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Additionally, several recessive loss\u2010of\u2010function alleles of <jats:italic>TMEM16E<\/jats:italic> also cause late\u2010onset limb girdle muscular dystrophy. In this study, we found that TMEM16E was rapidly degraded via the proteasome pathway, which was rescued by inhibition of the PI3K pathway and by the chemical chaperone, sodium butyrate. Moreover, TMEM16E<jats:sup>gdd<\/jats:sup> exhibited lower stability than TMEM16E, but showed similar propensity to be rescued. TMEM16E did not exhibit cell surface calcium\u2010dependent chloride channel (CaCC) activity, which was originally identified in TMEM16A and TMEM16B, due to their intracellular vesicle distribution. A putative pore\u2010forming domain of TMEM16E, which shared 39.8% similarity in 98 amino acids with TMEM16A, disrupted CaCC activity of TMEM16A via domain swapping. However, the Thr611Cys mutation in the swapped domain, which mimicked conserved cysteine residues between TMEM16A and TMEM16B, reconstituted CaCC activity. In addition, the GDD\u2010causing cysteine mutation made in TMEM16A drastically altered CaCC activity. Based on these findings, TMEM16E possesses distinct function other than CaCC and another protein\u2010stabilizing machinery toward the TMEM16E and TMEM16E<jats:sup>gdd<\/jats:sup> proteins should be considered for the on\u2010set regulation of their phenotypes in tissues. J. Cell. Physiol. 229: 181\u2013190, 2014. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.24431","type":"journal-article","created":{"date-parts":[[2013,7,11]],"date-time":"2013-07-11T10:35:24Z","timestamp":1373538924000},"page":"181-190","source":"Crossref","is-referenced-by-count":33,"title":["<scp>TMEM<\/scp>16<scp>E<\/scp> (<scp>GDD<\/scp>1) Exhibits Protein Instability and Distinct Characteristics in Chloride Channel\/<scp>P<\/scp>ore Forming Ability"],"prefix":"10.1002","volume":"229","author":[{"given":"Ta To","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Tobiume","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima 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