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UniProtKB/Swiss-Prot entry Q6NXK8


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ACCN2_MOUSE
Primary accession number Q6NXK8
Secondary accession number Q50K97
Integrated into Swiss-Prot on September 13, 2005
Sequence was last modified on July 5, 2004 (Sequence version 1)
Annotations were last modified on    June 10, 2008 (Entry version 39)
Name and origin of the protein
Protein name Amiloride-sensitive cation channel 2, neuronal
Synonyms Acid-sensing ion channel
Acid-sensing ion channel 1
Brain sodium channel 2
Gene name
Name: Accn2
Synonyms: Asic, Asic1, Bnac2
From
Mus musculus (Mouse) [TaxID: 10090] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Ugawa S., Shimada S.;
"Mus musculus mRNA for ASIC1b.";
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=C57BL/6;
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION.
DOI=10.1016/S0896-6273(02)00661-X; PubMed=11988176 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.";
Neuron 34:463-477(2002).
[4]
TISSUE SPECIFICITY, AND FUNCTION.
PubMed=12843249 [NCBI, ExPASy, EBI, Israel, Japan]
Wemmie J.A., Askwith C.C., Lamani E., Cassell M.D., Freeman J.H. Jr., Welsh M.J.;
"Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.";
J. Neurosci. 23:5496-5502(2003).
[5]
FUNCTION.
DOI=10.1016/j.cell.2004.08.026; PubMed=15369669 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.";
Cell 118:687-698(2004).
[6]
FUNCTION, AND TISSUE SPECIFICITY.
DOI=10.1053/j.gastro.2004.08.061; PubMed=15578512 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function.";
Gastroenterology 127:1739-1747(2004).
[7]
INTERACTION WITH STOM.
DOI=10.1074/jbc.M407708200; PubMed=15471860 [NCBI, ExPASy, EBI, Israel, Japan]
Price M.P., Thompson R.J., Eshcol J.O., Wemmie J.A., Benson C.J.;
"Stomatin modulates gating of acid-sensing ion channels.";
J. Biol. Chem. 279:53886-53891(2004).
[8]
FUNCTION.
DOI=10.1073/pnas.0608018103; PubMed=17060608 [NCBI, ExPASy, EBI, Israel, Japan]
Zha X.-M., Wemmie J.A., Green S.H., Welsh M.J.;
"Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines.";
Proc. Natl. Acad. Sci. U.S.A. 103:16556-16561(2006).
[9]
FUNCTION IN CONTROL OF FEAR.
DOI=10.1016/j.biopsych.2007.05.008; PubMed=17662962 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit.";
Biol. Psychiatry 62:1140-1148(2007).
Comments
  • FUNCTION: Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca(2+), Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) 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 Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.
  • SUBUNIT: Homotetramer or heterotetramer with other ASIC proteins (Probable). Interacts with PRKCABP and ACCN1 (By similarity). Interacts with STOM.
  • SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein (By similarity). Note=Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    SynonymsAsic1a, Asic alpha
    Isoform IDQ6NXK8-1
    This is the isoform sequence displayed in this entry.
    Name2
    SynonymsAsic1b, Asic beta
    Isoform IDQ6NXK8-2
    Features which should be applied to build the isoform sequence: VSP_015614, VSP_015615.
  • 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.
  • PTM: Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel (By similarity).
  • MISCELLANEOUS: Potentiated by Ca(2+), Mg(2+), Ba(2+), 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).
  • MISCELLANEOUS: Mice lacking Accn2 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.
  • SIMILARITY: Belongs to the amiloride-sensitive sodium channel family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AB208022; BAD97849.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067025; AAH67025.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_033727.1; -.
UniGene Mm.440107
3D structure databases
ModBase Q6NXK8.
PTM databases
PhosphoSite Q6NXK8; -.
Organism-specific databases
MGI MGI:1194915; Accn2.
GeneLynx Accn2; Mus musculus.
Gene expression databases
ArrayExpress Q6NXK8; -.
CleanEx MM_ACCN2; -.
GermOnline ENSMUSG00000023017; Mus musculus.
Ontologies
GO
GO:0005887; Cellular component: integral to plasma membrane (inferred from direct assay from MGI).
GO:0019717; Cellular component: synaptosome (inferred from direct assay from MGI).
GO:0005261; Molecular function: cation channel activity (inferred from direct assay from MGI).
GO:0008306; Biological process: associative learning (inferred from mutant phenotype from MGI).
GO:0006812; Biological process: cation transport (inferred from direct assay from MGI).
GO:0007613; Biological process: memory (inferred from mutant phenotype from MGI).
GO:0001101; Biological process: response to acid (inferred from direct assay from MGI).
QuickGo view.
Family and domain databases
InterPro IPR004724; EnaC.
IPR001873; Na+channel_ASC.
Graphical view of domain structure.
PANTHER PTHR11690; Na+channel_ASC; 1.
Pfam PF00858; ASC; 1.
Pfam graphical view of domain structure.
PRINTS PR01078; AMINACHANNEL.
TIGRFAMs TIGR00859; ENaC; 1.
PROSITE PS01206; ASC; 1.
BLOCKS Q6NXK8.
Genome annotation databases
Ensembl ENSMUSG00000023017; Mus musculus. [Contig view]
GeneID 11419; -.
KEGG mmu:11419; -.
Phylogenomic databases
HOGENOM Q6NXK8; -.
HOVERGEN Q6NXK8; -.
Other
SOURCE Accn2; Mus musculus.
ProtoNet Q6NXK8.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; Calcium; Calcium transport; Glycoprotein; Ion transport; Ionic channel; Membrane; Phosphoprotein; Sodium; Sodium channel; Sodium transport; Transmembrane; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   526  526     Amiloride-sensitive cation channel 2, neuronal. PRO_0000181295
TOPO_DOM   1    43  43     Cytoplasmic (Potential). 
TRANSMEM   44    65  22     Potential. 
TOPO_DOM   66   425  360     Extracellular (Potential). 
TRANSMEM   426   446  21     Potential. 
TOPO_DOM   447   526  80     Cytoplasmic (Potential). 
MOD_RES   477   477        Phosphoserine; by PKA (By similarity). 
CARBOHYD   366   366        N-linked (GlcNAc...) (Potential). 
CARBOHYD   393   393        N-linked (GlcNAc...) (Potential). 
VAR_SEQ   1   184        Missing (in isoform 2). VSP_015614
VAR_SEQ   185   185        K -> MPIQIFCSVSFSSGEEAPGSMGDIWGPHHHHRQQQDSSES EEEEEKEKESGMELDEGDSPRDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALGAFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNTNAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAFSGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFS (in isoform 2). VSP_015615
Sequence information
Length: 526 AA [This is the length of the unprocessed precursor] Molecular weight: 59668 Da [This is the MW of the unprocessed precursor] CRC64: 5462B3FEB5532726 [This is a checksum on the sequence]
        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 

Q6NXK8 in FASTA format

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