ASIC2_MOUSE
ID ASIC2_MOUSE Reviewed; 512 AA.
AC Q925H0; Q5SUU2; Q61203;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Acid-sensing ion channel 2;
DE Short=ASIC2;
DE AltName: Full=Amiloride-sensitive brain sodium channel;
DE AltName: Full=Amiloride-sensitive cation channel 1, neuronal;
DE AltName: Full=Brain sodium channel 1 {ECO:0000303|PubMed:11306621};
DE Short=BNC1;
DE Short=BNaC1 {ECO:0000303|PubMed:11306621};
GN Name=Asic2; Synonyms=Accn1, Bnac1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=9368048; DOI=10.1074/jbc.272.47.29778;
RA Lingueglia E., de Weille J.R., Bassilana F., Heurteaux C., Sakai H.,
RA Waldmann R., Lazdunski M.;
RT "A modulatory subunit of acid sensing ion channels in brain and dorsal root
RT ganglion cells.";
RL J. Biol. Chem. 272:29778-29783(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ;
RX PubMed=11306621; DOI=10.1523/jneurosci.21-08-02678.2001;
RA Garcia-Anoveros J., Samad T.A., Zuvela-Jelaska L., Woolf C.J., Corey D.P.;
RT "Transport and localization of the DEG/ENaC ion channel BNaC1alpha to
RT peripheral mechanosensory terminals of dorsal root ganglia neurons.";
RL J. Neurosci. 21:2678-2686(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP INTERACTION WITH STOM.
RX PubMed=15471860; DOI=10.1074/jbc.m407708200;
RA Price M.P., Thompson R.J., Eshcol J.O., Wemmie J.A., Benson C.J.;
RT "Stomatin modulates gating of acid-sensing ion channels.";
RL J. Biol. Chem. 279:53886-53891(2004).
RN [5]
RP TISSUE SPECIFICITY, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14762118; DOI=10.1523/jneurosci.4698-03.2004;
RA Ettaiche M., Guy N., Hofman P., Lazdunski M., Waldmann R.;
RT "Acid-sensing ion channel 2 is important for retinal function and protects
RT against light-induced retinal degeneration.";
RL J. Neurosci. 24:1005-1012(2004).
RN [6]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=15537887; DOI=10.1523/jneurosci.3196-04.2004;
RA Peng B.-G., Ahmad S., Chen S., Chen P., Price M.P., Lin X.;
RT "Acid-sensing ion channel 2 contributes a major component to acid-evoked
RT excitatory responses in spiral ganglion neurons and plays a role in noise
RT susceptibility of mice.";
RL J. Neurosci. 24:10167-10175(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND INDUCTION BY NEUROTROPHIN.
RX PubMed=15708491; DOI=10.1016/j.neuroscience.2004.11.030;
RA McIlwrath S.L., Hu J., Anirudhan G., Shin J.-B., Lewin G.R.;
RT "The sensory mechanotransduction ion channel ASIC2 (acid sensitive ion
RT channel 2) is regulated by neurotrophin availability.";
RL Neuroscience 131:499-511(2005).
RN [8]
RP INTERACTION WITH STOM.
RX PubMed=22850675; DOI=10.1038/emboj.2012.203;
RA Brand J., Smith E.S., Schwefel D., Lapatsina L., Poole K., Omerbasic D.,
RA Kozlenkov A., Behlke J., Lewin G.R., Daumke O.;
RT "A stomatin dimer modulates the activity of acid-sensing ion channels.";
RL EMBO J. 31:3635-3646(2012).
CC -!- FUNCTION: Cation channel with high affinity for sodium, which is gated
CC by extracellular protons and inhibited by the diuretic amiloride. Also
CC permeable for Li(+) and K(+). Generates a biphasic current with a fast
CC inactivating and a slow sustained phase. Heteromeric channel assembly
CC seems to modulate. {ECO:0000269|PubMed:14762118}.
CC -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins (By
CC similarity). Interacts with PRKCABP and ASIC3 (By similarity).
CC Interacts with STOM; this regulates channel activity (PubMed:15471860,
CC PubMed:22850675). Heterotrimer of Asic1a-Asic2a interacts with the
CC snake venom mambalgin-1, mambalgin-2 and mambalgin-3 (By similarity).
CC Heterotrimer of Asic1a-Asic2b interacts with the snake venom mambalgin-
CC 1 and mambalgin-2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q62962, ECO:0000269|PubMed:15471860,
CC ECO:0000269|PubMed:22850675}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15537887,
CC ECO:0000269|PubMed:15708491}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15537887, ECO:0000269|PubMed:15708491}.
