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Q9UHC3 (ASIC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 3

Short name=ASIC3
Short name=hASIC3
Alternative name(s):
Amiloride-sensitive cation channel 3
Neuronal amiloride-sensitive cation channel 3
Testis sodium channel 1
Short name=hTNaC1
Gene names
Name:ASIC3
Synonyms:ACCN3, SLNAC1, TNAC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length531 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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. Ref.2 Ref.3

Subunit structure

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM; this regulates channel activity. Interacts with DLG4 By similarity. Interacts with LIN7B, MAGI1/BAIAP1, GOPC and ASIC2. Ref.8 Ref.11

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Cytoplasm By similarity. Note: Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4. In part cytoplasmic in cochlea cells By similarity.

Tissue specificity

Expressed by sensory neurons. Strongly expressed in brain, spinal chord, lung, lymph nodes, kidney, pituitary, heart and testis. Ref.1 Ref.3

Developmental stage

Expressed in fetal tissues, expression increases in lung and kidney adult tissues. Ref.3

Domain

The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1.

Post-translational modification

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 channel By similarity. Ref.10

Miscellaneous

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

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC3 subfamily. [View classification]

Sequence caution

The sequence BAA25897.1 differs from that shown. Reason: Frameshift at positions 303, 305 and 313.

The sequence BAD92658.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdetection of chemical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

detection of mechanical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

detection of temperature stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

response to acid

Inferred from electronic annotation. Source: Ensembl

response to heat

Inferred from electronic annotation. Source: Ensembl

sensory perception

Traceable author statement Ref.2. Source: ProtInc

sensory perception of sour taste

Inferred from mutant phenotype PubMed 19812697. Source: UniProt

signal transduction

Traceable author statement Ref.2. Source: ProtInc

sodium ion transmembrane transport

Traceable author statement Ref.1. Source: GOC

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncation channel activity

Traceable author statement Ref.2. Source: ProtInc

enterobactin transporter activity

Inferred from electronic annotation. Source: Ensembl

ligand-gated sodium channel activity

Inferred from electronic annotation. Source: Ensembl

sodium channel activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UHC3-1)

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: Q9UHC3-2)

Also known as: ASIC3b;

The sequence of this isoform differs from the canonical sequence as follows:
     487-531: LQEGLGSHRT...HRTCYLVTQL → TSHPSLCRHQ...AFPSSPQIKS
Isoform 3 (identifier: Q9UHC3-3)

Also known as: ASIC3c;

The sequence of this isoform differs from the canonical sequence as follows:
     506-531: RPPTPPCAVTKTLSASHRTCYLVTQL → STLLCSEDLPPLPVPSPRLSPPPTAPATLSHSSRPAVCVLGAPP
Isoform 4 (identifier: Q9UHC3-4)

Also known as: c;

The sequence of this isoform differs from the canonical sequence as follows:
     356-407: DAMLRKDSCA...NRSEAYIAEN → GRTCWPWTSS...GPACSPSSRS
     408-531: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 531531Acid-sensing ion channel 3
PRO_0000181301

Regions

Topological domain1 – 4343Cytoplasmic Potential
Transmembrane44 – 6118Helical; Potential
Topological domain62 – 441380Extracellular Potential
Transmembrane442 – 46019Helical; Potential
Topological domain461 – 53171Cytoplasmic Potential
Motif528 – 5314PDZ-binding

Sites

Site261Potassium ion selectivity and permeability By similarity

Amino acid modifications

Glycosylation1751N-linked (GlcNAc...) Potential
Glycosylation3981N-linked (GlcNAc...) Potential
Disulfide bond92 ↔ 186 By similarity
Disulfide bond164 ↔ 171 By similarity
Disulfide bond282 ↔ 370 By similarity
Disulfide bond315 ↔ 366 By similarity
Disulfide bond319 ↔ 364 By similarity
Disulfide bond328 ↔ 350 By similarity
Disulfide bond330 ↔ 342 By similarity

