ASIC1_RAT
ID ASIC1_RAT Reviewed; 526 AA.
AC P55926; O88762; Q91YB8; Q99NA1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Acid-sensing ion channel 1 {ECO:0000303|PubMed:9062189};
DE Short=ASIC1 {ECO:0000303|PubMed:9062189};
DE AltName: Full=Amiloride-sensitive cation channel 2, neuronal;
DE AltName: Full=Brain sodium channel 2;
DE Short=BNaC2;
GN Name=Asic1; Synonyms=Accn2, Bnac2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP ACTIVITY REGULATION.
RX PubMed=9062189; DOI=10.1038/386173a0;
RA Waldmann R., Champigny G., Bassilana F., Heurteaux C., Lazdunski M.;
RT "A proton-gated cation channel involved in acid-sensing.";
RL Nature 386:173-177(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Spinal ganglion;
RX PubMed=9707631; DOI=10.1073/pnas.95.17.10240;
RA Chen C.-C., England S., Akopian A.N., Wood J.N.;
RT "A sensory neuron-specific, proton-gated ion channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10240-10245(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), DOMAIN, AND FUNCTION.
RC TISSUE=Inner ear;
RX PubMed=11448963; DOI=10.1074/jbc.m104030200;
RA Baessler E.-L., Ngo-Anh T.J., Geisler H.-S., Ruppersberg J.P., Gruender S.;
RT "Molecular and functional characterization of acid-sensing ion channel
RT (ASIC) 1b.";
RL J. Biol. Chem. 276:33782-33787(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Trigeminal ganglion;
RX PubMed=11588592; DOI=10.1097/00001756-200109170-00022;
RA Ugawa S., Ueda T., Takahashi E., Hirabayashi Y., Yoneda T., Komai S.,
RA Shimada S.;
RT "Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-
RT beta.";
RL NeuroReport 12:2865-2869(2001).
RN [5]
RP TISSUE SPECIFICITY, INTERACTION WITH ASIC1, MUTAGENESIS OF GLY-431, AND
RP FUNCTION.
RX PubMed=9360943; DOI=10.1074/jbc.272.46.28819;
RA Bassilana F., Champigny G., Waldmann R., de Weille J.R., Heurteaux C.,
RA Lazdunski M.;
RT "The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin
RT MDEG form a heteromultimeric H+-gated Na+ channel with novel properties.";
RL J. Biol. Chem. 272:28819-28822(1997).
RN [6]
RP INTERACTION WITH THE SPIDER VENOM PSALMOTOXIN-1 TOXIN, AND SUBUNIT.
RX PubMed=10829030; DOI=10.1074/jbc.m003643200;
RA Escoubas P., de Weille J.R., Lecoq A., Diochot S., Waldmann R.,
RA Champigny G., Moinier D., Menez A., Lazdunski M.;
RT "Isolation of a tarantula toxin specific for a class of proton-gated Na+
RT channels.";
RL J. Biol. Chem. 275:25116-25121(2000).
RN [7]
RP REGULATION BY FMRFAMIDE-RELATED PEPTIDES.
RX PubMed=10798398; DOI=10.1016/s0896-6273(00)81144-7;
RA Askwith C.C., Cheng C., Ikuma M., Benson C., Price M.P., Welsh M.J.;
RT "Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory
RT neurons and proton-gated DEG/ENaC channels.";
RL Neuron 26:133-141(2000).
RN [8]
RP INDUCTION, AND INHIBITION BY DRUGS.
RX PubMed=11588175; DOI=10.1523/jneurosci.21-20-08026.2001;
RA Voilley N., de Weille J.R., Mamet J., Lazdunski M.;
RT "Nonsteroid anti-inflammatory drugs inhibit both the activity and the
RT inflammation-induced expression of acid-sensing ion channels in
RT nociceptors.";
RL J. Neurosci. 21:8026-8033(2001).
