Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.24.18 extracted from

  • Prox, J.; Arnold, P.; Becker-Pauly, C.
    Meprin alpha and meprin beta: procollagen proteinases in health and disease (2015), Matrix Biol., 44-46, 7-13.
    View publication on PubMed

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
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

Metals/Ions Comment Organism Structure
Zn2+ a metalloprotease Mus musculus
Zn2+ a metalloprotease Homo sapiens

Molecular Weight [Da]

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

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
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 and Products (Substrate)

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

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

Synonyms Comment Organism
meprin alpha
-
Mus musculus
meprin alpha
-
Homo sapiens
procollagen proteinase
-
Mus musculus
procollagen proteinase
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0001
-
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 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