Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of a mutant peptide identical to SR-20, i.e. 344-SRNQLFLFKDEKYWLINNLV-363, except that the Lys-Asp-Glu-Lys motif found in mouse MMP12 is replaced by the human MMP9 sequence, Ser-Gly-Arg-Gln. The Lys-Asp-Glu-Lys motif is essential for the antimicrobial properties of mouse MMP12 C-terminal domain. Mmp12-/- mice exhibit impaired bacterial clearance and increased mortality when challenged with both Gram-negative and Gram-positive bacteria at macrophage-rich portals of entry, such as the peritoneum and lung | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
phagolysosome | macrophage | Mus musculus | 32010 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Mus musculus | MMP12 is involved in bacterial clearance. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The bacterial killing requires the SR20 sequence, 344-SRNQLFLFKDEKYWLINNLV-363, which alone is also active, but shorter four-amino-acid peptides, Ser-Gly-Arg-Gln, Lys-Asp-Asp-Lys and Lys-Asp-Glu-Lys, do not show antimicrobial activity, suggesting that the loop structure of the protein is required for bacterial killing | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
macrophage | MMP12 is an enzyme predominantly expressed in mature tissue macrophages | Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | MMP12 is involved in bacterial clearance. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The bacterial killing requires the SR20 sequence, 344-SRNQLFLFKDEKYWLINNLV-363, which alone is also active, but shorter four-amino-acid peptides, Ser-Gly-Arg-Gln, Lys-Asp-Asp-Lys and Lys-Asp-Glu-Lys, do not show antimicrobial activity, suggesting that the loop structure of the protein is required for bacterial killing | Mus musculus | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | the antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxy-terminal domain, which contains a unique four amino acid sequence on an exposed beta loop of the protein that is required for the observed antimicrobial activity, within the sequence designated SR-20, i.e. 344-SRNQLFLFKDEKYWLINNLV-363. Three-dimensional homology modeling of mouse MMP12 C-terminal domain, overview | Mus musculus |
Synonyms | Comment | Organism |
---|---|---|
matrix metalloproteinase 12 | - |
Mus musculus |
MMP12 | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
antimicrobial activity assay at | Mus musculus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
antimicrobial activity assay at | Mus musculus |
General Information | Comment | Organism |
---|---|---|
physiological function | MMP12 is involved in bacterial clearance. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The bacterial killing requires the SR20 sequence, 344-SRNQLFLFKDEKYWLINNLV-363, which alone is also active, but shorter four-amino-acid peptides, Ser-Gly-Arg-Gln, Lys-Asp-Asp-Lys and Lys-Asp-Glu-Lys, do not show antimicrobial activity, suggesting that the loop structure of the protein is required for bacterial killing. MMP12 is implicated in several disease processes, including emphysema | Mus musculus |