UniProtKB - Q9Y6H6 (KCNE3_HUMAN)
Protein
Potassium voltage-gated channel subfamily E member 3
Gene
KCNE3
Organism
Homo sapiens (Human)
Status
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. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:12954870). 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 that produces a current with nearly instantaneous activation with a linear current-voltage relationship.By similarity2 Publications
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
GO - Molecular functioni
- ion channel binding Source: GO_Central
- potassium channel regulator activity Source: UniProtKB
- voltage-gated potassium channel activity Source: InterPro
GO - Biological processi
- membrane repolarization during action potential Source: GO_Central
- membrane repolarization during ventricular cardiac muscle cell action potential Source: GOC
- negative regulation of delayed rectifier potassium channel activity Source: UniProtKB
- negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential Source: BHF-UCL
- negative regulation of potassium ion export across plasma membrane Source: BHF-UCL
- negative regulation of voltage-gated potassium channel activity Source: BHF-UCL
- positive regulation of voltage-gated calcium channel activity Source: Ensembl
- potassium ion export across plasma membrane Source: GO_Central
- regulation of heart rate by cardiac conduction Source: BHF-UCL
- regulation of ventricular cardiac muscle cell membrane repolarization Source: GO_Central
- ventricular cardiac muscle cell action potential Source: GO_Central
Keywordsi
Molecular function | Ion channel, Potassium channel, Voltage-gated channel |
Biological process | Ion transport, Potassium transport, Transport |
Ligand | Potassium |
Enzyme and pathway databases
PathwayCommonsi | Q9Y6H6 |
Reactomei | R-HSA-5576890, Phase 3 - rapid repolarisation R-HSA-5576893, Phase 2 - plateau phase |
Names & Taxonomyi
Protein namesi | Recommended name: Potassium voltage-gated channel subfamily E member 3Alternative name(s): MinK-related peptide 2 Minimum potassium ion channel-related peptide 2 Potassium channel subunit beta MiRP2 |
Gene namesi | Name:KCNE3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6243, KCNE3 |
MIMi | 604433, gene |
neXtProti | NX_Q9Y6H6 |
VEuPathDBi | HostDB:ENSG00000175538.10 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein Curated
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- Perikaryon 1 Publication
- dendrite 1 Publication
- Membrane raft 1 Publication
Note: Colocalizes with KCNB1 at high-density somatodendritic clusters on the surface of hippocampal neurons.1 Publication
Plasma Membrane
- neuronal cell body membrane Source: UniProtKB
- voltage-gated potassium channel complex Source: Ensembl
Other locations
- cytoplasm Source: UniProtKB
- dendrite Source: UniProtKB
- membrane raft Source: UniProtKB
- perikaryon Source: UniProtKB
- vesicle Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 58 – 78 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 79 – 103 | CytoplasmicSequence analysisAdd BLAST | 25 |
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 90 | D → N: Decreases current 4-fold in KCNH2/KCNE3 channel. 1 Publication | 1 |
Keywords - Diseasei
Brugada syndrome, Disease variantOrganism-specific databases
DisGeNETi | 10008 |
GeneReviewsi | KCNE3 |
MalaCardsi | KCNE3 |
MIMi | 613119, phenotype |
OpenTargetsi | ENSG00000175538 |
Orphaneti | 130, Brugada syndrome 681, Hypokalemic periodic paralysis |
PharmGKBi | PA393 |
Miscellaneous databases
Pharosi | Q9Y6H6, Tbio |
Chemistry databases
DrugBanki | DB00228, Enflurane DB01110, Miconazole DB01069, Promethazine |
Genetic variation databases
BioMutai | KCNE3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144289 | 1 – 103 | Potassium voltage-gated channel subfamily E member 3Add BLAST | 103 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 5 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 22 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 41 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
MassIVEi | Q9Y6H6 |
PaxDbi | Q9Y6H6 |
PeptideAtlasi | Q9Y6H6 |
PRIDEi | Q9Y6H6 |
ProteomicsDBi | 86686 |
PTM databases
GlyGeni | Q9Y6H6, 3 sites |
iPTMneti | Q9Y6H6 |
PhosphoSitePlusi | Q9Y6H6 |
Expressioni
Tissue specificityi
Expressed in hippocampal neurons (at protein level) (PubMed:12954870). Widely expressed with highest levels in kidney and moderate levels in small intestine.2 Publications
Gene expression databases
Bgeei | ENSG00000175538, Expressed in nasal cavity epithelium and 183 other tissues |
ExpressionAtlasi | Q9Y6H6, baseline and differential |
Genevisiblei | Q9Y6H6, HS |
Organism-specific databases
HPAi | ENSG00000175538, Tissue enhanced (gallbladder) |
Interactioni
Subunit structurei
Interacts with KCNB1.
