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Q9Y6J6 (KCNE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium voltage-gated channel subfamily E member 2
Alternative name(s):
MinK-related peptide 1
Minimum potassium ion channel-related peptide 1
Potassium channel subunit beta MiRP1
Gene names
Name:KCNE2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length123 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 KCNH2/HERG is proposed to form the rapidly activating component of the delayed rectifying potassium current in heart (IKr). May associate with KCNQ2 and/or KCNQ3 and modulate the native M-type current. May associate with KCNQ1/KVLTQ1 and elicit a voltage-independent current. May associate with HCN1 and HCN2 and increase potassium current.

Subunit structure

Associates with KCNH2/ERG1. May associate with KCNQ1/KVLQT1, KCNQ2 and KCNQ3. Associates with HCN1 and probably HCN2 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Highly expressed in brain, heart, skeletal muscle, pancreas, placenta, kidney, colon and thymus. A small but significant expression is found in liver, ovary, testis, prostate, small intestine and leukocytes. Very low expression, nearly undetectable, in lung and spleen. Ref.6

Involvement in disease

Long QT syndrome 6 (LQT6) [MIM:613693]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.9 Ref.11

Atrial fibrillation, familial, 4 (ATFB4) [MIM:611493]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the potassium channel KCNE family.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseAtrial fibrillation
Disease mutation
Long QT syndrome
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Potassium channel
Voltage-gated channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

cardiac muscle cell action potential involved in contraction

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

cellular protein localization

Inferred from electronic annotation. Source: Ensembl

cellular response to drug

Inferred from direct assay Ref.1. Source: BHF-UCL

membrane repolarization

Inferred from direct assay Ref.1. Source: BHF-UCL

membrane repolarization during action potential

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

positive regulation of proteasomal protein catabolic process

Inferred from direct assay PubMed 22180649. Source: BHF-UCL

potassium ion export

Inferred from direct assay Ref.1. Source: BHF-UCL

potassium ion import

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

potassium ion transmembrane transport

Inferred from direct assay Ref.1. Source: BHF-UCL

regulation of cyclic nucleotide-gated ion channel activity

Inferred from electronic annotation. Source: Ensembl

regulation of delayed rectifier potassium channel activity

Inferred from direct assay Ref.1. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

regulation of inward rectifier potassium channel activity

Inferred from direct assay Ref.1. Source: BHF-UCL

regulation of membrane repolarization

Inferred from direct assay Ref.1. Source: BHF-UCL

regulation of potassium ion transmembrane transport

Inferred from direct assay Ref.1. Source: BHF-UCL

regulation of ventricular cardiac muscle cell membrane repolarization

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

tongue development

Inferred from electronic annotation. Source: Ensembl

ventricular cardiac muscle cell action potential

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

   Cellular_componentcell surface

Inferred from direct assay PubMed 22180649. Source: BHF-UCL

lysosome

Inferred from direct assay PubMed 16780588. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 16780588. Source: UniProtKB

voltage-gated potassium channel complex

Inferred from direct assay Ref.1. Source: BHF-UCL

   Molecular_functiondelayed rectifier potassium channel activity

Inferred from electronic annotation. Source: Ensembl

inward rectifier potassium channel activity

Inferred from electronic annotation. Source: Ensembl

ion channel binding

Inferred from direct assay Ref.1. Source: BHF-UCL

potassium channel regulator activity

Inferred from direct assay Ref.1. Source: BHF-UCL

voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 123123Potassium voltage-gated channel subfamily E member 2
PRO_0000144285

Regions

Transmembrane49 – 6921Helical; Potential
Topological domain70 – 12354Cytoplasmic Potential

Amino acid modifications

Glycosylation61N-linked (GlcNAc...) Potential
Glycosylation291N-linked (GlcNAc...) Potential

Natural variations

Natural variant81T → A. Ref.1 Ref.11
Corresponds to variant rs2234916 [ dbSNP | Ensembl ].
VAR_008375
Natural variant81T → I.
Corresponds to variant rs35759083 [ dbSNP | Ensembl ].
VAR_037794
Natural variant91Q → E in LQT6; impedes activation and increases sensitivity to macrolide antibiotics; may lower current in KCNQ1/KCNE2 channel. Ref.1
Corresponds to variant rs16991652 [ dbSNP | Ensembl ].
VAR_008376
Natural variant271R → C in ATFB4; gain-of-function mutation associated with the initiation and/or maintenance of AF. Ref.10
VAR_037795
Natural variant541M → T in LQT6; forms I(KR) channels that deactivate twice as fast as wild type. Ref.1
VAR_008377
Natural variant571I → T in LQT6; may affect KCNQ1/KCNE2 channel. Ref.1 Ref.11
Corresponds to variant rs74315448 [ dbSNP | Ensembl ].
VAR_008378
Natural variant601F → L in LQT6; may be a rare polymorphism. Ref.11
Corresponds to variant rs16991654 [ dbSNP | Ensembl ].
VAR_029334
Natural variant651V → M in LQT6. Ref.9
VAR_015063
Natural variant661A → V.
Corresponds to variant rs16991656 [ dbSNP | Ensembl ].
VAR_022052
Natural variant771R → W in LQT6. Ref.11
VAR_035386

Experimental info

Mutagenesis751K → H: Increases tail current in KCNH2/KCNE2 channel. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Q9Y6J6 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: C3016415E1B44890

FASTA12314,472
        10         20         30         40         50         60 
MSTLSNFTQT LEDVFRRIFI TYMDNWRQNT TAEQEALQAK VDAENFYYVI LYLMVMIGMF 

        70         80         90        100        110        120 
SFIIVAILVS TVKSKRREHS NDPYHQYIVE DWQEKYKSQI LNLEESKATI HENIGAAGFK 


MSP 

« Hide

References

« Hide 'large scale' references
[1]"MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia."
Abbott G.W., Sesti F., Splawski I., Buck M.E., Lehmann M.H., Timothy K.W., Keating M.T., Goldstein S.A.N.
Cell 97:175-187(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LQT6 GLU-9; THR-54 AND THR-57, VARIANT ALA-8, INTERACTION WITH KCNH2.
Tissue: Heart.
[2]"Cloning of human MIRP1 cDNA."
Domenech A., Estivill X., de la Luna S.
Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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].
[6]"M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit."
Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M.
FEBS Lett. 480:137-141(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH KCNQ2/KCNQ3, TISSUE SPECIFICITY.
[7]"KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel."
Tinel N., Diochot S., Borsotto M., Lazdunski M., Barhanin J.
EMBO J. 19:6326-6330(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH KCNQ1.
[8]"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 LYS-75.
[9]"Identification and functional characterization of a novel KCNE2 (MiRP1) mutation that alters HERG channel kinetics."
Isbrandt D., Friederich P., Solth A., Haverkamp W., Ebneth A., Borggrefe M., Funke H., Sauter K., Breithardt G., Pongs O., Schulze-Bahr E.
J. Mol. Med. 80:524-532(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT6 MET-65.
[10]"Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation."
Yang Y., Xia M., Jin Q., Bendahhou S., Shi J., Chen Y., Liang B., Lin J., Liu Y., Liu B., Zhou Q., Zhang D., Wang R., Ma N., Su X., Niu K., Pei Y., Xu W. expand/collapse author list , Chen Z., Wan H., Cui J., Barhanin J., Chen Y.
Am. J. Hum. Genet. 75:899-905(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ATFB4 CYS-27, CHARACTERIZATION OF VARIANT ATFB4 CYS-27.
[11]"Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome."
Millat G., Chevalier P., Restier-Miron L., Da Costa A., Bouvagnet P., Kugener B., Fayol L., Gonzalez Armengod C., Oddou B., Chanavat V., Froidefond E., Perraudin R., Rousson R., Rodriguez-Lafrasse C.
Clin. Genet. 70:214-227(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT6 THR-57; LEU-60 AND TRP-77, VARIANT ALA-8.
+Additional computationally mapped references.

Web resources

LQTSdb

KCNE2 mutations page

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF071002 mRNA. Translation: AAD28086.1.
AF302095 mRNA. Translation: AAG13416.1.
DQ784804 Genomic DNA. Translation: ABQ01239.1.
CH471079 Genomic DNA. Translation: EAX09791.1.
BC093892 mRNA. Translation: AAH93892.1.
BC112087 mRNA. Translation: AAI12088.1.
RefSeqNP_751951.1. NM_172201.1.
UniGeneHs.551521.
Hs.736062.

3D structure databases

ProteinModelPortalQ9Y6J6.
SMRQ9Y6J6. Positions 51-100.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115313. 2 interactions.
STRING9606.ENSP00000290310.

PTM databases

PhosphoSiteQ9Y6J6.

Polymorphism databases

DMDM6685661.

Proteomic databases

PRIDEQ9Y6J6.

Protocols and materials databases

DNASU9992.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290310; ENSP00000290310; ENSG00000159197.
GeneID9992.
KEGGhsa:9992.
UCSCuc002ytt.1. human.

Organism-specific databases

CTD9992.
GeneCardsGC21P035736.
HGNCHGNC:6242. KCNE2.
HPACAB022640.
MIM603796. gene.
611493. phenotype.
613693. phenotype.
neXtProtNX_Q9Y6J6.
Orphanet334. Familial atrial fibrillation.
101016. Romano-Ward syndrome.
PharmGKBPA392.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43841.
HOGENOMHOG000113208.
HOVERGENHBG052227.
InParanoidQ9Y6J6.
KOK04896.
OMAWRRNTTA.
OrthoDBEOG7WDN4J.
PhylomeDBQ9Y6J6.
TreeFamTF336058.

Gene expression databases

ArrayExpressQ9Y6J6.
BgeeQ9Y6J6.
CleanExHS_KCNE2.
GenevestigatorQ9Y6J6.

Family and domain databases

InterProIPR000369. K_chnl_volt-dep_bsu_KCNE.
IPR005425. K_chnl_volt-dep_bsu_KCNE2.
[Graphical view]
PANTHERPTHR15259. PTHR15259. 1 hit.
PfamPF02060. ISK_Channel. 1 hit.
[Graphical view]
PRINTSPR01605. KCNE2CHANNEL.
ProtoNetSearch...

Other

GeneWikiKCNE2.
GenomeRNAi9992.
NextBio37747.
PROQ9Y6J6.
SOURCESearch...

Entry information

Entry nameKCNE2_HUMAN
AccessionPrimary (citable) accession number: Q9Y6J6
Secondary accession number(s): A5H1P3, D3DSF8, Q52LJ5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: April 16, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM