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General description
Tissue inhibitor of metalloproteinases 3 (TIMP3) is localized in the extracellular matrix (ECM) of epithelial cells associated with kidneys, eyes and lungs. It is majorly secreted in retinal pigment epithelium (RPE). TIMP3 gene is mapped to human chromosome 22q12.3 and is a CLOCK-dependent diurnal gene. TIMP proteins display a three-lobed structure and have conserved cysteine residues.
Biochem/physiol Actions
The TIMPs are endogenous inhibitors of the matrix metalloproteinases (MMPs). TIMP-3 inhibits ADAM-17 (TACE) at nanomolar concentrations and also inhibits other metalloproteinases (sheddases) that mediate the shedding of soluble receptors and other proteins from the surface of cells.
Tissue inhibitor of metalloproteinases 3 (TIMP3) is a matrix metalloproteinase inhibitor. TIMP proteins comprise the N-terminal region, which aids in the matrix metalloproteinase interaction. The C-terminal region is crucial for extracellular matrix (ECM) interaction. Elevated expression of TIMP3 favors apoptosis in cancer types. Its interaction with the vascular endothelial growth factor (VEGFR-2) leads to the regulation of angiogenesis. TIMP3 also aids in protection against ultra-violet (UV)-induced cellular responses. Missense mutations in the TIMP3 gene are implicated in Sorsby′s fundus dystrophy (SFD). Mutations in the TIMP3 gene also leads to increased accumulation of the protein resulting in the thickening of the Bruch membrane. This, in turn, reduces membrane permeability towards nutrients and metabolites.
Physical form
Lyophilized from a 0.2 μm filtered solution in 25 mM Tris and 0.15 M sodium chloride, pH 7.5.
Analysis Note
The biological activity is measured by its ability to inhibit human MMP-2 hydrolysis of a peptide substrate.
| biological source | human |
| Quality Level | 100 |
| recombinant | expressed in NSO cells |
| assay | >95% (SDS-PAGE) |
| form | lyophilized powder |
| mol wt | apparent mol wt ~30 kDa |
| technique(s) | inhibition assay: suitable |
| UniProt accession no. | P35625 |
| storage temp. | −20°C |
| Gene Information | human ... TIMP3(7078) |
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¥ 2707.32
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