proMMP1

proMMP1 is the latent zymogen form of matrix metalloproteinase-1 (MMP-1), a secreted collagenase that cleaves native fibrillar collagens such as types I, II, and III. As a proenzyme, proMMP1 is produced with an N-terminal signal peptide and a prodomain that preserves latency until activation. In humans, MMP-1 plays a role in extracellular matrix remodeling during development, wound healing, and inflammatory responses.

Activation of proMMP1 involves proteolytic removal of its prodomain, exposing the catalytic site. The prodomain contains a cysteine switch motif (PRCGVPD) that coordinates with the active-site zinc ion, keeping the enzyme inactive. Activation can occur through proteolysis by various proteases (for example, plasmin or other MMPs) or autolytic mechanisms in the extracellular environment. Once activated, the enzyme consists of a catalytic domain with a zinc-binding motif (HEXGHXXGXXH) and a hemopexin-like C-terminal domain that modulates substrate interaction and specificity.

ProMMP1 expression is found in a range of cell types, including fibroblasts, macrophages, osteoblasts, and epithelial cells, and its transcription is influenced by inflammatory mediators such as interleukin-1 and tumor necrosis factor-alpha. Its activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs), especially TIMP-1 and TIMP-2, which can limit extracellular matrix degradation by active MMP-1.

Clinically, MMP-1 activity, arising from proMMP1 activation, contributes to tissue remodeling but can also facilitate pathological processes such as inflammatory arthritis, periodontitis, and cancer invasion. Elevated levels of proMMP1 or activated MMP-1 in tissues or bodily fluids have been explored as biomarkers in various diseases. The MMP1 gene, located on chromosome 11q22-23, encodes proMMP1 and exhibits promoter polymorphisms (notably 1G/2G) that can influence transcriptional activity and disease susceptibility.