Table 1 Properties of human TIMPs, summarizing their activities in inhibiting metzincin metalloproteinases and in modulating phenotypic cell behavior [6]
Property | TIMP1 | TIMP2 | TIMP3 | TIMP4 |
|---|---|---|---|---|
Amino acid residues | 184 | 194 | 188 | 194 |
pI | 8.5 | 6.5 | 9.1 | 7.2 |
Protein kDa | 28 | 22 | 24 or 27 | 22 |
N-glycosylation sites | 2 | 0 | 1 | 0 |
Synapsin gene | SYN1 | n/a | SYN3 | SYN2 |
Protein localization | Soluble/cell surface | Soluble/cell surface | Extracellular matrix/cell surface | Soluble/cell surface |
Pro-MMP binding | proMMP9 | proMMP2 | proMMP2, 9 | proMMP2 |
MMPs poorly inhibited | MT1-MMP, MT3-MMP, MT5-MMP, MMP19 | None | None | None |
ADAM inhibition | ADAM10 | ADAM12 | ADAM10, ADAM12, ADAM17, ADAM19, ADAM33, ADAMTS1, ADAMTS4, ADAMTS5, ADAMTS2 (weak) | ADAM17, ADAM28 |
Binding partners | CD63, LRP1/MMP9 | α3β1integrin, LRP1 | EFEMP1, AngIIR, VEGFR |  |
Cell proliferation | ↑Erythroid precursors | ↑Erythroid precursors | ↑Smooth muscle cells and cancer cells | ↑Mammary tumor cells |
|  | ↑Tumor cells | ↑Tumor cells |  | ↓Wilm's tumor cells |
|  |  | ↑Fibroblasts |  |  |
|  |  | ↑Smooth muscle cells |  |  |
|  |  | ↓Endothelial cells |  |  |
Apoptosis | ↓Burkitt's lymphoma cells | ↑Colorectal cancer cells ↓Melanoma | ↑Smooth muscle ↑Tumor cells ↑Retinal pigment epithelial cells |  |
Tumor angiogenesis | ↑Mammary ↓Liver | ↓Melanoma ↓Mammary | ↓Melanoma |  |
Angiogenesis in 3D collagen or fibrin gels | No effect | Inhibits | Inhibits | Inhibits |
Tumorigenesis effects | Inhibits | Inhibits | Inhibits | Inhibits |
Metastasis effects | Stimulates | Â | Â | Stimulates |
Genetic defects | Â | Idiopathic scoliosis | Sorsby's fundus dystrophy | Kawasaki disease |