Q6NXK8 (ASIC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Asic1
Synonyms:	Accn2, Asic, Bnac2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	526 AA.
Sequence status	Complete.
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	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
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 process	Calcium transport Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Calcium Sodium
Molecular function	Ion channel Sodium channel
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	associative learning Inferred from mutant phenotype Ref.3. Source: MGI calcium ion transmembrane transport Inferred from mutant phenotype PubMed 19376200. Source: MGI memory Inferred from mutant phenotype Ref.3. Source: MGI negative regulation of neurotransmitter secretion Inferred from mutant phenotype PubMed 18094106. Source: MGI regulation of membrane potential Inferred from mutant phenotype PubMed 19376200. Source: MGI response to acid Inferred from direct assay PubMed 11854527. Source: MGI sodium ion transmembrane transport Inferred from electronic annotation. Source: GOC
Cellular_component	integral to plasma membrane Inferred from direct assay PubMed 11854527. Source: MGI synapse Inferred from direct assay Ref.3. Source: MGI
Molecular_function	cation channel activity Inferred from direct assay PubMed 11854527. Source: MGI ion gated channel activity Inferred from direct assay PubMed 14960591. Source: MGI ligand-gated sodium channel activity Inferred from electronic annotation. Source: InterPro
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	Acid-sensing ion channel 1		PRO_0000181295
Regions
	Topological domain	1 – 45	45	Cytoplasmic By similarity
	Transmembrane	46 – 69	24	Helical; By similarity
	Topological domain	70 – 425	356	Extracellular By similarity
	Transmembrane	426 – 452	27	Helical; By similarity
	Topological domain	453 – 526	74	Cytoplasmic By similarity
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
	Disulfide bond	93 ↔ 194		By similarity
	Disulfide bond	172 ↔ 179		By similarity
	Disulfide bond	290 ↔ 365		By similarity
	Disulfide bond	308 ↔ 361		By similarity
	Disulfide bond	312 ↔ 359		By similarity
	Disulfide bond	321 ↔ 343		By similarity
	Disulfide bond	323 ↔ 335		By similarity
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) [UniParc]. 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] [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.
IPI	IPI00346778. IPI00607080.
RefSeq	NP_033727.1. NM_009597.1.
UniGene	Mm.440107.
3D structure databases
ProteinModelPortal	Q6NXK8.
SMR	Q6NXK8. Positions 40-460.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29728N.
PTM databases
PhosphoSite	Q6NXK8.
Proteomic databases
PRIDE	Q6NXK8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000023758; ENSMUSP00000023758; ENSMUSG00000023017.
GeneID	11419.
KEGG	mmu:11419.
UCSC	uc007xqa.1. mouse. uc011zzg.1. mouse.
Organism-specific databases
CTD	41.
MGI	MGI:1194915. Asic1.
Phylogenomic databases
eggNOG	NOG262945.
GeneTree	ENSGT00640000091217.
HOGENOM	HOG000247010.
HOVERGEN	HBG004150.
KO	K04829.
OMA	PVPFPCH.
OrthoDB	EOG48GW36.
Gene expression databases
Bgee	Q6NXK8.
CleanEx	MM_ACCN2.
Genevestigator	Q6NXK8.
GermOnline	ENSMUSG00000023017. Mus musculus.
Family and domain databases
InterPro	IPR004724. EnaC. IPR001873. Na+channel_ASC. IPR020903. Na+channel_ASC_CS. [Graphical view]
PANTHER	PTHR11690. PTHR11690. 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
NextBio	278664.
SOURCE	Search...

Entry information

Entry name

ASIC1_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:	April 3, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program