Membrane-proximal domain of a disintegrin and metalloprotease 17 (ADAM17)
ADAM17 is a multi-domain protein that acts as a sheddase; is involved in the cleavage and release of the soluble ectodomain of tumor necrosis factor alpha from the cell surface and in the trans-Golgi network, as well as in the release of various other targets such as cytokines and cell adhesion molecules. This links ADAM17 to a variety of biological processes, including cellular differentiation and the progression of cancer. It was shown that the enzymatic activity of ADAM17 is regulated via a protein-disulfide isomerase (PDI). Specifically, the disulfide bridges within a CxxC motif of the membrane-proximal domain (MPD) are isomerized by PDI; the conversion triggers a conformational change between a closed and an opened form of the MPD, which may constitute a molecular switch that triggers the shedding activity of ADAM17.
Jiyao W et al.(2023). "The conserved domain database in 2023.",