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Protein

Acid-sensing ion channel 2

Gene

ASIC2

Organism
Homo sapiens (Human)
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. 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.

GO - Molecular functioni

  1. ion gated channel activity Source: Ensembl
  2. ligand-gated sodium channel activity Source: ProtInc
  3. voltage-gated sodium channel activity Source: Ensembl

GO - Biological processi

  1. cellular response to acid chemical Source: Ensembl
  2. cellular response to acidic pH Source: Ensembl
  3. central nervous system development Source: ProtInc
  4. detection of mechanical stimulus involved in sensory perception Source: Ensembl
  5. ion transmembrane transport Source: Reactome
  6. monovalent inorganic cation transport Source: ProtInc
  7. negative regulation of apoptotic process Source: Ensembl
  8. peripheral nervous system development Source: ProtInc
  9. phototransduction Source: Ensembl
  10. positive regulation of cation channel activity Source: Ensembl
  11. positive regulation of synapse assembly Source: Ensembl
  12. protein localization to synapse Source: Ensembl
  13. regulation of blood coagulation Source: UniProtKB
  14. regulation of gene expression Source: UniProtKB
  15. regulation of membrane potential Source: Ensembl
  16. regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback Source: Ensembl
  17. regulation of vasoconstriction Source: Ensembl
  18. sensory perception of sound Source: Ensembl
  19. sensory perception of sour taste Source: UniProtKB
  20. sodium ion transmembrane transport Source: GOC
  21. synaptic transmission Source: ProtInc
  22. transmembrane transport Source: Reactome
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

ReactomeiREACT_160189. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ASIC2
Synonyms:ACCN, ACCN1, BNAC1, MDEG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:99. ASIC2.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737CytoplasmicBy similarityAdd
BLAST
Transmembranei38 – 5821HelicalSequence AnalysisAdd
BLAST
Topological domaini59 – 427369ExtracellularBy similarityAdd
BLAST
Transmembranei428 – 44821HelicalSequence AnalysisAdd
BLAST
Topological domaini449 – 51264CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. dendritic spine Source: Ensembl
  2. integral component of plasma membrane Source: ProtInc
  3. neuronal cell body Source: Ensembl
  4. plasma membrane Source: Reactome
  5. synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24433.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 512512Acid-sensing ion channel 2PRO_0000181290Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi92 ↔ 193By similarity
Disulfide bondi171 ↔ 178By similarity
Disulfide bondi289 ↔ 364By similarity
Disulfide bondi307 ↔ 360By similarity
Disulfide bondi311 ↔ 358By similarity
Disulfide bondi320 ↔ 342By similarity
Disulfide bondi322 ↔ 334By similarity
Glycosylationi365 – 3651N-linked (GlcNAc...)By similarity
Glycosylationi392 – 3921N-linked (GlcNAc...)By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ16515.
PRIDEiQ16515.

PTM databases

PhosphoSiteiQ16515.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ16515.
CleanExiHS_ACCN1.
ExpressionAtlasiQ16515. baseline and differential.
GenevestigatoriQ16515.

Organism-specific databases

HPAiHPA052112.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM; this regulates channel activity (By similarity). Interacts with PRKCABP and ASIC3.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PICK1Q9NRD53EBI-79149,EBI-79165

Protein-protein interaction databases

BioGridi106558. 3 interactions.
IntActiQ16515. 1 interaction.
MINTiMINT-223746.
STRINGi9606.ENSP00000225823.

Structurei

3D structure databases

ProteinModelPortaliQ16515.
SMRiQ16515. Positions 50-450.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG262945.
GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ16515.
KOiK04828.
OMAiCESKALG.
OrthoDBiEOG72VH5P.
PhylomeDBiQ16515.
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: Q16515-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDLKESPSEG SLQPSSIQIF ANTSTLHGIR HIFVYGPLTI RRVLWAVAFV
60 70 80 90 100
GSLGLLLVES SERVSYYFSY QHVTKVDEVV AQSLVFPAVT LCNLNGFRFS
110 120 130 140 150
RLTTNDLYHA GELLALLDVN LQIPDPHLAD PSVLEALRQK ANFKHYKPKQ
160 170 180 190 200
FSMLEFLHRV GHDLKDMMLY CKFKGQECGH QDFTTVFTKY GKCYMFNSGE
210 220 230 240 250
DGKPLLTTVK GGTGNGLEIM LDIQQDEYLP IWGETEETTF EAGVKVQIHS
260 270 280 290 300
QSEPPFIQEL GFGVAPGFQT FVATQEQRLT YLPPPWGECR SSEMGLDFFP
310 320 330 340 350
VYSITACRID CETRYIVENC NCRMVHMPGD APFCTPEQHK ECAEPALGLL
360 370 380 390 400
AEKDSNYCLC RTPCNLTRYN KELSMVKIPS KTSAKYLEKK FNKSEKYISE
410 420 430 440 450
NILVLDIFFE ALNYETIEQK KAYEVAALLG DIGGQMGLFI GASILTILEL
460 470 480 490 500
FDYIYELIKE KLLDLLGKEE DEGSHDENVS TCDTMPNHSE TISHTVNVPL
510
QTTLGTLEEI AC
Length:512
Mass (Da):57,709
Last modified:November 1, 1997 - v1
Checksum:i7C95B0B32EFF2814
GO
Isoform 2 (identifier: Q16515-2) [UniParc]FASTAAdd to basket

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.Curated

Show »
Length:563
Mass (Da):62,887
Checksum:i821B2B1956DDB563
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti495 – 4951T → A in AAC50432 (PubMed:8626462).Curated
Isoform 2 (identifier: Q16515-2)
Sequence conflicti67 – 671H → R in CAD38879 (PubMed:17974005).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti354 – 3541D → G.
Corresponds to variant rs16967895 [ dbSNP | Ensembl ].
VAR_052036

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 184184Missing in isoform 2. 1 PublicationVSP_015590Add
BLAST
Alternative sequencei185 – 1851T → MSRIGGAGLPAAALTGPGRF RMAREEPAPAALAAAGQPGG GRGGERALQGPGVARRGRPS LSRAKLHGLRHMCAGRTAAG GSFQRRALWVLAFCTSFGLL LSWSSNRLLYWLSFPSHTRV HREWSRQLPFPAVTVCNNNP LRFPRLSKGDLYYAGHWLGL LLPNRTARPLVSELLRGDEP RRQWFRKLADFRLFLPPRHF EGISAAFMDRLGHQLEDMLL SCKYRGELCGPHNFSS in isoform 2. 1 PublicationVSP_015591

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11276.1. [Q16515-2]
CCDS42296.1. [Q16515-1]
RefSeqiNP_001085.2. NM_001094.4. [Q16515-1]
NP_899233.1. NM_183377.1. [Q16515-2]
UniGeneiHs.368417.

Genome annotation databases

EnsembliENST00000225823; ENSP00000225823; ENSG00000108684. [Q16515-2]
ENST00000359872; ENSP00000352934; ENSG00000108684. [Q16515-1]
GeneIDi40.
KEGGihsa:40.
UCSCiuc002hhu.3. human. [Q16515-1]

Polymorphism databases

DMDMi2500840.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11276.1. [Q16515-2]
CCDS42296.1. [Q16515-1]
RefSeqiNP_001085.2. NM_001094.4. [Q16515-1]
NP_899233.1. NM_183377.1. [Q16515-2]
UniGeneiHs.368417.

3D structure databases

ProteinModelPortaliQ16515.
SMRiQ16515. Positions 50-450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106558. 3 interactions.
IntActiQ16515. 1 interaction.
MINTiMINT-223746.
STRINGi9606.ENSP00000225823.

Chemistry

ChEMBLiCHEMBL1628467.
DrugBankiDB00594. Amiloride.
GuidetoPHARMACOLOGYi685.

PTM databases

PhosphoSiteiQ16515.

Polymorphism databases

DMDMi2500840.

Proteomic databases

PaxDbiQ16515.
PRIDEiQ16515.

Protocols and materials databases

DNASUi40.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000225823; ENSP00000225823; ENSG00000108684. [Q16515-2]
ENST00000359872; ENSP00000352934; ENSG00000108684. [Q16515-1]
GeneIDi40.
KEGGihsa:40.
UCSCiuc002hhu.3. human. [Q16515-1]

Organism-specific databases

CTDi40.
GeneCardsiGC17M031341.
HGNCiHGNC:99. ASIC2.
HPAiHPA052112.
MIMi601784. gene.
neXtProtiNX_Q16515.
PharmGKBiPA24433.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG262945.
GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ16515.
KOiK04828.
OMAiCESKALG.
OrthoDBiEOG72VH5P.
PhylomeDBiQ16515.
TreeFamiTF330663.

Enzyme and pathway databases

ReactomeiREACT_160189. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiASIC2. human.
GeneWikiiACCN1.
GenomeRNAii40.
NextBioi157.
PROiQ16515.
SOURCEiSearch...

Gene expression databases

BgeeiQ16515.
CleanExiHS_ACCN1.
ExpressionAtlasiQ16515. baseline and differential.
GenevestigatoriQ16515.

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. "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. 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.
    , 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.

Entry informationi

Entry nameiASIC2_HUMAN
AccessioniPrimary (citable) accession number: Q16515
Secondary accession number(s): E9PBX2
, Q13553, Q6DJU1, Q8N3E2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: January 7, 2015
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.