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Protein

Acid-sensing ion channel 2

Gene

Asic2

Organism
Rattus norvegicus (Rat)
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+. Activation by an extracellular pH drop is followed by a rapid pH-independent inactivation. Heteromeric channel assembly seems to modulate channel properties.3 Publications

GO - Molecular functioni

  • ion channel activity Source: RGD
  • ligand-gated sodium channel activity Source: InterPro
  • voltage-gated sodium channel activity Source: RGD

GO - Biological processi

  • cellular response to acidic pH Source: RGD
  • cellular response to drug Source: RGD
  • positive regulation of cation channel activity Source: RGD
  • sodium ion transport Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Protein family/group databases

TCDBi1.A.6.1.2. the epithelial na(+) channel (enac) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Acid-sensing ion channel 2
Short name:
ASIC2
Alternative name(s):
Amiloride-sensitive brain sodium channel
Amiloride-sensitive brain sodium channel 2
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
Short name:
MDEG
Gene namesi
Name:Asic2
Synonyms:Accn1, Bnac1, Mdeg
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2017. Asic2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37Cytoplasmic1 PublicationAdd BLAST37
Transmembranei38 – 58HelicalSequence analysisAdd BLAST21
Topological domaini59 – 427Extracellular1 PublicationAdd BLAST369
Transmembranei428 – 448HelicalSequence analysisAdd BLAST21
Topological domaini449 – 512Cytoplasmic1 PublicationAdd BLAST64

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4K → N: No effect on N-glycosylation. 1 Publication1
Mutagenesisi22N → S: No effect on N-glycosylation. 1 Publication1
Mutagenesisi37P → N: No effect on N-glycosylation. 1 Publication1
Mutagenesisi63R → N: No effect on N-glycosylation. 1 Publication1
Mutagenesisi67Y → N: No effect on N-glycosylation. 1 Publication1
Mutagenesisi72H → A: Inactive. Active at lower pH; when associated with V-430. 2 Publications1
Mutagenesisi72H → N: Increases N-glycosylation. 2 Publications1
Mutagenesisi81A → N: Increases N-glycosylation. 1 Publication1
Mutagenesisi109H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi127H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi145H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi158H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi162H → A: Loss of potentiation by Zn(2+). 1 Publication1
Mutagenesisi180H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi249H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi326H → A: No effect on pH dependence and function. 1 Publication1
Mutagenesisi339H → A: Loss of potentiation by Zn(2+). 1 Publication1
Mutagenesisi365N → S: Reduces N-glycosylation. Abolishes N-glycosylation; when associated with S-392. 1 Publication1
Mutagenesisi392N → S: Reduces N-glycosylation. Abolishes N-glycosylation; when associated with S-365. 1 Publication1
Mutagenesisi414Y → N: Increases N-glycosylation. 1 Publication1
Mutagenesisi423 – 425YEV → NES: Increases N-glycosylation. 1 Publication3
Mutagenesisi430G → C: Partial activation. 2 Publications1
Mutagenesisi430G → F: Constitutive activation causing cell death. Inactive; when associated with F-443. 2 Publications1
Mutagenesisi430G → K or T: Constitutive activation causing cell death. 2 Publications1
Mutagenesisi430G → S: No constitutive activation. 2 Publications1
Mutagenesisi430G → V: Constitutive activation causing cell death. Activated at lower pH; when associated with A-72. 2 Publications1
Mutagenesisi443S → F: Loss of function. Inactive; when associated with F-430. 1 Publication1
Mutagenesisi453 – 455YIY → NIS: No effect on N-glycosylation. 1 Publication3
Mutagenesisi478N → S: No effect on N-glycosylation. 1 Publication1
Mutagenesisi487N → S: No effect on N-glycosylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3562171.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812921 – 512Acid-sensing ion channel 2Add BLAST512

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8PhosphoserineCombined sources1
Modified residuei11PhosphoserineCombined sources1
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
Glycosylationi365N-linked (GlcNAc...)1 Publication1
Glycosylationi392N-linked (GlcNAc...)1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei478Not glycosylated1
Sitei487Not glycosylated1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiQ62962.

PTM databases

iPTMnetiQ62962.
PhosphoSitePlusiQ62962.

