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Protein

Acid-sensing ion channel 1

Gene

Asic1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Sitei71Important for channel gatingBy similarity1
Sitei79Important for channel desensitizingBy similarity1
Sitei287Important for channel gatingBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Calcium transport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calcium, Sodium

Enzyme and pathway databases

ReactomeiR-RNO-2672351. Stimuli-sensing channels.

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
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi71062. Asic1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 45CytoplasmicBy similarityAdd BLAST45
Transmembranei46 – 69HelicalBy similarityAdd BLAST24
Topological domaini70 – 425ExtracellularBy similarityAdd BLAST356
Transmembranei426 – 452Discontinuously helicalBy similarityAdd BLAST27
Topological domaini453 – 526CytoplasmicBy similarityAdd BLAST74

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi83S → P: No effect. Increases desensitization rates; when associated with L-84 and M-85. 1 Publication1
Mutagenesisi84Q → L: No effect. Increases desensitization rates; when associated with P-83 and M-85. 1 Publication1
Mutagenesisi85L → M: No effect. Increases desensitization rates; when associated with P-83 and L-84. 1 Publication1
Mutagenesisi100F → L: No effect on channel activation and inactivation. 1 Publication1
Mutagenesisi103V → L: No effect on channel activation and inactivation. 1 Publication1
Mutagenesisi105K → Y: Activated and inactivated at lower pH. 1 Publication1
Mutagenesisi106N → P: Activated and inactivated at lower pH. 1 Publication1
Mutagenesisi128 – 131QMAD → HLVE: No effect on desensitization rates. 1 Publication4
Mutagenesisi425E → G: Reduction of Ca(2+) block. Loss of Ca(2+) block; when associated with C-432. 1 Publication1
Mutagenesisi431G → V or F: Constitutive channel activity. 1 Publication1
Mutagenesisi432D → A: Reduction of Ca(2+) block. 1 Publication1
Mutagenesisi432D → C: Reduction of Ca(2+) block. Loss of Ca(2+) block; when associated with G-425. 1 Publication1
Mutagenesisi436Q → N: No effect on Ca(2+) block. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3562170.
GuidetoPHARMACOLOGYi684.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001813001 – 526Acid-sensing ion channel 1Add BLAST526

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi93 ↔ 194By similarity
Disulfide bondi172 ↔ 179By similarity
Disulfide bondi290 ↔ 365By similarity
Disulfide bondi308 ↔ 361By similarity
Disulfide bondi312 ↔ 359By similarity
Disulfide bondi321 ↔ 343By similarity
Disulfide bondi323 ↔ 335By similarity
Glycosylationi366N-linked (GlcNAc...)Sequence analysis1
Glycosylationi393N-linked (GlcNAc...)Sequence analysis1
Modified residuei477PhosphoserineBy similarity1
Modified residuei497PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP55926.

PTM databases

iPTMnetiP55926.
PhosphoSitePlusiP55926.
SwissPalmiP55926.

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.1 Publication

Gene expression databases

BgeeiENSRNOG00000018789.
ExpressionAtlasiP55926. baseline.
GenevisibleiP55926. RN.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM and PRKCABP (By similarity). Interacts with ASIC2.By similarity1 Publication

Protein-protein interaction databases

MINTiMINT-223538.

Structurei

3D structure databases

ProteinModelPortaliP55926.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 25Involved in divalent cations permeability6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi442 – 444Selectivity filterCurated3

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).By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiP55926.
KOiK04829.
OMAiPCHGHGV.
OrthoDBiEOG091G053J.
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. AlignAdd to basket

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

        10         20         30         40         50
MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF
60 70 80 90 100
LGSLAVLLCV CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF
110 120 130 140 150
SQVSKNDLYH AGELLALLNN RYEIPDTQMA DEKQLEILQD KANFRSFKPK
160 170 180 190 200
PFNMREFYDR AGHDIRDMLL SCHFRGEACS AEDFKVVFTR YGKCYTFNSG
210 220 230 240 250
QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS FEAGIKVQIH
260 270 280 290 300
SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF
310 320 330 340 350
DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF
360 370 380 390 400
LVEKDQEYCV CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG
410 420 430 440 450
ENILVLDIFF EVLNYETIEQ KKAYEIAGLL GDIGGQMGLF IGASILTVLE
460 470 480 490 500
LFDYAYEVIK HRLCRRGKCQ KEAKRSSADK GVALSLDDVK RHNPCESLRG
510 520
HPAGMTYAAN ILPHHPARGT FEDFTC
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 Ca2+. Mutagenesis of Asp-465 to Asn reduces Ca2+ block.Curated
Show »
Length:559
Mass (Da):62,217
Checksum:i0F438117B95C18E5
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 3 (identifier: P55926-3)
Sequence conflicti128T → S in CAA07080 (PubMed:9707631).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0155971 – 185Missing in isoform 2 and isoform 3. 3 PublicationsAdd BLAST185
Alternative sequenceiVSP_015598186V → MADIWGPHHHRQQQDSSESE EEEEKEMEAGSELDEGDDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_015599186V → MPIQIFCSVSFSSGEEAPGS MADIWGPHHHRQQQDSSESE EEEEKEMEAGSELDEGDDSP RDLVAFANSCTLHGASHVFV EGGPGPRQALWAVAFVIALG AFLCQVGDRVAYYLSYPHVT LLDEVATTELVFPAVTFCNT NAVRLSQLSYPDLLYLAPML GLDESDDPGVPLAPPGPEAF SGEPFNLHRFYNRSCHRLED MLLYCSYCGGPCGPHNFSV in isoform 3. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006257378.3. [P55926-3]
UniGeneiRn.37385.

Genome annotation databases

EnsembliENSRNOT00000077175; ENSRNOP00000072206; ENSRNOG00000059765. [P55926-2]
ENSRNOT00000088191; ENSRNOP00000068902; ENSRNOG00000059765. [P55926-1]
GeneIDi79123.
KEGGirno:79123.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006257378.3. [P55926-3]
UniGeneiRn.37385.

3D structure databases

ProteinModelPortaliP55926.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-223538.

Chemistry databases

ChEMBLiCHEMBL3562170.
GuidetoPHARMACOLOGYi684.

Protein family/group databases

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

PTM databases

iPTMnetiP55926.
PhosphoSitePlusiP55926.
SwissPalmiP55926.

Proteomic databases

PRIDEiP55926.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000077175; ENSRNOP00000072206; ENSRNOG00000059765. [P55926-2]
ENSRNOT00000088191; ENSRNOP00000068902; ENSRNOG00000059765. [P55926-1]
GeneIDi79123.
KEGGirno:79123.

Organism-specific databases

CTDi41.
RGDi71062. Asic1.

Phylogenomic databases

GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiP55926.
KOiK04829.
OMAiPCHGHGV.
OrthoDBiEOG091G053J.
PhylomeDBiP55926.
TreeFamiTF330663.

Enzyme and pathway databases

ReactomeiR-RNO-2672351. Stimuli-sensing channels.

Miscellaneous databases

PROiP55926.

Gene expression databases

BgeeiENSRNOG00000018789.
ExpressionAtlasiP55926. baseline.
GenevisibleiP55926. RN.

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 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: November 30, 2016
This is version 133 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

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.