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Q16515 (ASIC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acid-sensing ion channel 2

Short name=ASIC2
Alternative name(s):
Amiloride-sensitive brain sodium channel
Amiloride-sensitive cation channel 1, neuronal
Amiloride-sensitive cation channel neuronal 1
Brain sodium channel 1
Short name=BNC1
Short name=BNaC1
Mammalian degenerin homolog
Gene names
Name:ASIC2
Synonyms:ACCN, ACCN1, BNAC1, MDEG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length512 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. Also permeable for Li+ and K+. Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.

Subunit structure

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM; this regulates channel activity By similarity. Interacts with PRKCABP and ASIC3. Ref.7 Ref.8

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Note: Localized at the plasma membrane of neurons, in the soma and punctated peripheral processes By similarity.

Tissue specificity

Brain and spinal cord. Isoform 1 is also detected in testis, liver, colon and ovary. Ref.2 Ref.7

Miscellaneous

Inhibited by anti-inflammatory drugs like salicylic acid By similarity. Regulated by Zn2+.

Sequence similarities

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC2 subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcentral nervous system development

Traceable author statement Ref.1. Source: ProtInc

detection of mechanical stimulus involved in sensory perception

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

monovalent inorganic cation transport

Traceable author statement Ref.1. Source: ProtInc

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

peripheral nervous system development

Traceable author statement Ref.1. Source: ProtInc

phototransduction

Inferred from electronic annotation. Source: Ensembl

positive regulation of synapse assembly

Inferred from electronic annotation. Source: Ensembl

protein localization to synapse

Inferred from electronic annotation. Source: Ensembl

regulation of blood coagulation

Inferred from mutant phenotype PubMed 21810271. Source: UniProt

regulation of gene expression

Inferred from mutant phenotype PubMed 21810271. Source: UniProt

regulation of membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback

Inferred from electronic annotation. Source: Ensembl

regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

response to acid

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

sensory perception of sour taste

Inferred from mutant phenotype PubMed 19812697. Source: UniProt

sodium ion transmembrane transport

Traceable author statement Ref.1. Source: GOC

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentdendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionion gated channel activity

Inferred from electronic annotation. Source: Ensembl

ligand-gated sodium channel activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction Ref.8. Source: IntAct

voltage-gated sodium channel activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PICK1Q9NRD53EBI-79149,EBI-79165

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16515-1)

Also known as: Asic2a;

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: Q16515-2)

Also known as: Asic2b; MDEG2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-184: Missing.
     185-185: T → MSRIGGAGLP...ELCGPHNFSS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 512512Acid-sensing ion channel 2
PRO_0000181290

Regions

Topological domain1 – 3737Cytoplasmic By similarity
Transmembrane38 – 5821Helical; Potential
Topological domain59 – 427369Extracellular By similarity
Transmembrane428 – 44821Helical; Potential
Topological domain449 – 51264Cytoplasmic By similarity

Amino acid modifications

Glycosylation3651N-linked (GlcNAc...) By similarity
Glycosylation3921N-linked (GlcNAc...) By similarity
Disulfide bond92 ↔ 193 By similarity
Disulfide bond171 ↔ 178 By similarity
Disulfide bond289 ↔ 364 By similarity
Disulfide bond307 ↔ 360 By similarity
Disulfide bond311 ↔ 358 By similarity
Disulfide bond320 ↔ 342 By similarity
Disulfide bond322 ↔ 334 By similarity

Natural variations

Alternative sequence1 – 184184Missing in isoform 2.
VSP_015590
Alternative sequence1851T → MSRIGGAGLPAAALTGPGRF RMAREEPAPAALAAAGQPGG GRGGERALQGPGVARRGRPS LSRAKLHGLRHMCAGRTAAG GSFQRRALWVLAFCTSFGLL LSWSSNRLLYWLSFPSHTRV HREWSRQLPFPAVTVCNNNP LRFPRLSKGDLYYAGHWLGL LLPNRTARPLVSELLRGDEP RRQWFRKLADFRLFLPPRHF EGISAAFMDRLGHQLEDMLL SCKYRGELCGPHNFSS in isoform 2.
VSP_015591
Natural variant3541D → G.
Corresponds to variant rs16967895 [ dbSNP | Ensembl ].
VAR_052036

Experimental info

Sequence conflict4951T → A in AAC50432. Ref.1
Isoform 2:
Sequence conflict671H → R in CAD38879. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Asic2a) [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 7C95B0B32EFF2814

FASTA51257,709
        10         20         30         40         50         60 
MDLKESPSEG SLQPSSIQIF ANTSTLHGIR HIFVYGPLTI RRVLWAVAFV GSLGLLLVES 

        70         80         90        100        110        120 
SERVSYYFSY QHVTKVDEVV AQSLVFPAVT LCNLNGFRFS RLTTNDLYHA GELLALLDVN 

       130        140        150        160        170        180 
LQIPDPHLAD PSVLEALRQK ANFKHYKPKQ FSMLEFLHRV GHDLKDMMLY CKFKGQECGH 

