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 | Comment | Organism |
---|---|---|
additional information | generation of knock-out mice deficient for meprin alpha, phenotype, overview | Mus musculus |
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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
extracellular | meprin alpha is constitutively shed by furin during the secretory pathway and secreted into extracellular space. Meprin alpha tends to oligomerize to huge complexes ring and chain like structures up to the mega Dalton range, which makes it the largest extracellular protease | Mus musculus | - |
- |
extracellular | meprin alpha is constitutively shed by furin during the secretory pathway and secreted into extracellular space. Meprin alpha tends to oligomerize to huge complexes ring and chain like structures up to the mega Dalton range, which makes it the largest extracellular protease | Homo sapiens | - |
- |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | a metalloprotease | Mus musculus | |
Zn2+ | a metalloprotease | Homo sapiens |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
6400000 | - |
meprin alpha forms large oligomers up to 6.4 MDa | Mus musculus |
6400000 | - |
meprin alpha forms large oligomers up to 6.4 MDa | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
E-cadherin + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
E-cadherin + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
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 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 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 | - |
? | |
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 | - |
? | |
Fibronectin + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
Fibronectin + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
MMP1 protein + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
MMP1 protein + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
Muc2 protein + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
Muc2 protein + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
nidogen 1 + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
nidogen 1 + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? | |
tenascin-C + H2O | Mus musculus | an extracellular matrix-related substrate | ? | - |
? | |
tenascin-C + H2O | Homo sapiens | an extracellular matrix-related substrate | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
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 | Comment | Organism | Textmining |
---|---|---|---|
large intestine | enzyme expression | Mus musculus | - |
large intestine | enzyme expression | Homo sapiens | - |
leukocyte | enzyme expression | Mus musculus | - |
leukocyte | enzyme expression | Homo sapiens | - |
skin | the enzyme is highly up-regulated in keloid tissue | Mus musculus | - |
skin | the enzyme is highly up-regulated in keloid tissue | Homo sapiens | - |
small intestine | enzyme expression | Mus musculus | - |
small intestine | enzyme expression | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
E-cadherin + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
E-cadherin + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
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 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 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 | - |
? | |
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 | - |
? | |
Fibronectin + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
Fibronectin + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
MMP1 protein + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
MMP1 protein + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
Muc2 protein + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
Muc2 protein + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
nidogen 1 + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
nidogen 1 + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? | |
tenascin-C + H2O | an extracellular matrix-related substrate | Mus musculus | ? | - |
? | |
tenascin-C + H2O | an extracellular matrix-related substrate | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | meprin alpha is a multidomain metalloprotease, enzyme domain structure, overview. It tends to oligomerize to huge complexes ring and chain like structures up to the mega Dalton range, which makes it the largest extracellular protease. 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. Additionally, there is a so called inserted domain found in meprin alpha between the TRAF and the EGF like domain. This inserted domain is cleaved by furin resulting in secretion into extracellular space | Mus musculus |
More | meprin alpha is a multidomain metalloprotease, enzyme domain structure, overview. It tends to oligomerize to huge complexes ring and chain like structures up to the mega Dalton range, which makes it the largest extracellular protease. 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. Additionally, there is a so called inserted domain found in meprin alpha between the TRAF and the EGF like domain. This inserted domain is cleaved by furin resulting in secretion into extracellular space | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
meprin alpha | - |
Mus musculus |
meprin alpha | - |
Homo sapiens |
procollagen proteinase | - |
Mus musculus |
procollagen proteinase | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0001 | - |
pH and temperature not specified in the publication | Homo sapiens | actinonin |
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 alpha 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 | Mus musculus |
metabolism | meprins show higher substrate and cleavage specificity compared to matrix metalloproteases | Homo sapiens |
physiological function | 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 |
physiological function | 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 |