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Q6NXK8

- ASIC1_MOUSE

UniProt

Q6NXK8 - ASIC1_MOUSE

Protein

Acid-sensing ion channel 1

Gene

Asic1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 89 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    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

    1. acid-sensing ion channel activity Source: UniProtKB
    2. cation channel activity Source: MGI
    3. ion gated channel activity Source: MGI
    4. protein binding Source: MGI

    GO - Biological processi

    1. associative learning Source: MGI
    2. calcium ion transmembrane transport Source: MGI
    3. cation transport Source: MGI
    4. cellular response to pH Source: UniProtKB
    5. ion transmembrane transport Source: MGI
    6. memory Source: MGI
    7. negative regulation of neurotransmitter secretion Source: MGI
    8. protein homotrimerization Source: UniProtKB
    9. regulation of membrane potential Source: MGI
    10. response to acidic pH Source: MGI
    11. sodium ion transmembrane transport Source: UniProtKB

    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_196640. 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: Chromosome 15

    Organism-specific databases

    MGIiMGI:1194915. Asic1.

    Subcellular locationi

    Cell membrane By similarity; Multi-pass membrane protein By similarity
    Note: Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4.1 Publication

    GO - Cellular componenti

    1. cell surface Source: Ensembl
    2. integral component of plasma membrane Source: MGI
    3. synapse Source: MGI

    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

    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.
    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4545CytoplasmicBy similarityAdd
    BLAST
    Topological domaini70 – 425356ExtracellularBy similarityAdd
    BLAST
    Topological domaini453 – 52674CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei46 – 6924HelicalBy similarityAdd
    BLAST
    Transmembranei426 – 45227Discontinuously helicalBy similarityAdd
    BLAST

    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.
    GeneTreeiENSGT00640000091217.
    HOGENOMiHOG000247010.
    HOVERGENiHBG004150.
    KOiK04829.
    OMAiIQYYFLY.
    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. Align

    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

    MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF    50
    LGSLAVLLCV CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF 100
    SQVSKNDLYH AGELLALLNN RYEIPDTQMA DEKQLEILQD KANFRSFKPK 150
    PFNMREFYDR AGHDIRDMLL SCHFRGEACS AEDFKVVFTR YGKCYTFNSG 200
    QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS FEAGIKVQIH 250
    SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF 300
    DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF 350
    LVEKDQEYCV CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG 400
    ENILVLDIFF EVLNYETIEQ KKAYEIAGLL GDIGGQMGLF IGASILTVLE 450
    LFDYAYEVIK HRLCRRGKCQ KEAKRNSADK GVALSLDDVK RHNPCESLRG 500
    HPAGMTYAAN ILPHHPARGT FEDFTC 526
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB208022 mRNA. Translation: BAD97849.1 .
    BC067025 mRNA. Translation: AAH67025.1 .
    CCDSi CCDS27826.1. [Q6NXK8-1 ]
    RefSeqi NP_001276720.1. NM_001289791.1. [Q6NXK8-2 ]
    NP_033727.1. NM_009597.1. [Q6NXK8-1 ]
    UniGenei Mm.440107.

    3D structure databases

    ProteinModelPortali Q6NXK8.
    SMRi Q6NXK8. Positions 40-460.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 197918. 1 interaction.
    DIPi DIP-29728N.

    PTM databases

    PhosphoSitei Q6NXK8.

    Proteomic databases

    PRIDEi Q6NXK8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000023758 ; ENSMUSP00000023758 ; ENSMUSG00000023017 . [Q6NXK8-1 ]
    GeneIDi 11419.
    KEGGi mmu:11419.
    UCSCi uc007xqa.1. mouse. [Q6NXK8-1 ]
    uc011zzg.1. mouse. [Q6NXK8-2 ]

    Organism-specific databases

    CTDi 41.
    MGIi MGI:1194915. Asic1.

    Phylogenomic databases

    eggNOGi NOG262945.
    GeneTreei ENSGT00640000091217.
    HOGENOMi HOG000247010.
    HOVERGENi HBG004150.
    KOi K04829.
    OMAi IQYYFLY.
    OrthoDBi EOG72VH5P.
    PhylomeDBi Q6NXK8.
    TreeFami TF330663.

    Enzyme and pathway databases

    Reactomei REACT_196640. Stimuli-sensing channels.

    Miscellaneous databases

    NextBioi 278664.
    PROi Q6NXK8.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q6NXK8.
    CleanExi MM_ACCN2.
    Genevestigatori Q6NXK8.

    Family and domain databases

    InterProi IPR004724. EnaC.
    IPR001873. Na+channel_ASC.
    IPR020903. Na+channel_ASC_CS.
    [Graphical view ]
    PANTHERi PTHR11690. PTHR11690. 1 hit.
    Pfami PF00858. ASC. 1 hit.
    [Graphical view ]
    PRINTSi PR01078. AMINACHANNEL.
    TIGRFAMsi TIGR00859. ENaC. 1 hit.
    PROSITEi PS01206. ASC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 89 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