Table 1.
Functional properties of the tissue inhibitors of metalloproteinases (TIMPs) (based on reviews [1-4])
| Property | TIMP-1 | TIMP-2 | TIMP-3 | TIMP-4 |
| Approximate protein size | 28 kDa | 21 kDa | 24/27 kDa | 22 kDa |
| Localisation | Soluble | Soluble + cell surface | Extracellular matrix | Cell surface, tissue-specific |
| Intracellular activation | Receptor(s) Nuclear translocation | Receptor(s) | No | Not known |
| Proteinase type inhibition | Secreted MMP, ADAMTS | Secreted MMP, MT-MMP | MT-MMP, ADAMTS | Secreted MMP, MT-MMP |
| Apoptosis | Inhibits (BCL-2 regulation) | Inhibits | Promotes (TACE, death receptors) | Promotes |
| Angiogenesis | Inhibits | Inhibits | Inhibits | Inhibits |
| Proliferation | Stimulates | Stimulates | Inhibits | Stimulates |
| Tumour growth | Promotes | Promotes | Inhibits | Not known |
| Knockout mice | Resistance to Pseudomonas infection | Impaired pro-MMP2 activation | Lung emphysema, chronic hepatitis. High TNF-α | Not known |
ADAMTS, a disintegrin and metalloproteinase domain with thrombospondin motifs; MMP, matrix metallproteinase; MT-MMP, membrane-type matrix metalloproteinase; TACE, tumour-necrosis-factor-α-converting enzyme; TIMP, tissue inhibitor of metalloproteinases; TNF, tumour necrosis factor.