Expressioni

Tissue specificityi

Expressed in sciatic nerve and dorsal root ganglion (DRG) (at protein level). Both isoforms display the same expression pattern except in DRG where isoform 2 is more abundantly expressed. Widely distributed throughout the brain. Highly expressed in the main olfactory bulb, neo- and allo-cortical regions, hippocampal formation, habenula, basolateral amygdaloid nuclei, and cerebellum. In the olfactory system, expressed in the glomerular cell layer, the internal granular layer, and the mitral and internal plexiform cell layers. Within the glomerular layer, restricted to the periglomerular cells. In the neocortex, strongly expressed in the large pyramidal neurons in all cortical layers as well as in the oligo-, astro-, or micro-glia cells. In the hippocampal formation, expressed in dentate granule cells and hilar neurons, as well as in pyramidal cells of CA1-CA3 subfields. Expressed in stratum oriens and radiatum of all subfields. Within the thalamus, expressed moderately in the medial and lateral habenula. In the cerebellar cortex expressed in Purkinje cells and granule cells. Expressed at low levels in choroid plexus.4 Publications

Developmental stagei

Appears just before birth, reaches maximum levels after birth, then declines slightly until adulthood.

Inductioni

Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs.1 Publication

Gene expression databases

BgeeiENSRNOG00000007019.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with PRKCABP (By similarity). Interacts with STOM; this regulates channel activity. Interacts with ASIC1. Isoform 2 interacts with ASIC3.By similarity4 Publications

Protein-protein interaction databases

DIPiDIP-41193N.
MINTiMINT-223656.

Structurei

3D structure databases

ProteinModelPortaliQ62962.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ62962.
KOiK04828.
PhylomeDBiQ62962.
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: Q62962-1) [UniParc]FASTAAdd to basket
Also known as: Mdeg1, 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 PTVLEALRQK 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 GASLLTILEL
460 470 480 490 500
FDYIYELIKE KLLDLLGKEE EEGSHDENMS TCDTMPNHSE TISHTVNVPL
510
QTALGTLEEI AC
Length:512
Mass (Da):57,739
Last modified:November 1, 1997 - v1
Checksum:i38D0A77C3C430B03
GO
Isoform 2 (identifier: Q62962-2) [UniParc]FASTAAdd to basket
Also known as: Mdeg2, Asic2b

The sequence of this isoform differs from the canonical sequence as follows:
     1-184: Missing.
     185-185: T → MSRSGGARLP...ELCGPHNFSS

Note: Seems to be inactive as monomer or in a monomeric assembly and is not activated by mutagenesis of Gly-430. Mutagenesis of Ser-60 into Gly reduces activation by PKC through PRKCABP/PICK-1 of a ASIC3/ACCN3-ASIC2/ASIC2b channel.
Show »
Length:563
Mass (Da):63,115
Checksum:iDCE1B4A0A45F21E2
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0155941 – 184Missing in isoform 2. 1 PublicationAdd BLAST184
Alternative sequenceiVSP_015595185T → MSRSGGARLPATALSGPGRF RMAREQPAPVAVAAARQPGG DRSGDPALQGPGVARRGRPS LSRTKLHGLRHMCAGRTAAG GSFQRRALWVLAFCTSLGLL LSWSSNRLLYWLSFPSHTRV HREWSRQLPFPAVTVCNNNP LRFPRLSKGDLYYAGHWLGL LLPNRTARPLVSELLRGDEP RRQWFRKLADFRLFLPPRHF EGISAAFMDRLGHQLEDMLL SCKYRGELCGPHNFSS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53211 mRNA. Translation: AAC52588.1.
Y14635 mRNA. Translation: CAA74979.1.
RefSeqiNP_001029186.1. NM_001034014.1. [Q62962-1]
NP_037024.2. NM_012892.2. [Q62962-2]
UniGeneiRn.37523.

Genome annotation databases

GeneIDi25364.
KEGGirno:25364.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53211 mRNA. Translation: AAC52588.1.
Y14635 mRNA. Translation: CAA74979.1.
RefSeqiNP_001029186.1. NM_001034014.1. [Q62962-1]
NP_037024.2. NM_012892.2. [Q62962-2]
UniGeneiRn.37523.

3D structure databases

ProteinModelPortaliQ62962.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-41193N.
MINTiMINT-223656.

Chemistry databases

ChEMBLiCHEMBL3562171.

Protein family/group databases

TCDBi1.A.6.1.2. the epithelial na(+) channel (enac) family.

PTM databases

iPTMnetiQ62962.
PhosphoSitePlusiQ62962.

Proteomic databases

PRIDEiQ62962.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25364.
KEGGirno:25364.

Organism-specific databases

CTDi40.
RGDi2017. Asic2.

Phylogenomic databases

HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiQ62962.
KOiK04828.
PhylomeDBiQ62962.
TreeFamiTF330663.

Miscellaneous databases

PROiQ62962.

Gene expression databases

BgeeiENSRNOG00000007019.

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...

Entry informationi

Entry nameiASIC2_RAT
AccessioniPrimary (citable) accession number: Q62962
Secondary accession number(s): O55163
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.