RN [9]
RP MUTAGENESIS OF PHE-100; VAL-103; LYS-105 AND ASN-106, AND FUNCTION.
RX PubMed=12198124; DOI=10.1074/jbc.m205877200;
RA Babini E., Paukert M., Geisler H.-S., Gruender S.;
RT "Alternative splicing and interaction with di- and polyvalent cations
RT control the dynamic range of acid-sensing ion channel 1 (ASIC1).";
RL J. Biol. Chem. 277:41597-41603(2002).
RN [10]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11842212; DOI=10.1073/pnas.042688199;
RA Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M.;
RT "Functional implications of the localization and activity of acid-sensitive
RT channels in rat peripheral nervous system.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002).
RN [11]
RP MUTAGENESIS OF SER-83; GLN-84; LEU-85 AND 128-GLN--ASP-131.
RX PubMed=12947112; DOI=10.1074/jbc.m304441200;
RA Coric T., Zhang P., Todorovic N., Canessa C.M.;
RT "The extracellular domain determines the kinetics of desensitization in
RT acid-sensitive ion channel 1.";
RL J. Biol. Chem. 278:45240-45247(2003).
RN [12]
RP FUNCTION.
RX PubMed=15369669; DOI=10.1016/j.cell.2004.08.026;
RA Xiong Z.-G., Zhu X.-M., Chu X.-P., Minami M., Hey J., Wei W.-L.,
RA MacDonald J.F., Wemmie J.A., Price M.P., Welsh M.J., Simon R.P.;
RT "Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion
RT channels.";
RL Cell 118:687-698(2004).
RN [13]
RP MUTAGENESIS OF GLU-425; ASP-432 AND GLN-436.
RX PubMed=15452199; DOI=10.1085/jgp.200308973;
RA Paukert M., Babini E., Pusch M., Grunder S.;
RT "Identification of the Ca2+ blocking site of acid-sensing ion channel
RT (ASIC) 1: implications for channel gating.";
RL J. Gen. Physiol. 124:383-394(2004).
RN [14]
RP INTERACTION WITH SNAKE VENOM MAMBALGIN-1 AND MAMBALGIN-2, AND SUBUNIT.
RC TISSUE=Venom, and Venom gland;
RX PubMed=23034652; DOI=10.1038/nature11494;
RA Diochot S., Baron A., Salinas M., Douguet D., Scarzello S.,
RA Dabert-Gay A.-S., Debayle D., Friend V., Alloui A., Lazdunski M.,
RA Lingueglia E.;
RT "Black mamba venom peptides target acid-sensing ion channels to abolish
RT pain.";
RL Nature 490:552-555(2012).
RN [15]
RP INTERACTION WITH MAMBALGIN-1; MAMBALGIN-2 AND MAMBALGIN-3, SUBUNIT, AND
RP REVIEW.
RX PubMed=23624383; DOI=10.1016/j.toxicon.2013.04.008;
RA Baron A., Diochot S., Salinas M., Deval E., Noel J., Lingueglia E.;
RT "Venom toxins in the exploration of molecular, physiological and
RT pathophysiological functions of acid-sensing ion channels.";
RL Toxicon 75:187-204(2013).
RN [16]
RP MUTAGENESIS OF PHE-350, INTERACTION WITH MAMBALGIN-2, AND SUBUNIT.
RX PubMed=24323786; DOI=10.1002/anie.201308898;
RA Schroeder C.I., Rash L.D., Vila-Farres X., Rosengren K.J., Mobli M.,
RA King G.F., Alewood P.F., Craik D.J., Durek T.;
RT "Chemical synthesis, 3D structure, and ASIC binding site of the toxin
RT mambalgin-2.";
RL Angew. Chem. Int. Ed. 53:1017-1020(2014).
RN [17]
RP MUTAGENESIS OF ARG-190; 259-ASP-GLN-260; 349-ASP-PHE-350; ASP-349; PHE-350;
RP VAL-352; GLN-356 AND GLU-357, INTERACTION WITH MAMBALGIN-2, AND SUBUNIT.
