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Protein

Acid-sensing ion channel 3

Gene

Asic3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei26 – 261Potassium ion selectivity and permeabilityBy similarity

GO - Molecular functioni

  • cation channel activity Source: MGI
  • enterobactin transporter activity Source: MGI
  • ligand-gated sodium channel activity Source: MGI

GO - Biological processi

  • cation transport Source: MGI
  • detection of chemical stimulus involved in sensory perception Source: MGI
  • detection of chemical stimulus involved in sensory perception of pain Source: MGI
  • detection of mechanical stimulus involved in sensory perception Source: MGI
  • detection of mechanical stimulus involved in sensory perception of pain Source: MGI
  • detection of temperature stimulus involved in sensory perception Source: MGI
  • detection of temperature stimulus involved in sensory perception of pain Source: MGI
  • enterobactin transport Source: GOC
  • ion transmembrane transport Source: MGI
  • response to acidic pH Source: MGI
  • response to heat Source: MGI
  • response to mechanical stimulus Source: MGI
  • sensory perception of sour taste Source: MGI
  • sodium ion transport Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Acid-sensing ion channel 3
Short name:
ASIC3
Alternative name(s):
Amiloride-sensitive cation channel 3
Dorsal root ASIC
Short name:
DRASIC
Gene namesi
Name:Asic3
Synonyms:Accn3, Drasic
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:2159339. Asic3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4343CytoplasmicSequence analysisAdd
BLAST
Transmembranei44 – 6219HelicalSequence analysisAdd
BLAST
Topological domaini63 – 440378ExtracellularSequence analysisAdd
BLAST
Transmembranei441 – 46020HelicalSequence analysisAdd
BLAST
Topological domaini461 – 53070CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice display altered responses to mechanical and acid stimuli. They do not develop chronic hyperalgesia induced by repeated acid injection.1 Publication

Chemistry

ChEMBLiCHEMBL3232696.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 530530Acid-sensing ion channel 3PRO_0000181302Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi93 ↔ 187By similarity
Disulfide bondi165 ↔ 172By similarity
Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence analysis
Disulfide bondi283 ↔ 369By similarity
Disulfide bondi314 ↔ 365By similarity
Disulfide bondi318 ↔ 363By similarity
Disulfide bondi327 ↔ 349By similarity
Disulfide bondi329 ↔ 341By similarity
Glycosylationi397 – 3971N-linked (GlcNAc...)Sequence analysis
Modified residuei481 – 4811PhosphoserineBy similarity
Modified residuei501 – 5011PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by PKA. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ6X1Y6.
PaxDbiQ6X1Y6.
PRIDEiQ6X1Y6.

PTM databases

iPTMnetiQ6X1Y6.
PhosphoSiteiQ6X1Y6.

Expressioni

Tissue specificityi

Expressed in liver, lung, kidney, testis, brain, eye and cochlea. Expressed in spiral ganglion and sensory hair cells of the organ of Corti in the cochlea (at protein level). Expressed in dorsal root ganglion innervating muscles and spinal chord. Expressed in peripheral sensory nerve termimals like nerves of the Meissner corpuscle, palisades of lanceolate nerve endings, site of mechanoreception in guard hair follicles, and Merkel cell-neurite complexes.3 Publications

Gene expression databases

BgeeiQ6X1Y6.
CleanExiMM_ACCN3.
ExpressionAtlasiQ6X1Y6. baseline and differential.
GenevisibleiQ6X1Y6. MM.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with DLG4 and ASIC2 (By similarity). Interacts with LIN7B, MAGI1/BAIAP1 and GOPC. Interacts with STOM; this regulates channel activity.By similarity3 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000039914.

Structurei

3D structure databases

ProteinModelPortaliQ6X1Y6.
SMRiQ6X1Y6. Positions 53-452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi527 – 5304PDZ-bindingBy similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4294. Eukaryota.
ENOG410ZNFK. LUCA.
GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ6X1Y6.
KOiK04830.
OMAiICETRFL.
OrthoDBiEOG72VH5P.
PhylomeDBiQ6X1Y6.
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. AlignAdd to basket

Isoform 1 (identifier: Q6X1Y6-1) [UniParc]FASTAAdd to basket

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

        10         20         30         40         50
MKPPSGLEEA QRRQASDIRV FANSCTMHGL GHIFGPGGLT LRRGLWATAV
60 70 80 90 100
LLSLAAFLYQ VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR
110 120 130 140 150
SRLTPNDLHW AGTALLGLDP AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL
160 170 180 190 200
YARAGHSLED MLLDCRYRGQ PCGPENFTVI FTRMGQCYTF NSGAQGAELL
210 220 230 240 250
TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV QIHGQEEPPA
260 270 280 290 300
IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASVDP DFDPEPSDPL
310 320 330 340 350
GSPSSSPPYS LIGCRLACES RYVARKCGCR MMHMPGNSPV CSPQQYKDCA
360 370 380 390 400
SPALDAMLRK DTCVCPNPCA TTRYAKELSM VRIPSRASAR YLARKYNRSE
410 420 430 440 450
TYITENVLVL DIFFEALNYE AVEQKAAYEV SELLGDIGGQ MGLFIGASLL
460 470 480 490 500
TILEILDYLC EVFQDRVLGY FWNRRSSQRR SGNTLLQEEL NGHRTHVPHL
510 520 530
SLGPRPPTAP SAVTKTLAAS HRTCYLVTRL
Note: No experimental confirmation available.
Length:530
Mass (Da):58,704
Last modified:September 13, 2005 - v2
Checksum:i6C97378D2135D5F1
GO
Isoform 2 (identifier: Q6X1Y6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     355-440: DAMLRKDTCV...SELLGDIGGQ → GRMYWFWISS...ALATLCSRKS
     441-530: Missing.

