ASIC1_HUMAN
ID ASIC1_HUMAN Reviewed; 528 AA.
AC P78348; A3KN86; E5KBL7; P78349; Q96CV2;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Acid-sensing ion channel 1 {ECO:0000303|PubMed:10798398};
DE Short=ASIC1 {ECO:0000303|PubMed:10798398};
DE AltName: Full=Amiloride-sensitive cation channel 2, neuronal;
DE AltName: Full=Brain sodium channel 2 {ECO:0000303|PubMed:9037075};
DE Short=BNaC2 {ECO:0000303|PubMed:9037075};
GN Name=ASIC1; Synonyms=ACCN2, BNAC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=9037075; DOI=10.1073/pnas.94.4.1459;
RA Garcia-Anoveros J., Derfler B.H., Neville-Golden J., Hyman B.T.,
RA Corey D.P.;
RT "BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels
RT related to degenerins and epithelial sodium channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:1459-1464(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION (ISOFORMS 1; 2 AND 3), AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Spinal ganglion;
RX PubMed=21036899; DOI=10.1074/jbc.m110.171330;
RA Hoagland E.N., Sherwood T.W., Lee K.G., Walker C.J., Askwith C.C.;
RT "Identification of a calcium permeable human acid-sensing ion channel 1
RT transcript variant.";
RL J. Biol. Chem. 285:41852-41862(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Huque T., Cao J., Lischka F.W., Spielman A.I., Feldman R.S., Cowart B.J.,
RA Wise P.M., Pribitkin E.A., Mackler S.A., Brand J.G.;
RT "Acid sensing ion channels in human taste tissue.";
RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 231-528 (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 INTERACTION WITH PRKCABP.
RX PubMed=11802773; DOI=10.1042/0264-6021:3610443;
RA Hruska-Hageman A.M., Wemmie J.A., Price M.P., Welsh M.J.;
RT "Interaction of the synaptic protein PICK1 (protein interacting with C
RT kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+
RT channel 1) and ASIC (acid-sensing ion channel).";
RL Biochem. J. 361:443-450(2002).
RN [9]
RP PHOSPHORYLATION BY PKC.
RX PubMed=12244121; DOI=10.1074/jbc.m208995200;
RA Berdiev B.K., Xia J., Jovov B., Markert J.M., Mapstone T.B.,
RA Gillespie G.Y., Fuller C.M., Bubien J.K., Benos D.J.;
RT "Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function.";
RL J. Biol. Chem. 277:45734-45740(2002).
RN [10]
RP PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-478 AND SER-479, PHOSPHORYLATION
RP AT SER-479, INTERACTION WITH PRKCABP, AND SUBCELLULAR LOCATION.
RX PubMed=12578970; DOI=10.1073/pnas.252782799;
RA Leonard A.S., Yermolaieva O., Hruska-Hageman A., Askwith C.C., Price M.P.,
RA Wemmie J.A., Welsh M.J.;
RT "cAMP-dependent protein kinase phosphorylation of the acid-sensing ion
RT channel-1 regulates its binding to the protein interacting with C-kinase-
RT 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2029-2034(2003).
RN [11]
RP REGULATION BY SERINE PROTEASES.
RX PubMed=15247234; DOI=10.1074/jbc.m407381200;
RA Poirot O., Vukicevic M., Boesch A., Kellenberger S.;
RT "Selective regulation of acid-sensing ion channel 1 by serine proteases.";
RL J. Biol. Chem. 279:38448-38457(2004).
RN [12]
RP MUTAGENESIS OF PHE-352 AND ASP-357, SITES PHE-352 AND ASP-357, INTERACTION
RP WITH THE SPIDER VENOM PSALMOTOXIN-1, AND SUBUNIT.
RX PubMed=19654327; DOI=10.1074/jbc.m109.029009;
RA Sherwood T., Franke R., Conneely S., Joyner J., Arumugan P., Askwith C.;
RT "Identification of protein domains that control proton and calcium
RT sensitivity of ASIC1a.";
RL J. Biol. Chem. 284:27899-27907(2009).
RN [13]
RP INTERACTION WITH SNAKE VENOM MAMBALGIN-1, 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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SPIDER VENOM
RP PSALMOTOXIN-1, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=22760635; DOI=10.1038/ncomms1917;
RA Dawson R.J., Benz J., Stohler P., Tetaz T., Joseph C., Huber S., Schmid G.,
RA Hugin D., Pflimlin P., Trube G., Rudolph M.G., Hennig M., Ruf A.;
RT "Structure of the acid-sensing ion channel 1 in complex with the gating
RT modifier Psalmotoxin 1.";
RL Nat. Commun. 3:936-943(2012).
