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Protein

Acid-sensing ion channel 1

Gene

Asic1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.6 Publications

Enzyme regulationi

Inhibited by the diuretic amiloride.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei71 – 711Important for channel gatingBy similarity
Sitei79 – 791Important for channel desensitizingBy similarity
Sitei287 – 2871Important for channel gatingBy similarity

GO - Molecular functioni

GO - Biological processi

  • associative learning Source: MGI
  • calcium ion transmembrane transport Source: MGI
  • cation transport Source: MGI
  • cellular response to pH Source: UniProtKB
  • ion transmembrane transport Source: MGI
  • memory Source: MGI
  • monovalent inorganic cation transport Source: MGI
  • negative regulation of neurotransmitter secretion Source: MGI
  • protein homotrimerization Source: UniProtKB
  • regulation of membrane potential Source: MGI
  • response to acidic pH Source: MGI
  • sensory perception of sour taste Source: MGI
  • sodium ion transmembrane transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Calcium transport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calcium, Sodium

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Asic1
Synonyms:Accn2, Asic, Bnac2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1194915. Asic1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4545CytoplasmicBy similarityAdd
BLAST
Transmembranei46 – 6924HelicalBy similarityAdd
BLAST
Topological domaini70 – 425356ExtracellularBy similarityAdd
BLAST
Transmembranei426 – 45227Discontinuously helicalBy similarityAdd
BLAST
Topological domaini453 – 52674CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • dendritic shaft Source: MGI
  • dendritic spine Source: MGI
  • integral component of membrane Source: MGI
  • integral component of plasma membrane Source: MGI
  • synapse Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 526526Acid-sensing ion channel 1PRO_0000181295Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi93 ↔ 194By similarity
Disulfide bondi172 ↔ 179By similarity
Disulfide bondi290 ↔ 365By similarity
Disulfide bondi308 ↔ 361By similarity
Disulfide bondi312 ↔ 359By similarity
Disulfide bondi321 ↔ 343By similarity
Disulfide bondi323 ↔ 335By similarity
Glycosylationi366 – 3661N-linked (GlcNAc...)Sequence Analysis
Glycosylationi393 – 3931N-linked (GlcNAc...)Sequence Analysis
Modified residuei477 – 4771Phosphoserine; by PKABy similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ6NXK8.
PRIDEiQ6NXK8.

PTM databases

PhosphoSiteiQ6NXK8.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiQ6NXK8.
CleanExiMM_ACCN2.
ExpressionAtlasiQ6NXK8. baseline and differential.
GenevestigatoriQ6NXK8.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with PRKCABP and ASIC2 (By similarity). Interacts with STOM.By similarity1 Publication

Protein-protein interaction databases

BioGridi197918. 1 interaction.
DIPiDIP-29728N.

Structurei

3D structure databases

ProteinModelPortaliQ6NXK8.
SMRiQ6NXK8. Positions 40-460.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi442 – 4443Selectivity filterCurated

Domaini

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).By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG262945.
GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ6NXK8.
KOiK04829.
OMAiCESIRGH.
OrthoDBiEOG72VH5P.
PhylomeDBiQ6NXK8.
TreeFamiTF330663.

Family and domain databases

InterProiIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERiPTHR11690. PTHR11690. 1 hit.
PfamiPF00858. ASC. 1 hit.
[Graphical view]
PRINTSiPR01078. AMINACHANNEL.
TIGRFAMsiTIGR00859. ENaC. 1 hit.
PROSITEiPS01206. ASC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6NXK8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF
60 70 80 90 100
LGSLAVLLCV CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF
110 120 130 140 150
SQVSKNDLYH AGELLALLNN RYEIPDTQMA DEKQLEILQD KANFRSFKPK
160 170 180 190 200
PFNMREFYDR AGHDIRDMLL SCHFRGEACS AEDFKVVFTR YGKCYTFNSG
210 220 230 240 250
QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS FEAGIKVQIH
260 270 280 290 300
SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF
310 320 330 340 350
DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF
360 370 380 390 400
LVEKDQEYCV CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG
410 420 430 440 450
ENILVLDIFF EVLNYETIEQ KKAYEIAGLL GDIGGQMGLF IGASILTVLE
460 470 480 490 500
LFDYAYEVIK HRLCRRGKCQ KEAKRNSADK GVALSLDDVK RHNPCESLRG
510 520
HPAGMTYAAN ILPHHPARGT FEDFTC
Length:526
Mass (Da):59,668
Last modified:July 5, 2004 - v1
Checksum:i5462B3FEB5532726
GO
Isoform 2 (identifier: Q6NXK8-2) [UniParc]FASTAAdd to basket

