Matrix metalloproteinases (MMPs), also known to be called matrixins, are multi-domain proteins which play a vital role in the removal and degradation of the extracellular matrix (ECM). These proteinases are central to many biological processes, such as normal tissue remodelling, wound healing, angiogenesis and embryogenesis. They can also be found in many diseases for example in arthritis, tissue ulceration, atheroma and cancer. MMPs activities are found to be regulated by tissue inhibitors of metalloproteinases (TIMPs), these can be specific inhibitors of matrixins whilst also taking part in controlling the local activities of MMPs in tissues.
Based on domain organization and substrate preference, MMPs are commonly grouped into the following categories:
- Collagenases: MMP-1, MMP-8, MMP-13, and MMP-18 (Xenopus) are in this group. One of the key features is their ability to cleave interstitial collagens I, II, and III at a specific site three-fourths from the N-terminus.
- Gelatinases: MMP-2 (Gelatinase A) and MMP-9 (gelatinase B) are members of this group. These enzymes have three repeats of a type II fibronectin domain that are inserted in the catalytic domain – giving it the ability to bind collagens, laminin and gelatin. One notable feature is their ability to readily digest denatured gelatins and collagens.
- Stromelysins: MMP-3 (Stromelysin 1), MMP-10 (Stromelysin 2) belong in this group, both having similar substrate specificities, but the proteolytic efficiency of MMP-3 is generally higher than MMP-10. There is also MMP-11 (stromelysin 3) which is usually grouped with “other MMPs” since its sequence and substrate specificity diverge in comparison to MMP-3.
- Matrilysins: MMP-7 (Matrilysin 1) and MMP-26 (matrilysin 2) belong in this group and are characterised by their lack of hemopexin domain. MMP-26 is able to digest a number of ECM components, whereas MMP-7 processes cell surface molecules such as and E-cadherin, Fas-ligand, pro-TNF-α and pro–α-defensin.
- Membrane-Type MMPs: There are 6 membrane-type MMPs (MT-MMPs) in this family group. Four which contain MMP-14, MMP-15, MMP-16 and MMP-24 are type I transmembrane and the other two MMP-17 and MMP-25 are glycosylphosphatidylinositol (GPI) anchored proteins.
There are 7 MMPs which not classified under any of the above groups.
- MMP-12 (Metalloelastase): Essential for macrophage migration.
- MMP-19: Identified by cDNA cloning from liver.
- MMP-20 (Enamelysin): Primarily located within newly formed tooth enamel and also is able to digest amelogenin.
- MMP-22: First cloned from chicken fibroblasts but its functions is still unknown.
- MMP-23: Expressed mainly in reproductive tissues. Contains a cysteine-rich domain followed by an immunoglobulin-like domain.
- MMP-28 (Epilysin): Expressed mainly in keratinocytes and there is some suggestion that it might function in wound repair and in tissue hemostasis. This is the newest addition to the MMP family.
- MMP-11 (stromelysin 3): Since its sequence and substrate specificity diverge from MMP-3 (Stromelysin 1).