ASIC3_MOUSE
ID ASIC3_MOUSE Reviewed; 530 AA.
AC Q6X1Y6; Q7TQH4;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Acid-sensing ion channel 3;
DE Short=ASIC3;
DE AltName: Full=Amiloride-sensitive cation channel 3;
DE AltName: Full=Dorsal root ASIC;
DE Short=DRASIC;
GN Name=Asic3; Synonyms=Accn3, Drasic;
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), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND DISRUPTION PHENOTYPE.
RC TISSUE=Inner ear;
RX PubMed=15051137; DOI=10.1016/s0378-5955(04)00015-2;
RA Hildebrand M.S., de Silva M.G., Klockars T., Rose E., Price M.,
RA Smith R.J.H., McGuirt W.T., Christopoulos H., Petit C., Dahl H.-H.M.;
RT "Characterisation of DRASIC in the mouse inner ear.";
RL Hear. Res. 190:149-160(2004).
RN [2]
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 [3]
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 [4]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11754838; DOI=10.1016/s0896-6273(01)00547-5;
RA Price M.P., McIlwrath S.L., Xie J., Cheng C., Qiao J., Tarr D.E.,
RA Sluka K.A., Brennan T.J., Lewin G.R., Welsh M.J.;
RT "The DRASIC cation channel contributes to the detection of cutaneous touch
RT and acid stimuli in mice.";
RL Neuron 32:1071-1083(2001).
RN [5]
RP FUNCTION.
RX PubMed=12060708; DOI=10.1073/pnas.122245999;
RA Chen C.-C., Zimmer A., Sun W.-H., Hall J., Brownstein M.J., Zimmer A.;
RT "A role for ASIC3 in the modulation of high-intensity pain stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:8992-8997(2002).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14659506; DOI=10.1016/s0304-3959(03)00269-0;
RA Sluka K.A., Price M.P., Breese N.M., Stucky C.L., Wemmie J.A., Welsh M.J.;
RT "Chronic hyperalgesia induced by repeated acid injections in muscle is
RT abolished by the loss of ASIC3, but not ASIC1.";
RL Pain 106:229-239(2003).
RN [7]
RP INTERACTION WITH LIN7B; MAGI1; GOPC AND DLG4.
RX PubMed=15317815; DOI=10.1074/jbc.m405874200;
RA Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.;
RT "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have
RT opposite effects on H+- gated current.";
RL J. Biol. Chem. 279:46962-46968(2004).
RN [8]
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 [9]
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.
CC Generates a biphasic current with a fast inactivating and a slow
CC sustained phase. In sensory neurons is proposed to mediate the pain
CC induced by acidosis that occurs in ischemic, damaged or inflamed
CC tissue. May be involved in hyperalgesia. May play a role in
CC mechanoreception. Heteromeric channel assembly seems to modulate
CC channel properties. {ECO:0000269|PubMed:11754838,
CC ECO:0000269|PubMed:12060708, ECO:0000269|PubMed:14659506}.
CC -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins (By
CC similarity). Interacts with DLG4 and ASIC2 (By similarity). Interacts
CC with LIN7B, MAGI1/BAIAP1 and GOPC. Interacts with STOM; this regulates
CC channel activity. {ECO:0000250, ECO:0000269|PubMed:15317815,
CC ECO:0000269|PubMed:15471860, ECO:0000269|PubMed:22850675}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15051137};
CC Multi-pass membrane protein {ECO:0000269|PubMed:15051137}. Cytoplasm
CC {ECO:0000269|PubMed:15051137}. Note=Cell surface expression may be
CC stabilized by interaction with LIN7B and cytoplasmic retention by
CC interaction with DLG4 (By similarity). In part cytoplasmic in cochlea
CC cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6X1Y6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6X1Y6-2; Sequence=VSP_015606, VSP_015607;
CC -!- TISSUE SPECIFICITY: Expressed in liver, lung, kidney, testis, brain,
CC eye and cochlea. Expressed in spiral ganglion and sensory hair cells of
CC the organ of Corti in the cochlea (at protein level). Expressed in
CC dorsal root ganglion innervating muscles and spinal chord. Expressed in
CC peripheral sensory nerve termimals like nerves of the Meissner
CC corpuscle, palisades of lanceolate nerve endings, site of
CC mechanoreception in guard hair follicles, and Merkel cell-neurite
CC complexes. {ECO:0000269|PubMed:11754838, ECO:0000269|PubMed:14659506,
CC ECO:0000269|PubMed:15051137}.
CC -!- PTM: Phosphorylated by PKA. Phosphorylated by PKC. In vitro,
CC PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a
CC ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric
CC ASIC3/ACCN3 channel (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice display altered responses to mechanical and
CC acid stimuli. They do not develop chronic hyperalgesia induced by
CC repeated acid injection. {ECO:0000269|PubMed:15051137}.
CC -!- MISCELLANEOUS: Sensitized and potentiated by NPFF and NPSF. Inhibited
CC by anti-inflammatory drugs, like salicylic acid (By similarity).
CC Potentiated by FMRFamide-related neuropeptides. Regulated by lactate
CC and Ca(2+). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. ASIC3 subfamily. {ECO:0000305}.
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DR EMBL; AY261387; AAP88539.1; -; mRNA.
DR EMBL; AC113055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS51433.1; -. [Q6X1Y6-1]
DR CCDS; CCDS80225.1; -. [Q6X1Y6-2]
DR RefSeq; NP_001297403.1; NM_001310474.1. [Q6X1Y6-2]
DR RefSeq; NP_892045.2; NM_183000.2. [Q6X1Y6-1]
DR AlphaFoldDB; Q6X1Y6; -.