Show »
Length:440
Mass (Da):48,634
Checksum:i55DCDFB629CC728F
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei355 – 44086DAMLR…DIGGQ → GRMYWFWISSLKPSTMRPWN KRQLMKCRSCWETLGDRWDC LSEPACLPSSRSSTTSVRFF KTESWGTSGTEGALKGALAT LCSRKS in isoform 2. 1 PublicationVSP_015606Add
BLAST
Alternative sequencei441 – 53090Missing in isoform 2. 1 PublicationVSP_015607Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY261387 mRNA. Translation: AAP88539.1.
AC113055 Genomic DNA. No translation available.
CCDSiCCDS51433.1. [Q6X1Y6-1]
CCDS80225.1. [Q6X1Y6-2]
RefSeqiNP_001297403.1. NM_001310474.1. [Q6X1Y6-2]
NP_892045.2. NM_183000.2. [Q6X1Y6-1]
UniGeneiMm.299636.

Genome annotation databases

EnsembliENSMUST00000049346; ENSMUSP00000039914; ENSMUSG00000038276. [Q6X1Y6-2]
ENSMUST00000196296; ENSMUSP00000143083; ENSMUSG00000038276. [Q6X1Y6-1]
GeneIDi171209.
KEGGimmu:171209.
UCSCiuc008wrj.1. mouse. [Q6X1Y6-1]
uc008wrk.1. mouse. [Q6X1Y6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY261387 mRNA. Translation: AAP88539.1.
AC113055 Genomic DNA. No translation available.
CCDSiCCDS51433.1. [Q6X1Y6-1]
CCDS80225.1. [Q6X1Y6-2]
RefSeqiNP_001297403.1. NM_001310474.1. [Q6X1Y6-2]
NP_892045.2. NM_183000.2. [Q6X1Y6-1]
UniGeneiMm.299636.

3D structure databases

ProteinModelPortaliQ6X1Y6.
SMRiQ6X1Y6. Positions 53-452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000039914.

Chemistry

ChEMBLiCHEMBL3232696.

PTM databases

iPTMnetiQ6X1Y6.
PhosphoSiteiQ6X1Y6.

Proteomic databases

EPDiQ6X1Y6.
PaxDbiQ6X1Y6.
PRIDEiQ6X1Y6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000049346; ENSMUSP00000039914; ENSMUSG00000038276. [Q6X1Y6-2]
ENSMUST00000196296; ENSMUSP00000143083; ENSMUSG00000038276. [Q6X1Y6-1]
GeneIDi171209.
KEGGimmu:171209.
UCSCiuc008wrj.1. mouse. [Q6X1Y6-1]
uc008wrk.1. mouse. [Q6X1Y6-2]

Organism-specific databases

CTDi9311.
MGIiMGI:2159339. Asic3.

Phylogenomic databases

eggNOGiKOG4294. Eukaryota.
ENOG410ZNFK. LUCA.
GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ6X1Y6.
KOiK04830.
OMAiICETRFL.
OrthoDBiEOG72VH5P.
PhylomeDBiQ6X1Y6.
TreeFamiTF330663.

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Miscellaneous databases

NextBioi370694.
PROiQ6X1Y6.
SOURCEiSearch...

Gene expression databases

BgeeiQ6X1Y6.
CleanExiMM_ACCN3.
ExpressionAtlasiQ6X1Y6. baseline and differential.
GenevisibleiQ6X1Y6. MM.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
    Tissue: Inner ear.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "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.
  4. "The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice."
    Price M.P., McIlwrath S.L., Xie J., Cheng C., Qiao J., Tarr D.E., Sluka K.A., Brennan T.J., Lewin G.R., Welsh M.J.
    Neuron 32:1071-1083(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, FUNCTION.
  5. Cited for: FUNCTION.
  6. "Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1."
    Sluka K.A., Price M.P., Breese N.M., Stucky C.L., Wemmie J.A., Welsh M.J.
    Pain 106:229-239(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current."
    Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.
    J. Biol. Chem. 279:46962-46968(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LIN7B; MAGI1; GOPC AND DLG4.
  8. Cited for: INTERACTION WITH STOM.
  9. Cited for: INTERACTION WITH STOM.

Entry informationi

Entry nameiASIC3_MOUSE
AccessioniPrimary (citable) accession number: Q6X1Y6
Secondary accession number(s): Q7TQH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: September 13, 2005
Last modified: May 11, 2016
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Sensitized and potentiated by NPFF and NPSF. Inhibited by anti-inflammatory drugs, like salicylic acid (By similarity). Potentiated by FMRFamide-related neuropeptides. Regulated by lactate and Ca2+.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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.