Topological model of TMEM16B. TMEM16B contains eight putative transmembrane segments indicated as gray cylinders. The large N-terminal domain and the C terminus with the conserved PDZ class I binding motif are predicted to be present in the cytoplasmic space. Cysteine residues that are highly conserved among the TMEM16 protein family are encircled. Mutation of one of these cysteines (asterisk) in the TMEM16E paralog causes gnathodiaphyseal dysplasia 1. The positions of four N-linked glycosylation sites in the first and third extracellular loop are indicated; the encircled one is highly conserved among the TMEM16 paralogues.