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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:O35240
Protein Name:DRASIC
Length:533
Molecular Weight:59227.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Cytoplasm1 / Multi-pass membrane protein2
Substrate cations

Cross database links:

RefSeq: NP_775158.1   
Entrez Gene ID: 286920   
Pfam: PF00858   
KEGG: rno:286920   

Gene Ontology

GO:0005737 C:cytoplasm
GO:0005887 C:integral to plasma membrane
GO:0015280 F:amiloride-sensitive sodium channel activity
GO:0005515 F:protein binding
GO:0001101 P:response to acid
GO:0006814 P:sodium ion transport

References (17)

[1] “Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons.”  Waldmann R.et.al.   9261094
[2] “A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.”  Lingueglia E.et.al.   9368048
[3] “A sensory neuron-specific, proton-gated ion channel.”  Chen C.-C.et.al.   9707631
[4] “The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore.”  Coscoy S.et.al.   10187795
[5] “Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+.”  Babinski K.et.al.   10842183
[6] “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
[7] “Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons.”  Immke D.C.et.al.   11528414
[8] “Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF.”  Catarsi S.et.al.   11587714
[9] “Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons.”  Sutherland S.P.et.al.   11120882
[10] “Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels.”  Mamet J.et.al.   12486159
[11] “Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system.”  Alvarez de la Rosa D.et.al.   11842212
[12] “How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons.”  Mamet J.et.al.   14522957
[13] “Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.”  Immke D.C.et.al.   12526774
[14] “Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability.”  Deval E.et.al.   12668052
[15] “A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.”  Diochot S.et.al.   15044953
[16] “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
[17] “PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current.”  Hruska-Hageman A.M.et.al.   15317815

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FASTA formatted sequence
1:	MKPRSGLEEA QRRQASDIRV FASSCTMHGL GHIFGPGGLT LRRGLWATAV LLSLAAFLYQ 
61:	VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR SRLTPNDLHW AGTALLGLDP 
121:	AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL YARAGHSLED MLLDCRYRGQ PCGPENFTVI 
181:	FTRMGQCYTF NSGAHGAELL TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV 
241:	QIHSQDEPPA IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASLDP DDFDPEPSDP 
301:	LGSPRPRPSP PYSLIGCRLA CESRYVARKC GCRMMHMPGN SPVCSPQQYK DCASPALDAM 
361:	LRKDTCVCPN PCATTRYAKE LSMVRIPSRA SARYLARKYN RSESYITENV LVLDIFFEAL 
421:	NYEAVEQKAA YEVSELLGDI GGQMGLFIGA SLLTILEILD YLCEVFQDRV LGYFWNRRSA 
481:	QKRSGNTLLQ EELNGHRTHV PHLSLGPRPP TTPCAVTKTL SASHRTCYLV TRL