ASIC1

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. The cDNA of this gene was first cloned in 1996. The ASIC genes have splicing variants that encode different proteins that are called isoforms.

ASIC1
Identifiers
Aliases	ASIC1, ACCN2, ASIC, BNaC2, acid sensing ion channel subunit 1
External IDs	OMIM: 602866; MGI: 1194915; HomoloGene: 121755; GeneCards: ASIC1; OMA:ASIC1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12q13.12 Start 50,057,548 bp End 50,083,611 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15|15 F1 Start 99,568,249 bp End 99,599,011 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum ganglionic eminence putamen caudate nucleus nucleus accumbens right frontal lobe amygdala hypothalamus prefrontal cortex Brodmann area 9 Top expressed in superior frontal gyrus cerebellar cortex primary visual cortex trigeminal ganglion nucleus accumbens central gray substance of midbrain superior colliculus Rostral migratory stream facial motor nucleus dentate gyrus of hippocampal formation granule cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ion gated channel activity sodium channel activity ion channel activity protein binding cation channel activity ligand-gated sodium channel activity acid-sensing ion channel activity Cellular component integral component of membrane membrane synapse integral component of plasma membrane cell surface Golgi apparatus plasma membrane Biological process negative regulation of neurotransmitter secretion associative learning sodium ion transmembrane transport sodium ion transport regulation of membrane potential cation transport memory sensory perception of sour taste ion transport protein homotrimerization ion transmembrane transport cellular response to pH calcium ion transmembrane transport response to pH signal transduction response to acidic pH calcium ion transport behavioral fear response response to amphetamine Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 41 11419 Ensembl ENSG00000110881 ENSMUSG00000023017 UniProt P78348 Q6NXK8 RefSeq (mRNA) NM_001095 NM_001256830 NM_020039 NM_001289791 NM_009597 RefSeq (protein) NP_001086 NP_001243759 NP_064423 NP_001276720 NP_033727 Location (UCSC) Chr 12: 50.06 – 50.08 Mb Chr 15: 99.57 – 99.6 Mb PubMed search
Wikidata
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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.

Structure and function

This gene encodes a member of the ASIC/ENaC superfamily of proteins. 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.

Interactions

ASIC1 has been shown to interact with PICK1.

Further reading

• Corey DP, García-Añoveros J (1996). "Mechanosensation and the DEG/ENaC ion channels". Science. 273 (5273): 323–4. Bibcode:1996Sci...273..323C. doi:10.1126/science.273.5273.323. PMID 8685718. S2CID 9015840.
• 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. Bibcode:1997Natur.386..173W. doi:10.1038/386173a0. PMID 9062189. S2CID 4361943.
• 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. doi:10.1152/ajpcell.1999.276.6.C1405. 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. S2CID 14077330.
• 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". Pflügers Arch. 442 (5): 668–74. doi:10.1007/s004240100584. PMID 11512022. S2CID 19059975.
• 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. S2CID 2619519.
• 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. Bibcode:2003PNAS..100.2029L. 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. Bibcode:2004PNAS..101.3621W. 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.

External links

• Human ASIC1 genome location and ASIC1 gene details page in the UCSC Genome Browser.