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Gene Review

ASIC2  -  acid sensing (proton gated) ion channel 2

Homo sapiens

Synonyms: ACCN, ACCN1, ASIC2a, Acid-sensing ion channel 2, Amiloride-sensitive brain sodium channel, ...
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Disease relevance of ACCN1

  • Localization of the 17q breakpoint of a constitutional 1;17 translocation in a patient with neuroblastoma within a 25-kb segment located between the ACCN1 and TLK2 genes and near the distal breakpoints of two microdeletions in neurofibromatosis type 1 patients [1].
  • Thus, syntaxin 1A cannot inhibit Na(+) permeability in the absence of adequate plasma membrane ASIC2 expression, accounting for the observed functional expression of amiloride-sensitive currents in high grade glioma cells [2].
  • Immunoreactivity to ASIC1a and ASIC2a subunits was found in small vestibular ganglion neurons and afferent fibers that run throughout the macula utricle and crista stroma [3].

High impact information on ACCN1

  • Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells [4].
  • Extending telomerically from the SRO, two additional genes-BLMH, encoding a hydrolase involved in bleomycin resistance, and ACCN1, encoding an amiloride-sensitive cation channel expressed in the CNS-were located in the deleted intervals of seven and three patients, respectively [5].
  • Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells [6].
  • Thus, we used glycosylation studies to define the actual membrane topology of the ASIC2a subtype [7].
  • Although ASIC1 was present in all of the high grade glial cells examined, ASIC2 mRNA was detected in less than half [2].

Biological context of ACCN1


Anatomical context of ACCN1

  • To investigate the subunit composition of native ASICs in peripheral and central neurons, we co-injected human as well as rodent ASIC2a and ASIC3 subunits in Xenopus oocytes [11].
  • BNC1 has a unique pattern of expression with transcripts detected only in adult human brain and in spinal cord [12].
  • Our previous studies suggested that differential regulation of ASIC2 expression occurs between high-grade glial-derived tumor cells and normal astrocytes [9].
  • In human osteoblasts ASIC1, ASIC2, and ASIC3 mRNAs were shown [13].
  • In bone, ASIC2 and ASIC3 were most abundant, while in chondrocytes it was ASIC1 [13].

Associations of ACCN1 with chemical compounds

  • Purification and characterization of EDTA monooxygenase from the EDTA-degrading bacterium BNC1 [14].
  • EDTA-degrading activities were detected in cell extracts of bacterium BNC1 when flavin mononucleotide (FMN), NADH, and O2 were present [14].
  • Common radical initiators such as ACCN and triethylborane can be used [15].

Co-localisations of ACCN1

  • Transfection of rat cortical neurons with constructs encoding green fluorescent protein- or hemagglutinin-tagged channels showed expression of ASIC1a and ASIC2a in punctate and clustering patterns in dendrites that co-localized with AKAP150 [16].

Other interactions of ACCN1

  • RESULTS: In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers [17].
  • In contrast, the acid-gated Na(+) current associated with either the homomultimeric ASIC1a or ASIC2a channel was not influenced by wild type CFTR [18].
  • The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family [19].

