InterPro domain: IPR021190

The MEROPS peptidase family M10, subfamily M10A, consists of extracellular metalloproteases, such as collagenase and stromelysin, that degrade the extracellular matrix and are known as matrixins or matrix metalloproteinases (MMPs). They are zinc-dependent, calcium-activated proteases synthesised as inactive precursors(zymogens), which are proteolytically cleaved to yield the active enzyme [ 1 , 2 ].

All matrixins and related proteins possess two domains: an N-terminaldomain, and a zinc-binding active site domain. The N-terminal domainpeptide, cleaved during the activation step, includes a conserved PRCGVPDVoctapeptide, known as the cysteine switch, whose Cys residue chelates theactive site zinc atom, rendering the enzyme inactive [ 3 , 4 ]. The active enzyme degrades components of the extracellular matrix, playing a role in the initial steps of tissue remodelling during morphogenesis, wound healing, angiogenesis and tumour invasion [ 5 , 5 ]. Although it was initially thought that the primary function of these enzymes is to degrade proteins of the extracellular matrix, MMPs have a much broader spectrum of activity that includes the proteolytic processing of cytokines, growth factors, growth factor receptors, and cell adhesion molecules [ 5 , 6 ].

1. SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J. Biol. Chem. 264, 17213-21
2. Early expression of a collagenase-like hatching enzyme gene in the sea urchin embryo. EMBO J. 9, 3003-12
3. Structure-function relationships in the collagenase family member transin. J. Biol. Chem. 263, 11892-9
4. Mutational analysis of the transin (rat stromelysin) autoinhibitor region demonstrates a role for residues surrounding the "cysteine switch". J. Biol. Chem. 266, 1584-90
5. Matrix metalloproteinases: they're not just for matrix anymore! Curr. Opin. Cell Biol. 13, 534-40
6. Matrix metalloproteinases: what do they not do? New substrates and biological roles identified by murine models and proteomics. Biochim. Biophys. Acta 1803, 39-54