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P55926 (ASIC1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acid-sensing ion channel 1

Short name=ASIC1
Alternative name(s):
Amiloride-sensitive cation channel 2, neuronal
Brain sodium channel 2
Short name=BNaC2
Gene names
Name:Asic1
Synonyms:Accn2, Bnac2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length526 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Isoform 3 discrimates stronger than isoform 1 between monovalent cations. Isoform 3 can flux Ca2+ while isoform 1 cannot. Heteromeric channels composed of isoform 2 and isoform 3 are active but have a lower pH-sensitivity. 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. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.9 Ref.12

Enzyme regulation

Inhibited by the diuretic amiloride. Ref.1

Subunit structure

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM and PRKCABP By similarity. Interacts with ASIC2. Ref.5

Subcellular location

Cell membrane; Multi-pass membrane protein. Note: Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 By similarity. Ref.1 Ref.2 Ref.10

Tissue specificity

Expressed in dorsal root ganglia and sciatic nerve (at protein level). Widely distributed throughout the brain. Expressed in olfactory bulb, neo and allocortical regions, dentate granule cells, pyramidal cells of CA1-CA3 subfields of the hippocampal formation, habenula, basolateral amygdaloid nuclei, and in the Purkinje and granule cells of the cerebellum. Diffusely detected over most other regions of the basal ganglia, including thalamic nuclei, substantia nigra, striatum and globus pallidus, hypothalamus, midbrain, pons, medulla and choroid plexus. Isoform 3 is expressed only in dorsal root ganglion (DRG) while isoform 1 is expressed in DRG, spinal chord, trigeminal ganglia and the trigeminal mesencephalic nucleus. Ref.2 Ref.4 Ref.5 Ref.10

Induction

Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs. Ref.1 Ref.7 Ref.8

Domain

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. Ref.3

Post-translational modification

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

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. Isoform 1 homomultimeric channel is specifically and reversibly inhibited by PcTX1, a tarantula venom toxin, while isoform 2 and other ASICs are insensitive.

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily. [View classification]

Sequence caution

The sequence CAA07080.1 differs from that shown. Reason: Frameshift at positions 119, 122 and 142.

Isoform 3: The sequence CAA07080.1 differs from that shown. Reason: Frameshift at positions 7 and 14.

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandCalcium
Sodium
   Molecular functionIon channel
Sodium channel
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processassociative learning

Inferred from electronic annotation. Source: Ensembl

calcium ion transmembrane transport

Inferred from electronic annotation. Source: Ensembl

cellular response to pH

Inferred from sequence or structural similarity. Source: UniProtKB

ion transmembrane transport

Inferred from mutant phenotype PubMed 19074149. Source: RGD

memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of neurotransmitter secretion

Inferred from electronic annotation. Source: Ensembl

protein homotrimerization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of membrane potential

Inferred from electronic annotation. Source: Ensembl

response to acid

Inferred from electronic annotation. Source: Ensembl

sensory perception of pain

Non-traceable author statement Ref.2. Source: RGD

sodium ion transmembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell surface

Inferred from direct assay PubMed 19074149. Source: RGD

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionacid-sensing ion channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

ion channel activity

Inferred from direct assay Ref.2. Source: RGD

ion gated channel activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P55926-1)

Also known as: ASIC-alpha; asic1alpha;

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: P55926-2)

Also known as: ASIC-beta2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.
     186-186: V → MADIWGPHHH...VIALGAFLCQ
Note: Inactive.
Isoform 3 (identifier: P55926-3)

Also known as: ASIC-beta; ASIC1b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.
     186-186: V → MPIQIFCSVS...GPCGPHNFSV
Note: Blocked by Ca(2+). Mutagenesis of Asp-465 to Asn reduces Ca(2+) block.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 526526Acid-sensing ion channel 1
PRO_0000181300