Interacts with KCNC2 (By similarity). Associates with KCNC4/Kv3.4 (PubMed:11207363).
Interacts with KCNQ1; produces a current with nearly instantaneous activation with a linear current-voltage relationship and alters membrane raft localization (By similarity) (PubMed:20533308).
By similarity2 PublicationsGO - Molecular functioni
- ion channel binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 115326, 10 interactors |
CORUMi | Q9Y6H6 |
IntActi | Q9Y6H6, 10 interactors |
MINTi | Q9Y6H6 |
STRINGi | 9606.ENSP00000310557 |
Miscellaneous databases
RNActi | Q9Y6H6, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | Q9Y6H6 |
SMRi | Q9Y6H6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the potassium channel KCNE family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502S4UF, Eukaryota |
GeneTreei | ENSGT00940000155001 |
HOGENOMi | CLU_180169_0_0_1 |
InParanoidi | Q9Y6H6 |
OMAi | TETWYKS |
OrthoDBi | 1608208at2759 |
PhylomeDBi | Q9Y6H6 |
TreeFami | TF335981 |
Family and domain databases
DisProti | DP01608 |
InterProi | View protein in InterPro IPR000369, K_chnl_KCNE IPR005426, K_chnl_volt-dep_bsu_KCNE3 |
PANTHERi | PTHR15282, PTHR15282, 1 hit PTHR15282:SF6, PTHR15282:SF6, 1 hit |
Pfami | View protein in Pfam PF02060, ISK_Channel, 1 hit |
PRINTSi | PR01606, KCNE3CHANNEL PR00168, KCNECHANNEL |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
Q9Y6H6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
METTNGTETW YESLHAVLKA LNATLHSNLL CRPGPGLGPD NQTEERRASL
60 70 80 90 100
PGRDDNSYMY ILFVMFLFAV TVGSLILGYT RSRKVDKRSD PYHVYIKNRV
SMI
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ2N1I1 | Q2N1I1_HUMAN | Cardiac voltage-gated potassium cha... | KCNE3 | 99 | Annotation score: | ||
E9PJV9 | E9PJV9_HUMAN | Potassium voltage-gated channel sub... | KCNE3 | 52 | Annotation score: | ||
E9PN03 | E9PN03_HUMAN | Potassium voltage-gated channel sub... | KCNE3 | 49 | Annotation score: | ||
E9PJQ7 | E9PJQ7_HUMAN | Potassium voltage-gated channel sub... | KCNE3 | 12 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058635 | 4 | T → A1 PublicationCorresponds to variant dbSNP:rs200856070EnsemblClinVar. | 1 | |
Natural variantiVAR_058636 | 39 | P → R1 PublicationCorresponds to variant dbSNP:rs34604640EnsemblClinVar. | 1 | |
Natural variantiVAR_015064 | 83 | R → 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 PublicationsCorresponds to variant dbSNP:rs17215437EnsemblClinVar. | 1 | |
Natural variantiVAR_058637 | 99 | R → H in BRGDA6; also in a patient suffering from drug-induced torsades de pointes; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs121908441EnsemblClinVar. | 1 |
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. |
CCDSi | CCDS8232.1 |
RefSeqi | NP_005463.1, NM_005472.4 XP_016872536.1, XM_017017047.1 XP_016872537.1, XM_017017048.1 XP_016872538.1, XM_017017049.1 XP_016872539.1, XM_017017050.1 XP_016872540.1, XM_017017051.1 XP_016872541.1, XM_017017052.1 |
Genome annotation databases
Ensembli | ENST00000310128; ENSP00000310557; ENSG00000175538 ENST00000525550; ENSP00000433633; ENSG00000175538 |
GeneIDi | 10008 |
KEGGi | hsa:10008 |
UCSCi | uc001ovc.4, human |
Similar proteinsi
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. |
CCDSi | CCDS8232.1 |
RefSeqi | NP_005463.1, NM_005472.4 XP_016872536.1, XM_017017047.1 XP_016872537.1, XM_017017048.1 XP_016872538.1, XM_017017049.1 XP_016872539.1, XM_017017050.1 XP_016872540.1, XM_017017051.1 XP_016872541.1, XM_017017052.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2NDJ | NMR | - | A | 1-103 | [»] | |
6V00 | electron microscopy | 3.10 | C/F/I/L | 1-103 | [»] | |
6V01 | electron microscopy | 3.90 | C/F/I/L | 1-103 | [»] | |
BMRBi | Q9Y6H6 | |||||
SMRi | Q9Y6H6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115326, 10 interactors |
CORUMi | Q9Y6H6 |
IntActi | Q9Y6H6, 10 interactors |
MINTi | Q9Y6H6 |
STRINGi | 9606.ENSP00000310557 |
Chemistry databases
DrugBanki | DB00228, Enflurane DB01110, Miconazole DB01069, Promethazine |
PTM databases
GlyGeni | Q9Y6H6, 3 sites |
iPTMneti | Q9Y6H6 |
PhosphoSitePlusi | Q9Y6H6 |
Genetic variation databases
BioMutai | KCNE3 |
Proteomic databases
MassIVEi | Q9Y6H6 |
PaxDbi | Q9Y6H6 |
PeptideAtlasi | Q9Y6H6 |
PRIDEi | Q9Y6H6 |
ProteomicsDBi | 86686 |
Protocols and materials databases
Antibodypediai | 2753, 148 antibodies |
DNASUi | 10008 |
Genome annotation databases
Ensembli | ENST00000310128; ENSP00000310557; ENSG00000175538 ENST00000525550; ENSP00000433633; ENSG00000175538 |
GeneIDi | 10008 |
KEGGi | hsa:10008 |
UCSCi | uc001ovc.4, human |
Organism-specific databases
CTDi | 10008 |
DisGeNETi | 10008 |
GeneCardsi | KCNE3 |
GeneReviewsi | KCNE3 |
HGNCi | HGNC:6243, KCNE3 |
HPAi | ENSG00000175538, Tissue enhanced (gallbladder) |
MalaCardsi | KCNE3 |
MIMi | 604433, gene 613119, phenotype |
neXtProti | NX_Q9Y6H6 |
OpenTargetsi | ENSG00000175538 |
Orphaneti | 130, Brugada syndrome 681, Hypokalemic periodic paralysis |
PharmGKBi | PA393 |
VEuPathDBi | HostDB:ENSG00000175538.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S4UF, Eukaryota |
GeneTreei | ENSGT00940000155001 |
HOGENOMi | CLU_180169_0_0_1 |
InParanoidi | Q9Y6H6 |
OMAi | TETWYKS |
OrthoDBi | 1608208at2759 |
PhylomeDBi | Q9Y6H6 |
TreeFami | TF335981 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y6H6 |
Reactomei | R-HSA-5576890, Phase 3 - rapid repolarisation R-HSA-5576893, Phase 2 - plateau phase |
Miscellaneous databases
BioGRID-ORCSi | 10008, 4 hits in 991 CRISPR screens |
ChiTaRSi | KCNE3, human |
GeneWikii | KCNE3 |
GenomeRNAii | 10008 |
Pharosi | Q9Y6H6, Tbio |
PROi | PR:Q9Y6H6 |
RNActi | Q9Y6H6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000175538, Expressed in nasal cavity epithelium and 183 other tissues |
ExpressionAtlasi | Q9Y6H6, baseline and differential |
Genevisiblei | Q9Y6H6, HS |
Family and domain databases
DisProti | DP01608 |
InterProi | View protein in InterPro IPR000369, K_chnl_KCNE IPR005426, K_chnl_volt-dep_bsu_KCNE3 |
PANTHERi | PTHR15282, PTHR15282, 1 hit PTHR15282:SF6, PTHR15282:SF6, 1 hit |
Pfami | View protein in Pfam PF02060, ISK_Channel, 1 hit |
PRINTSi | PR01606, KCNE3CHANNEL PR00168, KCNECHANNEL |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KCNE3_HUMAN | |
Accessioni | Q9Y6H6Primary (citable) accession number: Q9Y6H6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | November 1, 1999 | |
Last modified: | April 7, 2021 | |
This is version 166 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families