ACCN2

Acid sensing (proton gated) ion channel 1

Identifiers

ASIC1 ; ACCN2; ASIC; BNaC2

External IDs

OMIM: 602866 MGI: 1194915 HomoloGene: 121755 IUPHAR: 684 ChEMBL: 1628477 GeneCards: ASIC1 Gene

Gene ontology
Molecular function	• protein binding • ligand-gated sodium channel activity • ion gated channel activity • acid-sensing ion channel activity
Cellular component	• plasma membrane • integral component of plasma membrane • cell surface
Biological process	• transport • sodium ion transport • signal transduction • memory • associative learning • response to pH • response to acidic pH • ion transmembrane transport • sodium ion transmembrane transport • regulation of membrane potential • negative regulation of neurotransmitter secretion • sensory perception of sour taste • transmembrane transport • protein homotrimerization • calcium ion transmembrane transport • cellular response to pH
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
50.06 – 50.08 Mb

Chr 15:
99.67 – 99.7 Mb

PubMed search

Amiloride-sensitive cation channel 2, neuronal is a protein that in humans is encoded by the ACCN2 gene.^[1]^[2]

Function

This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is expressed in most if not all brain neurons, and it may be an ion channel subunit; however, its function as an ion channel remains unknown. Alternative splicing of this gene generates 2 transcript products.^[2]

Interactions

ACCN2 has been shown to interact with PICK1.^[3]^[4]

References

↑ García-Añoveros J, Derfler B, Neville-Golden J, Hyman BT, Corey DP (March 1997). "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 94 (4): 1459–64. doi:10.1073/pnas.94.4.1459. PMC 19813. PMID 9037075.
1 2 "Entrez Gene: ACCN2 amiloride-sensitive cation channel 2, neuronal".
↑ Leonard AS, Yermolaieva O, Hruska-Hageman A, Askwith CC, Price MP, Wemmie JA, Welsh MJ (February 2003). "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. 100 (4): 2029–34. doi:10.1073/pnas.252782799. PMC 149953. PMID 12578970.
↑ Hruska-Hageman AM, Wemmie JA, Price MP, Welsh MJ (February 2002). "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. 361 (Pt 3): 443–50. doi:10.1042/0264-6021:3610443. PMC 1222326. PMID 11802773.

Corey DP, García-Añoveros J (1996). "Mechanosensation and the DEG/ENaC ion channels". Science 273 (5273): 323–4. doi:10.1126/science.273.5273.323. PMID 8685718.
Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M (1997). "A proton-gated cation channel involved in acid-sensing". Nature 386 (6621): 173–7. doi:10.1038/386173a0. PMID 9062189.
Bassilana F, Champigny G, Waldmann R, de Weille JR, Heurteaux C, Lazdunski M (1997). "The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties". J. Biol. Chem. 272 (46): 28819–22. doi:10.1074/jbc.272.46.28819. PMID 9360943.
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. PMID 10362604.
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. PMID 10798398.
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. PMID 11448963.
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. PMID 11512022.
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. PMID 11739374.
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. PMID 11748227.
Hruska-Hageman AM, Wemmie JA, Price MP, Welsh MJ (2002). "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. 361 (Pt 3): 443–50. doi:10.1042/0264-6021:3610443. PMC 1222326. PMID 11802773.
Wemmie JA, Chen J, Askwith CC, Hruska-Hageman AM, Price MP, Nolan BC, Yoder PG, Lamani E, Hoshi T, Freeman JH, Welsh MJ (2002). "The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory". Neuron 34 (3): 463–77. doi:10.1016/S0896-6273(02)00661-X. PMID 11988176.
Berdiev BK, Xia J, Jovov B, Markert JM, Mapstone TB, Gillespie GY, Fuller CM, Bubien JK, Benos DJ (2003). "Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function". J. Biol. Chem. 277 (48): 45734–40. doi:10.1074/jbc.M208995200. PMID 12244121.
Ugawa S, Ueda T, Ishida Y, Nishigaki M, Shibata Y, Shimada S (2002). "Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors". J. Clin. Invest. 110 (8): 1185–90. doi:10.1172/JCI15709. PMC 150796. PMID 12393854.
Leonard AS, Yermolaieva O, Hruska-Hageman A, Askwith CC, Price MP, Wemmie JA, Welsh MJ (2003). "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. 100 (4): 2029–34. doi:10.1073/pnas.252782799. PMC 149953. PMID 12578970.
Wemmie JA, Coryell MW, Askwith CC, Lamani E, Leonard AS, Sigmund CD, Welsh MJ (2004). "Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior". Proc. Natl. Acad. Sci. U.S.A. 101 (10): 3621–6. doi:10.1073/pnas.0308753101. PMC 373512. PMID 14988500.
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. PMID 15247234.
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. PMID 15471860.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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ACCN2

Function

Interactions

See also

References

Further reading