Q9Y6J6 (KCNE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	123 AA.
Sequence status	Complete.
Protein existence	Evidence 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 Familial atrial fibrillation 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 process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Atrial fibrillation Disease mutation Long QT syndrome
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood circulation Non-traceable author statement Ref.1. Source: ProtInc cellular protein localization Inferred from electronic annotation. Source: Compara muscle contraction Traceable author statement Ref.1. Source: ProtInc regulation of heart contraction Traceable author statement Ref.1. Source: ProtInc regulation of ventricular cardiac muscle cell action potential Inferred from electronic annotation. Source: Compara regulation of ventricular cardiac muscle cell membrane repolarization Inferred from electronic annotation. Source: Compara
Cellular_component	lysosome Inferred from direct assay PubMed 16780588. Source: UniProtKB voltage-gated potassium channel complex Traceable author statement Ref.1. Source: ProtInc
Molecular_function	potassium channel regulator activity Inferred from electronic annotation. Source: Compara voltage-gated potassium channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 123	123	Potassium voltage-gated channel subfamily E member 2		PRO_0000144285
Regions
	Transmembrane	49 – 69	21	Helical; Potential
	Topological domain	70 – 123	54	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	6	1	N-linked (GlcNAc...) Potential
	Glycosylation	29	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	8	1	T → A. Ref.1 Ref.11 Corresponds to variant rs2234916 [ dbSNP | Ensembl ].		VAR_008375
	Natural variant	8	1	T → I. Corresponds to variant rs35759083 [ dbSNP | Ensembl ].		VAR_037794
	Natural variant	9	1	Q → 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 variant	27	1	R → C in ATFB4; gain-of-function mutation associated with the initiation and/or maintenance of AF. Ref.10		VAR_037795
	Natural variant	54	1	M → T in LQT6; forms I(KR) channels that deactivate twice as fast as wild type. Ref.1		VAR_008377
	Natural variant	57	1	I → T in LQT6; may affect KCNQ1/KCNE2 channel. Ref.1 Ref.11		VAR_008378
	Natural variant	60	1	F → L in LQT6; may be a rare polymorphism. Ref.11 Corresponds to variant rs16991654 [ dbSNP | Ensembl ].		VAR_029334
	Natural variant	65	1	V → M in LQT6. Ref.9		VAR_015063
	Natural variant	66	1	A → V. Corresponds to variant rs16991656 [ dbSNP | Ensembl ].		VAR_022052
	Natural variant	77	1	R → W in LQT6. Ref.11		VAR_035386
Experimental info
	Mutagenesis	75	1	K → H: Increases tail current in KCNH2/KCNE2 channel. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6J6 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: C3016415E1B44890	FASTA	123	14,472
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00002366.
RefSeq	NP_751951.1. NM_172201.1.
UniGene	Hs.551521. Hs.736062.
3D structure databases
ProteinModelPortal	Q9Y6J6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000290310.
PTM databases
PhosphoSite	Q9Y6J6.
Polymorphism databases
DMDM	6685661.
Proteomic databases
PRIDE	Q9Y6J6.
Protocols and materials databases
DNASU	9992.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290310; ENSP00000290310; ENSG00000159197.
GeneID	9992.
KEGG	hsa:9992.
UCSC	uc002ytt.1. human.
Organism-specific databases
CTD	9992.
GeneCards	GC21P035736.
HGNC	HGNC:6242. KCNE2.
HPA	CAB022640.
MIM	603796. gene. 611493. phenotype. 613693. phenotype.
neXtProt	NX_Q9Y6J6.
Orphanet	334. Familial atrial fibrillation. 101016. Romano-Ward syndrome.
PharmGKB	PA392.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG43841.
HOGENOM	HOG000113208.
HOVERGEN	HBG052227.
InParanoid	Q9Y6J6.
KO	K04896.
OMA	WRRNTTA.
OrthoDB	EOG4Z62Q0.
PhylomeDB	Q9Y6J6.
Gene expression databases
ArrayExpress	Q9Y6J6.
Bgee	Q9Y6J6.
CleanEx	HS_KCNE2.
Genevestigator	Q9Y6J6.
GermOnline	ENSG00000159197. Homo sapiens.
Family and domain databases
InterPro	IPR000369. K_chnl_volt-dep_bsu_KCNE. IPR005425. K_chnl_volt-dep_bsu_KCNE2. [Graphical view]
PANTHER	PTHR15259. PTHR15259. 1 hit.
Pfam	PF02060. ISK_Channel. 1 hit. [Graphical view]
PRINTS	PR01605. KCNE2CHANNEL.
ProtoNet	Search...
Other
GenomeRNAi	9992.
NextBio	37747.
SOURCE	Search...

Entry information

Entry name

KCNE2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.