Regions

Topological domain1 – 4545Cytoplasmic By similarity
Transmembrane46 – 6924Helical; By similarity
Topological domain70 – 425356Extracellular By similarity
Transmembrane426 – 45227Discontinuously helical; By similarity
Topological domain453 – 52674Cytoplasmic By similarity
Region20 – 256Involved in divalent cations permeability
Motif442 – 4443Selectivity filter Probable

Sites

Site711Important for channel gating By similarity
Site791Important for channel desensitizing By similarity
Site2871Important for channel gating By similarity

Amino acid modifications

Modified residue4771Phosphoserine By similarity
Glycosylation3661N-linked (GlcNAc...) Potential
Glycosylation3931N-linked (GlcNAc...) Potential
Disulfide bond93 ↔ 194 By similarity
Disulfide bond172 ↔ 179 By similarity
Disulfide bond290 ↔ 365 By similarity
Disulfide bond308 ↔ 361 By similarity
Disulfide bond312 ↔ 359 By similarity
Disulfide bond321 ↔ 343 By similarity
Disulfide bond323 ↔ 335 By similarity

Natural variations

Alternative sequence1 – 185185Missing in isoform 2 and isoform 3.
VSP_015597
Alternative sequence1861V → MADIWGPHHHRQQQDSSESE EEEEKEMEAGSELDEGDDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQ in isoform 2.
VSP_015598
Alternative sequence1861V → MPIQIFCSVSFSSGEEAPGS MADIWGPHHHRQQQDSSESE EEEEKEMEAGSELDEGDDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNT NAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAF SGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFSV in isoform 3.
VSP_015599

Experimental info

Mutagenesis831S → P: No effect. Increases desensitization rates; when associated with L-84 and M-85. Ref.11
Mutagenesis841Q → L: No effect. Increases desensitization rates; when associated with P-83 and M-85. Ref.11
Mutagenesis851L → M: No effect. Increases desensitization rates; when associated with P-83 and L-84. Ref.11
Mutagenesis1001F → L: No effect on channel activation and inactivation. Ref.9
Mutagenesis1031V → L: No effect on channel activation and inactivation. Ref.9
Mutagenesis1051K → Y: Activated and inactivated at lower pH. Ref.9
Mutagenesis1061N → P: Activated and inactivated at lower pH. Ref.9
Mutagenesis128 – 1314QMAD → HLVE: No effect on desensitization rates. Ref.11
Mutagenesis4251E → G: Reduction of Ca(2+) block. Loss of Ca(2+) block; when associated with C-432. Ref.13
Mutagenesis4311G → V or F: Constitutive channel activity. Ref.5
Mutagenesis4321D → A: Reduction of Ca(2+) block. Ref.13
Mutagenesis4321D → C: Reduction of Ca(2+) block. Loss of Ca(2+) block; when associated with G-425. Ref.13
Mutagenesis4361Q → N: No effect on Ca(2+) block. Ref.13
Isoform 3:
Sequence conflict1281T → S in CAA07080. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ASIC-alpha) (asic1alpha) [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 5462A7786E2A1726

FASTA52659,641
        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 KEAKRSSADK 

       490        500        510        520 
GVALSLDDVK RHNPCESLRG HPAGMTYAAN ILPHHPARGT FEDFTC 

« Hide

Isoform 2 (ASIC-beta2) [UniParc].

Checksum: 8B4A9EDFCE348B89
Show »

FASTA42547,563
Isoform 3 (ASIC-beta) (ASIC1b) [UniParc].

Checksum: 0F438117B95C18E5
Show »

