Acid-sensing ion channel 1 (ASIC1) also known as amiloride-sensitive cation channel 2, neuronal (ACCN2) or brain sodium channel 2 (BNaC2) is a protein that in humans is encoded by the ASIC1 gene. The ASIC1 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in mammals.[1] The cDNA of this gene was first cloned in 1996.[2] The ASIC genes have splicing variants that encode different proteins that are called isoforms.
These genes are mainly expressed in the central and peripheral nervous system.
ASICs can form both homotrimeric (meaning composed of three identical subunits) and heterotrimeric channels.[3][4]
This gene encodes a member of the ASIC/ENaC superfamily of proteins.[5] The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobictransmembrane (TM) regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The TM regions are generally symbolized as TM1 (clone to N-terminus) and TM2 (close to C-terminus).
The pore of the channel through which ions selectively flow from the extracellular side into the cytoplasm is formed by the three TM2 regions of the trimer.[1]
↑ 1.01.1Hanukoglu I (2017). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity filters". FEBS Journal. 284 (4): 525–545. doi:10.1111/febs.13840. PMID27580245.
↑Babinski K, Catarsi S, Biagini G, Séguéla P (Sep 2000). "Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+". The Journal of Biological Chemistry. 275 (37): 28519–25. doi:10.1074/jbc.M004114200. PMID10842183.
↑Bassilana F, Champigny G, Waldmann R, de Weille JR, Heurteaux C, Lazdunski M (Nov 1997). "The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties". The Journal of Biological Chemistry. 272 (46): 28819–22. doi:10.1074/jbc.272.46.28819. PMID9360943.
Bubien JK, Keeton DA, Fuller CM, Gillespie GY, Reddy AT, Mapstone TB, Benos DJ (1999). "Malignant human gliomas express an amiloride-sensitive Na+ conductance". Am. J. Physiol. 276 (6 Pt 1): C1405–10. PMID10362604.
Askwith CC, Cheng C, Ikuma M, Benson C, Price MP, Welsh MJ (2000). "Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels". Neuron. 26 (1): 133–41. doi:10.1016/S0896-6273(00)81144-7. PMID10798398.
Bässler EL, Ngo-Anh TJ, Geisler HS, Ruppersberg JP, Gründer S (2001). "Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b". J. Biol. Chem. 276 (36): 33782–7. doi:10.1074/jbc.M104030200. PMID11448963.
Gunthorpe MJ, Smith GD, Davis JB, Randall AD (2001). "Characterisation of a human acid-sensing ion channel (hASIC1a) endogenously expressed in HEK293 cells". Pflugers Arch. 442 (5): 668–74. doi:10.1007/s004240100584. PMID11512022.
Duggan A, Garcia-Anoveros J, Corey DP (2002). "The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons". J. Biol. Chem. 277 (7): 5203–8. doi:10.1074/jbc.M104748200. PMID11739374.
Ji HL, Jovov B, Fu J, Bishop LR, Mebane HC, Fuller CM, Stanton BA, Benos DJ (2002). "Up-regulation of acid-gated Na(+) channels (ASICs) by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes". J. Biol. Chem. 277 (10): 8395–405. doi:10.1074/jbc.M109465200. PMID11748227.
Poirot O, Vukicevic M, Boesch A, Kellenberger S (2004). "Selective regulation of acid-sensing ion channel 1 by serine proteases". J. Biol. Chem. 279 (37): 38448–57. doi:10.1074/jbc.M407381200. PMID15247234.
Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (2005). "Stomatin modulates gating of acid-sensing ion channels". J. Biol. Chem. 279 (51): 53886–91. doi:10.1074/jbc.M407708200. PMID15471860.