RX PubMed=24695733; DOI=10.1074/jbc.m114.561076;
RA Salinas M., Besson T., Delettre Q., Diochot S., Boulakirba S., Douguet D.,
RA Lingueglia E.;
RT "Binding site and inhibitory mechanism of the mambalgin-2 pain-relieving
RT peptide on acid-sensing ion channel 1a.";
RL J. Biol. Chem. 289:13363-13373(2014).
RN [18]
RP MUTAGENESIS OF GLU-235; TYR-316; PHE-350 AND LYS-354, INTERACTION WITH THE
RP SPIDER VENOM PSALMOTOXIN-1 TOXIN, AND SUBUNIT.
RX PubMed=26248594; DOI=10.1111/bph.13267;
RA Saez N.J., Deplazes E., Cristofori-Armstrong B., Chassagnon I.R., Lin X.,
RA Mobli M., Mark A.E., Rash L.D., King G.F.;
RT "Molecular dynamics and functional studies define a hot spot of crystal
RT contacts essential for psalmotoxin-1 inhibition of acid-sensing ion channel
RT 1a.";
RL Br. J. Pharmacol. 172:4985-4995(2015).
RN [19]
RP MUTAGENESIS OF PHE-350, INTERACTION WITH MAMBALGIN-1, AND SUBUNIT.
RX PubMed=26680001; DOI=10.1074/jbc.m115.702373;
RA Mourier G., Salinas M., Kessler P., Stura E.A., Leblanc M., Tepshi L.,
RA Besson T., Diochot S., Baron A., Douguet D., Lingueglia E., Servent D.;
RT "Mambalgin-1 pain-relieving peptide, stepwise solid-phase synthesis,
RT crystal structure, and functional domain for acid-sensing ion channel 1a
RT inhibition.";
RL J. Biol. Chem. 291:2616-2629(2016).
RN [20]
RP MUTAGENESIS OF HIS-173; PHE-174; ARG-175; GLU-177; ALA-178 AND PHE-350,
RP INTERACTION WITH THE SPIDER VENOM PI-THERAPHOTOXIN-HM3A, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=28327374; DOI=10.1016/j.neuropharm.2017.03.020;
RA Er S.Y., Cristofori-Armstrong B., Escoubas P., Rash L.D.;
RT "Discovery and molecular interaction studies of a highly stable, tarantula
RT peptide modulator of acid-sensing ion channel 1.";
RL Neuropharmacology 114:3750-3755(2017).
RN [21]
RP MUTAGENESIS OF PHE-350, INTERACTION WITH THE SPIDER PI-HEXATOXIN-HI1A, AND
RP SUBUNIT.
RX PubMed=28320941; DOI=10.1073/pnas.1614728114;
RA Chassagnon I.R., McCarthy C.A., Chin Y.K., Pineda S.S., Keramidas A.,
RA Mobli M., Pham V., De Silva T.M., Lynch J.W., Widdop R.E., Rash L.D.,
RA King G.F.;
RT "Potent neuroprotection after stroke afforded by a double-knot spider-venom
RT peptide that inhibits acid-sensing ion channel 1a.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:3750-3755(2017).
CC -!- FUNCTION: Proton-gated sodium channel; it is activated by a drop of the
CC extracellular pH and then becomes rapidly desensitized. Generates a
CC biphasic current with a fast inactivating and a slow sustained phase.
CC Has high selectivity for sodium ions and can also transport lithium
CC ions with high efficiency. Can also transport potassium ions, but with
CC lower efficiency. It is nearly impermeable to the larger rubidium and
CC cesium ions. Isoform 3 discrimates stronger than isoform 1 between
CC monovalent cations. Isoform 3 can flux Ca(2+) while isoform 1 cannot.
