ANO1

Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a is_associated_with::protein that, in humans, is encoded by the ANO1 gene. Anoctamin-1 is a voltage-sensitive is_associated_with::calcium-activated chloride channel that is highly expressed in human is_associated_with::interstitial cells of Cajal (ICC) throughout the is_associated_with::gastrointestinal tract. Changes in ANO1 channel activity directly/positively correlate with ICC activity.

Function
ANO1 is a transmembrane protein that functions as a is_associated_with::calcium-activated chloride channel. Ca2+, Sr2+, and Ba2+ activate the channel.

Structure
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.

Clinical significance
ANO1 is highly expressed in human gastrointestinal is_associated_with::interstitial cells of Cajal and plays an important role in mediating is_associated_with::intestinal motility. ANO1 blockers like is_associated_with::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. is_associated_with::Carbachol has been shown to markedly activate the channel; in light of this, it's not surprising that is_associated_with::explosive secretory diarrhea is a Carbachol overdose symptom. is_associated_with::Crofelemer, an is_associated_with::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.