RN [15]
RP SUBUNIT, AND INTERACTION WITH PI-THERAPHOTOXIN-HM3A.
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).
CC -!- FUNCTION: Isoform 2 and isoform 3 function as proton-gated sodium
CC channels; they are activated by a drop of the extracellular pH and then
CC become rapidly desensitized. The channel generates a biphasic current
CC with a fast inactivating and a slow sustained phase. Has high
CC selectivity for sodium ions and can also transport lithium ions with
CC high efficiency. Isoform 2 can also transport potassium, but with lower
CC efficiency. It is nearly impermeable to the larger rubidium and cesium
CC ions. Isoform 3 can also transport calcium ions. Mediates glutamate-
CC independent Ca(2+) entry into neurons upon acidosis. This Ca(2+)
CC overloading is toxic for cortical neurons and may be in part
CC responsible for ischemic brain injury. Heteromeric channel assembly
CC seems to modulate channel properties. Functions as a postsynaptic
CC proton receptor that influences intracellular Ca(2+) concentration and
CC calmodulin-dependent protein kinase II phosphorylation and thereby the
CC density of dendritic spines. Modulates activity in the circuits
CC underlying innate fear. {ECO:0000269|PubMed:22760635}.
CC -!- FUNCTION: Isoform 1 does not display proton-gated cation channel
CC activity. {ECO:0000269|PubMed:22760635}.
CC -!- ACTIVITY REGULATION: Inhibited by the diuretic amiloride. Inhibited by
CC Cs(1+) ions. Inhibited by spider venom psalmotoxin-1; this locks the
CC channel into its desensitized conformation.
CC {ECO:0000269|PubMed:22760635}.
CC -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins (By
CC similarity). Interacts with STOM and ASIC2 (By similarity). Interacts
CC with PRKCABP. Homotrimer of Asic1a (ASIC1 isoform 2) interacts with
CC spider venom psalmotoxin-1 (PubMed:19654327, PubMed:22760635).
CC Homotrimer of Asic1a (ASIC1 isoform 2) and Asic1b (ASIC1 isoform 3)
CC interacts with the spider venom pi-theraphotoxin-Hm3a
CC (PubMed:28327374). Homotrimer of Asic1a (ASIC1 isoform 2) interacts
CC with the snake venom mambalgin-1 (PubMed:23034652). Heterotrimer of
CC Asic1a-Asic2a (ASIC1 isoform 2-ASIC2 isoform 1) interacts with the
CC snake venom mambalgin-1 (PubMed:23034652). {ECO:0000250,
CC ECO:0000269|PubMed:11802773, ECO:0000269|PubMed:12578970,
CC ECO:0000269|PubMed:22760635, ECO:0000269|PubMed:23034652}.
CC -!- INTERACTION:
CC P78348; Q8N743: KIR3DL3; NbExp=3; IntAct=EBI-79189, EBI-17272405;
CC P78348; Q99735: MGST2; NbExp=3; IntAct=EBI-79189, EBI-11324706;
CC P78348; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-79189, EBI-79165;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12578970,
CC ECO:0000269|PubMed:21036899, ECO:0000269|PubMed:22760635}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:12578970,
CC ECO:0000269|PubMed:21036899, ECO:0000269|PubMed:22760635}.
CC Note=Localizes in synaptosomes at dendritic synapses of neurons.
CC Colocalizes with DLG4 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=Asic1a, hvariant 2 {ECO:0000303|PubMed:21036899};
CC IsoId=P78348-2; Sequence=Displayed;
CC Name=1; Synonyms=hvariant 1 {ECO:0000303|PubMed:21036899};
CC IsoId=P78348-1; Sequence=VSP_015596;
CC Name=3; Synonyms=Asic1b, hvariant 3 {ECO:0000303|PubMed:21036899};
CC IsoId=P78348-3; Sequence=VSP_045298;
CC -!- TISSUE SPECIFICITY: Expressed in most or all neurons.
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 {ECO:0000269|PubMed:12244121, ECO:0000269|PubMed:12578970}.
CC -!- MISCELLANEOUS: Potentiated by Ca(2+), Mg(2+), Ba(2+) and multivalent
CC cations. Inhibited by anti-inflammatory drugs like salicylic acid (By
CC similarity). Potentiated by FMRFamide-related neuropeptides. PH
CC dependence may be regulated by serine proteases. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. ASIC1 subfamily. {ECO:0000305}.
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DR EMBL; U78180; AAB48980.1; -; mRNA.
DR EMBL; U78181; AAB48981.1; -; mRNA.
