Q9Y6H6 (KCNE3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

KCNE3

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	103 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 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.
Subunit structure	Associates with KCNC4/Kv3.4. May associate with KCNQ1/KCLQT1.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Widely expressed with highest levels in kidney and moderate levels in small intestine. Ref.4
Involvement in disease	Brugada syndrome 6 (BRGDA6) [MIM:613119]: A 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. 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.
Caution	Variant His-83 has been associated with periodic paralysis (Ref.5 and Ref.7). 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 (Ref.8 and Ref.9).

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Brugada syndrome Disease mutation
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	regulation of potassium ion transport Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	potassium channel regulator activity Inferred from electronic annotation. Source: Compara voltage-gated potassium channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 103	103	Potassium voltage-gated channel subfamily E member 3		PRO_0000144289
Regions
	Transmembrane	58 – 78	21	Helical; Potential
	Topological domain	79 – 103	25	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	5	1	N-linked (GlcNAc...) Potential
	Glycosylation	22	1	N-linked (GlcNAc...) Potential
	Glycosylation	41	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	4	1	T → A. Ref.11		VAR_058635
	Natural variant	39	1	P → R. Ref.11 Corresponds to variant rs34604640 [ dbSNP | Ensembl ].		VAR_058636
	Natural variant	83	1	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. Ref.5 Ref.7 Ref.8 Ref.9 Corresponds to variant rs17215437 [ dbSNP | Ensembl ].		VAR_015064
	Natural variant	99	1	R → H in BRGDA6; also in a patient suffering from drug-induced torsades de pointes. Ref.10 Ref.11		VAR_058637
Experimental info
	Mutagenesis	90	1	D → N: Decreases current 4-fold in KCNH2/KCNE3 channel. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6H6 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 5235385E8D08BF10	FASTA	103	11,710
	10 20 30 40 50 60 METTNGTETW YESLHAVLKA LNATLHSNLL CRPGPGLGPD NQTEERRASL PGRDDNSYMY 70 80 90 100 ILFVMFLFAV TVGSLILGYT RSRKVDKRSD PYHVYIKNRV SMI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome." Delpon E., Cordeiro J.M., Nunez L., Thomsen P.E., Guerchicoff A., Pollevick G.D., Wu Y., Kanters J.K., Larsen C.T., Hofman-Bang J., Burashnikov E., Christiansen M., Antzelevitch C. Circ. Arrhythm. Electrophysiol. 1:209-218(2008) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF076531 mRNA. Translation: AAD28089.1. AF302494 mRNA. Translation: AAG16255.1. BC032235 mRNA. No translation available.
IPI	IPI00002294.
RefSeq	NP_005463.1. NM_005472.4.
UniGene	Hs.523899.
3D structure databases
ProteinModelPortal	Q9Y6H6.
SMR	Q9Y6H6. Positions 20-99.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000310557.
Proteomic databases
PaxDb	Q9Y6H6.
PRIDE	Q9Y6H6.
Protocols and materials databases
DNASU	10008.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310128; ENSP00000310557; ENSG00000175538. ENST00000525550; ENSP00000433633; ENSG00000175538.
GeneID	10008.
KEGG	hsa:10008.
UCSC	uc001ovc.3. human.
Organism-specific databases
CTD	10008.
GeneCards	GC11M074165.
HGNC	HGNC:6243. KCNE3.
HPA	HPA014849.
MIM	604433. gene. 613119. phenotype.
neXtProt	NX_Q9Y6H6.
Orphanet	130. Brugada syndrome. 681. Hypokalemic periodic paralysis.
PharmGKB	PA393.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42036.
HOGENOM	HOG000113209.
HOVERGEN	HBG052228.
InParanoid	Q9Y6H6.
KO	K04897.
OMA	GPGPDNQ.
OrthoDB	EOG4B5P6P.
PhylomeDB	Q9Y6H6.
Gene expression databases
ArrayExpress	Q9Y6H6.
Bgee	Q9Y6H6.
CleanEx	HS_KCNE3.
Genevestigator	Q9Y6H6.
GermOnline	ENSG00000175538. Homo sapiens.
Family and domain databases
InterPro	IPR000369. K_chnl_volt-dep_bsu_KCNE. IPR005426. K_chnl_volt-dep_bsu_KCNE3. [Graphical view]
Pfam	PF02060. ISK_Channel. 1 hit. [Graphical view]
PRINTS	PR01606. KCNE3CHANNEL. PR00168. KCNECHANNEL.
ProtoNet	Search...
Other
GenomeRNAi	10008.
NextBio	37809.
SOURCE	Search...

Entry information

Entry name

KCNE3_HUMAN

Accession

Primary (citable) accession number: Q9Y6H6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 105 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.