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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:Q62962
Protein Name:Amiloride-sensitive cation channel 1, neuronal
Length:512
Molecular Weight:57739.00
Species: [10116]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate cations

Cross database links:

RefSeq: NP_001029186.1    NP_037024.2   
Entrez Gene ID: 25364   
Pfam: PF00858   
KEGG: rno:25364   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015280 F:amiloride-sensitive sodium channel activity
GO:0005248 F:voltage-gated sodium channel activity
GO:0001101 P:response to acid
GO:0019233 P:sensory perception of pain
GO:0050915 P:sensory perception of sour taste
GO:0006814 P:sodium ion transport

References (8)

[1] “The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans.”  Waldmann R.et.al.   8631835
[2] “A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.”  Lingueglia E.et.al.   9368048
[3] “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
[4] “Zn2+ and H+ are coactivators of acid-sensing ion channels.”  Baron A.et.al.   11457851
[5] “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
[6] “Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system.”  Alvarez de la Rosa D.et.al.   11842212
[7] “ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1.”  Deval E.et.al.   14976185
[8] “Analysis of the membrane topology of the acid-sensing ion channel 2a.”  Saugstad J.A.et.al.   15504740

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FASTA formatted sequence
1:	MDLKESPSEG SLQPSSIQIF ANTSTLHGIR HIFVYGPLTI RRVLWAVAFV GSLGLLLVES 
61:	SERVSYYFSY QHVTKVDEVV AQSLVFPAVT LCNLNGFRFS RLTTNDLYHA GELLALLDVN 
121:	LQIPDPHLAD PTVLEALRQK ANFKHYKPKQ FSMLEFLHRV GHDLKDMMLY CKFKGQECGH 
181:	QDFTTVFTKY GKCYMFNSGE DGKPLLTTVK GGTGNGLEIM LDIQQDEYLP IWGETEETTF 
241:	EAGVKVQIHS QSEPPFIQEL GFGVAPGFQT FVATQEQRLT YLPPPWGECR SSEMGLDFFP 
301:	VYSITACRID CETRYIVENC NCRMVHMPGD APFCTPEQHK ECAEPALGLL AEKDSNYCLC 
361:	RTPCNLTRYN KELSMVKIPS KTSAKYLEKK FNKSEKYISE NILVLDIFFE ALNYETIEQK 
421:	KAYEVAALLG DIGGQMGLFI GASLLTILEL FDYIYELIKE KLLDLLGKEE EEGSHDENMS 
481:	TCDTMPNHSE TISHTVNVPL QTALGTLEEI AC