ASIC2 explained

Acid-sensing ion channel 2 (ASIC2) also known as amiloride-sensitive cation channel 1, neuronal (ACCN1) or brain sodium channel 1 (BNaC1) is a protein that in humans is encoded by the ASIC2 gene. The ASIC2 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] [3] [4] [5]} 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.^{[6] [7]}

Structure and function

This gene encodes a member of the ASIC/ENaC superfamily of proteins.^[8] The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane (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.

Further reading

• Duggan A, Garcia-Anoveros J, Corey DP . 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 . The Journal of Biological Chemistry . 277 . 7 . 5203–8 . Feb 2002 . 11739374 . 10.1074/jbc.M104748200 . free .
• Hruska-Hageman AM, Wemmie JA, Price MP, Welsh MJ . Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel) . The Biochemical Journal . 361 . Pt 3 . 443–50 . Feb 2002 . 11802773 . 1222326 . 10.1042/0264-6021:3610443 .
• Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ . Stomatin modulates gating of acid-sensing ion channels . The Journal of Biological Chemistry . 279 . 51 . 53886–91 . Dec 2004 . 15471860 . 10.1074/jbc.M407708200 . free .
• Saugstad JA, Roberts JA, Dong J, Zeitouni S, Evans RJ . Analysis of the membrane topology of the acid-sensing ion channel 2a . The Journal of Biological Chemistry . 279 . 53 . 55514–9 . Dec 2004 . 15504740 . 2928846 . 10.1074/jbc.M411849200 . free .
• Vila-Carriles WH, Kovacs GG, Jovov B, Zhou ZH, Pahwa AK, Colby G, Esimai O, Gillespie GY, Mapstone TB, Markert JM, Fuller CM, Bubien JK, Benos DJ . Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells . The Journal of Biological Chemistry . 281 . 28 . 19220–32 . Jul 2006 . 16704974 . 10.1074/jbc.M603100200 . free .
• Chai S, Li M, Lan J, Xiong ZG, Saugstad JA, Simon RP . A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a . The Journal of Biological Chemistry . 282 . 31 . 22668–77 . Aug 2007 . 17548344 . 10.1074/jbc.M703624200 . 3799797 . free .
• Joch M, Ase AR, Chen CX, MacDonald PA, Kontogiannea M, Corera AT, Brice A, Séguéla P, Fon EA . Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels . Molecular Biology of the Cell . 18 . 8 . 3105–18 . Aug 2007 . 17553932 . 1949385 . 10.1091/mbc.E05-11-1027 .

Notes and References

1. Hanukoglu I . ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity filters . FEBS Journal . 284 . 4 . 525–545 . 2017 . 27580245 . 10.1111/febs.13840 . 24402104 .
2. Waldmann R, Voilley N, Mattéï MG, Lazdunski M . The human degenerin MDEG, an amiloride-sensitive neuronal cation channel, is localized on chromosome 17q11.2-17q12 close to the microsatellite D17S798 . Genomics . 37 . 2 . 269–70 . Oct 1996 . 8921408 . 10.1006/geno.1996.0558 .
3. Price MP, Snyder PM, Welsh MJ . Cloning and expression of a novel human brain Na+ channel . The Journal of Biological Chemistry . 271 . 14 . 7879–82 . Apr 1996 . 8626462 . 10.1074/jbc.271.14.7879 . free .
4. Waldmann R, Champigny G, Voilley N, Lauritzen I, Lazdunski M . The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans . The Journal of Biological Chemistry . 271 . 18 . 10433–6 . May 1996 . 8631835 . 10.1074/jbc.271.18.10433 . free .
5. García-Añoveros J, Derfler B, Neville-Golden J, Hyman BT, Corey DP . BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels . Proceedings of the National Academy of Sciences of the United States of America . 94 . 4 . 1459–64 . Feb 1997 . 9037075 . 19813 . 10.1073/pnas.94.4.1459 . 1997PNAS...94.1459G . free .
6. Babinski K, Catarsi S, Biagini G, Séguéla P . Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+ . The Journal of Biological Chemistry . 275 . 37 . 28519–25 . Sep 2000 . 10842183 . 10.1074/jbc.M004114200 . free . 11380/304669 . free .
7. Bassilana F, Champigny G, Waldmann R, de Weille JR, Heurteaux C, Lazdunski M . 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 . Nov 1997 . 9360943 . 10.1074/jbc.272.46.28819 . free .
8. Hanukoglu I, Hanukoglu A . Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. . Gene . 579 . 2 . 95–132 . Jan 2016 . 26772908 . 10.1016/j.gene.2015.12.061 . 4756657.