DR EMBL; HM991481; ADP44689.1; -; mRNA.
DR EMBL; EU078959; ABU48925.1; -; mRNA.
DR EMBL; AC025154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471111; EAW58118.1; -; Genomic_DNA.
DR EMBL; BC013891; AAH13891.2; -; mRNA.
DR EMBL; BC133707; AAI33708.1; -; mRNA.
DR CCDS; CCDS44876.1; -. [P78348-2]
DR CCDS; CCDS58228.1; -. [P78348-3]
DR CCDS; CCDS8796.1; -. [P78348-1]
DR RefSeq; NP_001086.2; NM_001095.3. [P78348-2]
DR RefSeq; NP_001243759.1; NM_001256830.1. [P78348-3]
DR RefSeq; NP_064423.2; NM_020039.3. [P78348-1]
DR PDB; 6L6I; X-ray; 3.24 A; A/B/C=25-464.
DR PDB; 6L6N; X-ray; 2.86 A; A/B/C=25-464.
DR PDB; 7CFS; EM; 3.56 A; A/B/C=1-468.
DR PDB; 7CFT; EM; 3.90 A; A/B/C=1-468.
DR PDB; 7RNN; EM; 2.86 A; D=1-528.
DR PDBsum; 6L6I; -.
DR PDBsum; 6L6N; -.
DR PDBsum; 7CFS; -.
DR PDBsum; 7CFT; -.
DR PDBsum; 7RNN; -.
DR AlphaFoldDB; P78348; -.
DR SMR; P78348; -.
DR BioGRID; 106559; 80.
DR IntAct; P78348; 12.
DR STRING; 9606.ENSP00000228468; -.
DR BindingDB; P78348; -.
DR ChEMBL; CHEMBL1628477; -.
DR DrugBank; DB00594; Amiloride.
DR DrugBank; DB00586; Diclofenac.
DR DrugCentral; P78348; -.
DR GuidetoPHARMACOLOGY; 684; -.
DR GlyGen; P78348; 2 sites.
DR iPTMnet; P78348; -.
DR PhosphoSitePlus; P78348; -.
DR SwissPalm; P78348; -.
DR BioMuta; ASIC1; -.
DR DMDM; 296439456; -.
DR jPOST; P78348; -.
DR MassIVE; P78348; -.
DR PeptideAtlas; P78348; -.
DR PRIDE; P78348; -.
DR ProteomicsDB; 15296; -.
DR ProteomicsDB; 57582; -. [P78348-2]
DR ProteomicsDB; 57583; -. [P78348-1]
DR Antibodypedia; 26132; 316 antibodies from 37 providers.
DR DNASU; 41; -.
DR Ensembl; ENST00000228468.8; ENSP00000228468.4; ENSG00000110881.12. [P78348-1]
DR Ensembl; ENST00000447966.7; ENSP00000400228.3; ENSG00000110881.12. [P78348-2]
DR Ensembl; ENST00000552438.5; ENSP00000450247.1; ENSG00000110881.12. [P78348-3]
DR GeneID; 41; -.
DR KEGG; hsa:41; -.
DR MANE-Select; ENST00000447966.7; ENSP00000400228.3; NM_001095.4; NP_001086.2.
DR UCSC; uc001rvv.5; human. [P78348-2]
DR CTD; 41; -.
DR DisGeNET; 41; -.
DR GeneCards; ASIC1; -.
DR HGNC; HGNC:100; ASIC1.
DR HPA; ENSG00000110881; Tissue enriched (brain).
DR MIM; 602866; gene.
DR neXtProt; NX_P78348; -.
DR OpenTargets; ENSG00000110881; -.
DR PharmGKB; PA24434; -.
DR VEuPathDB; HostDB:ENSG00000110881; -.
DR eggNOG; KOG4294; Eukaryota.
DR GeneTree; ENSGT00940000158414; -.
DR HOGENOM; CLU_020415_1_2_1; -.
DR InParanoid; P78348; -.
DR OMA; RNCSHLF; -.
DR PhylomeDB; P78348; -.
DR TreeFam; TF330663; -.
DR PathwayCommons; P78348; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; P78348; -.
DR SIGNOR; P78348; -.
DR BioGRID-ORCS; 41; 35 hits in 1072 CRISPR screens.
DR ChiTaRS; ASIC1; human.
DR GeneWiki; ACCN2; -.
DR GenomeRNAi; 41; -.
DR Pharos; P78348; Tchem.
DR PRO; PR:P78348; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P78348; protein.
DR Bgee; ENSG00000110881; Expressed in right hemisphere of cerebellum and 139 other tissues.
DR ExpressionAtlas; P78348; baseline and differential.
