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P55926

- ASIC1_RAT

UniProt

P55926 - ASIC1_RAT

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Protein

Acid-sensing ion channel 1

Gene
Asic1, Accn2, Bnac2
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 discrimates stronger than isoform 1 between monovalent cations. Isoform 3 can flux Ca2+ while isoform 1 cannot. Heteromeric channels composed of isoform 2 and isoform 3 are active but have a lower pH-sensitivity. 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.7 Publications

Enzyme regulationi

Inhibited by the diuretic amiloride.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei71 – 711Important for channel gating By similarity
Sitei79 – 791Important for channel desensitizing By similarity
Sitei287 – 2871Important for channel gating By similarity

GO - Molecular functioni

  1. acid-sensing ion channel activity Source: UniProtKB
  2. ion channel activity Source: RGD
  3. ion gated channel activity Source: Ensembl

GO - Biological processi

  1. associative learning Source: Ensembl
  2. calcium ion transmembrane transport Source: Ensembl
  3. cellular response to pH Source: UniProtKB
  4. ion transmembrane transport Source: RGD
  5. memory Source: Ensembl
  6. negative regulation of neurotransmitter secretion Source: Ensembl
  7. protein homotrimerization Source: UniProtKB
  8. regulation of membrane potential Source: Ensembl
  9. response to acid Source: Ensembl
  10. sensory perception of pain Source: RGD
  11. sodium ion transmembrane transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Calcium transport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calcium, 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 1
Short name:
ASIC1
Alternative name(s):
Amiloride-sensitive cation channel 2, neuronal
Brain sodium channel 2
Short name:
BNaC2
Gene namesi
Name:Asic1
Synonyms:Accn2, Bnac2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome X

Organism-specific databases

RGDi71062. Asic1.

Subcellular locationi

Cell membrane; Multi-pass membrane protein
Note: Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 By similarity.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4545Cytoplasmic By similarityAdd
BLAST
Transmembranei46 – 6924Helical; By similarityAdd
BLAST
Topological domaini70 – 425356Extracellular By similarityAdd
BLAST
Transmembranei426 – 45227Discontinuously helical; By similarityAdd
BLAST
Topological domaini453 – 52674Cytoplasmic By similarityAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: RGD
  2. integral component of plasma membrane Source: UniProtKB
  3. synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi83 – 831S → P: No effect. Increases desensitization rates; when associated with L-84 and M-85. 1 Publication
Mutagenesisi84 – 841Q → L: No effect. Increases desensitization rates; when associated with P-83 and M-85. 1 Publication
Mutagenesisi85 – 851L → M: No effect. Increases desensitization rates; when associated with P-83 and L-84. 1 Publication
Mutagenesisi100 – 1001F → L: No effect on channel activation and inactivation. 1 Publication
Mutagenesisi103 – 1031V → L: No effect on channel activation and inactivation. 1 Publication
Mutagenesisi105 – 1051K → Y: Activated and inactivated at lower pH. 1 Publication
Mutagenesisi106 – 1061N → P: Activated and inactivated at lower pH. 1 Publication
Mutagenesisi128 – 1314QMAD → HLVE: No effect on desensitization rates. 1 Publication
Mutagenesisi425 – 4251E → G: Reduction of Ca(2+) block. Loss of Ca(2+) block; when associated with C-432. 1 Publication
Mutagenesisi431 – 4311G → V or F: Constitutive channel activity. 1 Publication
Mutagenesisi432 – 4321D → A: Reduction of Ca(2+) block. 1 Publication
Mutagenesisi432 – 4321D → C: Reduction of Ca(2+) block. Loss of Ca(2+) block; when associated with G-425. 1 Publication
Mutagenesisi436 – 4361Q → N: No effect on Ca(2+) block. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 526526Acid-sensing ion channel 1PRO_0000181300Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi93 ↔ 194 By similarity
Disulfide bondi172 ↔ 179 By similarity
Disulfide bondi290 ↔ 365 By similarity
Disulfide bondi308 ↔ 361 By similarity
Disulfide bondi312 ↔ 359 By similarity
Disulfide bondi321 ↔ 343 By similarity
Disulfide bondi323 ↔ 335 By similarity
Glycosylationi366 – 3661N-linked (GlcNAc...) Reviewed prediction
Glycosylationi393 – 3931N-linked (GlcNAc...) Reviewed prediction
Modified residuei477 – 4771Phosphoserine By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP55926.

PTM databases

PhosphoSiteiP55926.

