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Protein

Acid-sensing ion channel 3

Gene

ASIC3

Organism
Homo sapiens (Human)
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. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei26Potassium ion selectivity and permeabilityBy similarity1

GO - Molecular functioni

  • acid-sensing ion channel activity Source: Reactome
  • cation channel activity Source: ProtInc
  • enterobactin transporter activity Source: Ensembl
  • sodium channel activity Source: ProtInc

GO - Biological processi

  • detection of chemical stimulus involved in sensory perception of pain Source: Ensembl
  • detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
  • detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
  • ion transmembrane transport Source: Reactome
  • response to acidic pH Source: Ensembl
  • response to heat Source: Ensembl
  • sensory perception Source: ProtInc
  • sensory perception of sour taste Source: UniProtKB
  • signal transduction Source: ProtInc
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

BioCyciZFISH:G66-32073-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Acid-sensing ion channel 3
Short name:
ASIC3
Short name:
hASIC3
Alternative name(s):
Amiloride-sensitive cation channel 3
Neuronal amiloride-sensitive cation channel 3
Testis sodium channel 1
Short name:
hTNaC1
Gene namesi
Name:ASIC3
Synonyms:ACCN3, SLNAC1, TNAC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:101. ASIC3.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Cytoplasm By similarity

  • Note: Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4. In part cytoplasmic in cochlea cells (By similarity).By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 43CytoplasmicSequence analysisAdd BLAST43
Transmembranei44 – 61HelicalSequence analysisAdd BLAST18
Topological domaini62 – 441ExtracellularSequence analysisAdd BLAST380
Transmembranei442 – 460HelicalSequence analysisAdd BLAST19
Topological domaini461 – 531CytoplasmicSequence analysisAdd BLAST71

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi528V → A: No effect on interaction with LIN7B, MAGI1 and GOPC. 1 Publication1
Mutagenesisi529T → A: Loss of interaction with LIN7B, MAGI1. 1 Publication1
Mutagenesisi530Q → A: Loss of interaction with GOPC. No effect on interaction LIN7B and MAGI1. 1 Publication1
Mutagenesisi531L → A: Loss of interaction with LIN7B, MAGI1 and GOPC. 1 Publication1

Organism-specific databases

DisGeNETi9311.
OpenTargetsiENSG00000213199.
PharmGKBiPA24435.

Chemistry databases

ChEMBLiCHEMBL5368.
GuidetoPHARMACOLOGYi686.

Polymorphism and mutation databases

BioMutaiASIC3.
DMDMi82582992.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001813011 – 531Acid-sensing ion channel 3Add BLAST531

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi92 ↔ 186By similarity
Disulfide bondi164 ↔ 171By similarity
Glycosylationi175N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi282 ↔ 370By similarity
Disulfide bondi315 ↔ 366By similarity
Disulfide bondi319 ↔ 364By similarity
Disulfide bondi328 ↔ 350By similarity
Disulfide bondi330 ↔ 342By similarity
Glycosylationi398N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Phosphorylated by PKA. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3 channel (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9UHC3.
PeptideAtlasiQ9UHC3.
PRIDEiQ9UHC3.

PTM databases

iPTMnetiQ9UHC3.
PhosphoSitePlusiQ9UHC3.

Expressioni

Tissue specificityi

Expressed by sensory neurons. Strongly expressed in brain, spinal chord, lung, lymph nodes, kidney, pituitary, heart and testis.2 Publications

Developmental stagei

Expressed in fetal tissues, expression increases in lung and kidney adult tissues.1 Publication

Gene expression databases

BgeeiENSG00000213199.
CleanExiHS_ACCN3.
ExpressionAtlasiQ9UHC3. baseline and differential.
GenevisibleiQ9UHC3. HS.

Organism-specific databases

HPAiHPA049155.

Interactioni

Subunit structurei

Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with STOM; this regulates channel activity. Interacts with DLG4 (By similarity). Interacts with LIN7B, MAGI1/BAIAP1, GOPC and ASIC2.By similarity2 Publications

Protein-protein interaction databases

BioGridi114723. 7 interactors.
STRINGi9606.ENSP00000297512.

Chemistry databases

BindingDBiQ9UHC3.

Structurei

3D structure databases

ProteinModelPortaliQ9UHC3.
SMRiQ9UHC3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi528 – 531PDZ-binding4

Domaini

The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4294. Eukaryota.
ENOG410ZNFK. LUCA.
GeneTreeiENSGT00760000119120.
HOVERGENiHBG004150.
InParanoidiQ9UHC3.
KOiK04830.
OMAiTCPNPCA.
PhylomeDBiQ9UHC3.
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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UHC3-1) [UniParc]FASTAAdd to basket

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
MKPTSGPEEA RRPASDIRVF ASNCSMHGLG HVFGPGSLSL RRGMWAAAVV
60 70 80 90 100
LSVATFLYQV AERVRYYREF HHQTALDERE SHRLIFPAVT LCNINPLRRS
110 120 130 140 150
RLTPNDLHWA GSALLGLDPA EHAAFLRALG RPPAPPGFMP SPTFDMAQLY
160 170 180 190 200
ARAGHSLDDM LLDCRFRGQP CGPENFTTIF TRMGKCYTFN SGADGAELLT
210 220 230 240 250
TTRGGMGNGL DIMLDVQQEE YLPVWRDNEE TPFEVGIRVQ IHSQEEPPII
260 270 280 290 300
DQLGLGVSPG YQTFVSCQQQ QLSFLPPPWG DCSSASLNPN YEPEPSDPLG
310 320 330 340 350
SPSPSPSPPY TLMGCRLACE TRYVARKCGC RMVYMPGDVP VCSPQQYKNC
360 370 380 390 400
AHPAIDAMLR KDSCACPNPC ASTRYAKELS MVRIPSRAAA RFLARKLNRS
410 420 430 440 450
EAYIAENVLA LDIFFEALNY ETVEQKKAYE MSELLGDIGG QMGLFIGASL
460 470 480 490 500
LTILEILDYL CEVFRDKVLG YFWNRQHSQR HSSTNLLQEG LGSHRTQVPH
510 520 530
LSLGPRPPTP PCAVTKTLSA SHRTCYLVTQ L
Length:531
Mass (Da):58,905
Last modified:September 13, 2005 - v2
Checksum:iA46DD64590EC4871
GO
Isoform 2 (identifier: Q9UHC3-2) [UniParc]FASTAAdd to basket
Also known as: ASIC3b

The sequence of this isoform differs from the canonical sequence as follows:
     487-531: LQEGLGSHRT...HRTCYLVTQL → TSHPSLCRHQ...AFPSSPQIKS

Show »
Length:543
Mass (Da):60,332
Checksum:i9411BD1485BA93F1
GO
Isoform 3 (identifier: Q9UHC3-3) [UniParc]FASTAAdd to basket
Also known as: ASIC3c

The sequence of this isoform differs from the canonical sequence as follows:
     506-531: RPPTPPCAVTKTLSASHRTCYLVTQL → STLLCSEDLPPLPVPSPRLSPPPTAPATLSHSSRPAVCVLGAPP

Show »
Length:549
Mass (Da):60,491
Checksum:iED2C4D628AF9E18F
GO
Isoform 4 (identifier: Q9UHC3-4) [UniParc]FASTAAdd to basket
Also known as: c

The sequence of this isoform differs from the canonical sequence as follows:
     356-407: DAMLRKDSCA...NRSEAYIAEN → GRTCWPWTSS...GPACSPSSRS
     408-531: Missing.

Show »
Length:407
Mass (Da):44,999
Checksum:i0C6D7DCF3F525596
GO

Sequence cautioni

The sequence BAA25897 differs from that shown. Reason: Frameshift at positions 303, 305 and 313.Curated
The sequence BAD92658 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13P → Q in BAA25897 (PubMed:9571199).Curated1
Sequence conflicti13P → Q in AAC62935 (PubMed:9886053).Curated1
Sequence conflicti14A → P in AAC62935 (PubMed:9886053).Curated1
Sequence conflicti85I → V in AAC62935 (PubMed:9886053).Curated1
Sequence conflicti243 – 244SQ → GH in BAA25897 (PubMed:9571199).Curated2
Sequence conflicti358M → I in AAC62935 (PubMed:9886053).Curated1
Sequence conflicti397L → F in BAA25897 (PubMed:9571199).Curated1
Sequence conflicti400S → R in BAA25897 (PubMed:9571199).Curated1
Sequence conflicti518L → F in BAA25897 (PubMed:9571199).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052037228N → S.Corresponds to variant rs1864545dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015600356 – 407DAMLR…YIAEN → GRTCWPWTSSLRPSTMRPWS RRRPMRCQSCLVTLGARWGC SSGPACSPSSRS in isoform 4. 1 PublicationAdd BLAST52
Alternative sequenceiVSP_015601408 – 531Missing in isoform 4. 1 PublicationAdd BLAST124
Alternative sequenceiVSP_015602487 – 531LQEGL…LVTQL → TSHPSLCRHQDSLRLPPHLL PCHTALDLLSVSSEPRPDIL DMPSLHVAFPSSPQIKS in isoform 2. 2 PublicationsAdd BLAST45
Alternative sequenceiVSP_015603506 – 531RPPTP…LVTQL → STLLCSEDLPPLPVPSPRLS PPPTAPATLSHSSRPAVCVL GAPP in isoform 3. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB010575 mRNA. Translation: BAA25897.1. Frameshift.
AF095897 mRNA. Translation: AAC64188.1.
AF057711 mRNA. Translation: AAC62935.1.
AF195024 mRNA. Translation: AAF19817.1.
AF195025 mRNA. Translation: AAF19818.1.
AK313926 mRNA. Translation: BAG36647.1.
AB209421 mRNA. Translation: BAD92658.1. Different initiation.
CH471173 Genomic DNA. Translation: EAW54052.1.
CCDSiCCDS5914.1. [Q9UHC3-2]
CCDS5915.1. [Q9UHC3-3]
CCDS5916.1. [Q9UHC3-1]
PIRiJE0091.
RefSeqiNP_004760.1. NM_004769.3. [Q9UHC3-1]
NP_064717.1. NM_020321.3. [Q9UHC3-3]
NP_064718.1. NM_020322.3. [Q9UHC3-2]
UniGeneiHs.647113.

