MMP1,3,13 (2, 7-12, 19) binding by Alpha-2 macroglubulin

Stable Identifier
Homo sapiens
MMP binding by alpha2-macroglobulin
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Alpha 2-macroglobulin (A2M) is a plasma glycoprotein consisting of 4 near-identical subunits (Andersen et al. 1995). A2M inhibits almost all endopeptidases regardless of their specificities (Barrett 1981). A2M binding to an endopeptidase is triggered by cleavage of a peptide bond in the 'bait region' of A2M, triggering a conformational change in A2M that in turn entraps the peptidase without blocking the active site (Barrett & Starkey 1973). This blocks enzyme activity against large protein substrates while not preventing activity on low molecular weight substrates.

Once bound, A2M-proteinase complexes are endocytosed by low density lipoprotein receptor-related protein-1 (LRP1) (Strickland et al. 1990).

Active metalloproteinases (MMPs) that can be entrapped by A2M include MMP3 (Enghild et al. 1989) MMP1 (Grinnell et al. 1998) and MMP 13 (Beekman et al. 1999).

The significance of this mechanism as a regulator of MMP activity is unclear (Baker et al. 2002, Nagase et al. 2006).

Literature References
PubMed ID Title Journal Year
1698775 Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor

Williams, S, Ashcom, JD, Burgess, WH, Migliorini, M, Strickland, DK, Argraves, WS

J Biol Chem 1990
Orthologous Events
Cite Us!