Metalloproteinase2

Metalloproteinase-2, commonly referred to as MMP-2 or gelatinase A, is a zinc-dependent endopeptidase in the matrix metalloproteinase family. It is produced as a secreted latent proenzyme of approximately 72 kDa and is activated to a catalytic enzyme of about 62 kDa.

The enzyme has an N-terminal signal peptide, a propeptide containing the cysteine switch motif PRCGVPD, a catalytic domain with the zinc-binding motif HEXGHXXGXXH, and a C-terminal hemopexin-like domain that influences substrate specificity and interactions with inhibitors and activators.

MMP-2 substrates include gelatin and basement membrane components such as type IV collagen, laminin, and other extracellular matrix proteins. Through remodeling of the extracellular matrix, MMP-2 participates in physiological processes such as development, wound healing, and angiogenesis, and in pathological settings including cancer invasion and metastasis, cardiovascular disease, and inflammatory disorders.

Activity is tightly regulated at transcriptional, zymogen activation, and inhibition levels. Pro-MMP-2 is activated at the cell surface by membrane-type 1 matrix metalloproteinase (MT1-MMP) in a complex with tissue inhibitor of metalloproteinases-2 (TIMP-2). Inhibitors such as TIMP-2 and TIMP-4 neutralize active MMP-2 to limit ECM degradation.

Altered MMP-2 expression and activity have been observed in multiple diseases and are studied as potential biomarkers and therapeutic targets, though clinical approaches targeting MMPs have faced challenges due to redundancy and side effects.