Genome annotation databases

EnsembliENST00000297512; ENSP00000297512; ENSG00000213199. [Q9UHC3-3]
ENST00000349064; ENSP00000344838; ENSG00000213199. [Q9UHC3-1]
ENST00000357922; ENSP00000350600; ENSG00000213199. [Q9UHC3-2]
ENST00000377904; ENSP00000367136; ENSG00000213199. [Q9UHC3-4]
ENST00000468325; ENSP00000418605; ENSG00000213199. [Q9UHC3-4]
GeneIDi9311.
KEGGihsa:9311.
UCSCiuc003win.4. human. [Q9UHC3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB010575 mRNA. Translation: BAA25897.1. Frameshift.
AF095897 mRNA. Translation: AAC64188.1.
AF057711 mRNA. Translation: AAC62935.1.
AF195024 mRNA. Translation: AAF19817.1.
AF195025 mRNA. Translation: AAF19818.1.
AK313926 mRNA. Translation: BAG36647.1.
AB209421 mRNA. Translation: BAD92658.1. Different initiation.
CH471173 Genomic DNA. Translation: EAW54052.1.
CCDSiCCDS5914.1. [Q9UHC3-2]
CCDS5915.1. [Q9UHC3-3]
CCDS5916.1. [Q9UHC3-1]
PIRiJE0091.
RefSeqiNP_004760.1. NM_004769.3. [Q9UHC3-1]
NP_064717.1. NM_020321.3. [Q9UHC3-3]
NP_064718.1. NM_020322.3. [Q9UHC3-2]
UniGeneiHs.647113.

3D structure databases

ProteinModelPortaliQ9UHC3.
SMRiQ9UHC3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114723. 7 interactors.
STRINGi9606.ENSP00000297512.

Chemistry databases

BindingDBiQ9UHC3.
ChEMBLiCHEMBL5368.
GuidetoPHARMACOLOGYi686.

PTM databases

iPTMnetiQ9UHC3.
PhosphoSitePlusiQ9UHC3.

Polymorphism and mutation databases

BioMutaiASIC3.
DMDMi82582992.

Proteomic databases

PaxDbiQ9UHC3.
PeptideAtlasiQ9UHC3.
PRIDEiQ9UHC3.

Protocols and materials databases

DNASUi9311.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297512; ENSP00000297512; ENSG00000213199. [Q9UHC3-3]
ENST00000349064; ENSP00000344838; ENSG00000213199. [Q9UHC3-1]
ENST00000357922; ENSP00000350600; ENSG00000213199. [Q9UHC3-2]
ENST00000377904; ENSP00000367136; ENSG00000213199. [Q9UHC3-4]
ENST00000468325; ENSP00000418605; ENSG00000213199. [Q9UHC3-4]
GeneIDi9311.
KEGGihsa:9311.
UCSCiuc003win.4. human. [Q9UHC3-1]

Organism-specific databases

CTDi9311.
DisGeNETi9311.
GeneCardsiASIC3.
HGNCiHGNC:101. ASIC3.
HPAiHPA049155.
MIMi611741. gene.
neXtProtiNX_Q9UHC3.
OpenTargetsiENSG00000213199.
PharmGKBiPA24435.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4294. Eukaryota.
ENOG410ZNFK. LUCA.
GeneTreeiENSGT00760000119120.
HOVERGENiHBG004150.
InParanoidiQ9UHC3.
KOiK04830.
OMAiTCPNPCA.
PhylomeDBiQ9UHC3.
TreeFamiTF330663.

Enzyme and pathway databases

BioCyciZFISH:G66-32073-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiASIC3. human.
GeneWikiiACCN3.
GenomeRNAii9311.
PROiQ9UHC3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213199.
CleanExiHS_ACCN3.
ExpressionAtlasiQ9UHC3. baseline and differential.
GenevisibleiQ9UHC3. 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 nameiASIC3_HUMAN
AccessioniPrimary (citable) accession number: Q9UHC3
Secondary accession number(s): B2R9V0
, O60263, O75906, Q59FN9, Q9UER8, Q9UHC4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: September 13, 2005
Last modified: November 2, 2016
This is version 134 of the entry and version 2 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 FMRFamide-related neuropeptides. Sensitized and potentiated by NPSF. Regulated by lactate and Ca2+. Inhibited by anti-inflammatory drugs, like salicylic acid (By similarity). Sensitized and potentiated by NPFF.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.