Acid-sensing ion channel 1

Details

Name
Acid-sensing ion channel 1
Synonyms
  • ACCN2
  • Amiloride-sensitive cation channel 2, neuronal
  • ASIC1
  • BNAC2
  • Brain sodium channel 2
Gene Name
ASIC1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036997|Acid-sensing ion channel 1
MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCV
CTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNN
RYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEVCS
AEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETS
FEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCKAVTMDSDLD
FFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEY
CVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETI
EQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRRGKCQKEAKRSSA
DKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC
Number of residues
528
Molecular Weight
59908.915
Theoretical pI
5.39
GO Classification
Functions
acid-sensing ion channel activity / ion gated channel activity / ligand-gated sodium channel activity
Processes
associative learning / calcium ion transmembrane transport / cellular response to pH / ion transmembrane transport / memory / negative regulation of neurotransmitter secretion / protein homotrimerization / regulation of membrane potential / response to acidic pH / response to pH / sensory perception of sour taste / signal transduction / sodium ion transmembrane transport / sodium ion transport / transmembrane transport / transport
Components
cell surface / integral component of plasma membrane / plasma membrane
General Function
Ligand-gated sodium channel activity
Specific Function
Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.Isoform 1 does not display proton-gated cation channel activity.
Pfam Domain Function
Transmembrane Regions
46-69 428-454
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010105|Acid-sensing ion channel 1 (ASIC1)
ATGGAACTGAAGGCCGAGGAGGAGGAGGTGGGTGGCGTCCAGCCGGTGAGCATCCAGGCC
TTCGCCAGCAGCTCCACACTGCACGGCCTGGCCCACATCTTCTCCTACGAGCGGCTGTCT
CTGAAGCGGGCACTGTGGGCCCTGTGCTTCCTGGGCTCGCTGGCTGTGCTGCTGTGTGTG
TGCACGGAGCGTGTGCAGTACTACTTCCACTACCACCATGTCACCAAGCTCGACGAGGTG
GCTGCCTCTCAGCTTACCTTCCCTGCTGTCACGCTGTGCAACCTCAACGAGTTCCGCTTT
AGCCAAGTCTCCAAGAATGACCTGTATCATGCTGGGGAGCTGCTGGCCCTGCTCAACAAC
AGGTATGAGATACCAGACACACAGATGGCAGATGAAAAGCAGCTGGAGATACTGCAGGAC
AAAGCCAACTTCCGCAGCTTCAAACCCAAACCCTTCAACATGCGTGAGTTCTACGACCGA
GCTGGGCACGACATTCGAGACATGCTGCTCTCCTGCCACTTCCGGGGGGAGGTCTGCAGC
GCTGAAGACTTCAAGGTGGTCTTCACACGCTATGGAAAGTGCTACACGTTCAACTCGGGC
CGAGATGGGCGGCCGCGGCTGAAGACCATGAAGGGTGGGACGGGCAATGGGCTGGAAATC
ATGCTGGACATCCAGCAGGACGAGTACCTGCCTGTGTGGGGGGAGACTGACGAGACGTCC
TTCGAAGCAGGCATCAAAGTGCAGATCCATAGTCAGGATGAACCTCCTTTCATCGACCAG
CTGGGCTTTGGCGTGGCCCCAGGCTTCCAGACCTTTGTGGCCTGCCAGGAGCAGCGGCTC
ATCTACCTGCCCCCACCCTGGGGCACCTGCAAAGCTGTTACCATGGACTCGGATTTGGAT
TTCTTCGACTCCTACAGCATCACTGCCTGCCGCATCGACTGTGAGACGCGCTACCTGGTG
GAGAACTGCAACTGCCGCATGGTGCACATGCCAGGGGATGCCCCATACTGTACTCCAGAG
CAGTACAAGGAGTGTGCAGATCCTGCTCTGGACTTCCTGGTGGAGAAGGACCAGGAGTAC
TGCGTGTGTGAAATGCCTTGCAACCTGACCCGCTATGGCAAAGAGCTGTCCATGGTCAAG
ATCCCCAGCAAAGCCTCAGCCAAGTACCTGGCCAAGAAGTTCAACAAATCTGAGCAATAC
ATAGGGGAGAACATCCTGGTGCTGGACATTTTCTTTGAAGTCCTCAACTATGAGACCATT
GAACAGAAGAAGGCCTATGAGATTGCAGGGCTCCTGGGTGACATCGGGGGCCAGATGGGG
CTGTTCATCGGGGCCAGCATCCTCACGGTGCTGGAGCTCTTTGACTACGCCTACGAGGTC
ATTAAGCACAAGCTGTGCCGACGAGGAAAATGCCAGAAGGAGGCCAAAAGGAGCAGTGCG
GACAAGGGCGTGGCCCTCAGCCTGGACGACGTCAAAAGACACAACCCGTGCGAGAGCCTT
CGGGGCCACCCTGCCGGGATGACATACGCTGCCAACATCCTACCTCACCATCCGGCCCGA
GGCACGTTCGAGGACTTTACCTGCTGA
Chromosome Location
12
Locus
12q12
External Identifiers
ResourceLink
UniProtKB IDP78348
UniProtKB Entry NameASIC1_HUMAN
GenBank Protein ID1871168
GenBank Gene IDU78180
GenAtlas IDACCN2
HGNC IDHGNC:100
General References
  1. Garcia-Anoveros 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. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1459-64. [PubMed:9037075]
  2. Hoagland EN, Sherwood TW, Lee KG, Walker CJ, Askwith CC: Identification of a calcium permeable human acid-sensing ion channel 1 transcript variant. J Biol Chem. 2010 Dec 31;285(53):41852-62. doi: 10.1074/jbc.M110.171330. Epub 2010 Oct 29. [PubMed:21036899]
  3. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [PubMed:16541075]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Askwith CC, Cheng C, Ikuma M, Benson C, Price MP, Welsh MJ: Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels. Neuron. 2000 Apr;26(1):133-41. [PubMed:10798398]
  6. 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). Biochem J. 2002 Feb 1;361(Pt 3):443-50. [PubMed:11802773]
  7. Berdiev BK, Xia J, Jovov B, Markert JM, Mapstone TB, Gillespie GY, Fuller CM, Bubien JK, Benos DJ: Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function. J Biol Chem. 2002 Nov 29;277(48):45734-40. Epub 2002 Sep 19. [PubMed:12244121]
  8. Leonard AS, Yermolaieva O, Hruska-Hageman A, Askwith CC, Price MP, Wemmie JA, Welsh MJ: cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2029-34. Epub 2003 Feb 10. [PubMed:12578970]
  9. Poirot O, Vukicevic M, Boesch A, Kellenberger S: Selective regulation of acid-sensing ion channel 1 by serine proteases. J Biol Chem. 2004 Sep 10;279(37):38448-57. Epub 2004 Jul 6. [PubMed:15247234]
  10. Dawson RJ, Benz J, Stohler P, Tetaz T, Joseph C, Huber S, Schmid G, Hugin D, Pflimlin P, Trube G, Rudolph MG, Hennig M, Ruf A: Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1. Nat Commun. 2012 Jul 3;3:936. doi: 10.1038/ncomms1917. [PubMed:22760635]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00594AmilorideapprovedunknowninhibitorDetails
DB00586Diclofenacapproved, vet_approvedunknowninhibitorDetails