CC Note=Localized at the plasma membrane, in the soma and punctated
CC peripheral processes of neurons.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=BNaC1-alpha {ECO:0000303|PubMed:11306621}, Asic2a;
CC IsoId=Q925H0-1; Sequence=Displayed;
CC Name=2; Synonyms=Mdeg2 {ECO:0000303|PubMed:9368048}, Asic2b;
CC IsoId=Q925H0-2; Sequence=VSP_015592, VSP_015593;
CC -!- TISSUE SPECIFICITY: Expressed by sensory neurons. Expressed by
CC nociceptive sensory neurons, spiral ganglion (SG) neurons and the
CC retina (at protein level). Isoform 1 and isoform 2 are expressed in
CC outer nuclear layer of retina (photoreceptors) and to a lower extent in
CC distal and proximal inner nuclear layer. {ECO:0000269|PubMed:14762118,
CC ECO:0000269|PubMed:15537887}.
CC -!- DEVELOPMENTAL STAGE: Expression changes dramatically during cochlear
CC development. Expression is detected at 11.5 dpc in otocyst and
CC increases in the SG neurons after 18.5 dpc. Also detected in the lumen
CC side of all cells forming the vestibular cavity and at the top of the
CC macula of saccule and utricle. Before birth expressed by epithelial
CC cells facing the endolymphatic space. Post-natally expressed by cells
CC in the apical turn of the cochlea, while expression on the lumen side
CC of the membranous labyrinth decreases. Expression shifts gradually
CC toward the top of supporting cells and the spiral limbus. Also
CC expressed by vestibular ganglion neurons. Restricted to the SG neurons
CC in the mature cochlea (at protein level).
CC {ECO:0000269|PubMed:15537887}.
CC -!- INDUCTION: Expression in a subset of neurons may be regulated by
CC neurotrophins. {ECO:0000269|PubMed:15708491}.
CC -!- DISRUPTION PHENOTYPE: Mice display altered rod phototransduction and
CC neurotransmission, associated with increased light-induced retina
CC damages. {ECO:0000269|PubMed:14762118}.
CC -!- MISCELLANEOUS: Regulated by Zn(2+). Inhibited by anti-inflammatory
CC drugs like salicylic acid (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. ASIC2 subfamily. {ECO:0000305}.
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DR EMBL; Y14634; CAA74978.1; -; mRNA.
DR EMBL; AF348465; AAK40101.1; -; mRNA.
DR EMBL; AL626807; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645626; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL663025; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25137.1; -. [Q925H0-2]
DR CCDS; CCDS36243.1; -. [Q925H0-1]
DR RefSeq; NP_001029185.1; NM_001034013.2. [Q925H0-1]
DR RefSeq; NP_031410.1; NM_007384.3. [Q925H0-2]
DR AlphaFoldDB; Q925H0; -.
DR SMR; Q925H0; -.
DR BioGRID; 197917; 2.
DR MINT; Q925H0; -.
DR BindingDB; Q925H0; -.
DR ChEMBL; CHEMBL3232695; -.
DR TCDB; 1.A.6.1.8; the epithelial na(+) channel (enac) family.
DR GlyConnect; 2417; 1 N-Linked glycan (1 site). [Q925H0-2]
DR GlyGen; Q925H0; 2 sites.
DR PhosphoSitePlus; Q925H0; -.
DR MaxQB; Q925H0; -.
DR PRIDE; Q925H0; -.
DR ProteomicsDB; 283185; -. [Q925H0-1]
DR ProteomicsDB; 283186; -. [Q925H0-2]
DR Antibodypedia; 15465; 218 antibodies from 32 providers.
DR DNASU; 11418; -.
DR Ensembl; ENSMUST00000021045; ENSMUSP00000021045; ENSMUSG00000020704. [Q925H0-2]
DR Ensembl; ENSMUST00000066197; ENSMUSP00000067095; ENSMUSG00000020704. [Q925H0-1]
DR GeneID; 11418; -.
DR KEGG; mmu:11418; -.
DR UCSC; uc007kmm.2; mouse. [Q925H0-1]
DR CTD; 40; -.
DR MGI; MGI:1100867; Asic2.
DR VEuPathDB; HostDB:ENSMUSG00000020704; -.
DR GeneTree; ENSGT00940000154991; -.