Expressioni

Tissue specificityi

Expressed in dorsal root ganglia and sciatic nerve (at protein level). Widely distributed throughout the brain. Expressed in olfactory bulb, neo and allocortical regions, dentate granule cells, pyramidal cells of CA1-CA3 subfields of the hippocampal formation, habenula, basolateral amygdaloid nuclei, and in the Purkinje and granule cells of the cerebellum. Diffusely detected over most other regions of the basal ganglia, including thalamic nuclei, substantia nigra, striatum and globus pallidus, hypothalamus, midbrain, pons, medulla and choroid plexus. Isoform 3 is expressed only in dorsal root ganglion (DRG) while isoform 1 is expressed in DRG, spinal chord, trigeminal ganglia and the trigeminal mesencephalic nucleus.4 Publications

Inductioni

Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs.3 Publications

Gene expression databases

GenevestigatoriP55926.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM and PRKCABP By similarity. Interacts with ASIC2.1 Publication

Protein-protein interaction databases

MINTiMINT-223538.

Structurei

3D structure databases

ProteinModelPortaliP55926.
SMRiP55926. Positions 40-460.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni20 – 256Involved in divalent cations permeability

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi442 – 4443Selectivity filter Inferred

Domaini

Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix By similarity.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG262945.
GeneTreeiENSGT00640000091217.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
KOiK04829.
OMAiIQYYFLY.
OrthoDBiEOG72VH5P.
PhylomeDBiP55926.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P55926-1) [UniParc]FASTAAdd to Basket

Also known as: ASIC-alpha, asic1alpha

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

MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF    50
LGSLAVLLCV CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF 100
SQVSKNDLYH AGELLALLNN RYEIPDTQMA DEKQLEILQD KANFRSFKPK 150
PFNMREFYDR AGHDIRDMLL SCHFRGEACS AEDFKVVFTR YGKCYTFNSG 200
QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS FEAGIKVQIH 250
SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF 300
DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF 350
LVEKDQEYCV CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG 400
ENILVLDIFF EVLNYETIEQ KKAYEIAGLL GDIGGQMGLF IGASILTVLE 450
LFDYAYEVIK HRLCRRGKCQ KEAKRSSADK GVALSLDDVK RHNPCESLRG 500
HPAGMTYAAN ILPHHPARGT FEDFTC 526
Length:526
Mass (Da):59,641
Last modified:November 1, 1997 - v1
Checksum:i5462A7786E2A1726
GO
Isoform 2 (identifier: P55926-2) [UniParc]FASTAAdd to Basket

Also known as: ASIC-beta2

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.
     186-186: V → MADIWGPHHH...VIALGAFLCQ

Note: Inactive.

Show »
Length:425
Mass (Da):47,563
Checksum:i8B4A9EDFCE348B89
GO
Isoform 3 (identifier: P55926-3) [UniParc]FASTAAdd to Basket

Also known as: ASIC-beta, ASIC1b

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: Missing.
     186-186: V → MPIQIFCSVS...GPCGPHNFSV

Note: Blocked by Ca(2+). Mutagenesis of Asp-465 to Asn reduces Ca(2+) block.

Show »
Length:559
Mass (Da):62,217
Checksum:i0F438117B95C18E5
GO

Sequence cautioni

The sequence CAA07080.1 differs from that shown. Reason: Frameshift at positions 119, 122 and 142.
Isoform 3 : The sequence CAA07080.1 differs from that shown. Reason: Frameshift at positions 7 and 14.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 185185Missing in isoform 2 and isoform 3. VSP_015597Add
BLAST
Alternative sequencei186 – 1861V → MADIWGPHHHRQQQDSSESE EEEEKEMEAGSELDEGDDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQ in isoform 2. VSP_015598
Alternative sequencei186 – 1861V → MPIQIFCSVSFSSGEEAPGS MADIWGPHHHRQQQDSSESE EEEEKEMEAGSELDEGDDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNT NAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAF SGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFSV in isoform 3. VSP_015599

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Isoform 3 (identifier: P55926-3)
Sequence conflicti128 – 1281T → S in CAA07080. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U94403 mRNA. Translation: AAB53002.1.
AJ006519 mRNA. Translation: CAA07080.1. Frameshift.
AJ309926 mRNA. Translation: CAC44267.1.
AB049451 mRNA. Translation: BAB39864.1.
RefSeqiNP_077068.1. NM_024154.2. [P55926-1]
XP_006257440.1. XM_006257378.1. [P55926-3]
XP_006257443.1. XM_006257381.1. [P55926-1]
UniGeneiRn.37385.

Genome annotation databases

EnsembliENSRNOT00000025476; ENSRNOP00000025476; ENSRNOG00000018789. [P55926-1]
ENSRNOT00000047887; ENSRNOP00000041786; ENSRNOG00000018789. [P55926-3]
GeneIDi79123.
KEGGirno:79123.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U94403 mRNA. Translation: AAB53002.1 .
AJ006519 mRNA. Translation: CAA07080.1 . Frameshift.
AJ309926 mRNA. Translation: CAC44267.1 .
AB049451 mRNA. Translation: BAB39864.1 .
RefSeqi NP_077068.1. NM_024154.2. [P55926-1 ]
XP_006257440.1. XM_006257378.1. [P55926-3 ]
XP_006257443.1. XM_006257381.1. [P55926-1 ]
UniGenei Rn.37385.

