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 | Stimulates | ||
| Genetic defects | Idiopathic scoliosis | Sorsby's fundus dystrophy | Kawasaki disease |
AngIIR, angiotensin II receptor; EFEMP1, EGF-containing fibulin-like extracellular matrix protein 1; VEGFR, vascular endothelial growth factor receptor