Reviewed, UniProtKB/Swiss-Prot Q6NXK8 (ACCN2_MOUSE)

Names and origin

Protein names

Recommended name:
    Amiloride-sensitive cation channel 2, neuronal
Alternative name(s):
    Acid-sensing ion channel
    Acid-sensing ion channel 1
    Brain sodium channel 2

Gene names

Name:	Accn2
Synonyms:	Asic, Asic1, Bnac2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	526 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca2+, Li+ and K+. Generates a biphasic current with a fast inactivating and a slow sustained phase. 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
Subunit structure	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.
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
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 family.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Ligand	Calcium Sodium
Molecular function	Ionic channel Sodium channel
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	associative learning Ref.3 Inferred from mutant phenotype. Source: MGI calcium ion transport Inferred from electronic annotation. Source: UniProtKB-KW memory Ref.3 Inferred from mutant phenotype. Source: MGI response to acid Ref.3 Inferred from direct assay. Source: MGI sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Inferred from direct assay. Source: MGI synaptosome Ref.3 Inferred from direct assay. Source: MGI
Molecular function	amiloride-sensitive sodium channel activity Inferred from electronic annotation. Source: InterPro calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW sodium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 526	526	Amiloride-sensitive cation channel 2, neuronal		PRO_0000181295
Regions
	Topological domain	1 – 43	43	Cytoplasmic Potential
	Transmembrane	44 – 65	22	Potential
	Topological domain	66 – 425	360	Extracellular Potential
	Transmembrane	426 – 446	21	Potential
	Topological domain	447 – 526	80	Cytoplasmic Potential
Amino acid modifications
	Modified residue	477	1	Phosphoserine; by PKA By similarity
	Glycosylation	366	1	N-linked (GlcNAc...) Potential
	Glycosylation	393	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 184	184	Missing in isoform 2.		VSP_015614
	Alternative sequence	185	1	K → MPIQIFCSVSFSSGEEAPGS MGDIWGPHHHHRQQQDSSES EEEEEKEKESGMELDEGDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNT NAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAF SGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFS in isoform 2.		VSP_015615

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Asic1a) (Asic alpha) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 5462B3FEB5532726	FASTA	526	59,668
	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
	Isoform 2 (Asic1b) (Asic beta). Checksum: EDB97A44CAF4A611	FASTA	559	62,309
	10 20 30 40 50 60 MPIQIFCSVS FSSGEEAPGS MGDIWGPHHH HRQQQDSSES EEEEEKEKES GMELDEGDSP 70 80 90 100 110 120 RDLVAFANSC TLHGASHVFV EGGPGPRQAL WAVAFVIALG AFLCQVGDRV AYYLSYPHVT 130 140 150 160 170 180 LLDEVATTEL VFPAVTFCNT NAVRLSQLSY PDLLYLAPML GLDESDDPGV PLAPPGPEAF 190 200 210 220 230 240 SGEPFNLHRF YNRSCHRLED MLLYCSYCGG PCGPHNFSVV FTRYGKCYTF NSGQDGRPRL 250 260 270 280 290 300 KTMKGGTGNG LEIMLDIQQD EYLPVWGETD ETSFEAGIKV QIHSQDEPPF IDQLGFGVAP 310 320 330 340 350 360 GFQTFVSCQE QRLIYLPSPW GTCNAVTMDS DFFDSYSITA CRIDCETRYL VENCNCRMVH 370 380 390 400 410 420 MPGDAPYCTP EQYKECADPA LDFLVEKDQE YCVCEMPCNL TRYGKELSMV KIPSKASAKY 430 440 450 460 470 480 LAKKFNKSEQ YIGENILVLD IFFEVLNYET IEQKKAYEIA GLLGDIGGQM GLFIGASILT 490 500 510 520 530 540 VLELFDYAYE VIKHRLCRRG KCQKEAKRNS ADKGVALSLD DVKRHNPCES LRGHPAGMTY 550 AANILPHHPA RGTFEDFTC

References

	« Hide 'large scale' referencesShow '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: 15489334] [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: 11988176] [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: 12843249] [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: 15369669] [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: 15578512] [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: 15471860] [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: 17060608] [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: 17662962] [Abstract] Cited for: FUNCTION IN CONTROL OF FEAR, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB208022 mRNA. Translation: BAD97849.1. BC067025 mRNA. Translation: AAH67025.1.
IPI	IPI00346778. IPI00607080.
RefSeq	NP_033727.1.
UniGene	Mm.440107
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q6NXK8.
Proteomic databases
PRIDE	Q6NXK8.
Genome annotation databases
Ensembl	ENSMUSG00000023017. Mus musculus. [Contig view]
GeneID	11419.
KEGG	mmu:11419.
Organism-specific databases
MGI	MGI:1194915. Accn2.
Phylogenomic databases
HOGENOM	Q6NXK8.
HOVERGEN	Q6NXK8.
OMA	Q6NXK8. PVPFPCH.
Gene expression databases
ArrayExpress	Q6NXK8.
Bgee	Q6NXK8.
CleanEx	MM_ACCN2.
GermOnline	ENSMUSG00000023017. Mus musculus.
Family and domain databases
InterPro	IPR004724. EnaC. IPR001873. Na+channel_ASC. [Graphical view]
PANTHER	PTHR11690. Na+channel_ASC. 1 hit.
Pfam	PF00858. ASC. 1 hit. [Graphical view]
PRINTS	PR01078. AMINACHANNEL.
TIGRFAMs	TIGR00859. ENaC. 1 hit.
PROSITE	PS01206. ASC. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	278664.
SOURCE	Search...

Entry information

Entry name

ACCN2_MOUSE

Accession

Primary (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:	June 16, 2009
This is version 47 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)