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FLASH GENE

Symbol

KCNE1

contributors: mct/npt/pgu - updated : 26-04-2017

HGNC name	potassium voltage-gated channel, Isk-related family, member 1
HGNC id	6240

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000219 3 - 3338 NP_000210 - 129 - 2006 16303284 NM_001127668 3 - 3199 NP_001121140 - 129 - 2006 16303284 NM_001127669 3 - 3171 NP_001121141 - 129 - 2006 16303284 NM_001127670 2 - 3392 NP_001121142 - 129 - 2006 16303284 NM_001270404 2 - 3239 NP_001257333 - 129 - 2006 16303284 NM_001270402 3 - 3350 NP_001257331 - 129 - 2006 16303284 NM_001270403 3 - 3298 NP_001257332 - 129 - 2006 16303284 NM_001270405 3 - 3151 NP_001257334 - 129 - 2006 16303284

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine small intestine         pharynx       moderately Nervous nerve       highly Reproductive female system ovary         male system testis       Respiratory lung           respiratory tract trachea     predominantly Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	apical surface of vestibular dark cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two N-linked glycosylation sites
	consensus sequences for two protein kinase C-mediated phosphorylation sites
	a transmembrane domain (TMD) of KCNE1 that plays a key role in mediating the physical association with KCNQ1 and in subsequent modulation of channel gating kinetics and conductance
	distal C-terminus interacts with the coiled-coil helix C of KCNQ1 tetramerization domain , and KCNE1 C-terminus could modulate gating property of KCNQ1

secondary structure

transmembrane domain (TMD) is a curved alpha-helix and is flanked by intra- and extracellular domains comprised of alpha-helices joined by flexible linkers

conjugated

GlycoP

mono polymer

heteromer , tetramer

HOMOLOGY

interspecies	homolog to rattus Kcne1 (78 pc)
	homolog to murine Kcne1 (77.2 pc)

Homologene

FAMILY	potassium channel KCNE family
	Isk-related subfamily (IRK)

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,lysosome
text	apical plasma membrane
	single-pass type I membrane protein

basic FUNCTION	forming with KCNQ1 the slowly activating delayed rectifier cardiac potassium channel
	acting as a potassium channel regulator
	modulating the gating kinetics and enhancing stability of the channel complex
	involved in blood circulation
	playing a role in epithelial celle maturation
	involved in muscle contraction
	playing a role in heart contraction
	modulating the function of KCNQ1 and certain other voltage-gated potassium channels (KV)
	probably the major K(+)-channel involved in regulatory volume decrease in spermatozoa, and channel activity is regulated beyond the extent of protein expression
	single-span membrane protein that modulates the voltage-gated potassium channel KCNQ1 by slowing activation and enhancing channel conductance to generate the slow delayed rectifier current critical for the repolarization phase of the cardiac action potential
	KCNQ1 voltage-gated potassium channel and its auxiliary subunit KCNE1 play a crucial role in the regulation of the heartbeat
	alters the voltage sensor movements necessary to open the KCNQ1 channel gate
	functional role of KCNE cleavage in regulating voltage-gated potassium channels
	in cardiac myocytes, KCNQ1/KCNE1 complexes are thought to give rise to the delayed rectifier current IKs, which contributes to cardiac action potential repolarization

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	potassium transport

PATHWAY

metabolism

signaling

sensory transduction/hearing

a component	heterotetramer KCNQ1/KCNJ1
	KCNQ1 and KCNE1 subunits coassemble to form the I(Ks) channel
	directly associates with KCNE4, and can co-associate together with KCNE1 in the same KCNQ1 complex to form a 'triple subunit' complex (KCNE1-KCNQ1-KCNE4)

INTERACTION

DNA

RNA

small molecule	metal binding,
	K+

protein	associating with KCNQ1 to generate the slow delayed IKR channel
	associating with KCNH2 (HERG) to modulate the rapid delayed rectifier IKJ channel central to the control of the heart rate and rhythm
	interaction with KCNH2 (during biogenesis of channels KCNH2, is more likely to assemble with KCNE1 than KCNE2 due to distinctly different trafficking rates and retention in the cell rather than differences in relative affinity
	protein-protein interaction between the KCNE1 C-terminal domain and the KCNQ1 S6 activation gate and S4-S5 linker
	CTNNB1 enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane
	KCNQ1 channels in both the absence and the presence of KCNE1 undergo likely sequential gating transitions leading to channel opening even before all voltage sensor domains (VSDs)have moved
	KCNQ1 is regulated by non-pore forming regulatory KCNE beta-subunits
	KCNE1 and KCNE2 cleavages are regulated by BACE1 and PSEN1/gamma-secretase activities under physiological conditions
	Klotho upregulates KCNQ1/KCNE1 channel activity by “mainly” enhancing channel protein abundance in the plasma cell membrane
	conductance and dynamics of KCNQ1 could be modulated by different single transmembrane helical auxiliary proteins (such as KCNE1, KCNE2)
	BACE1 modulates gating of KCNQ1 and cardiac delayed rectifier KCNQ1/KCNE1 (IKs)
	STK39 and OXSR1 participate in the regulation of KCNQ1/KCNE1 protein abundance and activity
	SGMS1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner
	KCNQ1/KCNE1 channel does not require INPP5J or PI(4)P for anterograde trafficking, but is heavily reliant on INPP5J for channel function once at the plasma membrane (PM)

cell & other

REGULATION

Other

a macromolecular complex including PRKARZA,PPP1CA and AKAP9

ASSOCIATED DISORDERS

corresponding disease(s)

JLNS2 , LQT5

related resource

Long QT Syndrome Database Congenital Long QT Syndrome at GeneDis Gene Connection for the Heart - Long QT Syndrome database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in mild-to-moderate chronic heart failure, contribute to the preferential prolongation of QT interval through reducing the net outward current during the plateau of the action potential

Susceptibility

to QT prolongation and risk of arrhythmia or sudden death to Ménière disease

Variant & Polymorphism SNP	G38S or D85N variant is involved in determining QT prolongation
	rs2283222 located in intron 11 in KCNQ1 remained significantly associated with sudden/arrhythmic death
	rs1805127, rs1805128, and rs17173510, in KCNE1 were found in patients with Ménière disease

Candidate gene	physical inteeraction between KCNQ1 and KCNE1 is potentially affected in some LQTS mutations
Marker
Therapy target

ANIMAL & CELL MODELS