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Literature summary for 3.4.24.63 extracted from
- Meprin alpha and meprin beta: procollagen proteinases in health and disease (2015), Matrix Biol., 44-46, 7-13.
Application
| Application | Comment | Organism |
|---|---|---|
| pharmacology | regulation of meprin activity by specific inhibition to reduce collagen maturation might be a suitable approach for the treatment of certain pathological conditions | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | generation of knock-out mice deficient for meprin alpha, phenotype, overview | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| actinonin | a hydroxamate derivate and naturally occurring compound produced in actinomycetes. Hydroxamate inhibitors chelate the zinc ion in the active site | Homo sapiens |  |
| actinonin | a hydroxamate derivate and naturally occurring compound produced in actinomycetes. Hydroxamate inhibitors chelate the zinc ion in the active site | Mus musculus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | meprin beta is expressed as a dimeric type 1 transmembrane protein | Homo sapiens | 16020 | - |
| membrane | meprin beta is expressed as a dimeric type 1 transmembrane protein | Mus musculus | 16020 | - |
| additional information | meprin beta can be shed from the cell surface by a disintegrin and metalloprotease 10 and 17 (ADAM10/17), the soluble meprin beta is no longer capable of cleaving amyloid precursor protein at the beta-site | Homo sapiens | - |
- |
| additional information | meprin beta can be shed from the cell surface by a disintegrin and metalloprotease 10 and 17 (ADAM10/17), the soluble meprin beta is no longer capable of cleaving amyloid precursor protein at the beta-site | Mus musculus | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Zn2+ | a metalloprotease | Homo sapiens | |
| Zn2+ | a 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 | - |
? | - |
? | |
| amyloid precursor protein + H2O | Mus musculus | - |
? | - |
? | |
| E-cadherin + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
| E-cadherin + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
| fibrillar procollagen type I + H2O | Homo sapiens | 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 | fibrillar collagen type I + fibrillar collagen type I propeptide | - |
? | |
| fibrillar procollagen type I + H2O | Mus musculus | 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 | fibrillar collagen type I + fibrillar collagen type I propeptide | - |
? | |
| fibrillar procollagen type III + H2O | Homo sapiens | the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III | fibrillar collagen type III + fibrillar collagen type I propeptide | - |
? | |
| fibrillar procollagen type III + H2O | Mus musculus | the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III | fibrillar collagen type III + fibrillar collagen type I propeptide | - |
? | |
| Fibronectin + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
| Fibronectin + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
| MMP1 protein + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
| MMP1 protein + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
| Muc2 protein + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
| Muc2 protein + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
| nidogen 1 + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
| nidogen 1 + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
| tenascin-C + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
| tenascin-C + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q16820 | - |
- |
| Mus musculus | Q61847 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | meprins are secreted as zymogens and are activated by trypsin-like serine proteases | Mus musculus |
| proteolytic modification | meprins are secreted as zymogens and are activated by trypsin-like serine proteases (e.g., human kallikrein related peptidases, KLK) | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| fibroblast | enzyme expression | Homo sapiens | - |
| fibroblast | enzyme expression | Mus musculus | - |
| large intestine | enzyme expression | Homo sapiens | - |
| large intestine | enzyme expression | Mus musculus | - |
| leukocyte | enzyme expression | Homo sapiens | - |
| leukocyte | enzyme expression | Mus musculus | - |
| lung | - |
Homo sapiens | - |
| skin | the enzyme is highly up-regulated in keloid tissue | Homo sapiens | - |
| skin | the enzyme is highly up-regulated in keloid tissue | Mus musculus | - |
| small intestine | enzyme expression | Homo sapiens | - |
| small intestine | enzyme expression | Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| amyloid precursor protein + H2O | - |
Homo sapiens | ? | - |
? | |
| amyloid precursor protein + H2O | - |
Mus musculus | ? | - |
? | |
| E-cadherin + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
| E-cadherin + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
| fibrillar procollagen type I + H2O | 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 | Homo sapiens | fibrillar collagen type I + fibrillar collagen type I propeptide | - |
? | |
| fibrillar procollagen type I + H2O | 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 | Mus musculus | fibrillar collagen type I + fibrillar collagen type I propeptide | - |
? | |
