ASIC1_MOUSE
ID ASIC1_MOUSE Reviewed; 526 AA.
AC Q6NXK8; Q50K97;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Acid-sensing ion channel 1;
DE Short=ASIC1;
DE AltName: Full=Acid-sensing ion channel;
DE AltName: Full=Amiloride-sensitive cation channel 2, neuronal;
DE AltName: Full=Brain sodium channel 2;
DE Short=BNaC2;
GN Name=Asic1; Synonyms=Accn2, Asic, Bnac2;
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).
RA Ugawa S., Shimada S.;
RT "Mus musculus mRNA for ASIC1b.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11988176; DOI=10.1016/s0896-6273(02)00661-x;
RA Wemmie J.A., Chen J., Askwith C.C., Hruska-Hageman A.M., Price M.P.,
RA Nolan B.C., Yoder P.G., Lamani E., Hoshi T., Freeman J.H. Jr., Welsh M.J.;
RT "The acid-activated ion channel ASIC contributes to synaptic plasticity,
RT learning, and memory.";
RL Neuron 34:463-477(2002).
RN [4]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=12843249; DOI=10.1523/jneurosci.23-13-05496.2003;
RA Wemmie J.A., Askwith C.C., Lamani E., Cassell M.D., Freeman J.H. Jr.,
RA Welsh M.J.;
RT "Acid-sensing ion channel 1 is localized in brain regions with high
RT synaptic density and contributes to fear conditioning.";
RL J. Neurosci. 23:5496-5502(2003).
RN [5]
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 [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15578512; DOI=10.1053/j.gastro.2004.08.061;
RA Page A.J., Brierley S.M., Martin C.M., Martinez-Salgado C., Wemmie J.A.,
RA Brennan T.J., Symonds E., Omari T., Lewin G.R., Welsh M.J., Blackshaw L.A.;
RT "The ion channel ASIC1 contributes to visceral but not cutaneous
RT mechanoreceptor function.";
RL Gastroenterology 127:1739-1747(2004).
RN [7]
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 [8]
RP FUNCTION.
RX PubMed=17060608; DOI=10.1073/pnas.0608018103;
RA Zha X.-M., Wemmie J.A., Green S.H., Welsh M.J.;
RT "Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects
RT the density of dendritic spines.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16556-16561(2006).
RN [9]
RP FUNCTION IN CONTROL OF FEAR, AND DISRUPTION PHENOTYPE.
RX PubMed=17662962; DOI=10.1016/j.biopsych.2007.05.008;
RA Coryell M.W., Ziemann A.E., Westmoreland P.J., Haenfler J.M.,
RA Kurjakovic Z., Zha X.-M., Price M., Schnizler M.K., Wemmie J.A.;
RT "Targeting ASIC1a reduces innate fear and alters neuronal activity in the
RT fear circuit.";
RL Biol. Psychiatry 62:1140-1148(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-497, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Mediates glutamate-independent Ca(2+) entry into neurons
CC upon acidosis. This Ca(2+) overloading is toxic for cortical neurons
CC and may be in part responsible for ischemic brain injury. Heteromeric
CC channel assembly seems to modulate channel properties. Functions as a
CC postsynaptic proton receptor that influences intracellular Ca(2+)
CC concentration and calmodulin-dependent protein kinase II
CC phosphorylation and thereby the density of dendritic spines. Modulates
CC activity in the circuits underlying innate fear.
CC {ECO:0000269|PubMed:11988176, ECO:0000269|PubMed:12843249,
CC ECO:0000269|PubMed:15369669, ECO:0000269|PubMed:15578512,
CC ECO:0000269|PubMed:17060608, ECO:0000269|PubMed:17662962}.
CC -!- ACTIVITY REGULATION: Inhibited by the diuretic amiloride.
CC -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins (By
CC similarity). Interacts with PRKCABP and ASIC2 (By similarity).
CC Interacts with STOM (PubMed:15471860). {ECO:0000250,
CC ECO:0000269|PubMed:15471860}.
CC -!- INTERACTION:
CC Q6NXK8-1; Q12791: KCNMA1; Xeno; NbExp=2; IntAct=EBI-15686410, EBI-1220676;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Note=Localizes in synaptosomes at dendritic
CC synapses of neurons. Colocalizes with DLG4.
CC {ECO:0000269|PubMed:11988176}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Asic1a, Asic alpha;
CC IsoId=Q6NXK8-1; Sequence=Displayed;
CC Name=2; Synonyms=Asic1b, Asic beta;
CC IsoId=Q6NXK8-2; Sequence=VSP_015614, VSP_015615;
CC -!- TISSUE SPECIFICITY: Expressed in brain areas receiving strong
CC excitatory corticofugal input. In hippocampus, expressed in the hilus
CC of the dentate gyrus. In the cerebral cortex expressed in anterior and
CC posterior cingulate cortex, sensory and motor cortices. In the sensory
CC cortex strongest expression is detected in the whisker barrel field. In
CC sensorimotor and cingulate cortex expression is elevated in layer III.
CC Also expressed in basal ganglia, striatum, ventral pallidum, olfactory
CC tubercle, and nucleus accumbens. Weakly expressed in thalamus with the
CC exception of the habenula and the medial septal nuclei. In olfactory
CC bulb, preferentially expressed in the glomerular layer, within
CC glomeruli. Expressed in cerebellum in the molecular and granule cell
CC layers. Strongly expressed in amygdala complex, particularly in the
CC lateral and basolateral nuclei. Isoform 1 is more abundant in brain
CC compared to isoform 2 (at protein level). Expressed in the nodose
CC ganglion and dorsal root ganglion. Expressed in dendritic spine cells.
