No atomic resolution structure of this channel has yet been obtained. However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits. From hydropathy plotting, each subunit is thought to encode a molecule with eight transmembrane domains, with a reentrant loop between the fifth and sixth transmembrane domains. The reentrant loop is thought to be a P loop-like structure responsible for the ion selectivity of the protein.
ANO1 is expressed in the human gastrointestinal epithelium and is highly expressed in the gastrointestinal interstitial cells of Cajal, where it plays an important role in epithelial chloride secretion mediating intestinal motility. ANO1 blockers like niflumic acid have been shown to block slow waves, which produce motility, in the human intestine. ANO1-knockout mice fail to produce slow waves altogether.Carbachol has been shown to markedly activate the channel; in light of this, it's not surprising that secretory diarrhea is a Carbachol overdose symptom.Crofelemer, an antidiarrhoeal, inhibits this channel. Consequently, ANO1 activation is necessary for normal function of the ICC and its generated pacemaker activity in the smooth muscles of the intestine.
Its overexpression was reported in esophageal squamous cell carcinoma and breast cancer progression.
^Katoh M, Katoh M (June 2003). "FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products". Int. J. Oncol.22 (6): 1375–81. doi:10.3892/ijo.22.6.1375. PMID12739008.
Miwa S, Nakajima T, Murai Y, et al. (2008). "Mutation assay of the novel gene DOG1 in gastrointestinal stromal tumors (GISTs)". J. Gastroenterol.43 (7): 531–7. doi:10.1007/s00535-008-2195-4. PMID18648740.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet.36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Liegl B, Hornick JL, Corless CL, Fletcher CD (2009). "Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes". Am. J. Surg. Pathol.33 (3): 437–46. doi:10.1097/PAS.0b013e318186b158. PMID19011564.