Fig.1 The mammalian family of matrix metalloproteinases. Structural classification of MMPs based on their domain arrangement.
1.1: Collagenases: This subgroup is composed of three enzymes, MMP-1, MMP-8 and MMP-13 (also known as collagenases-1, 2, and 3, respectively) whose name reflects their ability to cleave the collagen triple helix into characteristic 3/4 and 1/4 fragments.
1.2. Stromelysins: Stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) show the same structural design as collagenases and can degrade many different ECM components, but they are not able to cleave native collagen.
1.3.Other archetypal MMPs: There are four matrixins (MMP-12, -19, -20, -27) which cannot be classified in the previous subgroups because of their divergence in sequence and substrate specificity. MMP-12 or metalloelastase is the most potent elastolytic enzyme of the family although, as other MMPs, it can also degrade many other ECM proteins, including aggrecan, fibronectin, laminin, and type IV collagen.
1.4. Matrilysins: MMP-7 and MMP-26, also known as matrilysins-1 and -2, are expressed under normal and pathological conditions and have been implicated in the progression of several types of human cancers. Both proteases exhibit the simplest domain arrangement of all MMPs since they lack the carboxy-terminal hemopexin domain.
1.5.Gelatinases: MMP-2 (gelatinase-A) and MMP-9 (gelatinase-B) are constitutively expressed by many cell types including fibroblasts, keratinocytes, endothelial cells, chondrocytes and monocytes in the case of MMP-2, and alveolar macrophages, polymorphonuclear leukocytes and osteoclasts in the case of MMP-9.
1.6.Furin-activatable MMPs: All MMPs belonging to this category contain a furin recognition motif inserted between the propeptide and the catalytic domain. This sequence is recognized and cleaved by convertase proteases, providing the basis for furin-dependent activation of latent enzymes prior to secretion.
These furin-activatable MMPs include three secreted MMPs (MMP-11, -21, and -28), six membrane-type-MMPs (MMP-14, -15, -16, -17, -24, and -25) and two unusual type II trans-membrane MMPs (MMP-23A and -23B both having identical amino acid sequence, but are encoded by distinct genes in the human genome). These proteases are unique among the matrixin family because they lack the signal peptide, the cysteine-switch motif and the hemopexin domain characteristic of all MMPs, but contain cysteine-array (CA) and immunoglobulin (Ig) domains in their shortened C-terminal tail.
(“Matrix metalloproteinases: Evolution, gene regulation and functional analysis in mouse models”, MiriamFanjul, FernándezAlicia, R.Folgueras Sandra Cabrera & CarlosLópez-Otín https://doi.org/10.1016/j.bbamcr.2009.07.004 )
2.Gene evolution and genomic organization of MMPs:
Comparative genomic analyses have indicated that the impressive diversity characteristic of the family of vertebrate MMP genes mainly derives of a series of evolutionary events that occurred during early stages of vertebrate emergence.