MMP3 gene

The MMP3 gene (MMP3 stands for: Matrix Metallopeptidase 3) is a protein coding gene located on chromosome 11q22.2. The MMP3 gene is part of a cluster of MMP genes located on chromosome 11q22.3.

Proteins of the matrix metalloproteinase (MMP) family are involved in the degradation of the extracellular matrix in normal physiological processes such as embryonic development, reproduction and tissue remodeling as well as in disease processes such as arthritis and metastasis. Most MMPs are secreted as inactive proproteins that are activated when cleaved by extracellular proteinases.

The MMP3 gene encodes an enzyme, matrix metallopeptidase 3, which degrades fibronectin, laminin, collagens III, IV, IX and X and cartilage proteoglycans. It is assumed that the enzyme is involved in wound healing, the progression of atherosclerosis and the development of tumors.

Matrix metallopeptidase 3 is a proteinase with a fairly broad substrate specificity that can degrade fibronectin, laminin, type I, III, IV and V gelatin, collagens III, IV, X and IX and cartilage proteoglycans. The protease activates various molecules, including growth factors, plasminogen or other matrix metalloproteinases such as MMP9 (Arza B et al. (2000).

After release into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin signaling pathway (Nagase H et al. 1990). It also acts intracellularly. For example, it is activated in dopaminergic neurons under stress by the serine protease HTRA2 and plays a central role in the degeneration of DA neurons by mediating the activation of microglia and the cleavage of alpha-synuclein/SNCA (Choi DH et al. 2011). In addition, it plays a role in the immune response and has antiviral activity against various viruses such as vesicular stomatitis virus, influenza A virus (H1N1) and human herpesvirus 1. Mechanistically, it translocates from the cytoplasm to the nucleus during viral infection and influences NF-kappa B activities.

Diseases associated with MMP3 include coronary artery disease 6 and conjunctivochalasis. Related pathways include downstream GPCR signaling and collagen chain trimerization.

1. Arza B et al. (2000) Prostromelysin-1 (proMMP-3) stimulates plasminogen activation by tissue-type plasminogen activator. Eur J Biochem 267:6378-6384.
2. Choi DH et al. (2011) Role of matrix metalloproteinase 3-edt al. (2011) mediated alpha-synuclein cleavage in dopaminergic cell death. J Biol Chem 286:14168-77.
3. Nagase H et al. (1990) Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry 29:5783-5789.