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Protein

Acid-sensing ion channel 1

Gene

ASIC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel 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. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. 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.1 Publication
Isoform 1 does not display proton-gated cation channel activity.1 Publication

Enzyme regulationi

Inhibited by the diuretic amiloride. Inhibited by Cs1+ ions. Inhibited by spider venom psalmotoxin 1; this locks the channel into its desensitized conformation.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

  • acid-sensing ion channel activity Source: UniProtKB
  • ion gated channel activity Source: Ensembl
  • ligand-gated sodium channel activity Source: ProtInc

GO - Biological processi

  • associative learning Source: Ensembl
  • calcium ion transmembrane transport Source: Ensembl
  • cellular response to pH Source: UniProtKB
  • ion transmembrane transport Source: Reactome
  • memory Source: Ensembl
  • negative regulation of neurotransmitter secretion Source: Ensembl
  • protein homotrimerization Source: UniProtKB
  • regulation of membrane potential Source: Ensembl
  • response to acidic pH Source: Ensembl
  • response to pH Source: ProtInc
  • sensory perception of sour taste Source: UniProtKB
  • signal transduction Source: ProtInc
  • sodium ion transmembrane transport Source: UniProtKB
  • sodium ion transport Source: UniProtKB
  • transport Source: ProtInc
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

BioCyciZFISH:ENSG00000110881-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
SignaLinkiP78348.
SIGNORiP78348.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:100. ASIC1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 45CytoplasmicBy similarityAdd BLAST45
Transmembranei46 – 69HelicalBy similarityAdd BLAST24
Topological domaini70 – 427ExtracellularBy similarityAdd BLAST358
Transmembranei428 – 454Discontinuously helicalBy similarityAdd BLAST27
Topological domaini455 – 528CytoplasmicBy similarityAdd BLAST74

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi478S → A: No effect on phosphorylation. 1 Publication1
Mutagenesisi479S → A: Loss of phosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi41.
OpenTargetsiENSG00000110881.
PharmGKBiPA24434.

Chemistry databases

ChEMBLiCHEMBL1628477.
DrugBankiDB00594. Amiloride.
DB00586. Diclofenac.
GuidetoPHARMACOLOGYi684.

Polymorphism and mutation databases

BioMutaiASIC1.
DMDMi296439456.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812941 – 528Acid-sensing ion channel 1Add BLAST528

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi93 ↔ 194By similarity
Disulfide bondi172 ↔ 179By similarity
Disulfide bondi290 ↔ 367By similarity
Disulfide bondi310 ↔ 363By similarity
Disulfide bondi314 ↔ 361By similarity
Disulfide bondi323 ↔ 345By similarity
Disulfide bondi325 ↔ 337By similarity
Glycosylationi368N-linked (GlcNAc...)Sequence analysis1
Glycosylationi395N-linked (GlcNAc...)Sequence analysis1
Modified residuei479Phosphoserine; by PKA1 Publication1
Modified residuei499PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PeptideAtlasiP78348.
PRIDEiP78348.

PTM databases

iPTMnetiP78348.
PhosphoSitePlusiP78348.
SwissPalmiP78348.

Expressioni

Tissue specificityi

Expressed in most or all neurons.

Gene expression databases

BgeeiENSG00000110881.
CleanExiHS_ACCN2.
ExpressionAtlasiP78348. baseline and differential.
GenevisibleiP78348. HS.

Organism-specific databases

HPAiHPA065870.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM and ASIC2 (By similarity). Interacts with PRKCABP. Interacts with spider venom psalmotoxin 1.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PICK1Q9NRD53EBI-79189,EBI-79165

Protein-protein interaction databases

BioGridi106559. 12 interactors.
IntActiP78348. 2 interactors.

Chemistry databases

BindingDBiP78348.

Structurei

3D structure databases

ProteinModelPortaliP78348.
SMRiP78348.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi444 – 446Selectivity 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.
InParanoidiP78348.
KOiK04829.
OMAiPLGDIWG.
OrthoDBiEOG091G053J.
PhylomeDBiP78348.
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

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) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MELKAEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF
60 70 80 90 100
LGSLAVLLCV CTERVQYYFH YHHVTKLDEV AASQLTFPAV TLCNLNEFRF
110 120 130 140 150
SQVSKNDLYH AGELLALLNN RYEIPDTQMA DEKQLEILQD KANFRSFKPK
160 170 180 190 200
PFNMREFYDR AGHDIRDMLL SCHFRGEVCS AEDFKVVFTR YGKCYTFNSG
210 220 230 240 250
RDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS FEAGIKVQIH
260 270 280 290 300
SQDEPPFIDQ LGFGVAPGFQ TFVACQEQRL IYLPPPWGTC KAVTMDSDLD
310 320 330 340 350
FFDSYSITAC RIDCETRYLV ENCNCRMVHM PGDAPYCTPE QYKECADPAL
360 370 380 390 400
DFLVEKDQEY CVCEMPCNLT RYGKELSMVK IPSKASAKYL AKKFNKSEQY
410 420 430 440 450
IGENILVLDI FFEVLNYETI EQKKAYEIAG LLGDIGGQMG LFIGASILTV
460 470 480 490 500
LELFDYAYEV IKHKLCRRGK CQKEAKRSSA DKGVALSLDD VKRHNPCESL
510 520
RGHPAGMTYA ANILPHHPAR GTFEDFTC
Length:528
Mass (Da):59,909
Last modified:May 18, 2010 - v3
Checksum:i9E998F711C208450
GO
Isoform 1 (identifier: P78348-1) [UniParc]FASTAAdd to basket

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

Show »
Length:574
Mass (Da):64,783
Checksum:i04B7E51DF15F90BF
GO
Isoform 3 (identifier: P78348-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: MELKAEEEEV...GEVCSAEDFK → MPIQIFCSMS...GGPCGPHNFS

Show »
Length:562
Mass (Da):62,700
Checksum:i0EC8183120C02EC4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti212G → D in AAB48980 (PubMed:9037075).Curated1
Sequence conflicti212G → D in AAB48981 (PubMed:9037075).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0452981 – 185MELKA…AEDFK → MPIQIFCSMSFSSGEEAPGP LGDIWGPHHHQQQQDISESE EEEEEKEKEAVRKEASEGHS PMDLVAFANSCTLHGTNHIF VEGGPGPRQVLWAVAFVLAL GAFLCQVGDRVAYYLSYPHV TLLNEVATTELAFPAVTLCN TNAVRLSQLSYPDLLYLAPM LGLDESDDPGVPLAPPGPEA FSGEPFNLHRFYNRSCHRLE DMLLYCSYQGGPCGPHNFS in isoform 3. 1 PublicationAdd BLAST185
Alternative sequenceiVSP_015596433G → GELLMTPVPFSCHGHGVAPY HPKAGCSLLSHEGPPPQRPF PKPCCLG in isoform 1. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78180 mRNA. Translation: AAB48980.1.
U78181 mRNA. Translation: AAB48981.1.
HM991481 mRNA. Translation: ADP44689.1.
EU078959 mRNA. Translation: ABU48925.1.
AC025154 Genomic DNA. No translation available.
CH471111 Genomic DNA. Translation: EAW58118.1.
BC013891 mRNA. Translation: AAH13891.2.
BC133707 mRNA. Translation: AAI33708.1.
CCDSiCCDS44876.1. [P78348-2]
CCDS58228.1. [P78348-3]
CCDS8796.1. [P78348-1]
RefSeqiNP_001086.2. NM_001095.3. [P78348-2]
NP_001243759.1. NM_001256830.1. [P78348-3]
NP_064423.2. NM_020039.3. [P78348-1]
UniGeneiHs.274361.

Genome annotation databases

EnsembliENST00000228468; ENSP00000228468; ENSG00000110881. [P78348-1]
ENST00000447966; ENSP00000400228; ENSG00000110881. [P78348-2]
ENST00000552438; ENSP00000450247; ENSG00000110881. [P78348-3]
GeneIDi41.
KEGGihsa:41.
UCSCiuc001rvv.5. human. [P78348-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78180 mRNA. Translation: AAB48980.1.
U78181 mRNA. Translation: AAB48981.1.
HM991481 mRNA. Translation: ADP44689.1.
EU078959 mRNA. Translation: ABU48925.1.
AC025154 Genomic DNA. No translation available.
CH471111 Genomic DNA. Translation: EAW58118.1.
BC013891 mRNA. Translation: AAH13891.2.
BC133707 mRNA. Translation: AAI33708.1.
CCDSiCCDS44876.1. [P78348-2]
CCDS58228.1. [P78348-3]
CCDS8796.1. [P78348-1]
RefSeqiNP_001086.2. NM_001095.3. [P78348-2]
NP_001243759.1. NM_001256830.1. [P78348-3]
NP_064423.2. NM_020039.3. [P78348-1]
UniGeneiHs.274361.

3D structure databases

ProteinModelPortaliP78348.
SMRiP78348.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106559. 12 interactors.
IntActiP78348. 2 interactors.

Chemistry databases

BindingDBiP78348.
ChEMBLiCHEMBL1628477.
DrugBankiDB00594. Amiloride.
DB00586. Diclofenac.
GuidetoPHARMACOLOGYi684.

PTM databases

iPTMnetiP78348.
PhosphoSitePlusiP78348.
SwissPalmiP78348.

Polymorphism and mutation databases

BioMutaiASIC1.
DMDMi296439456.

Proteomic databases

PeptideAtlasiP78348.
PRIDEiP78348.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000228468; ENSP00000228468; ENSG00000110881. [P78348-1]
ENST00000447966; ENSP00000400228; ENSG00000110881. [P78348-2]
ENST00000552438; ENSP00000450247; ENSG00000110881. [P78348-3]
GeneIDi41.
KEGGihsa:41.
UCSCiuc001rvv.5. human. [P78348-2]

Organism-specific databases

CTDi41.
DisGeNETi41.
GeneCardsiASIC1.
HGNCiHGNC:100. ASIC1.
HPAiHPA065870.
MIMi602866. gene.
neXtProtiNX_P78348.
OpenTargetsiENSG00000110881.
PharmGKBiPA24434.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00760000119120.
HOGENOMiHOG000247010.
HOVERGENiHBG004150.
InParanoidiP78348.
KOiK04829.
OMAiPLGDIWG.
OrthoDBiEOG091G053J.
PhylomeDBiP78348.
TreeFamiTF330663.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110881-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
SignaLinkiP78348.
SIGNORiP78348.

Miscellaneous databases

GeneWikiiACCN2.
GenomeRNAii41.
PROiP78348.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110881.
CleanExiHS_ACCN2.
ExpressionAtlasiP78348. baseline and differential.
GenevisibleiP78348. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P78348
Secondary accession number(s): A3KN86
, E5KBL7, P78349, Q96CV2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 152 of the entry and version 3 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

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.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.