Natural variations

Alternative sequence356 – 40752DAMLR…YIAEN → GRTCWPWTSSLRPSTMRPWS RRRPMRCQSCLVTLGARWGC SSGPACSPSSRS in isoform 4.
VSP_015600
Alternative sequence408 – 531124Missing in isoform 4.
VSP_015601
Alternative sequence487 – 53145LQEGL…LVTQL → TSHPSLCRHQDSLRLPPHLL PCHTALDLLSVSSEPRPDIL DMPSLHVAFPSSPQIKS in isoform 2.
VSP_015602
Alternative sequence506 – 53126RPPTP…LVTQL → STLLCSEDLPPLPVPSPRLS PPPTAPATLSHSSRPAVCVL GAPP in isoform 3.
VSP_015603
Natural variant2281N → S.
Corresponds to variant rs1864545 [ dbSNP | Ensembl ].
VAR_052037

Experimental info

Mutagenesis5281V → A: No effect on interaction with LIN7B, MAGI1 and GOPC. Ref.11
Mutagenesis5291T → A: Loss of interaction with LIN7B, MAGI1. Ref.11
Mutagenesis5301Q → A: Loss of interaction with GOPC. No effect on interaction LIN7B and MAGI1. Ref.11
Mutagenesis5311L → A: Loss of interaction with LIN7B, MAGI1 and GOPC. Ref.11
Sequence conflict131P → Q in BAA25897. Ref.1
Sequence conflict131P → Q in AAC62935. Ref.3
Sequence conflict141A → P in AAC62935. Ref.3
Sequence conflict851I → V in AAC62935. Ref.3
Sequence conflict243 – 2442SQ → GH in BAA25897. Ref.1
Sequence conflict3581M → I in AAC62935. Ref.3
Sequence conflict3971L → F in BAA25897. Ref.1
Sequence conflict4001S → R in BAA25897. Ref.1
Sequence conflict5181L → F in BAA25897. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 13, 2005. Version 2.
Checksum: A46DD64590EC4871

FASTA53158,905
        10         20         30         40         50         60 
MKPTSGPEEA RRPASDIRVF ASNCSMHGLG HVFGPGSLSL RRGMWAAAVV LSVATFLYQV 

        70         80         90        100        110        120 
AERVRYYREF HHQTALDERE SHRLIFPAVT LCNINPLRRS RLTPNDLHWA GSALLGLDPA 

       130        140        150        160        170        180 
EHAAFLRALG RPPAPPGFMP SPTFDMAQLY ARAGHSLDDM LLDCRFRGQP CGPENFTTIF 

       190        200        210        220        230        240 
TRMGKCYTFN SGADGAELLT TTRGGMGNGL DIMLDVQQEE YLPVWRDNEE TPFEVGIRVQ 

       250        260        270        280        290        300 
IHSQEEPPII DQLGLGVSPG YQTFVSCQQQ QLSFLPPPWG DCSSASLNPN YEPEPSDPLG 

       310        320        330        340        350        360 
SPSPSPSPPY TLMGCRLACE TRYVARKCGC RMVYMPGDVP VCSPQQYKNC AHPAIDAMLR 

       370        380        390        400        410        420 
KDSCACPNPC ASTRYAKELS MVRIPSRAAA RFLARKLNRS EAYIAENVLA LDIFFEALNY 

       430        440        450        460        470        480 
ETVEQKKAYE MSELLGDIGG QMGLFIGASL LTILEILDYL CEVFRDKVLG YFWNRQHSQR 

       490        500        510        520        530 
HSSTNLLQEG LGSHRTQVPH LSLGPRPPTP PCAVTKTLSA SHRTCYLVTQ L 

« Hide

Isoform 2 (ASIC3b) [UniParc].

Checksum: 9411BD1485BA93F1
Show »

FASTA54360,332
Isoform 3 (ASIC3c) [UniParc].

Checksum: ED2C4D628AF9E18F
Show »

FASTA54960,491
Isoform 4 (c) [UniParc].

