3.4.24.65	casein + H2O	degradation	
3.4.24.65	Elastin + H2O	-	
3.4.24.65	Elastin + H2O	degradation	
3.4.24.65	Elastin + H2O	MMP-12 is active against multiple extracellular protein substrates such as elastin, its effect on elastin is central to emphysema in the lung and photoaging of skin, its expression in the skin increases on photodamaged skin and upon aging	
3.4.24.65	Elastin + H2O	a key structural component of the lung extracellular matrix	
3.4.24.65	extracellular matrix protein + H2O	may be required for macrophages to penetrate basement membranes and remodel injured tissue during inflammation	
3.4.24.65	Fibronectin + H2O	degradation	
3.4.24.65	Gelatin + H2O	-	
3.4.24.65	Laminin + H2O	degradation	
3.4.24.65	additional information	able to degrade all components of extracellular matrix	
3.4.24.65	additional information	important role in inflammatory processes contributing to tissue remodelling	
3.4.24.65	additional information	macrophage-derived overexpression of MMP-12 causes accelerated atherosclerosis. Overexpression of human MMP-12 in macrophages of rabbits results in enhanced atherosclerosis	
3.4.24.65	additional information	MMP-12 does not appear to be involved in the fibrogenic pathway of bleomycin-induced lung injury. MMP-12 deficiency does not influence the bleomycin-induced raise of neither TGF-beta-1 nor TIMP-1 in lung, which are described as important pro-fibrogenic effectors	
3.4.24.65	additional information	MMP-12 exacerbates atherosclerosis, emphysema, aortic aneurysm, rheumatoid arthritis, and inflammatory bowel disease	
3.4.24.65	additional information	protease-activated receptor 1, PAR-1, controls MMP-12 release	
3.4.24.65	additional information	the enzyme induces inflammation in murine airways after direct instillation eliciting the inflammatory response by neutrophil influx, cytokine release, and gelatinase activation, and delayed response by macrophage recruitment, overview	
3.4.24.65	additional information	the enzyme induces inflammation in murine airways after direct instillation eliciting the inflammatory response by neutrophil influx, cytokine release, and gelatinase activation, and delayed response by macrophage recruitment, resident alveolar macrophages and recruited neutrophils do not play a role in the delayed macrophage recruitment induced by MMP-12, overview	
3.4.24.65	additional information	the enzyme is important for allowing macrophage migration through extracellular matrix, and probably plays an important role in the causation of inflammatory bowel disease, IBD, MMP-12 expression is increased in ulcerative colitis and in Crohn’s disease	
3.4.24.65	additional information	the enzyme is involved in the development of chronic obstructive pulmonary disease and airway inflammation and is associated with allergic bronchial asthma, phenotype, overview	
3.4.24.65	additional information	the enzyme plays an important role in inflammatory processes and is involved in a number of physiological or pathological situations, such as conversion of plasminogen into angiostatin, allergic airway inflammation, vascular remodeling or alteration, as well as emphysema	
3.4.24.65	additional information	HME has the ability to convert plasminogen into angiostatin, an essential and potent inhibitor of endothelial cell proliferation and tumor angiogenesis	
3.4.24.65	additional information	MMP12 has a direct bactericidal activity but is unable to kill certain bacteria such as those that have the ability to escape the phagosome, which is exerted by the C-terminal domain, that also alone shows bacterial killing activity	
3.4.24.65	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	
3.4.24.65	additional information	the catalytic domain of MMP-12 is unique among MMPs in that it is very highly active on numerous substrates including elastin	
3.4.24.65	type-IV collagen + H2O	degradation