CC {ECO:0000269|PubMed:11988176, ECO:0000269|PubMed:12843249,
CC ECO:0000269|PubMed:15578512}.
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 -!- DISRUPTION PHENOTYPE: Mice display reduced spatial learning and memory
CC capability, associated with absence of proton-gated currents in
CC hippocampal neurons and impairment of hippocampal long term
CC potentiation (LTP). They also show an increased mechanosensitivity of
CC colonic and gastroesophageal mechanoreceptors and prolonged gastric
CC emptying and an altered fear conditioning.
CC {ECO:0000269|PubMed:17662962}.
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 (By similarity). {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; AB208022; BAD97849.1; -; mRNA.
DR EMBL; BC067025; AAH67025.1; -; mRNA.
DR CCDS; CCDS27826.1; -. [Q6NXK8-1]
DR CCDS; CCDS88841.1; -. [Q6NXK8-2]
DR RefSeq; NP_001276720.1; NM_001289791.1. [Q6NXK8-2]
DR RefSeq; NP_033727.1; NM_009597.1. [Q6NXK8-1]
DR AlphaFoldDB; Q6NXK8; -.
DR SMR; Q6NXK8; -.
DR BioGRID; 197918; 4.
DR DIP; DIP-29728N; -.
DR IntAct; Q6NXK8; 2.
DR STRING; 10090.ENSMUSP00000023758; -.
DR BindingDB; Q6NXK8; -.
DR ChEMBL; CHEMBL3232694; -.
DR GlyConnect; 2416; 1 N-Linked glycan (1 site). [Q6NXK8-2]
DR GlyGen; Q6NXK8; 2 sites.
DR iPTMnet; Q6NXK8; -.
DR PhosphoSitePlus; Q6NXK8; -.
DR MaxQB; Q6NXK8; -.
DR PaxDb; Q6NXK8; -.
DR PeptideAtlas; Q6NXK8; -.
DR PRIDE; Q6NXK8; -.
DR ProteomicsDB; 281843; -. [Q6NXK8-1]
DR ProteomicsDB; 281844; -. [Q6NXK8-2]
DR ABCD; Q6NXK8; 1 sequenced antibody.
DR Antibodypedia; 26132; 316 antibodies from 37 providers.
DR DNASU; 11419; -.
DR Ensembl; ENSMUST00000023758; ENSMUSP00000023758; ENSMUSG00000023017. [Q6NXK8-1]
DR Ensembl; ENSMUST00000228185; ENSMUSP00000154379; ENSMUSG00000023017. [Q6NXK8-2]
DR GeneID; 11419; -.
DR KEGG; mmu:11419; -.
DR UCSC; uc007xqa.2; mouse. [Q6NXK8-1]
DR UCSC; uc011zzg.2; mouse. [Q6NXK8-2]
DR CTD; 41; -.
DR MGI; MGI:1194915; Asic1.
DR VEuPathDB; HostDB:ENSMUSG00000023017; -.
DR eggNOG; KOG4294; Eukaryota.
DR GeneTree; ENSGT00940000158414; -.
DR HOGENOM; CLU_020415_1_2_1; -.
DR InParanoid; Q6NXK8; -.
DR OMA; RNCSHLF; -.
DR OrthoDB; 686369at2759; -.
DR PhylomeDB; Q6NXK8; -.
DR TreeFam; TF330663; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 11419; 3 hits in 77 CRISPR screens.
DR ChiTaRS; Asic1; mouse.
DR PRO; PR:Q6NXK8; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q6NXK8; protein.
DR Bgee; ENSMUSG00000023017; Expressed in cortical plate and 124 other tissues.
DR Genevisible; Q6NXK8; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0044736; F:acid-sensing ion channel activity; IDA:MGI.
DR GO; GO:0005261; F:cation channel activity; IDA:MGI.
DR GO; GO:0022890; F:inorganic cation transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; ISO:MGI.
DR GO; GO:0022839; F:ion gated channel activity; IDA:MGI.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IBA:GO_Central.
DR GO; GO:0008306; P:associative learning; IMP:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:MGI.
DR GO; GO:0006812; P:cation transport; IDA:MGI.
DR GO; GO:0071467; P:cellular response to pH; ISS:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISO:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:MGI.
DR GO; GO:0007613; P:memory; IMP:MGI.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IMP:MGI.
DR GO; GO:0007269; P:neurotransmitter secretion; IMP:MGI.
DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0010447; P:response to acidic pH; IDA:MGI.
DR GO; GO:0001975; P:response to amphetamine; IMP:MGI.
DR GO; GO:0050915; P:sensory perception of sour taste; ISO:MGI.
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_0000181295"
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 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 287
FT /note="Important for channel gating"
FT /evidence="ECO:0000250"
FT MOD_RES 477
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P78348"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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..184
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_015614"
FT VAR_SEQ 185
FT /note="K -> MPIQIFCSVSFSSGEEAPGSMGDIWGPHHHHRQQQDSSESEEEEEKE
FT KESGMELDEGDSPRDLVAFANSCTLHGASHVFVEGGPGPRQALWAVAFVIALGAFLCQV
FT GDRVAYYLSYPHVTLLDEVATTELVFPAVTFCNTNAVRLSQLSYPDLLYLAPMLGLDES
FT DDPGVPLAPPGPEAFSGEPFNLHRFYNRSCHRLEDMLLYCSYCGGPCGPHNFS (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_015615"
SQ SEQUENCE 526 AA; 59668 MW; 5462B3FEB5532726 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 KEAKRNSADK
GVALSLDDVK RHNPCESLRG HPAGMTYAAN ILPHHPARGT FEDFTC