CC Heteromeric channels composed of isoform 2 and isoform 3 are active but
CC have a lower pH-sensitivity. Mediates glutamate-independent Ca(2+)
CC entry into neurons upon acidosis. This Ca(2+) overloading is toxic for
CC cortical neurons and may be in part responsible for ischemic brain
CC injury. Heteromeric channel assembly seems to modulate channel
CC properties. {ECO:0000269|PubMed:11448963, ECO:0000269|PubMed:11588592,
CC ECO:0000269|PubMed:12198124, ECO:0000269|PubMed:15369669,
CC ECO:0000269|PubMed:9062189, ECO:0000269|PubMed:9360943,
CC ECO:0000269|PubMed:9707631}.
CC -!- ACTIVITY REGULATION: Inhibited by the diuretic amiloride.
CC {ECO:0000269|PubMed:9062189}.
CC -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins (By
CC similarity). Interacts with STOM and PRKCABP (By similarity). Interacts
CC with ASIC2. Interacts with the spider venom Pi-hexatoxin-Hi1a
CC (PubMed:28320941). Homotrimer of Asic1a interacts with the spider venom
CC psalmotoxin-1 (PubMed:10829030, PubMed:26248594). Homotrimer of Asic1a
CC (isoform 1) and Asic1b (isoform 3) and heterotrimer of Asic1a/Asic1b
CC interact with the spider venom Pi-theraphotoxin-Hm3a (PubMed:28327374).
CC Homotrimer of Asic1a (ASIC1 isoform 1) interacts with the snake venom
CC mambalgin-1, mambalgin-2 and mambalgin-3 (PubMed:23034652,
CC PubMed:23624383, PubMed:24323786, PubMed:24695733, PubMed:26680001).
CC Homotrimer of Asic1b (isoform 3) interacts with the snake venom
CC mambalgin-1, mambalgin-2 and mambalgin-3 (PubMed:23034652,
CC PubMed:23624383, PubMed:24323786, PubMed:26680001). Heterotrimer of
CC Asic1a-Asic1b (ASIC1 isoform 1-ASIC1 isoform 3) interacts with the
CC snake venom mambalgin-1 and mambalgin-2 (PubMed:23034652). Heterotrimer
CC of Asic1a-Asic2a interacts with the snake venom mambalgin-1, mambalgin-
CC 2 and mambalgin-3 (PubMed:23034652, PubMed:23624383, PubMed:26680001).
CC Heterotrimer of Asic1a-Asic2b (ASIC1 isoform 1-ASIC2 isoform 2)
CC interacts with the snake venom mambalgin-1 and mambalgin-2
CC (PubMed:23034652). {ECO:0000250, ECO:0000269|PubMed:10829030,
CC ECO:0000269|PubMed:23034652, ECO:0000269|PubMed:23624383,
CC ECO:0000269|PubMed:24323786, ECO:0000269|PubMed:24695733,
CC ECO:0000269|PubMed:26248594, ECO:0000269|PubMed:26680001,
CC ECO:0000269|PubMed:28320941, ECO:0000269|PubMed:28327374,
CC ECO:0000269|PubMed:9360943}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11842212,
CC ECO:0000269|PubMed:9062189, ECO:0000269|PubMed:9707631}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:11842212,
CC ECO:0000269|PubMed:9062189, ECO:0000269|PubMed:9707631}. Note=Localizes
CC in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=ASIC-alpha, asic1alpha, ASIC1a
CC {ECO:0000303|PubMed:11448963};
CC IsoId=P55926-1; Sequence=Displayed;
CC Name=2; Synonyms=ASIC-beta2;
CC IsoId=P55926-2; Sequence=VSP_015597, VSP_015598;
CC Name=3; Synonyms=ASIC-beta, ASIC1b {ECO:0000303|PubMed:11448963};
CC IsoId=P55926-3; Sequence=VSP_015597, VSP_015599;
CC -!- TISSUE SPECIFICITY: Expressed in dorsal root ganglia and sciatic nerve
CC (at protein level). Widely distributed throughout the brain. Expressed
CC in olfactory bulb, neo and allocortical regions, dentate granule cells,
CC pyramidal cells of CA1-CA3 subfields of the hippocampal formation,
CC habenula, basolateral amygdaloid nuclei, and in the Purkinje and
CC granule cells of the cerebellum. Diffusely detected over most other
CC regions of the basal ganglia, including thalamic nuclei, substantia
CC nigra, striatum and globus pallidus, hypothalamus, midbrain, pons,
CC medulla and choroid plexus. Isoform 3 is expressed only in dorsal root
CC ganglion (DRG) while isoform 1 is expressed in DRG, spinal chord,
CC trigeminal ganglia and the trigeminal mesencephalic nucleus.
