1.A.17.1.18
TMEM16 of 735 aas and 10 TMSs.  Operates as a Ca²⁺-activated lipid scramblase (Wang et al. 2018). Each subunit of the homodimer contains a hydrophilic membrane-traversing cavity that is exposed to the lipid bilayer as a potential site of catalysis. This cavity harbours a conserved Ca²⁺-binding site, located within the hydrophobic core of the membrane. Mutations of residues involved in Ca²⁺ coordination affect both lipid scrambling in N. haematococca TMEM16 and ion conduction in the Cl^- channel of TMEM16A. The structure reveals the general architecture of the family and its mode of Ca²⁺ activation (Brunner et al. 2014). While the cytoplasmic portion of the protein is important for function, it does not appear to regulate scramblase activity via a detectable conformational change (Andra et al. 2018). Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca²⁺-bound nhTMEM16 (Khelashvili et al. 2019) (see family description). Permeation of potassium ions through the lipid scrambling path of nhTMEM16 has been documented (Cheng et al. 2022). Citral amide derivatives possess antifungal activity against Rhizoctonia. solani (Zhang et al. 2024).