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Description

Anoctamin-1 (UniProt: Q8BHY3, also known as Transmembrane protein 16A, TMEM16A) is encoded by the Ano1 (also known as Tmem16a) gene (Gene ID: 101772) in murine species. Anoctamin-1 is a multi-pass membrane protein that along with TMEMB16B subunit serves as the calcium-activated chloride channels (CaCC). Two isoforms of Anoctamin-1 have been reported that are produced by alternative splicing. It is located in the apical membranes of epithelial cells in exocrine glands and in trachea. Its airway epithelial expression is increased in asthmatics. Hence, its abundance and activity may contribute to mucus secretion and airway hyper-responsiveness in asthma subjects. Anoctamin-1 is reported to be absent from smooth muscle cells, but present in the interstitial cells of Cajal (ICC), the pacemaker cells that control smooth muscle contraction. It acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. ATP and calmodulin are shown to be essential for its activation and the channel activity is inhibited by CFTR protein and by chloride channel inhibitors such as niflumic acid and 4, 4 -diisothiocyanatostilbene-2,2&prime,-disulfonic acid (DIDS). Mice with defective Tmem16a gene display severe tracheomalacia with gaps in the tracheal cartilage rings along the entire length of the trachea and over 90% of mutants die within the first nine days of postnatal life.