Checksum: 0C6D7DCF3F525596
Show »

FASTA40744,999

References

« Hide 'large scale' references
[1]"Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis."
Ishibashi K., Marumo F.
Biochem. Biophys. Res. Commun. 245:589-593(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Testis.
[2]"Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel."
de Weille J.R., Bassilana F., Lazdunski M., Waldmann R.
FEBS Lett. 433:257-260(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
Tissue: Embryo.
[3]"Molecular cloning and regional distribution of a human proton receptor subunit with biphasic functional properties."
Babinski K., Le K.-T., Seguela P.
J. Neurochem. 72:51-57(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, FUNCTION.
Tissue: Fetal brain.
[4]"ASIC3b and ASIC3c, new modulatory subunits of the acid sensing ion channel family."
Renard S., Besnard F., Partiseti M., Graham D.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[6]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Brain.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+."
Babinski K., Catarsi S., Biagini G., Seguela P.
J. Biol. Chem. 275:28519-28525(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ASIC1.
[9]"Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF."
Catarsi S., Babinski K., Seguela P.
Neuropharmacology 41:592-600(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY NPFF.
[10]"cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1."
Leonard A.S., Yermolaieva O., Hruska-Hageman A., Askwith C.C., Price M.P., Wemmie J.A., Welsh M.J.
Proc. Natl. Acad. Sci. U.S.A. 100:2029-2034(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKA.
[11]"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 AND GOPC, MUTAGENESIS OF VAL-528; THR-529; GLN-530 AND LEU-531.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB010575 mRNA. Translation: BAA25897.1. Frameshift.
AF095897 mRNA. Translation: AAC64188.1.
AF057711 mRNA. Translation: AAC62935.1.
AF195024 mRNA. Translation: AAF19817.1.
AF195025 mRNA. Translation: AAF19818.1.
AK313926 mRNA. Translation: BAG36647.1.
AB209421 mRNA. Translation: BAD92658.1. Different initiation.
CH471173 Genomic DNA. Translation: EAW54052.1.
CCDSCCDS5914.1. [Q9UHC3-2]
CCDS5915.1. [Q9UHC3-3]
CCDS5916.1. [Q9UHC3-1]
PIRJE0091.
RefSeqNP_004760.1. NM_004769.3. [Q9UHC3-1]
NP_064717.1. NM_020321.3. [Q9UHC3-3]
NP_064718.1. NM_020322.3. [Q9UHC3-2]
UniGeneHs.647113.

3D structure databases

ProteinModelPortalQ9UHC3.
SMRQ9UHC3. Positions 52-456.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114723. 7 interactions.
STRING9606.ENSP00000297512.

Chemistry

BindingDBQ9UHC3.
ChEMBLCHEMBL5368.
GuidetoPHARMACOLOGY686.

PTM databases

PhosphoSiteQ9UHC3.

Polymorphism databases

DMDM82582992.

Proteomic databases

PaxDbQ9UHC3.
PRIDEQ9UHC3.

Protocols and materials databases

DNASU9311.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297512; ENSP00000297512; ENSG00000213199. [Q9UHC3-3]
ENST00000349064; ENSP00000344838; ENSG00000213199. [Q9UHC3-1]
ENST00000357922; ENSP00000350600; ENSG00000213199. [Q9UHC3-2]
ENST00000377904; ENSP00000367136; ENSG00000213199. [Q9UHC3-4]
ENST00000468325; ENSP00000418605; ENSG00000213199. [Q9UHC3-4]
GeneID9311.
KEGGhsa:9311.
UCSCuc003win.3. human. [Q9UHC3-1]
uc003wio.3. human. [Q9UHC3-3]
uc003wip.3. human. [Q9UHC3-2]

Organism-specific databases

CTD9311.
GeneCardsGC07P150746.
HGNCHGNC:101. ASIC3.
HPAHPA049155.
MIM611741. gene.
neXtProtNX_Q9UHC3.
PharmGKBPA24435.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG262945.
HOVERGENHBG004150.
KOK04830.
OMAKDACACP.
OrthoDBEOG72VH5P.
PhylomeDBQ9UHC3.
TreeFamTF330663.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9UHC3.
BgeeQ9UHC3.
CleanExHS_ACCN3.
GenevestigatorQ9UHC3.

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

GeneWikiACCN3.
GenomeRNAi9311.
NextBio34875.
PROQ9UHC3.
SOURCESearch...

Entry information

Entry nameASIC3_HUMAN
AccessionPrimary (citable) accession number: Q9UHC3
Secondary accession number(s): B2R9V0 expand/collapse secondary AC list , O60263, O75906, Q59FN9, Q9UER8, Q9UHC4
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: September 13, 2005
Last modified: July 9, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM