ANO1 Membrane Protein Introduction

Introduction of ANO1

ANO1 (Anoctamin-1), also known as Transmembrane member 16A (TMEM16A), is a protein that, in humans, is encoded by the ANO1 gene. Anoctamin-1 is a voltage-sensitive calcium-activated chloride channel that is expressed in smooth muscle and epithelial cells. In addition, it is highly expressed in human interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. Changes in ANO1 channel activity is directly/positively correlated with ICC activity.

Basic Information of ANO1
Protein Name	Anoctamin-1
Gene Name	ANO1
Aliases	DOG1, ORAOV2, TAOS2, TMEM16A
Organism	Homo sapiens (Human)
UniProt ID	Q5XXA6
Transmembrane Times	8
Length (aa)	986
Sequence	MRVNEKYSTLPAEDRSVHIINICAIEDIGYLPSEGTLLNSLSVDPDAECKYGLYFRDGRRKVDYILVYHHKRPSGNRTLVRRVQHSDTPSGARSVKQDHPLPGKGASLDAGSGEPPMDYHEDDKRFRREEYEGNLLEAGLELERDEDTKIHGVGFVKIHAPWNVLCREAEFLKLKMPTKKMYHINETRGLLKKINSVLQKITDPIQPKVAEHRPQTMKRLSYPFSREKQHLFDLSDKDSFFDSKTRSTIVYEILKRTTCTKAKYSMGITSLLANGVYAAAYPLHDGDYNGENVEFNDRKLLYEEWARYGVFYKYQPIDLVRKYFGEKIGLYFAWLGVYTQMLIPASIVGIIVFLYGCATMDENIPSMEMCDQRHNITMCPLCDKTCSYWKMSSACATARASHLFDNPATVFFSVFMALWAATFMEHWKRKQMRLNYRWDLTGFEEEEEAVKDHPRAEYEARVLEKSLKKESRNKEKRRHIPEESTNKWKQRVKTAMAGVKLTDKVKLTWRDRFPAYLTNLVSIIFMIAVTFAIVLGVIIYRISMAAALAMNSSPSVRSNIRVTVTATAVIINLVVIILLDEVYGCIARWLTKIEVPKTEKSFEERLIFKAFLLKFVNSYTPIFYVAFFKGRFVGRPGDYVYIFRSFRMEECAPGGCLMELCIQLSIIMLGKQLIQNNLFEIGIPKMKKLIRYLKLKQQSPPDHEECVKRKQRYEVDYNLEPFAGLTPEYMEMIIQFGFVTLFVASFPLAPLFALLNNIIEIRLDAKKFVTELRRPVAVRAKDIGIWYNILRGIGKLAVIINAFVISFTSDFIPRLVYLYMYSKNGTMHGFVNHTLSSFNVSDFQNGTAPNDPLDLGYEVQICRYKDYREPPWSENKYDISKDFWAVLAARLAFVIVFQNLVMFMSDFVDWVIPDIPKDISQQIHKEKVLMVELFMREEQDKQQLLETWMEKERQKDEPPCNHHNTKACPDSLGSPAPSHAYHGGVL

Function of ANO1 Membrane Protein

ANO1 (Anoctamin-1), is a calcium-activated chloride channel (CaCC) which plays a role in transepithelial anion transport and smooth muscle contraction. It is documented that the changes of ANO1 activity are directly/positively correlated with interstitial cells of Cajal (ICC) activity. It is required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Furthermore, ANO1 acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.

Fig.1 Structure-Function of ANO1/TMEM16A. (Pedemonte, 2014)

Application of ANO1 Membrane Protein in Literature

Sonneville F., et.al. MicroRNA-9 downregulates the ANO1 chloride channel and contributes to cystic fibrosis lung pathology. Nat Commun. 2017, 8(1):710. PubMed ID: 28955034

Anoctamin 1 (ANO1/TMEM16A) was identified as the major Ca²⁺-activated Cl^- channel in airway epithelial cells, and the article demonstrated that downregulation of the anoctamin 1 channel in cystic fibrosis patients contributed to disease severity via an unknown mechanism. The authors showed that microRNA-9 targets anoctamin 1 and that inhibiting this interaction improved mucus dynamics in mouse models.
Godse N.R., et.al. TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression. Clin Cancer Res. 2017, 23(23):7324-7332. PubMed ID: 28899969

This article implicated that TMEM16A can be regarded as a contributor to tumor progression by limiting apoptosis and as a potential biomarker of more aggressive disease.
Duvvuri U. ANO1 plays a critical role in prostatic hyperplasia. Proc Natl Acad Sci U S A. 2015, 112(31):9506-7. PubMed ID: 26216998

This study indicated that Anoctamin 1 (TMEM16A) was essential for testosterone-induced prostate hyperplasia.
Cha J.Y., et.al. Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia. Proc Natl Acad Sci U S A. 2015, 112(31):9722-7. PubMed ID: 26153424

This article concluded that ANO1 was essential for the development of prostate hyperplasia and was a potential target for the treatment of BPH.
Whitlock J.M and Hartzell H.C. Anoctamins/TMEM16 Proteins: Chloride Channels Flirting with Lipids and Extracellular Vesicles. Annu Rev Physiol. 2017, 79:119-143. PubMed ID: 27860832

This article discussed the physiological implications of Ca²⁺-dependent phospholipid scrambling, the extracellular vesicles associated with this activity, and the roles of ANOs in these processes.

ANO1 Preparation Options

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Reference

Pedemonte N and Galietta L J. (2014). Structure and function of TMEM16 proteins (anoctamins). Physiol Rev. 94(2):419-59.

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