DR HOGENOM; CLU_020415_1_2_1; -.
DR InParanoid; Q925H0; -.
DR OMA; FPSHTQV; -.
DR OrthoDB; 686369at2759; -.
DR TreeFam; TF330663; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 11418; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Asic2; mouse.
DR PRO; PR:Q925H0; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q925H0; protein.
DR Bgee; ENSMUSG00000020704; Expressed in perirhinal cortex and 99 other tissues.
DR ExpressionAtlas; Q925H0; baseline and differential.
DR Genevisible; Q925H0; MM.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0005261; F:cation channel activity; IDA:MGI.
DR GO; GO:0005216; F:ion channel activity; IDA:MGI.
DR GO; GO:0022839; F:ion gated channel activity; IDA:MGI.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IDA:MGI.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI.
DR GO; GO:0006812; P:cation transport; IDA:MGI.
DR GO; GO:0071468; P:cellular response to acidic pH; ISO:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0050974; P:detection of mechanical stimulus involved in sensory perception; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0007602; P:phototransduction; IMP:MGI.
DR GO; GO:2001259; P:positive regulation of cation channel activity; ISO:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:MGI.
DR GO; GO:0035418; P:protein localization to synapse; IMP:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IMP:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0003026; P:regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback; IMP:MGI.
DR GO; GO:0019229; P:regulation of vasoconstriction; IMP:MGI.
DR GO; GO:0010447; P:response to acidic pH; IDA:MGI.
DR GO; GO:0009612; P:response to mechanical stimulus; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR GO; GO:0050915; P:sensory perception of sour taste; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IDA:MGI.
DR GO; GO:0007416; P:synapse assembly; IMP:MGI.
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; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sodium; Sodium channel; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..512
FT /note="Acid-sensing ion channel 2"
FT /id="PRO_0000181291"
FT TOPO_DOM 1..37
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..427
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 449..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62962"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62962"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 392
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 92..193
FT /evidence="ECO:0000250"
FT DISULFID 171..178
FT /evidence="ECO:0000250"
FT DISULFID 289..364
FT /evidence="ECO:0000250"
FT DISULFID 307..360
FT /evidence="ECO:0000250"
FT DISULFID 311..358
FT /evidence="ECO:0000250"
FT DISULFID 320..342
FT /evidence="ECO:0000250"
FT DISULFID 322..334
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..184
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9368048"
FT /id="VSP_015592"
FT VAR_SEQ 185
FT /note="T -> MSRSGGARLPATALSGPGRFRMAREQPAPAAVAAARQPGGDRSGDRE
FT LQGPGVARRGRPSLSRTKLHGLRHMCAGRTAAGGSFQRRALWVLAFCTSLGLLLSWSSN
FT RLLYWLSFPSHTRVHREWSRQLPFPAVTVCNNNPLRFPRLSKGDLYYAGHWLGLLLPNR
FT TARPLVSELLRGDEPRRQWFRKLADFRLFLPPRHFEGISAAFMDRLGHQLEDMLLSCKY
FT RGELCGPHNFSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9368048"
FT /id="VSP_015593"
SQ SEQUENCE 512 AA; 57739 MW; 7D81A77C3B347B04 CRC64;
MDLKESPSEG SLQPSSIQIF ANTSTLHGIR HIFVYGPLTI RRVLWAVAFV GSLGLLLVES
SERVSYYFSY QHVTKVDEVV AQSLVFPAVT LCNLNGFRFS RLTTNDLYHA GELLALLDVN
LQIPDPHLAD PTVLEALRQK ANFKHYKPKQ FSMLEFLHRV GHDLKDMMLY CKFKGQECGH
QDFTTVFTKY GKCYMFNSGE DGKPLLTTVK GGTGNGLEIM LDIQQDEYLP IWGETEETTF
EAGVKVQIHS QSEPPFIQEL GFGVAPGFQT FVATQEQRLT YLPPPWGECR SSEMGLDFFP
VYSITACRID CETRYIVENC NCRMVHMPGD APFCTPEQHK ECAEPALGLL AEKDSNYCLC
RTPCNLTRYN KELSMVKIPS KTSAKYLEKK FNKSEKYISE NILVLDIFFE ALNYETIEQK
KAYEVAALLG DIGGQMGLFI GASILTILEL FDYIYELIKE KLLDLLGKEE EEGSHDENMS
TCDTMPNHSE TISHTVNVPL QTALGTLEEI AC