       190        200        210        220        230        240 
QDFTTVFTKY GKCYMFNSGE DGKPLLTTVK GGTGNGLEIM LDIQQDEYLP IWGETEETTF 

       250        260        270        280        290        300 
EAGVKVQIHS QSEPPFIQEL GFGVAPGFQT FVATQEQRLT YLPPPWGECR SSEMGLDFFP 

       310        320        330        340        350        360 
VYSITACRID CETRYIVENC NCRMVHMPGD APFCTPEQHK ECAEPALGLL AEKDSNYCLC 

       370        380        390        400        410        420 
RTPCNLTRYN KELSMVKIPS KTSAKYLEKK FNKSEKYISE NILVLDIFFE ALNYETIEQK 

       430        440        450        460        470        480 
KAYEVAALLG DIGGQMGLFI GASILTILEL FDYIYELIKE KLLDLLGKEE DEGSHDENVS 

       490        500        510 
TCDTMPNHSE TISHTVNVPL QTTLGTLEEI AC 

« Hide

Isoform 2 (Asic2b) (MDEG2) [UniParc].

Checksum: 821B2B1956DDB563
Show »

FASTA56362,887

References

« Hide 'large scale' references
[1]"Cloning and expression of a novel human brain Na+ channel."
Price M.P., Snyder P.M., Welsh M.J.
J. Biol. Chem. 271:7879-7882(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans."
Waldmann R., Champigny G., Voilley N., Lauritzen I., Lazdunski M.
J. Biol. Chem. 271:10433-10436(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Brain.
[3]"BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels."
Garcia-Anoveros J., Derfler B.H., Neville-Golden J., Hyman B.T., Corey D.P.
Proc. Natl. Acad. Sci. U.S.A. 94:1459-1464(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Frontal cortex.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Amygdala.
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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).
Tissue: Brain.
[7]"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 ASIC3, TISSUE SPECIFICITY.
[8]"Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel)."
Hruska-Hageman A.M., Wemmie J.A., Price M.P., Welsh M.J.
Biochem. J. 361:443-450(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U50352 mRNA. Translation: AAC50432.1.
U53212 mRNA. Translation: AAC50498.1.
U57352 mRNA. Translation: AAB49182.1.
AL834182 mRNA. Translation: CAD38879.1.
AC003687 Genomic DNA. No translation available.
AC004147 Genomic DNA. No translation available.
AC005549 Genomic DNA. No translation available.
AC008133 Genomic DNA. No translation available.
AC011824 Genomic DNA. No translation available.
AC015751 Genomic DNA. No translation available.
AC024610 Genomic DNA. No translation available.
AC024614 Genomic DNA. No translation available.
AC025898 Genomic DNA. No translation available.
AC027233 Genomic DNA. No translation available.
AC078907 Genomic DNA. No translation available.
AC123769 Genomic DNA. No translation available.
BC075042 mRNA. Translation: AAH75042.1.
BC075043 mRNA. Translation: AAH75043.1.
CCDSCCDS11276.1. [Q16515-2]
CCDS42296.1. [Q16515-1]
RefSeqNP_001085.2. NM_001094.4. [Q16515-1]
NP_899233.1. NM_183377.1. [Q16515-2]
UniGeneHs.368417.

3D structure databases

ProteinModelPortalQ16515.
SMRQ16515. Positions 50-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106558. 3 interactions.
IntActQ16515. 1 interaction.
MINTMINT-223746.
STRING9606.ENSP00000225823.

Chemistry

ChEMBLCHEMBL1628467.
DrugBankDB00594. Amiloride.
GuidetoPHARMACOLOGY685.

PTM databases

PhosphoSiteQ16515.

Polymorphism databases

DMDM2500840.

Proteomic databases

PaxDbQ16515.
PRIDEQ16515.

Protocols and materials databases

DNASU40.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225823; ENSP00000225823; ENSG00000108684. [Q16515-2]
ENST00000359872; ENSP00000352934; ENSG00000108684. [Q16515-1]
GeneID40.
KEGGhsa:40.
UCSCuc002hhu.3. human. [Q16515-1]

Organism-specific databases

CTD40.
GeneCardsGC17M031341.
HGNCHGNC:99. ASIC2.
HPAHPA052112.
MIM601784. gene.
neXtProtNX_Q16515.
PharmGKBPA24433.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG262945.
HOGENOMHOG000247010.
HOVERGENHBG004150.
KOK04828.
OMALCNNNPL.
OrthoDBEOG72VH5P.
PhylomeDBQ16515.
TreeFamTF330663.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ16515.
BgeeQ16515.
CleanExHS_ACCN1.
GenevestigatorQ16515.

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

GeneWikiACCN1.
GenomeRNAi40.
NextBio157.
PROQ16515.
SOURCESearch...

Entry information

Entry nameASIC2_HUMAN
AccessionPrimary (citable) accession number: Q16515
Secondary accession number(s): E9PBX2 expand/collapse secondary AC list , Q13553, Q6DJU1, Q8N3E2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 135 of the entry and version 1 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 17

Human chromosome 17: entries, gene names and cross-references to MIM