ASIC3 explained

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.^[1] The cDNA of this gene was first cloned in 1998.^{[2] [3]} 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.^[4]

Structure and function

This gene encodes a member of the ASIC/ENaC superfamily of proteins.^[5] 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

ASIC3 has been shown to interact with LIN7B,^[6] GOPC^[6] and MAGI1.^[6]

Further reading

• Babinski K, Lê KT, Séguéla P . Molecular cloning and regional distribution of a human proton receptor subunit with biphasic functional properties . J. Neurochem. . 72 . 1 . 51–7 . 1999 . 9886053 . 10.1046/j.1471-4159.1999.0720051.x . 10506798 . free .
• Catarsi S, Babinski K, Séguéla P . Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF . Neuropharmacology . 41 . 5 . 592–600 . 2001 . 11587714 . 10.1016/S0028-3908(01)00107-1 . 568441 .
• Alvarez de la Rosa D, Zhang P, Shao D, White F, Canessa CM . 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 . 2002 . 11842212 . 122364 . 10.1073/pnas.042688199 . 2002PNAS...99.2326A . free .
• Anzai N, Deval E, Schaefer L, Friend V, Lazdunski M, Lingueglia E . 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 . 2002 . 11872753 . 10.1074/jbc.M201087200 . free .
• Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A . A role for ASIC3 in the modulation of high-intensity pain stimuli . Proc. Natl. Acad. Sci. U.S.A. . 99 . 13 . 8992–7 . 2002 . 12060708 . 124411 . 10.1073/pnas.122245999 . 2002PNAS...99.8992C . free .
• 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. . 100 . 4 . 2029–34 . 2003 . 12578970 . 149953 . 10.1073/pnas.252782799 . 2003PNAS..100.2029L . free .
• Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ . 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 . 2004 . 15317815 . 10.1074/jbc.M405874200 . free .
• Price MP, Thompson RJ, Eshcol JO, Wemmie JA, Benson CJ . Stomatin modulates gating of acid-sensing ion channels . J. Biol. Chem. . 279 . 51 . 53886–91 . 2004 . 15471860 . 10.1074/jbc.M407708200 . free .
• Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB . Acid-induced pain and its modulation in humans . J. Neurosci. . 24 . 48 . 10974–9 . 2004 . 15574747 . 10.1523/JNEUROSCI.2619-04.2004 . 6730214 . free .
• Su X, Li Q, Shrestha K, Cormet-Boyaka E, Chen L, Smith PR, Sorscher EJ, Benos DJ, Matalon S, Ji HL . Interregulation of proton-gated Na(+) channel 3 and cystic fibrosis transmembrane conductance regulator . J. Biol. Chem. . 281 . 48 . 36960–8 . 2006 . 17012229 . 10.1074/jbc.M608002200 . free .

Notes and References

1. Hanukoglu I . ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity filters . FEBS Journal . 284 . 4 . 525–545 . 2017 . 27580245 . 10.1111/febs.13840 . 24402104 .
2. Ishibashi K, Marumo F . Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis . Biochem. Biophys. Res. Commun. . 245 . 2 . 589–93 . June 1998 . 9571199 . 10.1006/bbrc.1998.8483 .
3. de Weille JR, Bassilana F, Lazdunski M, Waldmann R . Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel . FEBS Lett. . 433 . 3 . 257–60 . October 1998 . 9744806 . 10.1016/S0014-5793(98)00916-8 . 24431941 . free . 1998FEBSL.433..257D .
4. Babinski K, Catarsi S, Biagini G, Séguéla P . Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+ . The Journal of Biological Chemistry . 275 . 37 . 28519–25 . Sep 2000 . 10842183 . 10.1074/jbc.M004114200 . free . 11380/304669 . free .
5. Hanukoglu I, Hanukoglu A . Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. . Gene . 579 . 2 . 95–132 . Jan 2016 . 26772908 . 10.1016/j.gene.2015.12.061 . 4756657.
6. Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ . 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 . November 2004 . 15317815 . 10.1074/jbc.M405874200 . free .