Biology:ANO1
 Generic protein structure example |
Anoctamin-1 (ANO1) also known as Transmembrane member 16A (TMEM16A) is a protein that, in humans, is encoded by the ANO1 gene.[1][2] Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel[3] and a bicarbonate channel.[4] additionally Anoctamin-1 is apical iodide channel.
It is expressed in smooth muscle, epithelial cells,[5] vomeronasal neurons,[6] olfactory sustentacular cells,[7] and is highly expressed in interstitial cells of Cajal (ICC) throughout the gastrointestinal tract.[8]
Function
ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel.[9] Ca2+, Sr2+, and Ba2+ activate the channel.[10]
Structure
No atomic resolution structure of this channel has yet been obtained.[11] However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits.[12][13] 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.[14]
Clinical significance
In mice, the functional expression of the ANO1 channel is essential to life, as its absence leads to a premature death due to respiratory collapse.[15]
ANO1 is expressed in the gastrointestinal tract and is highly expressed in interstitial cells of Cajal, where it plays an important role in pacemaker activity, neurotransduction of enteric motor neurotransmitters and regulation of gastrointestinal motility.[8][16][5] ANO1 blockers like niflumic acid have been shown to block slow waves, which produce phasic contractions and the major patterns of gastrointestinal motility, such as peristalsis and segmentation.[8][16] ANO1-knockout mice fail to produce slow waves altogether.[8][16] Carbachol has been shown to markedly activate the channel due to its effect on release of Ca2+ from intracellular stores.[8][16] ANO1 activation is necessary for normal function of ICC and generation of normal patterns of activity in smooth muscles of the gastrointestinal tract.[8][16]
Its overexpression was reported in esophageal squamous cell carcinoma and breast cancer progression.[17][18]
References
- ↑ "Entrez Gene: anoctamin 1, calcium activated chloride channel". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55107.
- ↑ "FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products". International Journal of Oncology 22 (6): 1375–81. June 2003. doi:10.3892/ijo.22.6.1375. PMID 12739008.
- ↑ "TMEM16A confers receptor-activated calcium-dependent chloride conductance". Nature 455 (7217): 1210–5. October 2008. doi:10.1038/nature07313. PMID 18724360. Bibcode: 2008Natur.455.1210Y.
- ↑ "Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin". Proceedings of the National Academy of Sciences of the United States of America 110 (1): 360–5. January 2013. doi:10.1073/pnas.1211594110. PMID 23248295. Bibcode: 2013PNAS..110..360J.
- ↑ 5.0 5.1 "Structure and function of TMEM16 proteins (anoctamins)". Physiological Reviews 94 (2): 419–59. April 2014. doi:10.1152/physrev.00039.2011. PMID 24692353.
- ↑ "Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons". The Journal of General Physiology 145 (4): 285–301. April 2015. doi:10.1085/jgp.201411348. PMID 25779870.
- ↑ Henriques, Tiago; Agostinelli, Emilio; Hernandez-Clavijo, Andres; Maurya, Devendra Kumar; Rock, Jason R.; Harfe, Brian D.; Menini, Anna; Pifferi, Simone (2019-07-01). "TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium". The Journal of General Physiology 151 (7): 954–966. doi:10.1085/jgp.201812310. ISSN 0022-1295. PMID 31048412.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 "Anoctamins and gastrointestinal smooth muscle excitability". Experimental Physiology 97 (2): 200–6. February 2012. doi:10.1113/expphysiol.2011.058248. PMID 22002868.
- ↑ "Anoctamins". Pflügers Archiv 462 (2): 195–208. August 2011. doi:10.1007/s00424-011-0975-9. PMID 21607626.
- ↑ "Activation and inhibition of TMEM16A calcium-activated chloride channels". PLOS ONE 9 (1): e86734. 2014. doi:10.1371/journal.pone.0086734. PMID 24489780. Bibcode: 2014PLoSO...986734N.
- ↑ Pfam PF04547; PDB search for PF04547
- ↑ "TMEM16A(a)/anoctamin-1 shares a homodimeric architecture with CLC chloride channels". Molecular & Cellular Proteomics 10 (2): S1–S11. February 2011. doi:10.1074/mcp.M110.004697. PMID 20974900.
- ↑ "Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A". The Journal of Biological Chemistry 286 (2): 1381–8. January 2011. doi:10.1074/jbc.M110.174847. PMID 21056985.
- ↑ "Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop". Proceedings of the National Academy of Sciences of the United States of America 108 (21): 8891–6. May 2011. doi:10.1073/pnas.1102147108. PMID 21555582. Bibcode: 2011PNAS..108.8891X.
- ↑ "Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways". The Journal of Biological Chemistry 284 (22): 14875–80. May 2009. doi:10.1074/jbc.C109.000869. PMID 19363029.
- ↑ 16.0 16.1 16.2 16.3 16.4 "Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal". The Journal of Physiology 589 (Pt 18): 4565–82. September 2011. doi:10.1113/jphysiol.2011.211094. PMID 21768263.
- ↑ "Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers". Cancer Biology & Therapy 8 (1): 36–46. January 2009. doi:10.4161/cbt.8.1.7090. PMID 18981721.
- ↑ "Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling". Proceedings of the National Academy of Sciences of the United States of America 110 (11): E1026-34. March 2013. doi:10.1073/pnas.1217072110. PMID 23431153.
Further reading
- "Mutation assay of the novel gene DOG1 in gastrointestinal stromal tumors (GISTs)". Journal of Gastroenterology 43 (7): 531–7. 2008. doi:10.1007/s00535-008-2195-4. PMID 18648740.
- "Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes". The American Journal of Surgical Pathology 33 (3): 437–46. March 2009. doi:10.1097/PAS.0b013e318186b158. PMID 19011564.
- "Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract". American Journal of Physiology. Gastrointestinal and Liver Physiology 296 (6): G1370-81. June 2009. doi:10.1152/ajpgi.00074.2009. PMID 19372102.
- "TMEM16A confers receptor-activated calcium-dependent chloride conductance". Nature 455 (7217): 1210–5. October 2008. doi:10.1038/nature07313. PMID 18724360. Bibcode: 2008Natur.455.1210Y.
- "Identification and characterization of TMEM16E and TMEM16F genes in silico". International Journal of Oncology 24 (5): 1345–9. May 2004. doi:10.3892/ijo.24.5.1345. PMID 15067359.
- "Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels". The Journal of Physiology 587 (Pt 10): 2127–39. May 2009. doi:10.1113/jphysiol.2008.163709. PMID 19015192.
External links
- Human ANO1 genome location and ANO1 gene details page in the UCSC Genome Browser.
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