CC {ECO:0000269|PubMed:11588592, ECO:0000269|PubMed:11842212,
CC ECO:0000269|PubMed:9360943, ECO:0000269|PubMed:9707631}.
CC -!- INDUCTION: Up-regulation upon tissues inflammation is abolished by
CC anti-inflammatory drugs. {ECO:0000269|PubMed:11588175}.
CC -!- DOMAIN: Channel opening involves a conformation change that affects
CC primarily the extracellular domain and the second transmembrane helix
CC and its orientation in the membrane. In the open state, the second
CC transmembrane helix is nearly perpendicular to the plane of the
CC membrane; in the desensitized state it is strongly tilted. Besides, the
CC second transmembrane domain is discontinuously helical in the open
CC state. The GAS motif of the selectivity filter is in an extended
CC conformation, giving rise to a distinct kink in the polypeptide chain.
CC A domain swap between subunits gives rise to a full-length
CC transmembrane helix (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation by PKA regulates interaction with PRKCABP and
CC subcellular location. Phosphorylation by PKC may regulate the channel
CC (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Potentiated by Ca(2+), Mg(2+), Ba(2+), multivalent
CC cations and potentiated by FMRFamide-related neuropeptides. pH
CC dependence may be regulated by serine proteases. Inhibited by anti-
CC inflammatory drugs like salicylic acid. Isoform 1 homomultimeric
CC channel is specifically and reversibly inhibited by psalmotoxin-1, a
CC spider venom toxin, while isoform 2 and other ASICs are insensitive.
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Blocked by Ca(2+). Mutagenesis of Asp-465
CC to Asn reduces Ca(2+) block. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. ASIC1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA07080.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 3]:
CC Sequence=CAA07080.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U94403; AAB53002.1; -; mRNA.
DR EMBL; AJ006519; CAA07080.1; ALT_FRAME; mRNA.
DR EMBL; AJ309926; CAC44267.1; -; mRNA.
DR EMBL; AB049451; BAB39864.1; -; mRNA.
DR RefSeq; NP_077068.1; NM_024154.2. [P55926-1]
DR RefSeq; XP_006257440.1; XM_006257378.3. [P55926-3]
DR AlphaFoldDB; P55926; -.
DR SMR; P55926; -.
DR MINT; P55926; -.
DR BindingDB; P55926; -.
DR ChEMBL; CHEMBL3562170; -.
DR GuidetoPHARMACOLOGY; 684; -.
DR TCDB; 1.A.6.1.2; the epithelial na(+) channel (enac) family.
DR GlyGen; P55926; 2 sites.
DR iPTMnet; P55926; -.
DR PhosphoSitePlus; P55926; -.
DR SwissPalm; P55926; -.
DR PRIDE; P55926; -.
DR ABCD; P55926; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000077175; ENSRNOP00000072206; ENSRNOG00000059765. [P55926-3]
DR GeneID; 79123; -.
DR KEGG; rno:79123; -.
DR CTD; 41; -.
DR RGD; 71062; Asic1.
DR VEuPathDB; HostDB:ENSRNOG00000059765; -.
DR GeneTree; ENSGT00940000158414; -.