DR Genevisible; P78348; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0044736; F:acid-sensing ion channel activity; IDA:UniProtKB.
DR GO; GO:0022839; F:ion gated channel activity; IEA:Ensembl.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IBA:GO_Central.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0071467; P:cellular response to pH; IDA:UniProtKB.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0010447; P:response to acidic pH; IEA:Ensembl.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0009268; P:response to pH; TAS:ProtInc.
DR GO; GO:0050915; P:sensory perception of sour taste; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006814; P:sodium ion transport; NAS: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 3D-structure; Alternative splicing; Calcium; Calcium transport;
KW Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Sodium; Sodium channel;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..528
FT /note="Acid-sensing ion channel 1"
FT /id="PRO_0000181294"
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..427
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 428..454
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 455..528
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT MOTIF 444..446
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 287
FT /note="Important for channel gating"
FT /evidence="ECO:0000250"
FT SITE 352
FT /note="Important for interaction with the spider venom
FT psalmotoxin-1"
FT /evidence="ECO:0000269|PubMed:19654327"
FT SITE 357
FT /note="Key residue for defining the pH sensitivity of ASIC1
FT (isoform 1)"
FT /evidence="ECO:0000269|PubMed:19654327"
FT MOD_RES 479
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12578970"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NXK8"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
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..367
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 310..363
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 314..361
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 323..345
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT DISULFID 325..337
FT /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT VAR_SEQ 1..185
FT /note="MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLG
FT SLAVLLCVCTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHA
FT GELLALLNNRYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLL
FT SCHFRGEVCSAEDFK -> MPIQIFCSMSFSSGEEAPGPLGDIWGPHHHQQQQDISESE
FT EEEEEKEKEAVRKEASEGHSPMDLVAFANSCTLHGTNHIFVEGGPGPRQVLWAVAFVLA
FT LGAFLCQVGDRVAYYLSYPHVTLLNEVATTELAFPAVTLCNTNAVRLSQLSYPDLLYLA
FT PMLGLDESDDPGVPLAPPGPEAFSGEPFNLHRFYNRSCHRLEDMLLYCSYQGGPCGPHN
FT FS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21036899"
FT /id="VSP_045298"
FT VAR_SEQ 433
FT /note="G -> GELLMTPVPFSCHGHGVAPYHPKAGCSLLSHEGPPPQRPFPKPCCLG
FT (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9037075, ECO:0000303|Ref.3"
FT /id="VSP_015596"
FT MUTAGEN 352
FT /note="F->L: 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:19654327"
FT MUTAGEN 357
FT /note="D->A,N: Large decrease in response to pH 6.5
FT solutions."
FT /evidence="ECO:0000269|PubMed:19654327"
FT MUTAGEN 478
FT /note="S->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:12578970"
FT MUTAGEN 479
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:12578970"
FT CONFLICT 212
FT /note="G -> D (in Ref. 1; AAB48980/AAB48981)"
FT /evidence="ECO:0000305"
FT HELIX 25..34
FT /evidence="ECO:0007829|PDB:6L6I"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:6L6I"
FT TURN 46..50
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 51..61
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 73..81
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 105..111
FT /evidence="ECO:0007829|PDB:6L6N"
FT TURN 112..116
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 132..141
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:6L6I"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 243..250
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:7RNN"
FT HELIX 258..261
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 269..281
FT /evidence="ECO:0007829|PDB:6L6N"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 307..323
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 339..344
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 346..355
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:6L6I"
FT STRAND 366..382
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 384..393
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 398..404
FT /evidence="ECO:0007829|PDB:6L6N"
FT STRAND 405..426
FT /evidence="ECO:0007829|PDB:6L6N"
FT HELIX 429..448
FT /evidence="ECO:0007829|PDB:6L6N"
SQ SEQUENCE 528 AA; 59909 MW; 9E998F711C208450 CRC64;
MELKAEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV
CTERVQYYFH YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN
RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEVCS
AEDFKVVFTR YGKCYTFNSG RDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS
FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVACQEQRL IYLPPPWGTC KAVTMDSDLD
FFDSYSITAC RIDCETRYLV ENCNCRMVHM PGDAPYCTPE QYKECADPAL DFLVEKDQEY
CVCEMPCNLT RYGKELSMVK IPSKASAKYL AKKFNKSEQY IGENILVLDI FFEVLNYETI
EQKKAYEIAG LLGDIGGQMG LFIGASILTV LELFDYAYEV IKHKLCRRGK CQKEAKRSSA
DKGVALSLDD VKRHNPCESL RGHPAGMTYA ANILPHHPAR GTFEDFTC
