anoctamin-1; transmembrane protein 16A; discovered on gastrointestinal stromal tumors protein 1; oral cancer overexpressed protein 2; tumor amplified & overexpressed sequence 2 (TMEM16A, DOG1, ORAOV2, TAOS2, ANO1)

Function

• Ca+2-activated chloride channel
• role in transepithelial anion transport & smooth muscle contraction
• required for the normal functioning of the interstitial cells of Cajal which generate electrical pacemaker activity in gastrointestinal smooth muscles
• major contributor to basal & stimulated chloride conductance in airway epithelial cells
  • role in tracheal cartilage development
• ATP & calmodulin essential for activation
• channel activity is inhibited by CFTR protein & by chloride inhibitors such as niflumic acid (NFA) & 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
• interacts with CFTR
• interacts with TRPV4 (putative)

Structure

• homodimer
• the region spanning the 5th & 6th transmembrane domains probably forms the pore-forming region
• belongs to the anoctamin family,

Compartment

• cell membrane
• cytoplasmic localization seen in neoplastic cells of head & neck squamous cell carcinoma tumors

Alternative splicing

named isoforms=3

Expression

• broadly expressed with higher levels in liver, skeletal muscle & gastrointestinal muscles

Notes

• the term 'anoctamin' was coined because these channels are anion selective & have 8 (OCT) transmembrane segments*

* not certain that all members of this family are anion channels or have the 8-transmembrane topology

More general terms

• transmembrane 8 protein
• Cl- channel
• glycoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=55107
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:55107
• OMIM: https://mirror.omim.org/entry/610108
• UniProt: http://www.uniprot.org/uniprot/Q5XXA6.html