FASTA55962,217

References

[1]"A proton-gated cation channel involved in acid-sensing."
Waldmann R., Champigny G., Bassilana F., Heurteaux C., Lazdunski M.
Nature 386:173-177(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
[2]"A sensory neuron-specific, proton-gated ion channel."
Chen C.-C., England S., Akopian A.N., Wood J.N.
Proc. Natl. Acad. Sci. U.S.A. 95:10240-10245(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Spinal ganglion.
[3]"Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b."
Baessler E.-L., Ngo-Anh T.J., Geisler H.-S., Ruppersberg J.P., Gruender S.
J. Biol. Chem. 276:33782-33787(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), DOMAIN, FUNCTION.
Tissue: Inner ear.
[4]"Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-beta."
Ugawa S., Ueda T., Takahashi E., Hirabayashi Y., Yoneda T., Komai S., Shimada S.
NeuroReport 12:2865-2869(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, FUNCTION.
Tissue: Trigeminal ganglion.
[5]"The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties."
Bassilana F., Champigny G., Waldmann R., de Weille J.R., Heurteaux C., Lazdunski M.
J. Biol. Chem. 272:28819-28822(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INTERACTION WITH ASIC1, MUTAGENESIS OF GLY-431, FUNCTION.
[6]"Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels."
Escoubas P., de Weille J.R., Lecoq A., Diochot S., Waldmann R., Champigny G., Moinier D., Menez A., Lazdunski M.
J. Biol. Chem. 275:25116-25121(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY PCTX1 TOXIN.
[7]"Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels."
Askwith C.C., Cheng C., Ikuma M., Benson C., Price M.P., Welsh M.J.
Neuron 26:133-141(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY FMRFAMIDE-RELATED PEPTIDES.
[8]"Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors."
Voilley N., de Weille J.R., Mamet J., Lazdunski M.
J. Neurosci. 21:8026-8033(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, INHIBITION BY DRUGS.
[9]"Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1)."
Babini E., Paukert M., Geisler H.-S., Gruender S.
J. Biol. Chem. 277:41597-41603(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PHE-100; VAL-103; LYS-105 AND ASN-106, FUNCTION.
[10]"Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system."
Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M.
Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[11]"The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1."
Coric T., Zhang P., Todorovic N., Canessa C.M.
J. Biol. Chem. 278:45240-45247(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-83; GLN-84; LEU-85 AND 128-GLN--ASP-131.
[12]"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.
[13]"Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating."
Paukert M., Babini E., Pusch M., Grunder S.
J. Gen. Physiol. 124:383-394(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-425; ASP-432 AND GLN-436.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U94403 mRNA. Translation: AAB53002.1.
AJ006519 mRNA. Translation: CAA07080.1. Frameshift.
AJ309926 mRNA. Translation: CAC44267.1.
AB049451 mRNA. Translation: BAB39864.1.
RefSeqNP_077068.1. NM_024154.2. [P55926-1]
XP_006257440.1. XM_006257378.1. [P55926-3]
XP_006257443.1. XM_006257381.1. [P55926-1]
UniGeneRn.37385.

3D structure databases

ProteinModelPortalP55926.
SMRP55926. Positions 40-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-223538.

Chemistry

GuidetoPHARMACOLOGY684.

Protein family/group databases

TCDB1.A.6.1.2. the epithelial na(+) channel (enac) family.

PTM databases

PhosphoSiteP55926.

Proteomic databases

PRIDEP55926.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000025476; ENSRNOP00000025476; ENSRNOG00000018789. [P55926-1]
ENSRNOT00000047887; ENSRNOP00000041786; ENSRNOG00000018789. [P55926-3]
GeneID79123.
KEGGrno:79123.

Organism-specific databases

CTD41.
RGD71062. Asic1.

Phylogenomic databases

eggNOGNOG262945.
GeneTreeENSGT00640000091217.
HOGENOMHOG000247010.
HOVERGENHBG004150.
KOK04829.
OMAIQYYFLY.
OrthoDBEOG72VH5P.
PhylomeDBP55926.
TreeFamTF330663.

Gene expression databases

GenevestigatorP55926.

Family and domain databases

InterProIPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERPTHR11690. PTHR11690. 1 hit.
PfamPF00858. ASC. 1 hit.
[Graphical view]
PRINTSPR01078. AMINACHANNEL.
TIGRFAMsTIGR00859. ENaC. 1 hit.
PROSITEPS01206. ASC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio614550.
PROP55926.

Entry information

Entry nameASIC1_RAT
AccessionPrimary (citable) accession number: P55926
Secondary accession number(s): O88762, Q91YB8, Q99NA1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 11, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families