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Q6NXK8 (ASIC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acid-sensing ion channel 1

Short name=ASIC1
Alternative name(s):
Acid-sensing ion channel
Amiloride-sensitive cation channel 2, neuronal
Brain sodium channel 2
Short name=BNaC2
Gene names
Name:Asic1
Synonyms:Accn2, Asic, Bnac2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length526 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Mediates glutamate-independent Ca2+ entry into neurons upon acidosis. This Ca2+ overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca2+ concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear. Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9

Enzyme regulation

Inhibited by the diuretic amiloride.

Subunit structure

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with PRKCABP and ASIC2 By similarity. Interacts with STOM. Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Note: Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4. Ref.3

Tissue specificity

Expressed in brain areas receiving strong excitatory corticofugal input. In hippocampus, expressed in the hilus of the dentate gyrus. In the cerebral cortex expressed in anterior and posterior cingulate cortex, sensory and motor cortices. In the sensory cortex strongest expression is detected in the whisker barrel field. In sensorimotor and cingulate cortex expression is elevated in layer III. Also expressed in basal ganglia, striatum, ventral pallidum, olfactory tubercle, and nucleus accumbens. Weakly expressed in thalamus with the exception of the habenula and the medial septal nuclei. In olfactory bulb, preferentially expressed in the glomerular layer, within glomeruli. Expressed in cerebellum in the molecular and granule cell layers. Strongly expressed in amygdala complex, particularly in the lateral and basolateral nuclei. Isoform 1 is more abundant in brain compared to isoform 2 (at protein level). Expressed in the nodose ganglion and dorsal root ganglion. Expressed in dendritic spine cells. Ref.3 Ref.4 Ref.6

Domain

Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix By similarity.

Post-translational modification

Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel By similarity.

Disruption phenotype

Mice display reduced spatial learning and memory capability, associated with absence of proton-gated currents in hippocampal neurons and impairment of hippocampal long term potentiation (LTP). They also show an increased mechanosensitivity of colonic and gastroesophageal mechanoreceptors and prolonged gastric emptying and an altered fear conditioning. Ref.9

Miscellaneous

Potentiated by Ca2+, Mg2+, Ba2+, multivalent cations and potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases. Inhibited by anti-inflammatory drugs like salicylic acid By similarity.

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily. [View classification]

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandCalcium
Sodium
   Molecular functionIon channel
Sodium channel
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processassociative learning

Inferred from mutant phenotype Ref.3. Source: MGI

calcium ion transmembrane transport

Inferred from mutant phenotype PubMed 19376200. Source: MGI

cation transport

Inferred from direct assay PubMed 11854527. Source: MGI

cellular response to pH

Inferred from sequence or structural similarity. Source: UniProtKB

ion transmembrane transport

Inferred from direct assay PubMed 14960591. Source: MGI

memory

Inferred from mutant phenotype Ref.3. Source: MGI

negative regulation of neurotransmitter secretion

Inferred from mutant phenotype PubMed 18094106. Source: MGI

protein homotrimerization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of membrane potential

Inferred from mutant phenotype PubMed 19376200. Source: MGI

response to acidity

Inferred from direct assay PubMed 11854527. Source: MGI

sodium ion transmembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from direct assay PubMed 11854527. Source: MGI

synapse

Inferred from direct assay Ref.3. Source: MGI

   Molecular_functionacid-sensing ion channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

cation channel activity

Inferred from direct assay PubMed 11854527. Source: MGI

ion gated channel activity

Inferred from direct assay PubMed 14960591. Source: MGI

protein binding

Inferred from physical interaction PubMed 19571134. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6NXK8-1)

Also known as: Asic1a; Asic alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q6NXK8-2)

Also known as: Asic1b; Asic beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-184: Missing.
     185-185: K → MPIQIFCSVS...GGPCGPHNFS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 526526Acid-sensing ion channel 1
PRO_0000181295

Regions

Topological domain1 – 4545Cytoplasmic By similarity
Transmembrane46 – 6924Helical; By similarity
Topological domain70 – 425356Extracellular By similarity
Transmembrane426 – 45227Discontinuously helical; By similarity
Topological domain453 – 52674Cytoplasmic By similarity
Motif442 – 4443Selectivity filter Probable

Sites

Site711Important for channel gating By similarity
Site791Important for channel desensitizing By similarity
Site2871Important for channel gating By similarity

Amino acid modifications

Modified residue4771Phosphoserine; by PKA By similarity
Glycosylation3661N-linked (GlcNAc...) Potential
Glycosylation3931N-linked (GlcNAc...) Potential
Disulfide bond93 ↔ 194 By similarity
Disulfide bond172 ↔ 179 By similarity
Disulfide bond290 ↔ 365 By similarity
Disulfide bond308 ↔ 361 By similarity
Disulfide bond312 ↔ 359 By similarity
Disulfide bond321 ↔ 343 By similarity
Disulfide bond323 ↔ 335 By similarity

