Update of human and mouse matrix metalloproteinase families

The extracellular matrix (ECM) plays a role in adhesion, growth, apoptosis and cell-cell communication, and regulation of these functions is critical to cellular activities. One family of proteins which functions in the regulation of the ECM is the matrix metalloproteinases (MMPs; also called matrixins). MMPs belong to the metzincin superfamily (zinc endopeptidases), which consists of ADAMs (a disintegrin and metalloproteinase), ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs), bone morphogenetic protein 1/tolloid-like metalloproteinases (BMPI/TLLs), meprins and MMPs [1]. MMPs are zinc proteases which have the ability to degrade most components of the ECM, as well as act on an extremely broad array of extracellular components [2]. The first MMP -- an interstitial collagenase (MMP1) -- was discovered by Gross et al.[3] in 1962, and had the ability to degrade collagen. In the Matrix Metalloproteinase Conference (Destin, Florida 1989), MMPs were assigned sequential names and defined using biochemical characteristics, including: appearance in a latent form; inhibition by tissue inhibitor of metalloproteinase (TIMP); ability to hydrolyse at least one ECM component; and presence of zinc as an intrinsic metal ion [4]. Since then, research on MMPs has expanded greatly, and 23 human and 23 mouse MMPs are known, of which most, but not all, share orthology.MMPs are typically synthesised as preproenzymes and secreted immediately (exceptions include MMP8 and MMP9, which can be stored in the granules of neutrophils [5]) in an inactive form. Activation of MMPs can occur extracellularly by proteolytic cleavage by other MMPs or by serine proteinases (eg plasmin). Alternatively, MMPs with a furin recognition sequence (MT-MMPs, MMP11, MMP21, MMP23B and MMP28) are activated in the Golgi apparatus and released in a proteolytically active form. Active MMPs are regulated by inhibitors such as TIMPs and the general plasma proteinase inhibitor α2-macroglobulin [6]. O