ASIC3

Identifiers

ASIC3, ACCN3, DRASIC, SLNAC1, TNaC1, acid sensing ion channel subunit 3

External IDs

MGI: 2159339 HomoloGene: 20999 GeneCards: ASIC3

Targeted by Drug

agmatine, Hydron, amiloride, aspirin, diclofenac, nafamostat, salicylic acid^[1]

Gene ontology
Molecular function	• PDZ domain binding • enterobactin transporter activity • sodium channel activity • cation channel activity • ligand-gated sodium channel activity • acid-sensing ion channel activity
Cellular component	• cytoplasm • integral component of membrane • membrane • plasma membrane • integral component of plasma membrane
Biological process	• detection of temperature stimulus involved in sensory perception • sensory perception • sodium ion transmembrane transport • detection of chemical stimulus involved in sensory perception of pain • detection of mechanical stimulus involved in sensory perception • sodium ion transport • enterobactin transport • response to mechanical stimulus • cation transport • response to heat • sensory perception of sour taste • ion transport • detection of chemical stimulus involved in sensory perception • cation transmembrane transport • detection of temperature stimulus involved in sensory perception of pain • ion transmembrane transport • transport • signal transduction • response to acidic pH • detection of mechanical stimulus involved in sensory perception of pain
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


9311


171209

Ensembl


ENSG00000213199


ENSMUSG00000038276

UniProt


Q9UHC3


Q6X1Y6

RefSeq (mRNA)


NM_004769 NM_020321 NM_020322


NM_183000 NM_001310474

RefSeq (protein)


NP_004760.1 NP_064717.1 NP_064718.1


NP_001297403.1 NP_892045.2

Location (UCSC)

Chr 7: 151.05 – 151.05 Mb

Chr 5: 24.41 – 24.42 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Acid-sensing ion channel 3 (ASIC3) also known as amiloride-sensitive cation channel 3 (ACCN3) or testis sodium channel 1 (TNaC1) is a protein that in humans is encoded by the ASIC3 gene. The ASIC3 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 1998.^[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]

Structure and function

This gene encodes a member of the ASIC/ENaC superfamily of proteins.^[7] 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. ^[8]

Interactions

ASIC3 has been shown to interact with LIN7B,^[9] GOPC^[9] and MAGI1.^[9]

References

↑ "Drugs that physically interact with Acid-sensing ion channel 3 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Ishibashi K, Marumo F (June 1998). "Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis". Biochem. Biophys. Res. Commun. 245 (2): 589–93. doi:10.1006/bbrc.1998.8483. PMID 9571199.
↑ de Weille JR, Bassilana F, Lazdunski M, Waldmann R (October 1998). "Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel". FEBS Lett. 433 (3): 257–60. doi:10.1016/S0014-5793(98)00916-8. PMID 9744806.
↑ Babinski K, Catarsi S, Biagini G, Séguéla P (Sep 2000). "Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+". The Journal of Biological Chemistry. 275 (37): 28519–25. doi:10.1074/jbc.M004114200. PMID 10842183.
↑ Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases.". Gene. 579 (2): 95–132. doi:10.1016/j.gene.2015.12.061. PMC 4756657. PMID 26772908.
↑ Hanukoglu I (2016). "ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity filters". FEBS Journal. doi:10.1111/febs.13840. PMID 27580245.
1 2 3 Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ (November 2004). "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. Chem. 279 (45): 46962–8. doi:10.1074/jbc.M405874200. PMID 15317815.

External links

Human ASIC3 genome location and ASIC3 gene details page in the UCSC Genome Browser.

Babinski K, Lê KT, Séguéla P (1999). "Molecular cloning and regional distribution of a human proton receptor subunit with biphasic functional properties". J. Neurochem. 72 (1): 51–7. doi:10.1046/j.1471-4159.1999.0720051.x. PMID 9886053.
Catarsi S, Babinski K, Séguéla P (2001). "Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF". Neuropharmacology. 41 (5): 592–600. doi:10.1016/S0028-3908(01)00107-1. PMID 11587714.
Alvarez de la Rosa D, Zhang P, Shao D, White F, Canessa CM (2002). "Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 2326–31. doi:10.1073/pnas.042688199. PMC 122364. PMID 11842212.
Anzai N, Deval E, Schaefer L, Friend V, Lazdunski M, Lingueglia E (2002). "The multivalent PDZ domain-containing protein CIPP is a partner of acid-sensing ion channel 3 in sensory neurons". J. Biol. Chem. 277 (19): 16655–61. doi:10.1074/jbc.M201087200. PMID 11872753.
Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A (2002). "A role for ASIC3 in the modulation of high-intensity pain stimuli". Proc. Natl. Acad. Sci. U.S.A. 99 (13): 8992–7. doi:10.1073/pnas.122245999. PMC 124411. PMID 12060708.
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.
Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ (2004). "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current". J. Biol. Chem. 279 (45): 46962–8. doi:10.1074/jbc.M405874200. PMID 15317815.
Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ (2004). "Stomatin modulates gating of acid-sensing ion channels". J. Biol. Chem. 279 (51): 53886–91. doi:10.1074/jbc.M407708200. PMID 15471860.
Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB (2004). "Acid-induced pain and its modulation in humans". J. Neurosci. 24 (48): 10974–9. doi:10.1523/JNEUROSCI.2619-04.2004. PMID 15574747.
Su X, Li Q, Shrestha K, Cormet-Boyaka E, Chen L, Smith PR, Sorscher EJ, Benos DJ, Matalon S, Ji HL (2006). "Interregulation of proton-gated Na(+) channel 3 and cystic fibrosis transmembrane conductance regulator". J. Biol. Chem. 281 (48): 36960–8. doi:10.1074/jbc.M608002200. PMID 17012229.

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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ASIC3

Structure and function

Interactions

References

External links

Further reading