Analytical, diagnostic and therapeutic context of ACCN1


  1. Localization of the 17q breakpoint of a constitutional 1;17 translocation in a patient with neuroblastoma within a 25-kb segment located between the ACCN1 and TLK2 genes and near the distal breakpoints of two microdeletions in neurofibromatosis type 1 patients. Van Roy, N., Vandesompele, J., Berx, G., Staes, K., Van Gele, M., De Smet, E., De Paepe, A., Laureys, G., van der Drift, P., Versteeg, R., Van Roy, F., Speleman, F. Genes Chromosomes Cancer (2002) [Pubmed]
  2. Acid-sensing ion channels in malignant gliomas. Berdiev, B.K., Xia, J., McLean, L.A., Markert, J.M., Gillespie, G.Y., Mapstone, T.B., Naren, A.P., Jovov, B., Bubien, J.K., Ji, H.L., Fuller, C.M., Kirk, K.L., Benos, D.J. J. Biol. Chem. (2003) [Pubmed]
  3. Acid-sensing ionic channels in the rat vestibular endorgans and ganglia. Mercado, F., López, I.A., Acuna, D., Vega, R., Soto, E. J. Neurophysiol. (2006) [Pubmed]
  4. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Alvarez de la Rosa, D., Zhang, P., Shao, D., White, F., Canessa, C.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. NF1 microdeletion syndrome: refined FISH characterization of sporadic and familial deletions with locus-specific probes. Riva, P., Corrado, L., Natacci, F., Castorina, P., Wu, B.L., Schneider, G.H., Clementi, M., Tenconi, R., Korf, B.R., Larizza, L. Am. J. Hum. Genet. (2000) [Pubmed]
  6. Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells. Vila-Carriles, W.H., Kovacs, G.G., Jovov, B., Zhou, Z.H., Pahwa, A.K., Colby, G., Esimai, O., Gillespie, G.Y., Mapstone, T.B., Markert, J.M., Fuller, C.M., Bubien, J.K., Benos, D.J. J. Biol. Chem. (2006) [Pubmed]
  7. Analysis of the membrane topology of the acid-sensing ion channel 2a. Saugstad, J.A., Roberts, J.A., Dong, J., Zeitouni, S., Evans, R.J. J. Biol. Chem. (2004) [Pubmed]
  8. The human degenerin MDEG, an amiloride-sensitive neuronal cation channel, is localized on chromosome 17q11.2-17q12 close to the microsatellite D17S798. Waldmann, R., Voilley, N., Mattéï, M.G., Lazdunski, M. Genomics (1996) [Pubmed]
  9. Molecular cloning and characterization of human acid sensing ion channel (ASIC)2 gene promoter. Xia, J., Zhou, Z.H., Bubien, J.K., Fuller, C.M., Markert, J.M., Mapstone, T.B., Yancey Gillespie, G., Benos, D.J. Gene (2003) [Pubmed]
  10. Peptides inhibitors of acid-sensing ion channels. Diochot, S., Salinas, M., Baron, A., Escoubas, P., Lazdunski, M. Toxicon (2007) [Pubmed]
  11. Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. Babinski, K., Catarsi, S., Biagini, G., Séguéla, P. J. Biol. Chem. (2000) [Pubmed]
  12. Cloning and expression of a novel human brain Na+ channel. Price, M.P., Snyder, P.M., Welsh, M.J. J. Biol. Chem. (1996) [Pubmed]
  13. Identification of acid-sensing ion channels in bone. Jahr, H., van Driel, M., van Osch, G.J., Weinans, H., van Leeuwen, J.P. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. Purification and characterization of EDTA monooxygenase from the EDTA-degrading bacterium BNC1. Payne, J.W., Bolton, H., Campbell, J.A., Xun, L. J. Bacteriol. (1998) [Pubmed]
  15. Tributylgermanium hydride as a replacement for tributyltin hydride in radical reactions. Russell Bowman, W., Krintel, S.L., Schilling, M.B. Org. Biomol. Chem. (2004) [Pubmed]
  16. A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a. Chai, S., Li, M., Lan, J., Xiong, Z.G., Saugstad, J.A., Simon, R.P. J. Biol. Chem. (2007) [Pubmed]
  17. Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Yiangou, Y., Facer, P., Smith, J.A., Sangameswaran, L., Eglen, R., Birch, R., Knowles, C., Williams, N., Anand, P. European journal of gastroenterology & hepatology. (2001) [Pubmed]
  18. Up-regulation of acid-gated Na(+) channels (ASICs) by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes. Ji, H.L., Jovov, B., Fu, J., Bishop, L.R., Mebane, H.C., Fuller, C.M., Stanton, B.A., Benos, D.J. J. Biol. Chem. (2002) [Pubmed]
  19. Tetraethylammonium block of the BNC1 channel. Adams, C.M., Price, M.P., Snyder, P.M., Welsh, M.J. Biophys. J. (1999) [Pubmed]
  20. Malignant human gliomas express an amiloride-sensitive Na+ conductance. Bubien, J.K., Keeton, D.A., Fuller, C.M., Gillespie, G.Y., Reddy, A.T., Mapstone, T.B., Benos, D.J. Am. J. Physiol. (1999) [Pubmed]
  21. Immunohistochemical analysis of acid-sensing ion channel 2 expression in rat dorsal root ganglion and effects of axotomy. Kawamata, T., Ninomiya, T., Toriyabe, M., Yamamoto, J., Niiyama, Y., Omote, K., Namiki, A. Neuroscience (2006) [Pubmed]
  22. Identification of sour-taste receptor genes. Ugawa, S. Anatomical science international / Japanese Association of Anatomists. (2003) [Pubmed]
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