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

Show »
Length:559
Mass (Da):62,309
Checksum:iEDB97A44CAF4A611
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 184184Missing in isoform 2. 1 PublicationVSP_015614Add
BLAST
Alternative sequencei185 – 1851K → MPIQIFCSVSFSSGEEAPGS MGDIWGPHHHHRQQQDSSES EEEEEKEKESGMELDEGDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNT NAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAF SGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFS in isoform 2. 1 PublicationVSP_015615

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB208022 mRNA. Translation: BAD97849.1.
BC067025 mRNA. Translation: AAH67025.1.
CCDSiCCDS27826.1. [Q6NXK8-1]
RefSeqiNP_001276720.1. NM_001289791.1. [Q6NXK8-2]
NP_033727.1. NM_009597.1. [Q6NXK8-1]
UniGeneiMm.440107.

Genome annotation databases

EnsembliENSMUST00000023758; ENSMUSP00000023758; ENSMUSG00000023017. [Q6NXK8-1]
GeneIDi11419.
KEGGimmu:11419.
UCSCiuc007xqa.1. mouse. [Q6NXK8-1]
uc011zzg.1. mouse. [Q6NXK8-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB208022 mRNA. Translation: BAD97849.1.
BC067025 mRNA. Translation: AAH67025.1.
CCDSiCCDS27826.1. [Q6NXK8-1]
RefSeqiNP_001276720.1. NM_001289791.1. [Q6NXK8-2]
NP_033727.1. NM_009597.1. [Q6NXK8-1]
UniGeneiMm.440107.

3D structure databases

ProteinModelPortaliQ6NXK8.
SMRiQ6NXK8. Positions 40-460.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi197918. 1 interaction.
DIPiDIP-29728N.

Chemistry

ChEMBLiCHEMBL3232694.
GuidetoPHARMACOLOGYi684.

PTM databases

PhosphoSiteiQ6NXK8.

Proteomic databases

MaxQBiQ6NXK8.
PRIDEiQ6NXK8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023758; ENSMUSP00000023758; ENSMUSG00000023017. [Q6NXK8-1]
GeneIDi11419.
KEGGimmu:11419.
UCSCiuc007xqa.1. mouse. [Q6NXK8-1]
uc011zzg.1. mouse. [Q6NXK8-2]

Organism-specific databases

CTDi41.
MGIiMGI:1194915. Asic1.

Phylogenomic databases

eggNOGiNOG262945.
GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ6NXK8.
KOiK04829.
OMAiCESIRGH.
OrthoDBiEOG72VH5P.
PhylomeDBiQ6NXK8.
TreeFamiTF330663.

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Miscellaneous databases

NextBioi278664.
PROiQ6NXK8.
SOURCEiSearch...

Gene expression databases

BgeeiQ6NXK8.
CleanExiMM_ACCN2.
ExpressionAtlasiQ6NXK8. baseline and differential.
GenevestigatoriQ6NXK8.

Family and domain databases

InterProiIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERiPTHR11690. PTHR11690. 1 hit.
PfamiPF00858. ASC. 1 hit.
[Graphical view]
PRINTSiPR01078. AMINACHANNEL.
TIGRFAMsiTIGR00859. ENaC. 1 hit.
PROSITEiPS01206. ASC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. 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.

Entry informationi

Entry nameiASIC1_MOUSE
AccessioniPrimary (citable) accession number: Q6NXK8
Secondary accession number(s): Q50K97
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: July 5, 2004
Last modified: April 1, 2015
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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).By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.