ANO1

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Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ANO1 gene.[1][2] Anoctamin-1 is a voltage-sensitive calcium-activated chloride channel that is expressed in smooth muscle and epithelial cells;[3] it is highly expressed in human interstitial cells of Cajal (ICC) throughout the gastrointestinal tract.[4] Changes in ANO1 channel activity directly/positively correlate with ICC activity.[4]

Function

ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel.[5] Ca2+, Sr2+, and Ba2+ activate the channel.[6]

Structure

No atomic resolution structure of this channel has yet been obtained.[7] However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits.[8][9] 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.[10]

Clinical significance

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.[4][11][3] ANO1 blockers like niflumic acid have been shown to block slow waves, which produce motility, in the human intestine.[4][11] ANO1-knockout mice fail to produce slow waves altogether.[4][11] Carbachol has been shown to markedly activate the channel;[4][11] in light of this, it's not surprising that secretory diarrhea is a Carbachol overdose symptom.[12] Crofelemer, an antidiarrhoeal, inhibits this channel.[13][14] Consequently, ANO1 activation is necessary for normal function of the ICC and its generated pacemaker activity in the smooth muscles of the intestine.[4][11]

Its overexpression was reported in esophageal squamous cell carcinoma and breast cancer progression.[15][16]

References

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  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Lua error in package.lua at line 80: module 'strict' not found.
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  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Pfam PF04547; PDB search for PF04547
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 Lua error in package.lua at line 80: module 'strict' not found.
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  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.

Further reading

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