ANO2 Membrane Protein Introduction

Introduction of ANO2

ANO2 (Anoctamin-2), also known as Transmembrane member 16B (TMEM16B), is a protein that, in humans, is encoded by the ANO2 gene. It functions as Ca²⁺-activated Cl⁻ channels (CaCCs), a type of ion channel that plays important functions such as transepithelial ion transport, smooth muscle contraction, olfaction, phototransduction, nociception, and control of neuronal excitability.

Basic Information of ANO2
Protein Name	Anoctamin-2
Gene Name	ANO2
Aliases	C12orf3, TMEM16B
Organism	Homo sapiens (Human)
UniProt ID	Q9NQ90
Transmembrane Times	8
Length (aa)	1003
Sequence	MATPGPRDIPLLPGSPRRLSPQAGSRGGQGPKHGQQCLKMPGPRAPGLQGGSNRDPGQPCGGESTRSSSVINNYLDANEPVSLEARLSRMHFHDSQRKVDYVLAYHYRKRGVHLAQGFPGHSLAIVSNGETGKEPHAGGPGDIELGPLDALEEERKEQREEFEHNLMEAGLELEKDLENKSQGSIFVRIHAPWQVLAREAEFLKIKVPTKKEMYEIKAGGSIAKKFSAALQKLSSHLQPRVPEHSNNKMKNLSYPFSREKMYLYNIQEKDTFFDNATRSRIVHEILKRTACSRANNTMGINSLIANNIYEAAYPLHDGEYDSPEDDMNDRKLLYQEWARYGVFYKFQPIDLIRKYFGEKIGLYFAWLGLYTSFLIPSSVIGVIVFLYGCATIEEDIPSREMCDQQNAFTMCPLCDKSCDYWNLSSACGTAQASHLFDNPATVFFSIFMALWATMFLENWKRLQMRLGYFWDLTGIEEEEERAQEHSRPEYETKVREKMLKESNQSAVQKLETNTTECGDEDDEDKLTWKDRFPGYLMNFASILFMIALTFSIVFGVIVYRITTAAALSLNKATRSNVRVTVTATAVIINLVVILILDEIYGAVAKWLTKIEVPKTEQTFEERLILKAFLLKFVNAYSPIFYVAFFKGRFVGRPGSYVYVFDGYRMEECAPGGCLMELCIQLSIIMLGKQLIQNNIFEIGVPKLKKLFRKLKDETEAGETDSAHSKHPEQWDLDYSLEPYTGLTPEYMEMIIQFGFVTLFVASFPLAPVFALLNNVIEVRLDAKKFVTELRRPDAVRTKDIGIWFDILSGIGKFSVISNAFVIAITSDFIPRLVYQYSYSHNGTLHGFVNHTLSFFNVSQLKEGTQPENSQFDQEVQFCRFKDYREPPWAPNPYEFSKQYWFILSARLAFVIIFQNLVMFLSVLVDWMIPDIPTDISDQIKKEKSLLVDFFLKEEHEKLKLMDEPALRSPGGGDRSRSRAASSAPSGQSQLGSMMSSGSQHTNV

Function of ANO2 Membrane Protein

As a calcium-activated chloride channel, ANO2 may play a role in olfactory signal transduction. Odorant molecules bind to odor-sensing receptors (OSRs), leading to an increase in calcium entry that activates CaCC current which amplifies the depolarization of the OSR cells. ANO2 seems to be the underlying chloride channel involved in this process. In addition, ANO2 may mediate light perception amplification in the retina. It’s also identified as an autoimmune target found in multiple sclerosis. Furthermore, ANO2 has been identified as an autoimmune target in multiple sclerosis (MS) and the pathogenic role of ANO2 autoantibodies in MS has been revealed.

Fig.1 TMEM16A and TMEM16B function in neurons. (Pedemonte, 2014)

Application of ANO2 Membrane Protein in Literature

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 discusses the physiological implications of Ca²⁺-dependent phospholipid scrambling, the extracellular vesicles associated with this activity, and the roles of ANOs in these processes.
Ayoglu B., et al. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proc Natl Acad Sci U S A. 2016, 113(8):2188-93. PubMed ID: 26862169

This article demonstrates that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.
Pedemonte N and Galietta L.J. Structure and function of TMEM16 proteins (anoctamins). Physiol Rev. 2014, 94(2):419-59. PubMed ID: 24692353

This study suggests that dual function is an ancestral characteristic of TMEM16 proteins and that some members, such as TMEM16A and TMEM16B/ANO2, have evolved to a pure channel function.
Stephan A.B., et al. ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification. Proc Natl Acad Sci U S A. 2009, 106(28):11776-81. PubMed ID: 19561302

This article proposes that ANO2 constitutes the olfactory calcium-activated chloride channel.
Tian Y., et al. Anoctamins are a family of Ca²⁺-activated Cl^- channels. J Cell Sci. 2012, 125(Pt 21):4991-8. PubMed ID: 22946059

This article demonstrates that anoctamins are a family of Ca(2+)-activated Cl(-) channels, which also induce permeability for cations. They may operate as Cl(-) channels located in the plasma membrane or in intracellular compartments.

ANO2 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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