DR HOGENOM; CLU_020415_1_2_1; -.
DR InParanoid; P55926; -.
DR OMA; RNCSHLF; -.
DR OrthoDB; 686369at2759; -.
DR PhylomeDB; P55926; -.
DR TreeFam; TF330663; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:P55926; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000059765; Expressed in cerebellum and 16 other tissues.
DR ExpressionAtlas; P55926; baseline and differential.
DR Genevisible; P55926; RN.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0044736; F:acid-sensing ion channel activity; ISS:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; ISO:RGD.
DR GO; GO:0022890; F:inorganic cation transmembrane transporter activity; IDA:MGI.
DR GO; GO:0005216; F:ion channel activity; IDA:RGD.
DR GO; GO:0022839; F:ion gated channel activity; ISO:RGD.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IBA:GO_Central.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:RGD.
DR GO; GO:0006812; P:cation transport; ISO:RGD.
DR GO; GO:0071467; P:cellular response to pH; ISS:UniProtKB.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IMP:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; ISO:RGD.
DR GO; GO:0007269; P:neurotransmitter secretion; IEA:Ensembl.
DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:0010447; P:response to acidic pH; ISO:RGD.
DR GO; GO:0001975; P:response to amphetamine; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; NAS:RGD.
DR GO; GO:0050915; P:sensory perception of sour taste; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR InterPro; IPR001873; ENaC.
DR InterPro; IPR004724; ENaC_chordates.
DR InterPro; IPR020903; ENaC_CS.
DR PANTHER; PTHR11690; PTHR11690; 1.
DR Pfam; PF00858; ASC; 1.
DR PRINTS; PR01078; AMINACHANNEL.
DR TIGRFAMs; TIGR00859; ENaC; 1.
DR PROSITE; PS01206; ASC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium transport; Cell membrane;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sodium; Sodium channel;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..526
FT /note="Acid-sensing ion channel 1"
FT /id="PRO_0000181300"
FT TOPO_DOM 1..45
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 46..69
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 70..425
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 426..452
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 453..526
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 20..25
FT /note="Involved in divalent cations permeability"
FT MOTIF 442..444
FT /note="Selectivity filter"
FT /evidence="ECO:0000305"
FT SITE 71
FT /note="Important for channel gating"
FT /evidence="ECO:0000250"
FT SITE 79
FT /note="Important for channel desensitizing"
FT /evidence="ECO:0000250"
FT SITE 175
FT /note="Important residue in interaction with the spider
FT venom Pi-theraphotoxin-Hm3a, which can explain functional
FT difference between ASIC1a and ASIC1b"
FT /evidence="ECO:0000269|PubMed:28327374"
FT SITE 177
FT /note="Important residue for interaction with the spider
FT venom Pi-theraphotoxin-Hm3a, which can explain functional
FT difference between ASIC1a and ASIC1b"
FT /evidence="ECO:0000269|PubMed:28327374"
FT SITE 287
FT /note="Important for channel gating"
FT /evidence="ECO:0000250"
FT SITE 349
FT /note="Important for interaction with the snake venom
FT mambalgin-2"
FT /evidence="ECO:0000269|PubMed:24695733"
FT SITE 350
FT /note="Important for interaction with the snake venom
FT mambalgin-1 and mambalgin-2 toxins, probably binds to its
FT residue L-53; Important for interaction with the spider
FT venom Pi-hexatoxin-Hi1a and psalmotoxin-1"
FT /evidence="ECO:0000269|PubMed:24323786,
FT ECO:0000269|PubMed:24695733, ECO:0000269|PubMed:26248594,
