Calcium-activated chloride channel

Calcium-activated chloride channel
Symbol CLCA_N
Pfam PF08434
InterPro IPR013642
TCDB 1.A.17
OPM superfamily 517
OPM protein 4wis

The calcium-activated chloride channels (CaCCs),[1] are heterogeneous groups of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells. They include proteins from several structurally different families: chloride channel accessory (CLCA),[2] bestrophin (BEST),[3][4] and anoctamin (ANO or TMEM16) channels[3][4][5][6] ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal, which are proteins which serve as intestinal pacemakers for peristalsis.[5] In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors.[7]

In humans

CaCCs that are known to occur in humans include:


Secrete chloride into lumen


  1. The anoctamins are only expressed in eukaryotes, with 10 members in vertebrates.[6] Although all anoctamins are calcium-activated, not all members of this family are ion channels like ANO1; some are phospholipid scramblases.[6] ANO1 was the first anoctamin discovered, with three research groups independently identifying it in 2008.[6] A single protein homologue to the vertebrate anoctamins has been found in fungi and yeast, Aspergillus fumigatus and Saccharomyces cerevisiae, respsectively.[6]


  1. 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.
  2. "CLCA1 chloride channel accessory 1 [Homo sapiens (human)]". Gene. National Center for Biotechnology Information. 13 January 2015.
  3. 1 2 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.
  4. 1 2 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.
  5. 1 2 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 3272164Freely accessible. PMID 22002868.
  6. 1 2 3 4 5 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.
  7. 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 1383427Freely accessible. PMID 15284223.
  8. 1 2 "Calcium activated chloride channel". IUPHAR/BPS Guide to Pharmacology. Retrieved 7 October 2015. The bestrophins encoded by genes BEST1-4 have a topology more consistent with ion channels [9] and form chloride channels that are activated by physiological concentrations of Ca2+, but whether such activation is direct is not known [9]. However, currents generated by bestrophin over-expression do not resemble native CaCC currents. The evidence for and against bestrophin proteins forming CaCC is critically reviewed by Duran et al. in their 2010 paper [5]. Recently, a new gene family, TMEM16 (anoctamin) consisting of 10 members (TMEM16A-K; anoctamin 1–10) has been identified and there is firm evidence that some of these members form chloride channels [4,10]. TMEM16A (anoctamin 1; Ano 1) produces Ca2+-activated Cl- currents with kinetics similar to native CaCC currents recorded from different cell types [2,18-19,21]. ... There are also reports that TMEM16B (anoctamin 2; Ano 2) supports CaCC activity (e.g.[17]) and in TMEM16B(-/-) mice Ca-activated Cl- currents in the main olfactory epithelium (MOE) and in the vomeronasal organ are virtually absent[1]

External links

This article incorporates text from the public domain Pfam and InterPro IPR013642

This article is issued from Wikipedia - version of the 11/24/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.