ASIC4
{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox gene}}
Acid-sensing ion channel 4 (ASIC4) also known as amiloride-sensitive cation channel 4 (ACCN4) is a protein that in humans is encoded by the ASIC4 gene. The ASIC4 gene is one of the five paralogous genes that encode proteins that form trimeric acid-sensing ion channels (ASICs) in mammals.{{cite journal | vauthors = Hanukoglu I | title = ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity filters | journal = The FEBS Journal | volume = 284 | issue = 4 | pages = 525–545 | date = Feb 2017 | pmid = 27580245 | doi = 10.1111/febs.13840 | s2cid = 24402104 | url = https://zenodo.org/record/890906 }} The cDNA of this gene was first cloned in 2000.{{cite journal | vauthors = Gründer S, Geissler HS, Bässler EL, Ruppersberg JP | title = A new member of acid-sensing ion channels from pituitary gland | journal = NeuroReport | volume = 11 | issue = 8 | pages = 1607–1611 | date = Jun 2000 | pmid = 10852210 | doi = 10.1097/00001756-200006050-00003 | s2cid = 46420660 }}{{cite journal | vauthors = Gründer S, Geisler HS, Rainier S, Fink JK | title = Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation, and evaluation as a candidate for paroxysmal dystonia | journal = European Journal of Human Genetics | volume = 9 | issue = 9 | pages = 672–676 | date = Sep 2001 | pmid = 11571555 | doi = 10.1038/sj.ejhg.5200699 | doi-access = free }} 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.{{cite journal | vauthors = Babinski K, Catarsi S, Biagini G, Séguéla P | title = Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+ | journal = The Journal of Biological Chemistry | volume = 275 | issue = 37 | pages = 28519–28525 | date = Sep 2000 | pmid = 10842183 | doi = 10.1074/jbc.M004114200 | doi-access = free | hdl = 11380/304669 | hdl-access = free }}
Structure and function
This gene encodes a member of the ASIC/ENaC superfamily of proteins.{{cite journal | vauthors = Hanukoglu I, Hanukoglu A | title = Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. | journal = Gene | volume = 579 | issue = 2 | pages = 95–132 | date = Jan 2016 | pmid = 26772908 | pmc = 4756657 | doi = 10.1016/j.gene.2015.12.061 }} 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.
References
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Further reading
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- {{cite journal | vauthors = Chen X, Polleichtner G, Kadurin I, Gründer S | title = Zebrafish acid-sensing ion channel (ASIC) 4, characterization of homo- and heteromeric channels, and identification of regions important for activation by H+ | journal = Journal of Biological Chemistry | volume = 282 | issue = 42 | pages = 30406–30413 | date = Oct 2007 | pmid = 17686779 | doi = 10.1074/jbc.M702229200 | doi-access = free }}
- {{cite journal | vauthors = Donier E, Rugiero F, Jacob C, Wood JN | title = Regulation of ASIC activity by ASIC4--new insights into ASIC channel function revealed by a yeast two-hybrid assay | journal = The European Journal of Neuroscience | volume = 28 | issue = 1 | pages = 74–86 | date = Jul 2008 | pmid = 18662336 | doi = 10.1111/j.1460-9568.2008.06282.x | s2cid = 29369987 }}
- {{cite journal | vauthors = ((Sanger Center)), ((Genome Sequencing Center)) | title = Toward a complete human genome sequence | journal = Genome Research | volume = 8 | issue = 11 | pages = 1097–1108 | date = Nov 1998 | pmid = 9847074 | doi = 10.1101/gr.8.11.1097 | doi-access = free }}
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