FT ECO:0000269|PubMed:26680001, ECO:0000269|PubMed:28320941"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78348"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NXK8"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 93..194
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 172..179
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 290..365
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 308..361
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 312..359
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 321..343
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 323..335
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT VAR_SEQ 1..185
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11448963,
FT ECO:0000303|PubMed:11588592, ECO:0000303|PubMed:9707631"
FT /id="VSP_015597"
FT VAR_SEQ 186
FT /note="V -> MADIWGPHHHRQQQDSSESEEEEEKEMEAGSELDEGDDSPRDLVAFA
FT NSCTLHGASHVFVEGGPGPRQALWAVAFVIALGAFLCQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11588592"
FT /id="VSP_015598"
FT VAR_SEQ 186
FT /note="V -> MPIQIFCSVSFSSGEEAPGSMADIWGPHHHRQQQDSSESEEEEEKEM
FT EAGSELDEGDDSPRDLVAFANSCTLHGASHVFVEGGPGPRQALWAVAFVIALGAFLCQV
FT GDRVAYYLSYPHVTLLDEVATTELVFPAVTFCNTNAVRLSQLSYPDLLYLAPMLGLDES
FT DDPGVPLAPPGPEAFSGEPFNLHRFYNRSCHRLEDMLLYCSYCGGPCGPHNFSV (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:11448963,
FT ECO:0000303|PubMed:9707631"
FT /id="VSP_015599"
FT MUTAGEN 83
FT /note="S->P: No effect. Increases desensitization rates;
FT when associated with L-84 and M-85."
FT /evidence="ECO:0000269|PubMed:12947112"
FT MUTAGEN 84
FT /note="Q->L: No effect. Increases desensitization rates;
FT when associated with P-83 and M-85."
FT /evidence="ECO:0000269|PubMed:12947112"
FT MUTAGEN 85
FT /note="L->M: No effect. Increases desensitization rates;
FT when associated with P-83 and L-84."
FT /evidence="ECO:0000269|PubMed:12947112"
FT MUTAGEN 100
FT /note="F->L: No effect on channel activation and
FT inactivation."
FT /evidence="ECO:0000269|PubMed:12198124"
FT MUTAGEN 103
FT /note="V->L: No effect on channel activation and
FT inactivation."
FT /evidence="ECO:0000269|PubMed:12198124"
FT MUTAGEN 105
FT /note="K->Y: Activated and inactivated at lower pH."
FT /evidence="ECO:0000269|PubMed:12198124"
FT MUTAGEN 106
FT /note="N->P: Activated and inactivated at lower pH."
FT /evidence="ECO:0000269|PubMed:12198124"
FT MUTAGEN 128..131
FT /note="QMAD->HLVE: No effect on desensitization rates."
FT /evidence="ECO:0000269|PubMed:12947112"
FT MUTAGEN 173
FT /note="H->S: No significant decrease in inhibition by the
FT spider pi-theraphotoxin-Hm3a."
FT /evidence="ECO:0000269|PubMed:28327374"
FT MUTAGEN 174
FT /note="F->Y: No significant decrease in inhibition by the
FT spider pi-theraphotoxin-Hm3a."
FT /evidence="ECO:0000269|PubMed:28327374"
FT MUTAGEN 175
FT /note="R->C: 18-fold decrease in inhibition by the spider
FT pi-theraphotoxin-Hm3a."
FT /evidence="ECO:0000269|PubMed:28327374"
FT MUTAGEN 177
FT /note="E->G: 10-fold decrease in inhibition by the spider
FT pi-theraphotoxin-Hm3a."
FT /evidence="ECO:0000269|PubMed:28327374"
FT MUTAGEN 178
FT /note="A->P: No significant decrease in inhibition by the
FT spider pi-theraphotoxin-Hm3a."
FT /evidence="ECO:0000269|PubMed:28327374"
FT MUTAGEN 178
FT /note="A->V: No significant decrease in inhibition by the
FT spider pi-theraphotoxin-Hm3a."
FT /evidence="ECO:0000269|PubMed:28327374"
FT MUTAGEN 190
FT /note="R->K: Small decrease in inhibition by the snake
FT mambalgin-2 toxin; RDQ-KQE mutant."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 235
FT /note="E->A: No change in the shift of pH for both
FT activation and desensitization by the spider venom
FT psalmotoxin-1."
