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Protein

Acid-sensing ion channel 3

Gene

ASIC3

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

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

Sites

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Sodium channel
Biological processIon transport, Sodium transport, Transport
LigandSodium

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000213199.7
HGNCiHGNC:101 ASIC3
MIMi611741 gene
neXtProtiNX_Q9UHC3

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 – 43CytoplasmicSequence analysisAdd BLAST43
Transmembranei44 – 61HelicalSequence analysisAdd BLAST18
Topological domaini62 – 441ExtracellularSequence analysisAdd BLAST380
Transmembranei442 – 460HelicalSequence analysisAdd BLAST19
Topological domaini461 – 531CytoplasmicSequence analysisAdd BLAST71

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
DrugBankiDB08838 Agmatine
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...) asparagineSequence analysis1
Disulfide bondi282 ↔ 370By similarity
Disulfide bondi315 ↔ 366By similarity
Disulfide bondi319 ↔ 364By similarity
Disulfide bondi328 ↔ 350By similarity
Disulfide bondi330 ↔ 342By similarity
Glycosylationi398N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi84307
84308 [Q9UHC3-2]
84309 [Q9UHC3-3]
84310 [Q9UHC3-4]

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 Expressed in 115 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_ACCN3
ExpressionAtlasiQ9UHC3 baseline and differential
GenevisibleiQ9UHC3 HS

Organism-specific databases

HPAiHPA049155
HPA054805

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
OMAiTPKGGMG
PhylomeDBiQ9UHC3
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 (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C4W0H7C4W0_HUMAN
Acid-sensing ion channel 3
ASIC3
149Annotation score:
H7C5N6H7C5N6_HUMAN
Acid-sensing ion channel 3
ASIC3
144Annotation score:

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 dbSNP:rs1864545Ensembl.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

Similar proteinsi

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
DrugBankiDB08838 Agmatine
GuidetoPHARMACOLOGYi686

PTM databases

iPTMnetiQ9UHC3
PhosphoSitePlusiQ9UHC3

Polymorphism and mutation databases

BioMutaiASIC3
DMDMi82582992

Proteomic databases

PaxDbiQ9UHC3
PeptideAtlasiQ9UHC3
PRIDEiQ9UHC3
ProteomicsDBi84307
84308 [Q9UHC3-2]
84309 [Q9UHC3-3]
84310 [Q9UHC3-4]

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
EuPathDBiHostDB:ENSG00000213199.7
GeneCardsiASIC3
HGNCiHGNC:101 ASIC3
HPAiHPA049155
HPA054805
MIMi611741 gene
neXtProtiNX_Q9UHC3
OpenTargetsiENSG00000213199
PharmGKBiPA24435
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4294 Eukaryota
ENOG410ZNFK LUCA
GeneTreeiENSGT00760000119120
HOVERGENiHBG004150
InParanoidiQ9UHC3
KOiK04830
OMAiTPKGGMG
PhylomeDBiQ9UHC3
TreeFamiTF330663

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels

Miscellaneous databases

ChiTaRSiASIC3 human
GeneWikiiACCN3
GenomeRNAii9311
PROiPR:Q9UHC3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213199 Expressed in 115 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_ACCN3
ExpressionAtlasiQ9UHC3 baseline and differential
GenevisibleiQ9UHC3 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 nameiASIC3_HUMAN
AccessioniPrimary (citable) accession number: Q9UHC3
Secondary accession number(s): B2R9V0
, O60263, O75906, Q59FN9, Q9UER8, Q9UHC4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: September 13, 2005
Last modified: November 7, 2018
This is version 145 of the entry and version 2 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. 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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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