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Degradation of the extracellular matrix

Matrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the metzincin family. They contain a characteristic zinc-binding motif HEXXHXXGXXH (Stocker & Bode 1995) and a conserved Methionine which forms a Met-turn. Humans have 24 MMP genes giving rise to 23 MMP proteins, as MMP23 is encoded by two identical genes. All MMPs contain an N-terminal secretory signal peptide and a prodomain with a conserved PRCGXPD motif that in the inactive enzyme is localized with the catalytic site, the cysteine acting as a fourth unpaired ligand for the catalytic zinc atom. Activation involves delocalization of the domain containing this cysteine by a conformational change or proteolytic cleavage, a mechanism referred to as the cysteine-switch (Van Wart & Birkedal-Hansen 1990). Most MMPs are secreted but the membrane type MT-MMPs are membrane anchored and some MMPs may act on intracellular proteins. Various domains determine substrate specificity, cell localization and activation (Hadler-Olsen et al. 2011). MMPs are regulated by transcription, cellular location (most are not activated until secreted), activating proteinases that can be other MMPs, and by metalloproteinase inhibitors such as the tissue inhibitors of metalloproteinases (TIMPs). MMPs are best known for their role in the degradation and removal of ECM molecules. In addition, cleavage of the ECM and other cell surface molecules can release ECM-bound growth factors, and a number of non-ECM proteins are substrates of MMPs (Nagase et al. 2006). MMPs can be divided into subgroups based on domain structure and substrate specificity but it is clear that these are somewhat artificial, many MMPs belong to more than one functional group (Vise & Nagase 2003, Somerville et al. 2003).

from REACTOME source record: R-HSA-1474228
Type: pathway
Taxonomic scope
organism-specific biosystem
Homo sapiens

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