Natural variations

Alternative sequence1 – 184184Missing in isoform 2.
VSP_015614
Alternative sequence1851K → MPIQIFCSVSFSSGEEAPGS MGDIWGPHHHHRQQQDSSES EEEEEKEKESGMELDEGDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNT NAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAF SGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFS in isoform 2.
VSP_015615

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Asic1a) (Asic alpha) [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 5462B3FEB5532726

FASTA52659,668
        10         20         30         40         50         60 
MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV 

        70         80         90        100        110        120 
CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN 

       130        140        150        160        170        180 
RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEACS 

       190        200        210        220        230        240 
AEDFKVVFTR YGKCYTFNSG QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS 

       250        260        270        280        290        300 
FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF 

       310        320        330        340        350        360 
DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF LVEKDQEYCV 

       370        380        390        400        410        420 
CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG ENILVLDIFF EVLNYETIEQ 

       430        440        450        460        470        480 
KKAYEIAGLL GDIGGQMGLF IGASILTVLE LFDYAYEVIK HRLCRRGKCQ KEAKRNSADK 

       490        500        510        520 
GVALSLDDVK RHNPCESLRG HPAGMTYAAN ILPHHPARGT FEDFTC 

« Hide

Isoform 2 (Asic1b) (Asic beta) [UniParc].

Checksum: EDB97A44CAF4A611
Show »

FASTA55962,309

References

« Hide 'large scale' references
[1]"Mus musculus mRNA for ASIC1b."
Ugawa S., Shimada S.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6.
Tissue: Brain.
[3]"The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory."
Wemmie J.A., Chen J., Askwith C.C., Hruska-Hageman A.M., Price M.P., Nolan B.C., Yoder P.G., Lamani E., Hoshi T., Freeman J.H. Jr., Welsh M.J.
Neuron 34:463-477(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
[4]"Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning."
Wemmie J.A., Askwith C.C., Lamani E., Cassell M.D., Freeman J.H. Jr., Welsh M.J.
J. Neurosci. 23:5496-5502(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, FUNCTION.
[5]"Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels."
Xiong Z.-G., Zhu X.-M., Chu X.-P., Minami M., Hey J., Wei W.-L., MacDonald J.F., Wemmie J.A., Price M.P., Welsh M.J., Simon R.P.
Cell 118:687-698(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function."
Page A.J., Brierley S.M., Martin C.M., Martinez-Salgado C., Wemmie J.A., Brennan T.J., Symonds E., Omari T., Lewin G.R., Welsh M.J., Blackshaw L.A.
Gastroenterology 127:1739-1747(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]"Stomatin modulates gating of acid-sensing ion channels."
Price M.P., Thompson R.J., Eshcol J.O., Wemmie J.A., Benson C.J.
J. Biol. Chem. 279:53886-53891(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STOM.
[8]"Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines."
Zha X.-M., Wemmie J.A., Green S.H., Welsh M.J.
Proc. Natl. Acad. Sci. U.S.A. 103:16556-16561(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit."
Coryell M.W., Ziemann A.E., Westmoreland P.J., Haenfler J.M., Kurjakovic Z., Zha X.-M., Price M., Schnizler M.K., Wemmie J.A.
Biol. Psychiatry 62:1140-1148(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CONTROL OF FEAR, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB208022 mRNA. Translation: BAD97849.1.
BC067025 mRNA. Translation: AAH67025.1.
CCDSCCDS27826.1. [Q6NXK8-1]
RefSeqNP_001276720.1. NM_001289791.1. [Q6NXK8-2]
NP_033727.1. NM_009597.1. [Q6NXK8-1]
UniGeneMm.440107.

3D structure databases

ProteinModelPortalQ6NXK8.
SMRQ6NXK8. Positions 40-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197918. 1 interaction.
DIPDIP-29728N.

PTM databases

PhosphoSiteQ6NXK8.

Proteomic databases

PRIDEQ6NXK8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000023758; ENSMUSP00000023758; ENSMUSG00000023017. [Q6NXK8-1]
GeneID11419.
KEGGmmu:11419.
UCSCuc007xqa.1. mouse. [Q6NXK8-1]
uc011zzg.1. mouse. [Q6NXK8-2]

Organism-specific databases

CTD41.
MGIMGI:1194915. Asic1.

Phylogenomic databases

eggNOGNOG262945.
GeneTreeENSGT00640000091217.
HOGENOMHOG000247010.
HOVERGENHBG004150.
KOK04829.
OMAIQYYFLY.
OrthoDBEOG72VH5P.
PhylomeDBQ6NXK8.
TreeFamTF330663.

Gene expression databases

BgeeQ6NXK8.
CleanExMM_ACCN2.
GenevestigatorQ6NXK8.

Family and domain databases

InterProIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERPTHR11690. PTHR11690. 1 hit.
PfamPF00858. ASC. 1 hit.
[Graphical view]
PRINTSPR01078. AMINACHANNEL.
TIGRFAMsTIGR00859. ENaC. 1 hit.
PROSITEPS01206. ASC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio278664.
PROQ6NXK8.
SOURCESearch...

Entry information

Entry nameASIC1_MOUSE
AccessionPrimary (citable) accession number: Q6NXK8
Secondary accession number(s): Q50K97
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot