The family of calcium-activated chloride channels (CaCCs), which includes chloride channel accessory (CLCA), bestrophin (BEST), and anoctamin (ANO) channels (also known as the TMEM16 family), have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells. ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal. In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors.
Human calcium-activated chloride channels
- Accessories: CLCA1; CLCA2; CLCA3; CLCA4;
- Anoctamins: ANO1, ANO2, ...
- Anoctamins are only expressed in eukaryotes, with 10 members in vertebrates.
- Though all anoctamins are calcium-activated, not all members of this family are ion channels; some are phospholipid scramblases
- The first anoctamin was described in 2008, by three research groups independently, that being ANO1.
- A single protein homologue to the vertebrate anoctamins has been found in fungi and yeast, Aspergillus fumigatus and Saccharomyces cerevisiae, respsectively.
- Bestrophins: BEST1, BEST2, ...
ANO1 is inhibited by the anti-diarrhoea drug crofelemer and activated by the cholinergic drug, carbachol.
- ^ Hartzell, Criss; Putzler, Ilva; Arreola, Jorge (March 2005). "Calcium-activated Chloride Channels". Annual Review of Physiology 76: 719–58. doi:10.1146/annurev.physiol.67.032003.154341. PMID 15709976.
- ^ "CLCA1 chloride channel accessory 1 [Homo sapiens (human)]". Gene. National Center for Biotechnology Information. 13 January 2015.
- ^ a b Kunzelmann, K; Kongsuphol, P.; Chootip, K. et al. (January 2011). "Role of the Ca2+ -activated Cl- channels bestrophin and anoctamin in epithelial cells". Biological Chemistry 392 (1–2): 125–34. doi:10.1515/BC.2011.010. PMID 21194364.
- ^ a b Kunzelmann, K; Kongsuphol, P; Aldehni, F et al. (October 2009). "Bestrophin and TMEM16-Ca(2+) activated Cl(-) channels with different functions". Cell Calcium 46 (4): 233–41. doi:10.1016/j.ceca.2009.09.003. PMID 19783045.
- ^ a b Sanders, KM; Zhu, MH; Britton, F et al. (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Experimental Physiology 97 (2): 200–6. doi:10.1113/expphysiol.2011.058248. PMC 3272164. PMID 22002868.
- ^ a b c d e Brunner, Janine D.; Lim, Novandy K.; Schenck, Stephen et al. (11 December 2014). "X-ray structure of a calcium-activated TMEM16 lipid scramblase". Nature 516 (7530): 207–12. doi:10.1038/nature13984.
- ^ Evans, SR; Thoreson, WB; Beck, CL (2004). "Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine". Journal of Biological Chemistry 279 (40): 41792–800. doi:10.1074/jbc.M408354200. PMC 1383427. PMID 15284223.
This article incorporates text from the public domain Pfam and InterPro IPR013642