ANO1


Description

The ANO1 (anoctamin 1) is a protein-coding gene located on chromosome 11.

Anoctamin-1 (ANO1), also known as Transmembrane member 16A (TMEM16A), is a protein encoded by the ANO1 gene in humans. ANO1 is a voltage-gated calcium-activated anion channel, acting as a chloride channel and a bicarbonate channel. It is also an apical iodide channel. ANO1 is expressed in smooth muscle, epithelial cells, vomeronasal neurons, olfactory sustentacular cells, and is highly expressed in interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel. Ca2+, Sr2+, and Ba2+ activate the channel. No atomic resolution structure of this channel has yet been obtained. However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits. From hydropathy plotting, each subunit is thought to encode a molecule with eight transmembrane domains, with a reentrant loop between the fifth and sixth transmembrane domains. The reentrant loop is thought to be a P loop-like structure responsible for the ion selectivity of the protein.

ANO1, also known as calcium-activated chloride channel (CaCC), plays a crucial role in various physiological processes, including:

  • Transepithelial anion transport and smooth muscle contraction.
  • Normal functioning of interstitial cells of Cajal (ICCs), which generate electrical pacemaker activity in the gastrointestinal system.
  • Chloride conductance in airway epithelial cells, contributing to tracheal cartilage development.
  • Activation of CFTR by enhancing endoplasmic reticulum Ca(2+) store release and facilitating CFTR membrane expression.
  • Basal and ATP-dependent mucus secretion in airways and intestines, likely through exocytosis of mucus-filled granules by regulating Ca(2+) in an apical signaling compartment.
  • Airway mucus expression induced by interleukins IL3 and IL8, and by the asthma-associated protein CLCA1. It is involved in the expression of mucin MUC5AC, although this role has been contested in another study.
  • Propagation of Ca(2+) waves in the cochlea's Kolliker's organ and contributes to the refinement of auditory brainstem circuitries before hearing onset.
  • Modulating spontaneous firing patterns in vomeronasal sensory neurons, both in the absence and presence of pheromone-induced activity.
  • Calcium-activated chloride channel activity in type I taste cells of the vallate papillae.
  • Heat sensing in nociceptive neurons.
  • Mediating non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-dependent itching in dorsal root ganglion neurons, acting as a downstream effector of MRGPRs.
  • Ca(2+)-dependent process extension of radial glial cells in the developing brain.
  • Calcium-activated chloride secretion in human sweat gland epithelial cells. It shows increased basal chloride permeability and decreased Ca(2+)-induced chloride permeability.
  • Increased sensitivity to intracellular Ca(2+) in its function as a calcium-activated chloride channel (CaCC).

ANO1 is also known as DOG1, INDMS, MYMY7, ORAOV2, TAOS2, TMEM16A.

Associated Diseases



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