ANO1

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Protein-coding gene in the species Homo sapiens

title: "ANO1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["chloride-channels"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "general/chloride-channels" source: "https://en.wikipedia.org/wiki/ANO1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Anoctamin-1 (ANO1), also known as Transmembrane member 16A (TMEM16A), is a protein that, in humans, is encoded by the ANO1 gene. Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel and a bicarbonate channel. additionally Anoctamin-1 is apical iodide channel.

It is expressed in smooth muscle, epithelial cells, vomeronasal neurons, olfactory sustentacular cells, and is highly expressed in interstitial cells of Cajal (ICC) throughout the gastrointestinal tract.

Function

ANO1 is a transmembrane protein that functions as a 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

In mice, the functional expression of the ANO1 channel is essential to life, as its absence leads to a premature death due to respiratory collapse.

ANO1 is expressed in the gastrointestinal tract and is highly expressed in interstitial cells of Cajal, where it plays an important role in pacemaker activity, neurotransduction of enteric motor neurotransmitters and regulation of gastrointestinal motility. ANO1 blockers like niflumic acid have been shown to block slow waves, which produce phasic contractions and the major patterns of gastrointestinal motility, such as peristalsis and segmentation. ANO1-knockout mice fail to produce slow waves altogether. Carbachol has been shown to markedly activate the channel due to its effect on release of Ca2+ from intracellular stores. ANO1 activation is necessary for normal function of ICC and generation of normal patterns of activity in smooth muscles of the gastrointestinal tract.

Its overexpression was reported in esophageal squamous cell carcinoma and breast cancer progression.

References

References

  1. "Entrez Gene: anoctamin 1, calcium activated chloride channel".
  2. (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". International Journal of Oncology.
  3. (October 2008). "TMEM16A confers receptor-activated calcium-dependent chloride conductance". Nature.
  4. (January 2013). "Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin". Proceedings of the National Academy of Sciences of the United States of America.
  5. (April 2015). "Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons". The Journal of General Physiology.
  6. (2019-07-01). "TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium". The Journal of General Physiology.
  7. (August 2011). "Anoctamins". Pflügers Archiv: European Journal of Physiology.
  8. (2014). "Activation and inhibition of TMEM16A calcium-activated chloride channels". PLOS ONE.
  9. {{Pfam. (March 2024)
  10. (February 2011). "TMEM16A(a)/anoctamin-1 shares a homodimeric architecture with CLC chloride channels". Molecular & Cellular Proteomics.
  11. (January 2011). "Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A". The Journal of Biological Chemistry.
  12. (May 2011). "Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop". Proceedings of the National Academy of Sciences of the United States of America.
  13. (May 2009). "Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways". The Journal of Biological Chemistry.
  14. (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Experimental Physiology.
  15. (September 2011). "Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal". The Journal of Physiology.
  16. (April 2014). "Structure and function of TMEM16 proteins (anoctamins)". Physiological Reviews.
  17. (January 2009). "Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers". Cancer Biology & Therapy.
  18. (March 2013). "Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling". Proceedings of the National Academy of Sciences of the United States of America.

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chloride-channels