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1.A.6.1.2
Amiloride-sensitive cation channel, ASIC1/ASIC3 (also called ASIC1a, BNC1, MDEG, ACCN2 and BNAC2), which is an acid-sensitive (proton-gated) homo- or hetero-oligomeric cation (Na+ (high affinity), Ca2+, K+) channel. It it 98% identical to the human ortholog and associates with DRASIC tomediate touch sensation, being a mechanosensor (lead inhibited) channel (Wang et al., 2006). In pulmonary tissue (lung epithelial cells) it and CFTR interregulate each other (Su et al., 2006). ASIC3 is a sensor of acidic and primary inflammatory pain (Deval et al., 2008).  Acid sensing ion channel-1b (ASIC1b), virtually identical to  the rat and human orthologs, is stimulated by hypotonic stimuli  (Ugawa et al., 2007; Deval et al., 2008). This protein is 98% idientical to the human ortholog Z(as noted above), which is an excitatory neuronal cation channel, involved in physiopathological processes related to extracellular pH fluctuation such as nociception, ischaemia, perception of sour taste and synaptic transmission. The spider peptide toxin psalmotoxin 1 (PcTx1) inhibits its proton-gated cation channel activity (Salinas et al. 2006). ASIC1a localizes to the proximal tubular and contributes to ischaemia/reperfusion (I/)R induced kidney injury (Song et al. 2019). Stomatin (STOM; TC# 8.A.21.1.1) is an inhibitor of ASIC3, and it is anchored to the ASIC3 channel via a site on the distal C-terminus of the channel to stabilizes the desensitized state  via an interaction with TMS1 (Klipp et al. 2020). Sun et al. 2020 presented single-particle cryo-EM structures of human ASIC1a (hASIC1a) and the hASIC1a-Mamba1 complex at resolutions of 3.56 and 3.90 Å, respectively. The structures revealed the inhibited conformation of hASIC1a upon Mamba1 binding. Mamba1 prefers to bind hASIC1a in a closed state and reduces the proton sensitivity of the channel, representing a closed-state trapping mechanism. Kinetic analyses of ASIC1a delineated conformational signaling from proton-sensing domains to the channel gate (Vullo et al. 2021). An arginine residue in the outer segment of hASIC1a TMS1 affects both proton affinity and channel desensitization (Chen et al. 2021). Acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium ratio approximately 10:1), while ENaCs show a high preference for sodium over potassium (>500:1). The pre-TMS1 and TMS1 regions of mASIC1a channels are major determinants of ion selectivity (Sheikh et al. 2021).

Accession Number:P55926
Protein Name:ASIC1 aka ACCN2 aka BNAC2
Length:526
Molecular Weight:59641.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate cations

Cross database links:

RefSeq: NP_077068.1   
Entrez Gene ID: 79123   
Pfam: PF00858   
KEGG: rno:79123   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015280 F:amiloride-sensitive sodium channel activity
GO:0006816 P:calcium ion transport
GO:0019233 P:sensory perception of pain
GO:0006814 P:sodium ion transport

References (13)

[1] “A proton-gated cation channel involved in acid-sensing.”  Waldmann R.et.al.   9062189
[2] “A sensory neuron-specific, proton-gated ion channel.”  Chen C.-C.et.al.   9707631
[3] “Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.”  Baessler E.-L.et.al.   11448963
[4] “Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-beta.”  Ugawa S.et.al.   11588592
[5] “The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties.”  Bassilana F.et.al.   9360943
[6] “Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.”  Escoubas P.et.al.   10829030
[7] “Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels.”  Askwith C.C.et.al.   10798398
[8] “Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors.”  Voilley N.et.al.   11588175
[9] “Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1).”  Babini E.et.al.   12198124
[10] “Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system.”  Alvarez de la Rosa D.et.al.   11842212
[11] “The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1.”  Coric T.et.al.   12947112
[12] “Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.”  Xiong Z.-G.et.al.   15369669
[13] “Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating.”  Paukert M.et.al.   15452199

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FASTA formatted sequence
1:	MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV 
61:	CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN 
121:	RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEACS 
181:	AEDFKVVFTR YGKCYTFNSG QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS 
241:	FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF 
301:	DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF LVEKDQEYCV 
361:	CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG ENILVLDIFF EVLNYETIEQ 
421:	KKAYEIAGLL GDIGGQMGLF IGASILTVLE LFDYAYEVIK HRLCRRGKCQ KEAKRSSADK 
481:	GVALSLDDVK RHNPCESLRG HPAGMTYAAN ILPHHPARGT FEDFTC