amyloid precursor protein + H2O | APP, cleavage mechanism by meprin beta, overview | Mus musculus | ? | - |
? | |
| amyloid precursor protein + H2O | APP, cleavage mechanism by meprin beta, overview. Generation of truncated Abeta2-x peptides | Homo sapiens | ? | - |
? | |
| additional information | 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 | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homodimer | domain composition and dimeric structure of the metalloprotease meprin beta, overview. The enzyme consists of propeptide, catalytic domain, meprin A5 protein tyrosine phosphatase micro domain, tumour-necrosis-factor-receptor-associated factor domain, epidermal growth factor-like domain, transmembrane region, and C-terminal part | Homo sapiens |
| homodimer | domain composition and dimeric structure of the metalloprotease meprin beta, overview. The enzyme consists of propeptide, catalytic domain, meprin A5 protein tyrosine phosphatase micro domain, tumour-necrosis-factor-receptor-associated factor domain, epidermal growth factor-like domain, transmembrane region, and C-terminal part | Mus musculus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| beta-secretase | - |
Homo sapiens |
| beta-secretase | - |
Mus musculus |
| meprin beta | - |
Homo sapiens |
| meprin beta | - |
Mus musculus |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | absence of N-APP fragments and increased endogenous sAPPalpha levels in the brains of meprin beta knockout mice | Mus musculus |
| malfunction | 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 | Homo sapiens |
| metabolism | important beta-site cleaving enzyme 1 (BACE-1)-independent contribution of the metalloprotease meprin beta within the amyloidogenic pathway. The anti-amyloidogenic alpha-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a direct competitor for APP at the cell surface, but also a sheddase of inactive pro-meprin beta. The activity of meprin beta is strictly extracellularly regulated within the protease web. Meprin beta itself is identified as an inducer of ADAM10 activity | Homo sapiens |
| additional information | meprin beta activity and localization is strictly regulated | Homo sapiens |
| additional information | meprin beta activity and localization is strictly regulated | Mus musculus |
| physiological function | neurotoxic amyloid-beta (Abeta) plaques are one of the pathological hallmarks in Alzheimer disease patient brains. Abeta accumulates in the brain upon sequential, proteolytic processing of the amyloid precursor protein (APP) by beta- and gamma-secretases. The metalloproteinase meprin beta acts as an alternative beta-secretase, besides BACE-1, capable of generating truncated Abeta2-x peptides. Regulation of the alternative beta-secretase meprin beta by ADAM-mediated shedding. In the small intestine, meprin beta is essential for the detachment of the mucus by cleaving mucine 2 (MUC2). This is crucial for the functionality of the mucus barrier to impede bacterial overgrowth and infection. Meprin beta is an alternative beta-secretase within the complex protease web, regulating APP processing in health and disease, overview. Shed meprin beta does not act as sheddase | Homo sapiens |
| physiological function | neurotoxic amyloid-beta (Abeta) plaques are one of the pathological hallmarks in Alzheimer disease patient brains. Abeta accumulates in the brain upon sequential, proteolytic processing of the amyloid precursor protein (APP) by beta- and gamma-secretases. The metalloproteinase meprin beta acts as an alternative beta-secretase, besides BACE-1, capable of generating truncated Abeta2-x peptides. Regulation of the alternative beta-secretase meprin beta by ADAM-mediated shedding. Regulation of the alternative beta-secretase meprin beta by ADAM-mediated shedding. In the small intestine, meprin beta is essential for the detachment of the mucus by cleaving mucine 2 (MUC2). This is crucial for the functionality of the mucus barrier to impede bacterial overgrowth and infection. Meprin beta co-fractionates with APP and PS1 in the same high molecular weight fraction in wild-type mouse brains, and this fraction is responsible for the majority of Abeta generation | Mus musculus |
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