Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Acid-sensing ion channel 1

Gene

ASIC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

Activity 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
Sitei352Important for interaction with the spider venom psalmotoxin-11 Publication1
Sitei357Key residue for defining the pH sensitivity of ASIC1 (isoform 1)1 Publication1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionIon channel, Sodium channel
Biological processCalcium transport, Ion transport, Sodium transport, Transport
LigandCalcium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SignaLinkiP78348
SIGNORiP78348

Names & Taxonomyi

Protein namesi
Recommended name:
Acid-sensing ion channel 11 Publication
Short name:
ASIC11 Publication
Alternative name(s):
Amiloride-sensitive cation channel 2, neuronal
Brain sodium channel 21 Publication
Short name:
BNaC21 Publication
Gene namesi
Name:ASIC1
Synonyms:ACCN2, BNAC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000110881.11
HGNCiHGNC:100 ASIC1
MIMi602866 gene
neXtProtiNX_P78348

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi352F → L: Complete loss in the shift of pH for both activation and desensitization by the spider venom psalmotoxin-1. 1 Publication1
Mutagenesisi357D → A or N: Large decrease in response to pH 6.5 solutions. 1 Publication1
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...) asparagineSequence analysis1
Glycosylationi395N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi57582
57583 [P78348-1]

PTM databases

iPTMnetiP78348
PhosphoSitePlusiP78348
SwissPalmiP78348

Expressioni

Tissue specificityi

Expressed in most or all neurons.

Gene expression databases

BgeeiENSG00000110881 Expressed in 148 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_ACCN2
ExpressionAtlasiP78348 baseline and differential
GenevisibleiP78348 HS

Organism-specific databases

HPAiHPA058870

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM and ASIC2 (By similarity). Interacts with PRKCABP. Homotrimer of Asic1a (ASIC1 isoform 1) interacts with spider venom psalmotoxin-1 (PubMed:19654327, PubMed:22760635). Homotrimer of Asic1a (ASIC1 isoform 1) and Asic1b (ASIC1 isoform 3) interacts with the spider venom pi-theraphotoxin-Hm3a (PubMed:28327374). Homotrimer of Asic1a (ASIC1 isoform 1) interacts with the snake venom mambalgin-1 (PubMed:23034652). Heterotrimer of Asic1a-Asic2a (ASIC1 isoform 1-ASIC2 isoform 1) interacts with the snake venom mambalgin-1 (PubMed:23034652).By similarity4 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi106559, 22 interactors
IntActiP78348, 3 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
OMAiCSDKKHK
OrthoDBiEOG091G053J
PhylomeDBiP78348
TreeFamiTF330663

Family and domain databases

InterProiView protein in InterPro
IPR001873 ENaC
IPR004724 ENaC_chordates
IPR020903 ENaC_CS
PANTHERiPTHR11690 PTHR11690, 1 hit
PfamiView protein in Pfam
PF00858 ASC, 1 hit
PRINTSiPR01078 AMINACHANNEL
TIGRFAMsiTIGR00859 ENaC, 1 hit
PROSITEiView protein in PROSITE
PS01206 ASC, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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
Also known as: Asic1b

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C1W9H7C1W9_HUMAN
Acid-sensing ion channel 1
ASIC1
396Annotation score:
F8VSK4F8VSK4_HUMAN
Acid-sensing ion channel 1
ASIC1
263Annotation score:
H0YHD6H0YHD6_HUMAN
Acid-sensing ion channel 1
ASIC1
127Annotation score:

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

Similar proteinsi

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, 22 interactors
IntActiP78348, 3 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
ProteomicsDBi57582
57583 [P78348-1]

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
EuPathDBiHostDB:ENSG00000110881.11
GeneCardsiASIC1
HGNCiHGNC:100 ASIC1
HPAiHPA058870
MIMi602866 gene
neXtProtiNX_P78348
OpenTargetsiENSG00000110881
PharmGKBiPA24434
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00760000119120
HOGENOMiHOG000247010
HOVERGENiHBG004150
InParanoidiP78348
KOiK04829
OMAiCSDKKHK
OrthoDBiEOG091G053J
PhylomeDBiP78348
TreeFamiTF330663

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SignaLinkiP78348
SIGNORiP78348

Miscellaneous databases

ChiTaRSiASIC1 human
GeneWikiiACCN2
GenomeRNAii41
PROiPR:P78348
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110881 Expressed in 148 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_ACCN2
ExpressionAtlasiP78348 baseline and differential
GenevisibleiP78348 HS

Family and domain databases

InterProiView protein in InterPro
IPR001873 ENaC
IPR004724 ENaC_chordates
IPR020903 ENaC_CS
PANTHERiPTHR11690 PTHR11690, 1 hit
PfamiView protein in Pfam
PF00858 ASC, 1 hit
PRINTSiPR01078 AMINACHANNEL
TIGRFAMsiTIGR00859 ENaC, 1 hit
PROSITEiView protein in PROSITE
PS01206 ASC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiASIC1_HUMAN
AccessioniPrimary (citable) accession number: P78348
Secondary accession number(s): A3KN86
, E5KBL7, P78349, Q96CV2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 167 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again