Table 2.
TMEM16 (Anoctamin) family.
| Anoctamins | Expression | Function | Human disease | KO mouse | Pharmacology | References |
|---|---|---|---|---|---|---|
| TMEM16A (Ano1) | Epithelial tissue, smooth muscle, interstitial cells of Cajal, dorsal root ganglion neurons | ClCa channel, involved in fluid secretion, muscle contraction, gastrointestinal contractility, pain processing | Tumor growth, cystic fibrosis, asthma | Low blood pressure | Inhibitors: CaCCinh-A01, CaCCinh-B01, Niflumic acid (NFA), and NPPB, agonists: INS37217 | Chen et al., 2007; Yang et al., 2008; Huang et al., 2009; Stöhr et al., 2009; Namkung et al., 2011; Jin et al., 2013; Neureither et al., 2017 |
| TMEM16B (Ano2) | Brain (hippocampal and thalamocortical neurons, olfactory bulb, inferior olive, Purkinje cells), retina, muscle | ClCa channel, involved in neuronal excitability, olfactory and sensory signal transduction and smooth muscle contraction | ? | Impaired motor behavior, partial reduction of electrical response to odorants, normal olfaction | Inhibitors: CaCCinh-A01, CaCCinh-B01, Niflumic acid (NFA) agonists: INS37217 | Stöhr et al., 2009; Billig et al., 2011; Huang et al., 2012; Dauner et al., 2013; Zhang et al., 2015, 2017; Ha et al., 2016 |
| TMEM16C (Ano3) | Brain (dorsal root ganglion cells), blood vessels, lung | Phospholipid scrambling, KNa channel regulator | Craniocervical dystonia, tremor, asthma | Impaired endoplasmic reticulum-dependent Ca2+ signaling | Charlesworth et al., 2012; Huang et al., 2013a; Suzuki et al., 2013; Miltgen et al., 2016 | |
| TMEM16E (Ano5) | Muscle, bone, sperm | Phospholipid scrambling | Muscular dystrophy, gnathodiaphyseal dysplasia | Katoh, 2004; Tsutsumi et al., 2004; Gyobu et al., 2016 | ||
| TMEM16F (Ano6) | Blood vessels, endosomes, brain? | Phospholipid scrambling, blood coagulation, SCANCa channel, ClCa channel, involved in membrane excitability | Scott syndrome | Lysosomal storage disease | Suzuki et al., 2010, 2013; Yang et al., 2012; Grubb et al., 2013; Shimizu et al., 2013; Yu et al., 2015 | |
| TMEM16J (Ano9) | Epithelial cells, colonic tissue | Phospholipid scrambling | Colorectal carcinoma | Suzuki et al., 2013; Li et al., 2015 | ||
| TMEM16K (Ano10) | Epithelial cells, cerebellum? | Intracellular protein involved in intracellular Ca2+ signaling, essential for apoptosis | Autosomal recessive cerebellar ataxia | Vermeer et al., 2010; Renaud et al., 2014; Chamard et al., 2016; Mišković et al., 2016; Wanitchakool et al., 2017 |