General Information of This Target
Target ID
BTDT00159
Target Name
Acid-sensing ion channel 1 (Asic1)
Target Bioclass
Transporter and channel
Uniprot ID
Q6NXK8
3D Structure
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2D Sequence
3D Structure
Source
Predict by Alphafold2
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Alphafold Parameters: msa_mode: mmseqs2_uniref_env model_type: auto num_recycles: auto
Gene Name
Asic1
Gene ID
11419
Synonym
Accn2; Asic; Bnac2; Acid-sensing ion channel; Amiloride-sensitive cation channel 2, neuronal; Brain sodium channel 2
Sequence
MELKTEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCV
CTERVQYYFCYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNN
RYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEACS
AEDFKVVFTRYGKCYTFNSGQDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETS
FEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVSCQEQRLIYLPSPWGTCNAVTMDSDFF
DSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEYCV
CEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETIEQ
KKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHRLCRRGKCQKEAKRNSADK
GVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC

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Family
the amiloride-sensitive sodium channel family
Function
Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.

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Taxonomy ID
10090
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Mus
Species: Mus musculus
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    PcTX1 IC50
0.35 - 3.9 nM
[1- 16]
References
Ref 1 Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J Biol Chem. 2000 Aug 18;275(33):25116-21. doi: 10.1074/jbc.M003643200.
Ref 2 The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity. J Gen Physiol. 2005 Jul;126(1):71-9. doi: 10.1085/jgp.200509303. Epub 2005 Jun 13.
Ref 3 Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent. J Gen Physiol. 2006 Mar;127(3):267-76. doi: 10.1085/jgp.200509409. Epub 2006 Feb 14.
Ref 4 Native and recombinant ASIC1a receptors conduct negligible Ca2+ entry. Cell Calcium. 2009 Apr;45(4):319-25. doi: 10.1016/j.ceca.2008.12.002. Epub 2009 Jan 29.
Ref 5 Identification of a calcium permeable human acid-sensing ion channel 1 transcript variant. J Biol Chem. 2010 Dec 31;285(53):41852-62. doi: 10.1074/jbc.M110.171330. Epub 2010 Oct 29.
Ref 6 Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death. J Neurosci. 2011 Jun 29;31(26):9723-34. doi: 10.1523/JNEUROSCI.1665-11.2011.
Ref 7 Protons and Psalmotoxin-1 reveal nonproton ligand stimulatory sites in chicken acid-sensing ion channel: Implication for simultaneous modulation in ASICs. Channels (Austin). 2014;8(1):49-61. doi: 10.4161/chan.26978. Epub 2013 Nov 21.
Ref 8 Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a. Br J Pharmacol. 2015 Oct;172(20):4985-95. doi: 10.1111/bph.13267. Epub 2015 Sep 22.
Ref 9 PcTx1 affords neuroprotection in a conscious model of stroke in hypertensive rats via selective inhibition of ASIC1a. Neuropharmacology. 2015 Dec;99:650-7. doi: 10.1016/j.neuropharm.2015.08.040. Epub 2015 Aug 29.
Ref 10 Functional and pharmacological characterization of two different ASIC1a/2a heteromers reveals their sensitivity to the spider toxin PcTx1. Sci Rep. 2016 Jun 9;6:27647. doi: 10.1038/srep27647.
Ref 11 Potent neuroprotection after stroke afforded by a double-knot spider-venom peptide that inhibits acid-sensing ion channel 1a. Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3750-3755. doi: 10.1073/pnas.1614728114. Epub 2017 Mar 20.
Ref 12 Acid-sensing ion channel (ASIC) structure and function: Insights from spider, snake and sea anemone venoms. Neuropharmacology. 2017 Dec;127:173-184. doi: 10.1016/j.neuropharm.2017.04.042. Epub 2017 Apr 27.
Ref 13 Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Sci. 2003 Jul;12(7):1332-43. doi: 10.1110/ps.0307003.
Ref 14 A dynamic pharmacophore drives the interaction between Psalmotoxin-1 and the putative drug target acid-sensing ion channel 1a. Mol Pharmacol. 2011 Nov;80(5):796-808. doi: 10.1124/mol.111.072207. Epub 2011 Aug 8.
Ref 15 Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes. Nature. 2012 Sep 20;489(7416):400-5. doi: 10.1038/nature11375. Epub 2012 Jul 29.
Ref 16 Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1. Nat Commun. 2012 Jul 3;3:936. doi: 10.1038/ncomms1917.
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