Tissue inhibitors of metalloproteinases (TIMPs) are a family of secreted proteins that regulate the activation and proteolytic activity of the zinc enzymes known as matrix metalloproteinases (MMPs). There are four known members of the family, TIMP-1, -2, -3, and -4. TIMP-4 is produced by a wide range of tissues, particularly brain, heart, ovary and skeletal muscle (1, 2). Limited studies have shown that TIMP-4 has a tumor suppressive effect against Wilm’s tumor, exhibits negative correlation with glioma maligancy and is found in breast carcinoma cells (3, 5). TIMP-4 inhibits MMP-mediated proteolysis by forming a noncovalent binary complex with the MMP active site through its N-terminal domain. In addition, it binds to the hemopexin-like domain of proMMP-2 through its C-terminal domain in a manner similar to TIMP-2 (6). However, unlike TIMP-2, TIMP-4 does not promote proMMP-2 activation by MT1-MMP (MMP-14) (7). Although TIMP-4 is a potent inhibitor of most MMPs, it is not an effective inhibitor of ADAMs, such as TACE (8, 9).
Source:Recombinant protein corresponding to aa1-224, Met1-Pro224, from mouse TIMP-4, NS0-derived.
Molecular Weight:~25-26kD
Endotoxin:<0.10EU/1ug (LAL method).
Biological Activity:Measured by its ability to inhibit human MMP-2 cleavage of a fluorogenic peptide substrate Mca-PLGL-Dpa-AR-NH2. The IC50 value is <3nM, as measured under the described conditions.
Storage and Stability:May be stored at 4°C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
