MMP-9 (also referred to as gelatinase B, 92 kDa type IV collagenase, 92 kDa gelatinase, and type V collagenase) is secreted as a glycosylated proenzyme. Activation of the proenzyme involves proteolytic removal of the N-terminal pro region, resulting in the 82 kDa active enzyme. Active human MMP-9 shares 72% and 74% amino acid sequence identity with mouse and rat MMP-9, respectively. In addition to the zinc-binding site, the catalytic domain also contains three contiguous fibronectin type II homology units responsible for binding gelatin. A proline-rich hinge region links the catalytic domain to the C-terminal hemopexin-like domain. In vitro treatment of the proenzyme with 4-aminophenylmercuric acetate (APMA) produces not only the active enzyme but also a C-terminal truncated form with activity comparable to that of the active form. MMP-9 degrades components of the ECM with high specific activity for denatured collagens (gelatin). It can cleave native collagens of type III, IV, V, and XI, as well as Elastin, Nidogen-1, and Vitronectin. MMP-9 can also cleave a variety of chemokines and growth factors (e.g. IL-1 beta, CXCL8/IL-8, CXCL7, CXCL4, CXCL1, Latent TGF-beta, membrane bound TNF-alpha, VEGF, and FGF basic), Amyloid beta peptide, Substance P, and Myelin Basic Protein. This action can increase or decrease the biological activity of soluble factors and can also liberate them from association with the ECM. MMP-9 can also trigger signaling through various transmembrane proteins or inhibit signaling by inducing their shedding from the cell surface (e.g. CD44, E-Cadherin, Integrins, ICAM-1, and IL-2 R alpha ).