Cloned (Comment) | Organism |
---|---|
gene MEP1A, gene MEP1A is genetically associated with inflammatory bowel disease, on the basis of single nucleotide polymorphisms in ulcerative colitis patients | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | generation of meprin beta knockout mice | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
actinonin | - |
Homo sapiens | |
batimastat | - |
Homo sapiens | |
captopril | - |
Homo sapiens | |
cystatin C | - |
Homo sapiens | |
DL-Pro-DL-Leu-Gly-NH2 | - |
Homo sapiens | |
fetuin-A | - |
Homo sapiens | |
galardin | - |
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 | - |
Mus musculus | 31526 | - |
brush border membrane | - |
Homo sapiens | 31526 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Zn2+ | a metalloprotease | Mus musculus | |
Zn2+ | a metalloprotease | Homo sapiens | |
Zn2+ | a metalloprotease | Danio rerio |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
B-type natriuretic peptide + H2O | Homo sapiens | - |
? | - |
? | |
vascular endothelial growth factor A + H2O | Danio rerio | - |
? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Danio rerio | - |
- |
- |
Homo sapiens | - |
gene MEP1A | - |
Mus musculus | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | activation of the inactive zymogen by proteases | Mus musculus |
proteolytic modification | activation of the inactive zymogen by proteases | Danio rerio |
proteolytic modification | activation of the inactive zymogen by proteases. In colon carcinoma Caco-2 cells, meprin alpha is activated by plasmin | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
intestine | - |
Mus musculus | - |
intestine | - |
Homo sapiens | - |
kidney | - |
Mus musculus | - |
kidney | meprin alpha is secreted into the lumen of the proximal tubule | Homo sapiens | - |
additional information | broad expression pattern for meprins | Danio rerio | - |
skin | meprin alpha is expressed in basal epidermis | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
B-type natriuretic peptide + H2O | - |
Homo sapiens | ? | - |
? | |
additional information | enzyme cleavage specificity, overview | Homo sapiens | ? | - |
? | |
vascular endothelial growth factor A + H2O | - |
Danio rerio | ? | - |
? | |
VEGF-A + H2O | human meprin alpha cleaves VEGF-A in vitro, generating proteolytic fragments as found in wild-type zebrafish | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
homodimer | homodimer linked by a disulfide bridge, domain structure of human meprins, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
meprin alpha | - |
Mus musculus |
meprin alpha | - |
Homo sapiens |
meprin alpha | - |
Danio rerio |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00002 | - |
actinonin | pH and temperature not specified in the publication | Homo sapiens | |
0.00014 | - |
galardin | pH and temperature not specified in the publication | Homo sapiens | |
0.0004 | - |
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 | |
0.00053 | - |
DL-Pro-DL-Leu-Gly-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
0.0015 | - |
N-[4-(hydroxyamino)-2-(2-methylpropyl)pent-4-enoyl]-3-methylvalyl-N-(2-aminoethyl)-DL-alaninamide | pH and temperature not specified in the publication | Homo sapiens | |
0.0022 | - |
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 | pH and temperature not specified in the publication | Homo sapiens | |
0.0044 | - |
batimastat | pH and temperature not specified in the publication | Homo sapiens | |
0.74 | - |
captopril | pH and temperature not specified in the publication | Homo sapiens |
Organism | Comment | Expression |
---|---|---|
Homo sapiens | during intestinal inflammation, mRNA expression of MEP1A in the epithelium is directly downregulated, mediated by the homeobox transcription factor CDX2 | down |
General Information | Comment | Organism |
---|---|---|
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 | Danio rerio |
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 | mice lacking meprin alpha and meprin beta are significantly protected against renal ischaemia/reperfusion injury and bladder inflammation. Meprin alpha-knockout mice exhibit less renal damage compared with wild-type mice | Mus musculus |
malfunction | the knockdown of meprin beta in zebrafish embryos leads to a general failure in organogenesis, resulting in the death of the embryos between days 1 and 3 postfertilization | Danio rerio |
physiological function | besides its contribution in the regulation of angiogenesis, meprin alpha is involved in cardiovascular homoeostasis by enzymatic cleavage of the 32-amino acid B-type natriuretic peptide in vitro and in vivo, leading to its reduced bioactivity. Procollagen III is processed to its mature form by meprin alpha and meprin beta, an essential step in collagen fibril assembly. The metalloprotease meprin alpha is involved in inflammation, neurodegeneration, cancer and fibrosis, overview. Gene MEP1A is genetically associated with inflammatory bowel disease, on the basis of single nucleotide polymorphisms in ulcerative colitis patients. Meprin alpha induces inflammation by transactivation of the EGF receptor through the release of its ligands transforming growth factor alpha and EGF from the cell surface, meprin alpha is able to release soluble EGF and TGFalpha, consequently activating the EGFR and ERK1/2 (extracellular-signal-regulated kinase 1/2) signalling cascade in a ligand-dependent manner. Meprin alpha expressed in basal epidermis promotes cell proliferation | Homo sapiens |
physiological function | the metalloproteases meprin alpha and meprin beta are involved in inflammation, neurodegeneration, cancer and fibrosis, overview | Mus musculus |