| fibrillar procollagen type III + H2O | the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III | Homo sapiens | fibrillar collagen type III + fibrillar collagen type I propeptide | - |
? | |
| fibrillar procollagen type III + H2O | the enzyme is capable of cleaving off the globular C- and N-terminal prodomains of fibrillar collagen type I and type III | Mus musculus | fibrillar collagen type III + fibrillar collagen type I propeptide | - |
? | |
| Fibronectin + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
| Fibronectin + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
| MMP1 protein + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
| MMP1 protein + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
| Muc2 protein + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
| Muc2 protein + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
| nidogen 1 + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
| nidogen 1 + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
| tenascin-C + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
| tenascin-C + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | meprin beta is a multidomain metalloprotease and a dimeric type 1 transmembrane protein, enzyme domain structure, overview. The enzyme consists of a propeptide (PRO), a catalytic domain (CAT), a MAM (meprin A5 protein tyrosine phosphatase mu) domain, a TRAF (tumor-necrosis-factor-receptor-associated factor) domain, an EGF (epidermal growth factor) like domain, a transmembrane region and a C-terminal part | Homo sapiens |
| dimer | meprin beta is a multidomain metalloprotease and a dimeric type 1 transmembrane protein, enzyme domain structure, overview. The enzyme consists of a propeptide (PRO), a catalytic domain (CAT), a MAM (meprin A5 protein tyrosine phosphatase mu) domain, a TRAF (tumor-necrosis-factor-receptor-associated factor) domain, an EGF (epidermal growth factor) like domain, a transmembrane region and a C-terminal part | Mus musculus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| meprin beta | - |
Homo sapiens |
| meprin beta | - |
Mus musculus |
| procollagen proteinase | - |
Homo sapiens |
| procollagen proteinase | - |
Mus musculus |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.002 | - |
pH and temperature not specified in the publication | Homo sapiens | actinonin | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | enzyme downregulation causes impaired intestinal mucin release and barrier function, and decreases tensile strength in the skin, but it also leads to protection against sepsis and renal injury. Enzyme upregulation can cause fibrosis, pulmonary hypertension, the Kawasaki syndrome, inflammatory bowel disease, and is involved in nephritis, cancer, and Alzheimer's disease, overview | Homo sapiens |
| malfunction | meprin beta is the highest up-regulated gene in the lungs of Fosl2 transgenic mice compared to wild-type animals. Meprin beta knock-out mice exhibit decreased collagen deposition in skin resulting in impaired tensile strength, overview. Overexpression of meprin metalloproteases occurs under fibrotic conditions in the skin (keloids) and the lung (pulmonary hypertension) | Mus musculus |
| metabolism | meprins show higher substrate and cleavage specificity compared to matrix metalloproteases | Homo sapiens |
| metabolism | meprins show higher substrate and cleavage specificity compared to matrix metalloproteases | Mus musculus |
| additional information | transcriptional regulation of meprin beta expression by the heterodimeric transcription factor AP-1 (activator protein 1), overview | Homo sapiens |
| additional information | transcriptional regulation of meprin beta expression by the heterodimeric transcription factor AP-1 (activator protein 1), overview | Mus musculus |
| physiological function | meprin beta acts as a sheddase at the cell surface where it releases the entire ectodomain of amyloid precursor protein, this cleavage event at the so-called beta-site enables gamma-secretase to further cleave the remaining C-terminal fragment of APP within the membrane, thereby releasing amyloid beta-peptides, which are known to be involved in the onset and progression of Alzheimer's disease. The enzyme is involved in inflammation by the release and maturation of cytokines and proteoglycans, it induces extracellular matrix assembly and fibrosis, and enhances cancer progression through transactivation of epidermal growth factor receptors. The cleavage of fibrillar procollagen by the enzyme is required and sufficient to induce collagen fibril assembly | Homo sapiens |
| physiological function | meprin beta acts as a sheddase at the cell surface where it releases the entire ectodomain of amyloid precursor protein, this cleavage event at the so-called beta-site enables gamma-secretase to further cleave the remaining C-terminal fragment of APP within the membrane, thereby releasing amyloid beta-peptides, which are known to be involved in the onset and progression of Alzheimer's disease. The enzyme is involved in inflammation by the release and maturation of cytokines and proteoglycans, it induces extracellular matrix assembly and fibrosis, and enhances cancer progression through transactivation of epidermal growth factor receptors. The cleavage of fibrillar procollagen by the enzyme is required and sufficient to induce collagen fibril assembly | Mus musculus |
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