3D structure databases

ProteinModelPortali P55926.
SMRi P55926. Positions 40-460.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

MINTi MINT-223538.

Chemistry

GuidetoPHARMACOLOGYi 684.

Protein family/group databases

TCDBi 1.A.6.1.2. the epithelial na(+) channel (enac) family.

PTM databases

PhosphoSitei P55926.

Proteomic databases

PRIDEi P55926.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000025476 ; ENSRNOP00000025476 ; ENSRNOG00000018789 . [P55926-1 ]
ENSRNOT00000047887 ; ENSRNOP00000041786 ; ENSRNOG00000018789 . [P55926-3 ]
GeneIDi 79123.
KEGGi rno:79123.

Organism-specific databases

CTDi 41.
RGDi 71062. Asic1.

Phylogenomic databases

eggNOGi NOG262945.
GeneTreei ENSGT00640000091217.
HOGENOMi HOG000247010.
HOVERGENi HBG004150.
KOi K04829.
OMAi IQYYFLY.
OrthoDBi EOG72VH5P.
PhylomeDBi P55926.
TreeFami TF330663.

Miscellaneous databases

NextBioi 614550.
PROi P55926.

Gene expression databases

Genevestigatori P55926.

Family and domain databases

InterProi IPR004724. EnaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view ]
PANTHERi PTHR11690. PTHR11690. 1 hit.
Pfami PF00858. ASC. 1 hit.
[Graphical view ]
PRINTSi PR01078. AMINACHANNEL.
TIGRFAMsi TIGR00859. ENaC. 1 hit.
PROSITEi PS01206. ASC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "A proton-gated cation channel involved in acid-sensing."
    Waldmann R., Champigny G., Bassilana F., Heurteaux C., Lazdunski M.
    Nature 386:173-177(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Spinal ganglion.
  3. "Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b."
    Baessler E.-L., Ngo-Anh T.J., Geisler H.-S., Ruppersberg J.P., Gruender S.
    J. Biol. Chem. 276:33782-33787(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), DOMAIN, FUNCTION.
    Tissue: Inner ear.
  4. "Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-beta."
    Ugawa S., Ueda T., Takahashi E., Hirabayashi Y., Yoneda T., Komai S., Shimada S.
    NeuroReport 12:2865-2869(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, FUNCTION.
    Tissue: Trigeminal ganglion.
  5. "The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties."
    Bassilana F., Champigny G., Waldmann R., de Weille J.R., Heurteaux C., Lazdunski M.
    J. Biol. Chem. 272:28819-28822(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INTERACTION WITH ASIC1, MUTAGENESIS OF GLY-431, FUNCTION.
  6. "Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels."
    Escoubas P., de Weille J.R., Lecoq A., Diochot S., Waldmann R., Champigny G., Moinier D., Menez A., Lazdunski M.
    J. Biol. Chem. 275:25116-25121(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITION BY PCTX1 TOXIN.
  7. "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] [Europe PMC] [Abstract]
    Cited for: REGULATION BY FMRFAMIDE-RELATED PEPTIDES.
  8. "Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors."
    Voilley N., de Weille J.R., Mamet J., Lazdunski M.
    J. Neurosci. 21:8026-8033(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, INHIBITION BY DRUGS.
  9. "Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1)."
    Babini E., Paukert M., Geisler H.-S., Gruender S.
    J. Biol. Chem. 277:41597-41603(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF PHE-100; VAL-103; LYS-105 AND ASN-106, FUNCTION.
  10. "Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system."
    Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M.
    Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  11. "The extracellular domain determines the kinetics of desensitization in acid-sensitive ion channel 1."
    Coric T., Zhang P., Todorovic N., Canessa C.M.
    J. Biol. Chem. 278:45240-45247(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-83; GLN-84; LEU-85 AND 128-GLN--ASP-131.
  12. "Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels."
    Xiong Z.-G., Zhu X.-M., Chu X.-P., Minami M., Hey J., Wei W.-L., MacDonald J.F., Wemmie J.A., Price M.P., Welsh M.J., Simon R.P.
    Cell 118:687-698(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating."
    Paukert M., Babini E., Pusch M., Grunder S.
    J. Gen. Physiol. 124:383-394(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-425; ASP-432 AND GLN-436.

Entry informationi

Entry nameiASIC1_RAT
AccessioniPrimary (citable) accession number: P55926
Secondary accession number(s): O88762, Q91YB8, Q99NA1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 11, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Potentiated by Ca2+, Mg2+, Ba2+, multivalent cations and potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases. Inhibited by anti-inflammatory drugs like salicylic acid. Isoform 1 homomultimeric channel is specifically and reversibly inhibited by PcTX1, a tarantula venom toxin, while isoform 2 and other ASICs are insensitive.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi