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Protein

Potassium voltage-gated channel subfamily E member 3

Gene

KCNE3

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

Functioni

Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Associated with KCNC4/Kv3.4 is proposed to form the subthreshold voltage-gated potassium channel in skeletal muscle and to establish the resting membrane potential (RMP) in muscle cells. Associated with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily E member 3
Alternative name(s):
MinK-related peptide 2
Minimum potassium ion channel-related peptide 2
Potassium channel subunit beta MiRP2
Gene namesi
Name:KCNE3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6243. KCNE3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei58 – 7821HelicalSequence AnalysisAdd
BLAST
Topological domaini79 – 10325CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • dendrite Source: UniProtKB
  • neuronal cell body membrane Source: UniProtKB
  • perikaryon Source: UniProtKB
  • voltage-gated potassium channel complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Brugada syndrome 6 (BRGDA6)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.

See also OMIM:613119
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti99 – 991R → H in BRGDA6; also in a patient suffering from drug-induced torsades de pointes. 2 Publications
Corresponds to variant rs121908441 [ dbSNP | Ensembl ].
VAR_058637

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi90 – 901D → N: Decreases current 4-fold in KCNH2/KCNE3 channel. 1 Publication

Keywords - Diseasei

Brugada syndrome, Disease mutation

Organism-specific databases

MIMi613119. phenotype.
Orphaneti130. Brugada syndrome.
681. Hypokalemic periodic paralysis.
PharmGKBiPA393.

Polymorphism and mutation databases

BioMutaiKCNE3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 103103Potassium voltage-gated channel subfamily E member 3PRO_0000144289Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi5 – 51N-linked (GlcNAc...)Sequence Analysis
Glycosylationi22 – 221N-linked (GlcNAc...)Sequence Analysis
Glycosylationi41 – 411N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9Y6H6.
PRIDEiQ9Y6H6.

Expressioni

Tissue specificityi

Widely expressed with highest levels in kidney and moderate levels in small intestine.1 Publication

Gene expression databases

BgeeiQ9Y6H6.
CleanExiHS_KCNE3.
ExpressionAtlasiQ9Y6H6. baseline and differential.
GenevisibleiQ9Y6H6. HS.

Organism-specific databases

HPAiHPA014849.

Interactioni

Subunit structurei

Heteromultimer with KCNC2. Interacts with KCNC2 (By similarity). Associates with KCNC4/Kv3.4 (PubMed:11207363). May associate with KCNQ1/KCLQT1 (PubMed:10646604).By similarity2 Publications

Protein-protein interaction databases

BioGridi115326. 10 interactions.
IntActiQ9Y6H6. 10 interactions.
MINTiMINT-8247512.
STRINGi9606.ENSP00000310557.

Structurei

3D structure databases

ProteinModelPortaliQ9Y6H6.
SMRiQ9Y6H6. Positions 58-99.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the potassium channel KCNE family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42036.
GeneTreeiENSGT00390000008537.
HOGENOMiHOG000113209.
HOVERGENiHBG052228.
InParanoidiQ9Y6H6.
KOiK04897.
OMAiGPGPDNQ.
PhylomeDBiQ9Y6H6.
TreeFamiTF335981.

Family and domain databases

InterProiIPR000369. K_chnl_KCNE.
IPR005426. K_chnl_volt-dep_bsu_KCNE3.
[Graphical view]
PfamiPF02060. ISK_Channel. 1 hit.
[Graphical view]
PRINTSiPR01606. KCNE3CHANNEL.
PR00168. KCNECHANNEL.

Sequencei

Sequence statusi: Complete.

Q9Y6H6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METTNGTETW YESLHAVLKA LNATLHSNLL CRPGPGLGPD NQTEERRASL
60 70 80 90 100
PGRDDNSYMY ILFVMFLFAV TVGSLILGYT RSRKVDKRSD PYHVYIKNRV

SMI
Length:103
Mass (Da):11,710
Last modified:November 1, 1999 - v1
Checksum:i5235385E8D08BF10
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti4 – 41T → A.1 Publication
Corresponds to variant rs200856070 [ dbSNP | Ensembl ].
VAR_058635
Natural varianti39 – 391P → R.1 Publication
Corresponds to variant rs34604640 [ dbSNP | Ensembl ].
VAR_058636
Natural varianti83 – 831R → H in some patients with periodic paralysis; unknown pathological significance; alters voltage dependence, lowers current and diminishes open probability in KCNC4/KCNE3 channel; lowers current in KCNQ1/KCNE3 channel. 2 Publications
Corresponds to variant rs17215437 [ dbSNP | Ensembl ].
VAR_015064
Natural varianti99 – 991R → H in BRGDA6; also in a patient suffering from drug-induced torsades de pointes. 2 Publications
Corresponds to variant rs121908441 [ dbSNP | Ensembl ].
VAR_058637

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076531 mRNA. Translation: AAD28089.1.
AF302494 mRNA. Translation: AAG16255.1.
BC032235 mRNA. No translation available.
CCDSiCCDS8232.1.
RefSeqiNP_005463.1. NM_005472.4.
UniGeneiHs.523899.

Genome annotation databases

EnsembliENST00000310128; ENSP00000310557; ENSG00000175538.
ENST00000525550; ENSP00000433633; ENSG00000175538.
GeneIDi10008.
KEGGihsa:10008.
UCSCiuc001ovc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076531 mRNA. Translation: AAD28089.1.
AF302494 mRNA. Translation: AAG16255.1.
BC032235 mRNA. No translation available.
CCDSiCCDS8232.1.
RefSeqiNP_005463.1. NM_005472.4.
UniGeneiHs.523899.

3D structure databases

ProteinModelPortaliQ9Y6H6.
SMRiQ9Y6H6. Positions 58-99.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115326. 10 interactions.
IntActiQ9Y6H6. 10 interactions.
MINTiMINT-8247512.
STRINGi9606.ENSP00000310557.

Polymorphism and mutation databases

BioMutaiKCNE3.

Proteomic databases

PaxDbiQ9Y6H6.
PRIDEiQ9Y6H6.

Protocols and materials databases

DNASUi10008.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310128; ENSP00000310557; ENSG00000175538.
ENST00000525550; ENSP00000433633; ENSG00000175538.
GeneIDi10008.
KEGGihsa:10008.
UCSCiuc001ovc.3. human.

Organism-specific databases

CTDi10008.
GeneCardsiGC11M074165.
GeneReviewsiKCNE3.
HGNCiHGNC:6243. KCNE3.
HPAiHPA014849.
MIMi604433. gene.
613119. phenotype.
neXtProtiNX_Q9Y6H6.
Orphaneti130. Brugada syndrome.
681. Hypokalemic periodic paralysis.
PharmGKBiPA393.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42036.
GeneTreeiENSGT00390000008537.
HOGENOMiHOG000113209.
HOVERGENiHBG052228.
InParanoidiQ9Y6H6.
KOiK04897.
OMAiGPGPDNQ.
PhylomeDBiQ9Y6H6.
TreeFamiTF335981.

Miscellaneous databases

ChiTaRSiKCNE3. human.
GeneWikiiKCNE3.
GenomeRNAii10008.
NextBioi37809.
PROiQ9Y6H6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y6H6.
CleanExiHS_KCNE3.
ExpressionAtlasiQ9Y6H6. baseline and differential.
GenevisibleiQ9Y6H6. HS.

Family and domain databases

InterProiIPR000369. K_chnl_KCNE.
IPR005426. K_chnl_volt-dep_bsu_KCNE3.
[Graphical view]
PfamiPF02060. ISK_Channel. 1 hit.
[Graphical view]
PRINTSiPR01606. KCNE3CHANNEL.
PR00168. KCNECHANNEL.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Abbott G.W., Sesti F., Buck M.E., Goldstein S.A.N.
    Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Structural determinants of KvLQT1 control by the KCNE family of proteins."
    Melman Y.F., Domenech A., de La Luna S., McDonald T.V.
    J. Biol. Chem. 276:6439-6444(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Blood.
  4. "A constitutively open potassium channel formed by KCNQ1 and KCNE3."
    Schroeder B.C., Waldegger S., Fehr S., Bleich M., Warth R., Greger R., Jentsch T.J.
    Nature 403:196-199(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION WITH KCNQ1, TISSUE SPECIFICITY.
  5. "MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis."
    Abbott G.W., Butler M.H., Bendahhou S., Dalakas M.C., Ptacek L.J., Goldstein S.A.N.
    Cell 104:217-231(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION WITH KCNC4, VARIANT HIS-83.
  6. "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism."
    Abbott G.W., Goldstein S.A.N.
    FASEB J. 16:390-400(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASP-90.
  7. "A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis."
    Dias Da Silva M.R., Cerutti J.M., Arnaldi L.A.T., Maciel R.M.B.
    J. Clin. Endocrinol. Metab. 87:4881-4884(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT HIS-83.
  8. "Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis."
    Sternberg D., Tabti N., Fournier E., Hainque B., Fontaine B.
    Neurology 61:857-859(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF ASSOCIATION OF VARIANT HIS-83 WITH PERIODIC PARALISIS.
  9. "Periodic paralysis mutation MiRP2-R83H in controls: Interpretations and general recommendation."
    Jurkat-Rott K., Lehmann-Horn F.
    Neurology 62:1012-1015(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: LACK OF ASSOCIATION OF VARIANT HIS-83 WITH PERIODIC PARALISIS.
  10. Cited for: VARIANT BRGDA6 HIS-99.
  11. "Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome."
    Ohno S., Toyoda F., Zankov D.P., Yoshida H., Makiyama T., Tsuji K., Honda T., Obayashi K., Ueyama H., Shimizu W., Miyamoto Y., Kamakura S., Matsuura H., Kita T., Horie M.
    Hum. Mutat. 30:557-563(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ALA-4; ARG-39 AND HIS-99.

Entry informationi

Entry nameiKCNE3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6H6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: June 24, 2015
This is version 122 of the entry and version 1 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

Caution

Variant His-83 has been associated with periodic paralysis (PubMed:11207363 and PubMed:12414843). The association could not be confirmed by further studies leading to the conclusion that His-83 does not play a causative role in the disease (PubMed:14504341 and PubMed:15037716).Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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

External Data

Dasty 3

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 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.