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Reviewed, UniProtKB/Swiss-Prot P78348 (ACCN2_HUMAN)

Last modified October 13, 2009. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Amiloride-sensitive cation channel 2, neuronal
Alternative name(s):
    Acid-sensing ion channel 1
      Short name=ASIC1
    Brain sodium channel 2
    BNaC2
Gene names
Name: ACCN2
Synonyms: ASIC1, BNAC2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length528 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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 Ca2+, Li+ and K+. Generates a biphasic current with a fast inactivating and a slow sustained phase. 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. Functions as a postsynaptic proton receptor that influences intracellular Ca2+ concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear By similarity.

Subunit structure

Homotetramer or heterotetramer with other ASIC proteins Probable. Interacts with STOM and ACCN1 By similarity. Interacts with PRKCABP.

Subcellular location

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

Tissue specificity

Expressed in most or all neurons.

Post-translational modification

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

Miscellaneous

Potentiated by Ca2+, Mg2+, Ba2+ and multivalent cations. Inhibited by anti-inflammatory drugs like salicylic acid By similarity. Potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases.

Sequence similarities

Belongs to the amiloride-sensitive sodium channel family.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

PICK1Q9NRD51EBI-79189,EBI-79165

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: The splice variant from ASIC1a described in mouse and rat, which gives rise to an isoform with different N-termini (Asic1b), does not seem to exist in human.
Isoform 2 (identifier: P78348-2)

Also known as: Asic1a;

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 1 (identifier: P78348-1)

The sequence of this isoform differs from the canonical sequence as follows:
     433-433: G → GELLMTPVPFSCHGHGVAPYHPKAGCSLLSHEGPPPQRPFPKPCCLG

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 528528Amiloride-sensitive cation channel 2, neuronal
PRO_0000181294

Regions

Topological domain1 – 4444Cytoplasmic Potential
Transmembrane45 – 6521 Potential
Topological domain66 – 427362Extracellular Potential
Transmembrane428 – 44821 Potential
Topological domain449 – 52880Cytoplasmic Potential

Amino acid modifications

Modified residue4791Phosphoserine; by PKA Ref.6
Glycosylation3681N-linked (GlcNAc...) Potential
Glycosylation3951N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence4331G → GELLMTPVPFSCHGHGVAPY HPKAGCSLLSHEGPPPQRPF PKPCCLG in isoform 1.
VSP_015596

Experimental info

Mutagenesis4781S → A: No effect on phosphorylation. Ref.6
Mutagenesis4791S → A: Loss of phosphorylation. Ref.6

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Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (Asic1a) [UniParc].

Last modified September 13, 2005. Version 2.
Checksum: 22AA007002F04B50

FASTA52859,967
        10         20         30         40         50         60 
MELKAEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV 

        70         80         90        100        110        120 
CTERVQYYFH YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN 

       130        140        150        160        170        180 
RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEVCS 

       190        200        210        220        230        240 
AEDFKVVFTR YGKCYTFNSG RDGRPRLKTM KDGTGNGLEI MLDIQQDEYL PVWGETDETS 

       250        260        270        280        290        300 
FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVACQEQRL IYLPPPWGTC KAVTMDSDLD 

       310        320        330        340        350        360 
FFDSYSITAC RIDCETRYLV ENCNCRMVHM PGDAPYCTPE QYKECADPAL DFLVEKDQEY 

       370        380        390        400        410        420 
CVCEMPCNLT RYGKELSMVK IPSKASAKYL AKKFNKSEQY IGENILVLDI FFEVLNYETI 

       430        440        450        460        470        480 
EQKKAYEIAG LLGDIGGQMG LFIGASILTV LELFDYAYEV IKHKLCRRGK CQKEAKRSSA 

       490        500        510        520 
DKGVALSLDD VKRHNPCESL RGHPAGMTYA ANILPHHPAR GTFEDFTC

« Hide

Isoform 1.

Checksum: 8A981A8B1488CD3A
Show »

FASTA57464,841

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References

« Hide 'large scale' references
[1]"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: 9037075] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain.
[2]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 231-528 (ISOFORM 1).
Tissue: Ovary.
[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: 10798398] [Abstract]
Cited for: REGULATION BY FMRFAMIDE-RELATED PEPTIDES.
[4]"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: 11802773] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[5]"Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function."
Berdiev B.K., Xia J., Jovov B., Markert J.M., Mapstone T.B., Gillespie G.Y., Fuller C.M., Bubien J.K., Benos D.J.
J. Biol. Chem. 277:45734-45740(2002) [PubMed: 12244121] [Abstract]
Cited for: PHOSPHORYLATION BY PKC.
[6]"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: 12578970] [Abstract]
Cited for: PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-478 AND SER-479, PHOSPHORYLATION AT SER-479, INTERACTION WITH PRKCABP, SUBCELLULAR LOCATION.
[7]"Selective regulation of acid-sensing ion channel 1 by serine proteases."
Poirot O., Vukicevic M., Boesch A., Kellenberger S.
J. Biol. Chem. 279:38448-38457(2004) [PubMed: 15247234] [Abstract]
Cited for: REGULATION BY SERINE PROTEASES.
+Additional computationally mapped references.

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Cross-references

Sequence databases

U78180 mRNA. Translation: AAB48980.1.
U78181 mRNA. Translation: AAB48981.1.
BC013891 mRNA. Translation: AAH13891.2.
IPIIPI00293398.
IPI00293399.
RefSeqNP_001086.2.
NP_064423.2.
UniGeneHs.274361
Hs.647113

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActP78348. 1 interaction.
STRINGP78348.

Proteomic databases

PRIDEP78348.

Genome annotation databases

EnsemblENST00000228468; ENSP00000228468; ENSG00000110881; Homo sapiens. [Genome view]
ENST00000447966; ENSP00000400228; ENSG00000110881; Homo sapiens. [Genome view]
ENST00000453327; ENSP00000402896; ENSG00000110881; Homo sapiens. [Genome view]
GeneID41.
KEGGhsa:41.
UCSCuc001rvv.1. human.

Organism-specific databases

CTD41.
GeneCardsGC12P048737.
H-InvDBHIX0036785.
HGNCHGNC:100. ACCN2.
MIM602866. gene.
PharmGKBPA24434.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP78348.

Gene expression databases

BgeeP78348.
CleanExHS_ACCN2.
GenevestigatorP78348.

Family and domain databases

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

Other Resources

DrugBankDB00594. Amiloride.
NextBio167.
SOURCESearch...

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Entry information

Entry nameACCN2_HUMAN
AccessionPrimary (citable) accession number: P78348
Secondary accession number(s): P78349, Q96CV2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: September 13, 2005
Last modified: October 13, 2009
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Relevant documents

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents