P15382 (KCNE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily E member 1

Alternative name(s):
Delayed rectifier potassium channel subunit IsK
IKs producing slow voltage-gated potassium channel subunit beta Mink
Minimal potassium channel

Gene names

Name:

KCNE1

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	129 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. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr).
Subunit structure	Associates with KCNQ1/KVLQT1 and KCNH2/HERG.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in heart, lung, kidney, testis, ovaries, small intestine, peripheral blood leukocytes. Not detected in pancreas, spleen, prostate and colon. Restrictively localized in the apical membrane portion of epithelial cells. Ref.6
Post-translational modification	Phosphorylation inhibits the potassium current By similarity. N-glycosylation at Asn-26 occurs post-translationally, and requires prior cotranslational glycosylation at Asn-5.
Involvement in disease	Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.13 Ref.14 Ref.17 Long QT syndrome 5 (LQT5) [MIM:613695]: 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.15 Ref.16 Ref.17 Ref.18 Ref.19
Sequence similarities	Belongs to the potassium channel KCNE family.
Sequence caution	The sequence AAH36452.1 differs from that shown. Reason: Erroneous termination at position 106. Translated as Cys.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation Long QT syndrome
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood circulation Non-traceable author statement PubMed 9020846. Source: ProtInc epithelial cell maturation Inferred from electronic annotation. Source: Compara heart contraction Inferred from electronic annotation. Source: Compara membrane depolarization Inferred from direct assay PubMed 8900283. Source: BHF-UCL muscle contraction Traceable author statement PubMed 9020846. Source: ProtInc positive regulation of potassium ion transmembrane transport Inferred from direct assay PubMed 8900283. Source: BHF-UCL potassium ion export Inferred from direct assay PubMed 17289006PubMed 8900283. Source: BHF-UCL protein N-linked glycosylation Inferred from direct assay Ref.10. Source: UniProtKB protein O-linked glycosylation Inferred from direct assay Ref.10. Source: UniProtKB regulation of heart contraction Inferred by curator PubMed 8900283. Source: BHF-UCL regulation of heart rate by cardiac conduction Inferred from electronic annotation. Source: Compara sensory perception of sound Traceable author statement PubMed 9020846. Source: ProtInc
Cellular_component	Z disc Inferred from sequence or structural similarity PubMed 11697903. Source: BHF-UCL apical plasma membrane Inferred from electronic annotation. Source: Compara lysosome Inferred from direct assay PubMed 16780588. Source: UniProtKB voltage-gated potassium channel complex Inferred from direct assay PubMed 17289006. Source: BHF-UCL
Molecular_function	delayed rectifier potassium channel activity Traceable author statement Ref.15. Source: ProtInc potassium channel regulator activity Inferred from direct assay PubMed 8900283. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 129

129

Potassium voltage-gated channel subfamily E member 1

PRO_0000144278

Regions

Transmembrane

44 – 66

23

Helical; Potential

Topological domain

67 – 129

63

Cytoplasmic Potential

Amino acid modifications

Modified residue

102

1

Phosphoserine; by PKC By similarity

Glycosylation

5

1

N-linked (GlcNAc...) Ref.9 Ref.10

Glycosylation

7

1

O-linked (GalNAc...) Ref.10

Glycosylation

26

1

N-linked (GlcNAc...) Ref.9

Natural variations

Natural variant

7

1

T → I in JLNS2; impairs glycosylation at N-5. Ref.9 Ref.14
Corresponds to variant rs28933384 [ dbSNP | Ensembl ].

VAR_008897

Natural variant

32

1

R → H in LQT5; uncertain pathological significance. Ref.5 Ref.18
Corresponds to variant rs17857111 [ dbSNP | Ensembl ].

VAR_009906

Natural variant

38

1

S → G. Ref.2 Ref.5 Ref.21
Corresponds to variants rs17846179 [ dbSNP | Ensembl ] and rs1805127 [ dbSNP | Ensembl ].

VAR_001558

Natural variant

47

1

V → F in JLNS2. Ref.17

VAR_008898

Natural variant

51

1

L → H in JLNS2. Ref.17

VAR_008899

Natural variant

52

1

G → A.
Corresponds to variant rs17173509 [ dbSNP | Ensembl ].

VAR_048024

Natural variant

58 – 59

2

TL → PP in JLNS2.

VAR_001559

Natural variant

74

1

S → L in LQT5. Ref.15

VAR_008900

Natural variant

76

1

D → N in LQT5 and JLNS2; suppresses KCNQ1 currents markedly. Ref.14 Ref.15 Ref.16 Ref.17

VAR_008901

Natural variant

85

1

D → N Predisposes to acquired LQT5 susceptibility; shows a significant difference in current density and midpoint potential between the mutant and the wildt-ype channels. Ref.12 Ref.20 Ref.21
Corresponds to variant rs1805128 [ dbSNP | Ensembl ].

VAR_008902

Natural variant

87

1

W → R in LQT5. Ref.17

VAR_008903

Natural variant

98

1

R → W in LQT5. Ref.18

VAR_009907

Natural variant

109

1

V → I in LQT5; mild phenotype; significantly reduced the wild-type I(KS) current amplitude. Ref.19

VAR_012802

Natural variant

127

1

P → T in LQT5. Ref.18

VAR_009908

Experimental info

Mutagenesis

5

1

N → Q: No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5; when associated with T-28. Ref.10

Mutagenesis

6

1

T → F: No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex. Loss of glycosylation at T-7. Ref.10

Mutagenesis

7

1

T → A: 50% reduction of cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5 and T-7; when associated with T-28. Ref.10

Mutagenesis

28

1

S → T: No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5; when associated with Q-5. 50% reduction of cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5 and T-7; when associated with A-7. Ref.10

Mutagenesis

69

1

K → H: Lowers current 2-fold and leads to faster deactivation of KCNQ1/KCNE1 channel. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

129

Helix Strand Turn

Details...

Helix

4 – 9

6

Helix

13 – 22

10

Helix

30 – 32

3

Helix

46 – 71

26

Turn

77 – 81

5

Turn

84 – 86

3

Helix

92 – 105

14

Beta strand

114 – 116

3

Sequences

	Sequence		Length	Mass (Da)
	P15382 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 5442D70929D4E87E	FASTA	129	14,675
	10 20 30 40 50 60 MILSNTTAVT PFLTKLWQET VQQGGNMSGL ARRSPRSSDG KLEALYVLMV LGFFGFFTLG 70 80 90 100 110 120 IMLSYIRSKK LEHSNDPFNV YIESDAWQEK DKAYVQARVL ESYRSCYVVE NHLAIEQPNT HLPETKPSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of human genomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity." Murai T., Kakizuka A., Takumi T., Ohkubo H., Nakanishi S. Biochem. Biophys. Res. Commun. 161:176-181(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Polymorphism of the gene encoding a human minimal potassium ion channel (minK)." Lai L.P., Deng C.L., Moss A.J., Kass R.S., Liang C.S. Gene 151:339-340(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-38. Tissue: Leukocyte.
[3]	"Delayed rectifier potassium channel subunit from human cornea epithelium." Rae J.L. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cornea.
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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], VARIANTS HIS-32 AND GLY-38. Tissue: Testis.
[6]	"Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias." Chouabe C., Neyroud N., Guicheney P., Lazdunski M., Romey G., Barhanin J. EMBO J. 16:5472-5479(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"A minK-HERG complex regulates the cardiac potassium current I(Kr)." McDonald T.V., Yu Z., Ming Z., Palma E., Meyers M.B., Wang K.-W., Goldstein S.A.N., Fishman G.I. Nature 388:289-292(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNH2.
[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-69.
[9]	"Post-translational N-glycosylation of type I transmembrane KCNE1 peptides: implications for membrane protein biogenesis and disease." Bas T., Gao G.Y., Lvov A., Chandrasekhar K.D., Gilmore R., Kobertz W.R. J. Biol. Chem. 286:28150-28159(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-5 AND ASN-26, CHARACTERIZATION OF VARIANT JLNS2 ILE-7.
[10]	"O-glycosylation of the cardiac I(Ks) complex." Chandrasekhar K.D., Lvov A., Terrenoire C., Gao G.Y., Kass R.S., Kobertz W.R. J. Physiol. (Lond.) 589:3721-3730(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-5 AND THR-7, MUTAGENESIS OF ASN-5; THR-6; THR-7 AND SER-28.
[11]	"Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel." Kang C., Tian C., Soennichsen F.D., Smith J.A., Meiler J., George A.L. Jr., Vanoye C.G., Kim H.J., Sanders C.R. Biochemistry 47:7999-8006(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[12]	"Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome." Tesson F., Donger C., Denjoy I., Berthet M., Bennaceur M., Petit C., Coumel P., Schwartz K., Guicheney P. J. Mol. Cell. Cardiol. 28:2051-2055(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASN-85.
[13]	"IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome." Tyson J., Tranebjaerg L., Bellman S., Wren C., Taylor J.F.N., Bathen J., Aslaksen B., Soerland S.J., Lund O., Malcolm S., Pembrey M., Bhattacharya S., Bitner-Glindzicz M. Hum. Mol. Genet. 6:2179-2185(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT JLNS2 58-PRO-PRO-59.
[14]	"KCNE1 mutations cause Jervell and Lange-Nielsen syndrome." Schulze-Bahr E., Wang Q., Wedekind H., Haverkamp W., Chen Q., Sun Y., Rubie C., Hordt M., Towbin J.A., Borggrefe M., Assmann G., Qu X., Somberg J.C., Breithardt G., Oberti C., Funke H. Nat. Genet. 17:267-268(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS JLNS2 ILE-7 AND ASN-76.
[15]	"Mutations in the hminK gene cause long QT syndrome and suppress IKs function." Splawski I., Tristani-Firouzi M., Lehmann M.H., Sanguinetti M.C., Keating M.T. Nat. Genet. 17:338-340(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT5 LEU-74 AND ASN-76.
[16]	"Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome." Duggal P., Vesely M.R., Wattanasirichaigoon D., Villafane J., Kaushik V., Beggs A.H. Circulation 97:142-146(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT5 ASN-76.
[17]	"Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome." Bianchi L., Shen Z., Dennis A.T., Priori S.G., Napolitano C., Ronchetti E., Bryskin R., Schwartz P.J., Brown A.M. Hum. Mol. Genet. 8:1499-1507(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS JLNS2 PHE-47; HIS-51 AND ASN-76, VARIANT LQT5 ARG-87.
[18]	"Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2." Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S.G., Robinson J.L., Moss A.J., Schwartz P.J., Towbin J.A., Vincent G.M., Keating M.T. Circulation 102:1178-1185(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LQT5 HIS-32; TRP-98 AND THR-127.
[19]	"A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype." Schulze-Bahr E., Schwarz M., Hauenschild S., Wedekind H., Funke H., Haverkamp W., Breithardt W., Pongs O., Isbrandt D., Breithardt G. J. Mol. Med. 79:504-509(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LQT5 ILE-109.
[20]	"Compound mutations: a common cause of severe long-QT syndrome." Westenskow P., Splawski I., Timothy K.W., Keating M.T., Sanguinetti M.C. Circulation 109:1834-1841(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASN-85.
[21]	"The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss." Van Laer L., Carlsson P.-I., Ottschytsch N., Bondeson M.-L., Konings A., Vandevelde A., Dieltjens N., Fransen E., Snyders D., Borg E., Raes A., Van Camp G. Hum. Mutat. 27:786-795(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLY-38 AND ASN-85, CHARACTERIZATION OF VARIANT ASN-85.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M26685 Genomic DNA. Translation: AAA36129.1.
L33815 Genomic DNA. Translation: AAA63905.1.
L28168 mRNA. Translation: AAA58418.1.
AF135188 mRNA. Translation: AAD25096.1.
DQ784803 Genomic DNA. Translation: ABQ01238.1.
BC036452 mRNA. Translation: AAH36452.1. Sequence problems.

IPI

IPI00305022.

PIR

A32447.

RefSeq

NP_000210.2. NM_000219.4.
NP_001121140.1. NM_001127668.2.
NP_001121141.1. NM_001127669.2.
NP_001121142.1. NM_001127670.2.
NP_001257331.1. NM_001270402.1.
NP_001257332.1. NM_001270403.1.
NP_001257333.1. NM_001270404.1.
NP_001257334.1. NM_001270405.1.

UniGene

Hs.121495.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K21	NMR	-	A	1-129	[»]

ProteinModelPortal

P15382.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000337255.

PTM databases

PhosphoSite

P15382.

Polymorphism databases

DMDM

116416.

Proteomic databases

PaxDb

P15382.

PRIDE

P15382.

Protocols and materials databases

DNASU

3753.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000337385; ENSP00000337255; ENSG00000180509.
ENST00000399284; ENSP00000382225; ENSG00000180509.
ENST00000399286; ENSP00000382226; ENSG00000180509.
ENST00000399289; ENSP00000382228; ENSG00000180509.
ENST00000416357; ENSP00000416258; ENSG00000180509.
ENST00000432085; ENSP00000412498; ENSG00000180509.

GeneID

3753.

KEGG

hsa:3753.

UCSC

uc002ytz.3. human.

Organism-specific databases

CTD

3753.

GeneCards

GC21M035818.

HGNC

HGNC:6240. KCNE1.

HPA

HPA013752.

MIM

176261. gene.
612347. phenotype.
613695. phenotype.

neXtProt

NX_P15382.

Orphanet

334. Familial atrial fibrillation.
90647. Jervell and Lange-Nielsen syndrome.
101016. Romano-Ward syndrome.

PharmGKB

PA211.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41824.

HOGENOM

HOG000113207.

HOVERGEN

HBG052226.

InParanoid

P15382.

KO

K04894.

OMA

ALYILMV.

OrthoDB

EOG41G35J.

PhylomeDB

P15382.

Gene expression databases

ArrayExpress

P15382.

Bgee

P15382.

CleanEx

HS_KCNE1.

Genevestigator

P15382.

GermOnline

ENSG00000180509. Homo sapiens.

Family and domain databases

InterPro

IPR000369. K_chnl_volt-dep_bsu_KCNE.
IPR005424. K_chnl_volt-dep_bsu_KCNE1.
[Graphical view]

PANTHER

PTHR17028. PTHR17028. 1 hit.

Pfam

PF02060. ISK_Channel. 1 hit.
[Graphical view]

PRINTS

PR01604. KCNE1CHANNEL.
PR00168. KCNECHANNEL.

ProtoNet

Search...

Other

BindingDB

P15382.

ChEMBL

CHEMBL4872.

DrugBank

DB00808. Indapamide.

EvolutionaryTrace

P15382.

GenomeRNAi

3753.

NextBio

14697.

SOURCE

Search...

Entry information

Entry name

KCNE1_HUMAN

Accession

Primary (citable) accession number: P15382
Secondary accession number(s): A5H1P2, Q8N709, Q91Z94

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 142 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.