FT /evidence="ECO:0000269|PubMed:26248594"
FT MUTAGEN 259..260
FT /note="DQ->QE: Small decrease in inhibition by the snake
FT mambalgin-2 toxin; RDQ-KQE mutant."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 316
FT /note="Y->A: No change in the shift of pH for both
FT activation and desensitization by the spider venom
FT psalmotoxin-1."
FT /evidence="ECO:0000269|PubMed:26248594"
FT MUTAGEN 349..350
FT /note="DF->GL: Complete loss in inhibition by 200 nM of the
FT snake mambalgin-2 toxin."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 349
FT /note="D->G: High decrease in inhibition by the snake
FT mambalgin-2 toxin."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 350
FT /note="F->A: Complete loss of inhibition by the spider Pi-
FT hexatoxin-Hi1a, and by the snake mambalgin-2 toxin.
FT Potentiated by the spider pi-theraphotoxin-Hm3a (at both pH
FT 7.35 and 7.45) and inhibited at higher toxin concentration
FT at pH 7.35. Complete loss in the shift of pH for both
FT activation and desensitization by the spider venom
FT psalmotoxin-1."
FT /evidence="ECO:0000269|PubMed:24323786,
FT ECO:0000269|PubMed:26248594, ECO:0000269|PubMed:28320941,
FT ECO:0000269|PubMed:28327374"
FT MUTAGEN 350
FT /note="F->L: 37-fold decrease in inbibition by the snake
FT mambalgin-1 toxin. Very high decrease in inhibition by the
FT snake mambalgin-2 toxin."
FT /evidence="ECO:0000269|PubMed:24695733,
FT ECO:0000269|PubMed:26680001"
FT MUTAGEN 352
FT /note="V->A: Moderate decrease in inhibition by the snake
FT mambalgin-2 toxin."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 354
FT /note="K->A: No change in the shift of pH for both
FT activation and desensitization by the spider venom
FT psalmotoxin-1."
FT /evidence="ECO:0000269|PubMed:26248594"
FT MUTAGEN 356
FT /note="Q->S: Moderate decrease in inhibition by the snake
FT mambalgin-2 toxin."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 357
FT /note="E->N: Moderate decrease in inhibition by the snake
FT mambalgin-2 toxin."
FT /evidence="ECO:0000269|PubMed:24695733"
FT MUTAGEN 425
FT /note="E->G: Reduction of Ca(2+) block. Loss of Ca(2+)
FT block; when associated with C-432."
FT /evidence="ECO:0000269|PubMed:15452199"
FT MUTAGEN 431
FT /note="G->V,F: Constitutive channel activity."
FT /evidence="ECO:0000269|PubMed:9360943"
FT MUTAGEN 432
FT /note="D->A: Reduction of Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:15452199"
FT MUTAGEN 432
FT /note="D->C: Reduction of Ca(2+) block. Loss of Ca(2+)
FT block; when associated with G-425."
FT /evidence="ECO:0000269|PubMed:15452199"
FT MUTAGEN 436
FT /note="Q->N: No effect on Ca(2+) block."
FT /evidence="ECO:0000269|PubMed:15452199"
FT CONFLICT P55926-3:128
FT /note="T -> S (in Ref. 2; CAA07080)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 526 AA; 59641 MW; 5462A7786E2A1726 CRC64;
MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV
CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN
RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEACS
AEDFKVVFTR YGKCYTFNSG QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS
FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF
DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF LVEKDQEYCV
CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG ENILVLDIFF EVLNYETIEQ
KKAYEIAGLL GDIGGQMGLF IGASILTVLE LFDYAYEVIK HRLCRRGKCQ KEAKRSSADK
GVALSLDDVK RHNPCESLRG HPAGMTYAAN ILPHHPARGT FEDFTC
