ANO8 Membrane Protein Introduction

Introduction of ANO8

ANO8 is also known as Anoctamin-8, transmembrane protein 16H and TMEM16H. It belongs to the transmembrane protein 16 (TMEM16) family which is a large family of membrane proteins and consists of ten members (TMEM16A, B, C, D, E, F, G, H, J and K) in mammals. The TMEM16 family of proteins has been identified as Ca²⁺ activated Cl⁻ channels and all homologues might share a similar function. Meanwhile, the predicted structure of ANO8 indicates that ANO8 have eight transmembrane domains.

Basic Information of ANO8
Protein Name	Anoctamin-8
Gene Name	ANO8
Aliases	Transmembrane protein 16H, TMEM16H
Organism	Homo sapiens (Human)
UniProt ID	Q9HCE9
Transmembrane Times	8
Length (aa)	1232
Sequence	MAEAASGAGGTSLEGERGKRPPPEGEPAAPASGVLDKLFGKRLLQAGRYLVSHKAWMKTVPTENCDVLMTFPDTTDDHTLLWLLNHIRVGIPELIVQVRHHRHTRAYAFFVTATYESLLRGADELGLRKAVKAEFGGGTRGFSCEEDFIYENVESELRFFTSQERQSIIRFWLQNLRAKQGEALHNVRFLEDQPIIPELAARGIIQQVFPVHEQRILNRLMKSWVQAVCENQPLDDICDYFGVKIAMYFAWLGFYTSAMVYPAVFGSVLYTFTEADQTSRDVSCVVFALFNVIWSTLFLEEWKRRGAELAYKWGTLDSPGEAVEEPRPQFRGVRRISPITRAEEFYYPPWKRLLFQLLVSLPLCLACLVCVFLLMLGCFQLQELVLSVKGLPRLARFLPKVMLALLVSVSAEGYKKLAIWLNDMENYRLESAYEKHLIIKVVLFQFVNSYLSLFYIGFYLKDMERLKEMLATLLITRQFLNVREVLQQPHLYRRLGRGELGLRAVWELARALLGLLSLRRPAPRRLEPQADEGGGGGSGGGGRRCLSGGCGAPEEEEEAALVERRRAGEGGEEGDGPPGGKEEDEDDEEEEDEEEEEDEEEGEEGGLLDCGLRLKKVSFAERGAGRRRPGPSPEALLEEGSPTMVEKGLEPGVFTLAEEDDEAEGAPGSPEREPPAILFRRAGGEGRDQGPDGGPDPEPGSNSDSTRRQRRQNRSSWIDPPEEEHSPQLTQAELESCMKKYEDTFQDYQEMFVQFGYVVLFSSAFPLAALCALVNNLIEIRSDAFKLCTGLQRPFGQRVESIGQWQKVMEAMGVLAIVVNCYLIGQCGQLQRLFPWLSPEAAIVSVVVLEHFALLLKYLIHVAIPDIPGWVAEEMAKLEYQRREAFKRHERQAQHRYQQQQRRRREEEERQRHAEHHARREHDSGGREEARAEGSGLDPATSSEKASAKAKGSTAGGHGPERPKRPGSLLAPNNVMKLKQIIPLQGKFLSSGATSSLAAAGAGATTRPPPAQSPTGSDTRLPAFLSFKFLKSPETRRDSERSHSPPKAFHAGKLFPFGGTRAEPGSNGAGGQARPDGTPSSGSSRVQRSGPVDEALAEELEAPRPEEEGSGTALAPVGAPALRTRRSRSPAPPPPMPLPRPPTPPAGCWQWDGPWGCGGEGAAPRQALAAAECPPCAMAGPPPAPQPLPGDASFYSLPPPPLPPTSDPLETPAPSPSPSPSPQAVCWPSGWH

Function of ANO8 Membrane Protein

ANO8 belongs to the TMEM16 family, which functions as Ca²⁺-activated Cl⁻ channels. ANO8 mRNA is expressed in all electrolyte transporting tissues like trachea, pancreas, colon, salivary gland, prostate tissue and the thyroid gland. Compared with ANO1, expression of the other epithelial anoctamins ANO8 can be induced by very little Ca²⁺ (ATP)-activated Cl- conductance. In cells expressing ANO8, whole-cell currents of variable magnitudes are activated by ATP and the activation of ANO8 by ATP can induce the increase of the intracellular Ca²⁺. The increase of Ca²⁺ may not only activate the Cl- channel, but also trigger inhibition of anoctamins via CAMKII, which may actually counteract further activation. CAMKII is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The inhibition of anoctamins via CAMKII suggests that ANO8 is involved in the signaling pathway of CAMKII. However, the detailed mechanism remains to be solved.

Fig.1 Possible structure of ANO8 membrane protein (Andra, 2018).

Application of ANO8 Membrane Protein in Literature

Katoh, M., et al. "Identification and characterization of TMEM16H gene in silico". International Journal of Molecular Medicine. 2005, 15.2: 353-358. PubMed ID: 15647853

This paper reports the identification and characterization of the ANO8 gene as well as on the molecular evolution of ANO8 for the first time.
Hartzell H.C., et al. Anoctamin/TMEM16 family members are Ca²⁺-activated Cl⁻ channels. The Journal of Physiology. 2009, 587(Pt 10):2127-2139. PubMed ID: 19015192

The article reviews that the newly described anoctamin family and some members of this family are up-regulated in a number of tumors and functional deficiency in others is linked to developmental defects.
Milenkovic V.M., et al. Evolution and functional divergence of the anoctamin family of membrane proteins. BMC Evol. Biol. 2010, 10(1):319. PubMed ID: 20964844

This article focuses on the anoctamin protein paralogs evolved from several gene duplication events followed by functional divergence of vertebrate anoctamins. The results of this article suggest that anoctamins have evolved by a series of duplication events, and that they are constrained by purifying selection.
Tian Y., et al. Anoctamins are a family of Ca²⁺ activated Cl⁻ channels. J. Cell Sci. 2012, 125(21):4991. PubMed ID: 22946059

The results of this article demonstrate that anoctamins are a family of Ca²⁺ activated Cl⁻ channels and increase our understanding of the physiological significance of anoctamins and their role in disease.
Schreiber R., et al. Expression and Function of Epithelial Anoctamins. J. Biol. Chem. 2010, 285(10):7838-7845. PubMed ID: 20056604

The authors of this article analyze the expression pattern of all ten members (ANO1-ANO10) in a broad range of murine tissues and detected predominant expression of ANO1, 6, 7, 8, 9, 10 in epithelial tissues, while ANO2, 3, 4, 5 are common in neuronal and muscle tissues.

ANO8 Preparation Options

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Reference

Andra K K., et al. (2018). Structural mapping of fluorescently-tagged, functional nhTMEM16 scramblase in a lipid bilayer. J. Biol. Chem.

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