8.A.77.1.2
Disintegrin or ADAM17, a metaloprotease (sheddase) of 824 aas and 2 TMSs near the protein's N- and C-termini.  Sheds many membrane-bound proteins, especially receptors, with a preference for acidic amino acids at the P1' position. Cleaves membrane proteins and modifies their activities while releasing the proteotytic products into the external medium (Pupovac and Sluyter 2016).  ANO6 (TC# 1.A.17.1.4), by virtue of its scramblase activity, may play a role as a regulator of the ADAM-network in the plasma membrane. It is responsible for the proteolytic release of several cell-surface proteins, including the p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (Thathiah et al. 2003). It acts as an activator of the Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (Boskovski et al. 2013). Blocking ADAM17 as an immune modulator together with appropriate antibiotics provides a therapeutic avenue for sepsis treatment (Mishra et al. 2020). ADAM17 in the proximal kidney tubule impacts on glomerular inflammation and fibrosis (Palau et al. 2021).  An ADAM17 selective inhibitor promotes glucose uptake by activating AMPK (Toma et al. 2024).