Anoctamin-1 | ANO-1 | TMEM -16A

Overview:

Anoctamin-1 (ANO1), also known as Transmembrane member 16A (TMEM16A), functions as a calcium-activated chloride channel. Ca²⁺, Sr²⁺, and Ba²⁺ activate the channel in smooth muscle and epithelial cells. ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). ANO1 is essential for chloride secretion from epithelial tissues, and has been shown to be a specific marker for cells of Cajal, the pacemaker cells that control smooth muscle contraction. Anoctamin 1 knockout mice exhibit an altered gastric smooth muscle rhythmic contraction. Research studies have identified Anoctamin 1 as a heat sensor in nociceptive neurons. Heat above 44ºC triggers anoctamin 1-dependent depolarization, contributing to the mediation of thermal nociception.

Data Sheet:

Gene:
ANO1

Human Protein:
UniProt Q5XXA6

Tissue:
ANO-1 is found in smooth muscle and epithelial cells. It is broadly expressed with higher levels in liver, skeletal muscle and gastrointestinal muscles, especially in human interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. Furthermore, Ano-1 is found in nociceptice neurons.

Function/ Application:
Transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.

Pathology:
Frontal Sinus Squamous Cell Carcinoma, Liver Leiomyoma, multiple myeloma, breast carcinoma, oral cancer, gastrointestinal stromal tumor, frontal sinus cancer

Interaction:
Ezrin, radixin, moesin, RhoA, VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c

Modulator:
Niflumic acid (NFA), carbachol, crofelemer, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), tannic acid, fluoxetine, flufenamic acid, talniflumate

Assays:
Patch Clamp: whole cell, intracellular solution exchange, temperature control

Recommended Reviews:

• Huang et al.: International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels(2012) . Pharmacol Rev 64(1):1-15

Transporter classification database:

• 1.A.17.1.1 The plasma membrane Ca2 -activated chloride (IClCa) channel, TMEM16A (Anoctamin 1a; ANO1a)

UniProt:

• Anoctamin-1 (ANO1, Homo sapiens)

IUPHAR/PBS:

• Calcium activated chloride channel