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Literature summary for 3.4.24.18 extracted from

  • Broder, C.; Becker-Pauly, C.
    The metalloproteases meprin alpha and meprin beta: Unique enzymes in inflammation, neurodegeneration, cancer and fibrosis (2013), Biochem. J., 450, 253-264.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

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

Protein Variants Comment Organism
additional information generation of meprin beta knockout mice Mus musculus

Inhibitors

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

Localization Comment Organism GeneOntology No. Textmining
brush border membrane
-
Mus musculus 31526
-
brush border membrane
-
Homo sapiens 31526
-

Metals/Ions

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

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Danio rerio
-
-
-
Homo sapiens
-
gene MEP1A
-
Mus musculus
-
-
-

Posttranslational Modification

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

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 and Products (Substrate)

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

Subunits Comment Organism
homodimer homodimer linked by a disulfide bridge, domain structure of human meprins, overview Homo sapiens

Synonyms

Synonyms Comment Organism
meprin alpha
-
Mus musculus
meprin alpha
-
Homo sapiens
meprin alpha
-
Danio rerio

Ki Value [mM]

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

Expression

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

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