Cloned (Comment) | Organism |
---|---|
gene MEP1B | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
crystal structure analysis of the ectodomain of dimeric human meprin beta, PDB codes 4GWN and 4GWM | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | generation of meprin alpha knockout mice | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
actinonin | - |
Homo sapiens | |
batimastat | - |
Homo sapiens | |
captopril | - |
Homo sapiens | |
DL-Pro-DL-Leu-Gly-NH2 | - |
Homo sapiens | |
fetuin-A | - |
Homo sapiens | |
galardin | - |
Homo sapiens | |
additional information | no inhibition by cystatin C | Homo sapiens | |
N-[1-[(1-amino-1-oxopropan-2-yl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]-4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enamide | - |
Homo sapiens | |
N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide | - |
Homo sapiens | |
N4-hydroxy-N1-[3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
brush border membrane | - |
Homo sapiens | 31526 | - |
brush border membrane | - |
Mus musculus | 31526 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | a metalloprotease | Danio rerio | |
Zn2+ | a metalloprotease | Homo sapiens | |
Zn2+ | a metalloprotease | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
alpha-secretase + H2O | Homo sapiens | meprin beta-mediated activation of the alpha-secretase | ? | - |
? | |
amyloid precursor protein + H2O | Homo sapiens | meprin beta initially sheds amyloid precursor protein, releasing different amyloid beta species with several cleavage sites identical with or proximal to the known beta-secretase cleavage site | amyloid beta peptides | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Danio rerio | - |
- |
- |
Homo sapiens | Q16820 | gene MEP1B | - |
Mus musculus | Q61847 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | activation of the inactive zymogen by proteases | Danio rerio |
proteolytic modification | activation of the inactive zymogen by proteases | Homo sapiens |
proteolytic modification | activation of the inactive zymogen by proteases | Mus musculus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
intestine | - |
Homo sapiens | - |
intestine | - |
Mus musculus | - |
keratinocyte | terminally differentiated | Homo sapiens | - |
kidney | - |
Mus musculus | - |
kidney | meprin beta is tethered to the apical plasma membrane | Homo sapiens | - |
additional information | broad expression pattern for meprins | Danio rerio | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
alpha-secretase + H2O | meprin beta-mediated activation of the alpha-secretase | Homo sapiens | ? | - |
? | |
amyloid precursor protein + H2O | meprin beta initially sheds amyloid precursor protein, releasing different amyloid beta species with several cleavage sites identical with or proximal to the known beta-secretase cleavage site | Homo sapiens | amyloid beta peptides | - |
? | |
antileucoproteinase + H2O | a serine protease inhibitor | Homo sapiens | ? | - |
? | |
elafin + H2O | a serine protease inhibitor | Homo sapiens | ? | - |
? | |
lymphoepithelial Kazal-type-related inhibitor + H2O | a serine protease inhibitor | Homo sapiens | ? | - |
? | |
additional information | enzyme cleavage specificity, overview | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
homodimer | homodimer linked by a disulfide bridge, domain structure of human meprins, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
meprin beta | - |
Danio rerio |
meprin beta | - |
Homo sapiens |
meprin beta | - |
Mus musculus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.002 | - |
actinonin | pH and temperature not specified in the publication | Homo sapiens | |
0.0074 | - |
N4-hydroxy-N1-[3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide | pH and temperature not specified in the publication | Homo sapiens | |
0.0089 | - |
galardin | pH and temperature not specified in the publication | Homo sapiens | |
0.014 | - |
DL-Pro-DL-Leu-Gly-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
0.018 | - |
batimastat | pH and temperature not specified in the publication | Homo sapiens | |
0.41 | - |
captopril | pH and temperature not specified in the publication | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.2 | - |
pH and temperature not specified in the publication | Homo sapiens | N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide | |
0.4 | - |
pH and temperature not specified in the publication | Homo sapiens | N-[1-[(1-amino-1-oxopropan-2-yl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]-4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enamide |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | in the ileal mucosa of Crohn's disease patients, mRNA levels of meprin beta are decreased | down |
General Information | Comment | Organism |
---|---|---|
evolution | meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily | Danio rerio |
evolution | meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily | Mus musculus |
evolution | meprin metalloproteases belong to the astacin family of zinc endopeptidases and the metzincin superfamily. Meprins belong to the astacin family of metalloproteases, comprising only six members in humans. These enzymes are characterized by a conserved zinc-binding motif (HExxHxxGxxHxxxRxDR) and by a sequence in close proximity to the active-site cleft, the so called Met-turn, that includes a tyrosine residue as a fifth zinc ligand. Within the astacin family, meprins exhibit a unique domain composition | Homo sapiens |
malfunction | meprin beta-knockout mice exhibit a reduced activation of the pro-inflammatory interleukin-18 and are therefore less susceptible to intestinal inflammation compared with wild-type mice. Mice lacking meprin alpha and meprin beta are significantly protected against renal ischaemia/reperfusion injury and bladder inflammation. Meprin beta-deficient mice show lower levels of the inflammatory marker interleukin-6 and decreased leucocyte infiltration after renal injury | Mus musculus |
malfunction | the knockdown of meprin expression in zebrafish embryos reveals an important contribution of meprin alpha in angiogenesis with reduced blood vessel formation in the morpholino-injected animals | Danio rerio |
physiological function | procollagen III is processed to its mature form by meprin alpha and meprin beta, an essential step in collagen fibril assembly. The metalloprotease meprin beta is involved in inflammation, neurodegeneration, cancer and fibrosis, overview. The enzyme mediates intestinal leucocyte infiltration, in accordance with its ability to cleave adhesion molecules and components of the extracellular matrix. Meprin beta induces cell death in terminally differentiated keratinocytes. Increased meprin activity at the basement membrane leads to degradation of the renal tubular laminin-nidogen complex and other components of the basement membrane, and to the cleavage of cell-adhesion molecules (E-cadherin and tenascin-C), consequently injuring the tubular basement membrane and leading to leucocyte infiltration | Homo sapiens |
physiological function | the metalloproteases meprin alpha and meprin beta are involved in inflammation, neurodegeneration, cancer and fibrosis, overview | Mus musculus |