DR SMR; Q6X1Y6; -.
DR BioGRID; 228517; 2.
DR STRING; 10090.ENSMUSP00000039914; -.
DR ChEMBL; CHEMBL3232696; -.
DR GlyGen; Q6X1Y6; 2 sites.
DR iPTMnet; Q6X1Y6; -.
DR PhosphoSitePlus; Q6X1Y6; -.
DR EPD; Q6X1Y6; -.
DR PaxDb; Q6X1Y6; -.
DR PRIDE; Q6X1Y6; -.
DR Antibodypedia; 18677; 180 antibodies from 28 providers.
DR Ensembl; ENSMUST00000049346; ENSMUSP00000039914; ENSMUSG00000038276. [Q6X1Y6-2]
DR Ensembl; ENSMUST00000196296; ENSMUSP00000143083; ENSMUSG00000038276. [Q6X1Y6-1]
DR GeneID; 171209; -.
DR KEGG; mmu:171209; -.
DR UCSC; uc008wrj.1; mouse. [Q6X1Y6-1]
DR UCSC; uc008wrk.1; mouse. [Q6X1Y6-2]
DR CTD; 9311; -.
DR MGI; MGI:2159339; Asic3.
DR VEuPathDB; HostDB:ENSMUSG00000038276; -.
DR eggNOG; KOG4294; Eukaryota.
DR GeneTree; ENSGT00940000162081; -.
DR HOGENOM; CLU_020415_1_3_1; -.
DR InParanoid; Q6X1Y6; -.
DR OMA; SDICVFA; -.
DR OrthoDB; 686369at2759; -.
DR PhylomeDB; Q6X1Y6; -.
DR TreeFam; TF330663; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 171209; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q6X1Y6; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q6X1Y6; protein.
DR Bgee; ENSMUSG00000038276; Expressed in lumbar dorsal root ganglion and 52 other tissues.
DR ExpressionAtlas; Q6X1Y6; baseline and differential.
DR Genevisible; Q6X1Y6; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0044736; F:acid-sensing ion channel activity; IBA:GO_Central.
DR GO; GO:0005261; F:cation channel activity; IDA:MGI.
DR GO; GO:0042931; F:enterobactin transmembrane transporter activity; IMP:MGI.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; ISO:MGI.
DR GO; GO:0006812; P:cation transport; IDA:MGI.
DR GO; GO:0050907; P:detection of chemical stimulus involved in sensory perception; IMP:MGI.
DR GO; GO:0050968; P:detection of chemical stimulus involved in sensory perception of pain; IMP:MGI.
DR GO; GO:0050974; P:detection of mechanical stimulus involved in sensory perception; IMP:MGI.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:MGI.
DR GO; GO:0050961; P:detection of temperature stimulus involved in sensory perception; IMP:MGI.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IMP:MGI.
DR GO; GO:0010447; P:response to acidic pH; IDA:MGI.
DR GO; GO:0009408; P:response to heat; IMP:MGI.
DR GO; GO:0009612; P:response to mechanical stimulus; 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; ISO: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; Cytoplasm; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..530
FT /note="Acid-sensing ion channel 3"
FT /id="PRO_0000181302"
FT TOPO_DOM 1..43
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 44..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..440
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..460
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..530
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 285..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 527..530
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT SITE 26
FT /note="Potassium ion selectivity and permeability"
FT /evidence="ECO:0000250"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 93..187
FT /evidence="ECO:0000250"
FT DISULFID 165..172
FT /evidence="ECO:0000250"
FT DISULFID 283..369
FT /evidence="ECO:0000250"
FT DISULFID 314..365
FT /evidence="ECO:0000250"
FT DISULFID 318..363
FT /evidence="ECO:0000250"
FT DISULFID 327..349
FT /evidence="ECO:0000250"
FT DISULFID 329..341
FT /evidence="ECO:0000250"
FT VAR_SEQ 355..440
FT /note="DAMLRKDTCVCPNPCATTRYAKELSMVRIPSRASARYLARKYNRSETYITEN
FT VLVLDIFFEALNYEAVEQKAAYEVSELLGDIGGQ -> GRMYWFWISSLKPSTMRPWNK
FT RQLMKCRSCWETLGDRWDCLSEPACLPSSRSSTTSVRFFKTESWGTSGTEGALKGALAT
FT LCSRKS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15051137"
FT /id="VSP_015606"
FT VAR_SEQ 441..530
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15051137"
FT /id="VSP_015607"
SQ SEQUENCE 530 AA; 58704 MW; 6C97378D2135D5F1 CRC64;
MKPPSGLEEA QRRQASDIRV FANSCTMHGL GHIFGPGGLT LRRGLWATAV LLSLAAFLYQ
VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR SRLTPNDLHW AGTALLGLDP
AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL YARAGHSLED MLLDCRYRGQ PCGPENFTVI
FTRMGQCYTF NSGAQGAELL TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV
QIHGQEEPPA IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASVDP DFDPEPSDPL
GSPSSSPPYS LIGCRLACES RYVARKCGCR MMHMPGNSPV CSPQQYKDCA SPALDAMLRK
DTCVCPNPCA TTRYAKELSM VRIPSRASAR YLARKYNRSE TYITENVLVL DIFFEALNYE
AVEQKAAYEV SELLGDIGGQ MGLFIGASLL TILEILDYLC EVFQDRVLGY FWNRRSSQRR
SGNTLLQEEL NGHRTHVPHL SLGPRPPTAP SAVTKTLAAS HRTCYLVTRL
