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FLASH GENE

Symbol

KCNK3

contributors: npt/mct - updated : 28-02-2017

HGNC name	potassium channel, subfamily K, member 3
HGNC id	6278

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_002246 2 - 3978 NP_002237 - 394 - 1998 9721223

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         Homo sapiens Endocrine adrenal gland cortex     highly Nervous brain hindbrain cerebellum     Homo sapiens   spinal cord anterior horn       Homo sapiens Reproductive female system uterus         male system prostate       Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose brown     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Nervous oligodendrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	highly, in placenta, and in myometrium from pregnant women

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four transmembrane segments
	two pore forming regions (P domains) arranged like a tandem
	an extended external loop M1P1 with intracellular N and C termini, of outward rectifier channels (open acid sensitive two P domains channel)
	C-terminal residues are critical for KCNK3 endocytosis and define a novel K+ channel endocytic signal

conjugated

GlycoP

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY	two pore domain potassium channel (tc 1.a.1.8) family
	potassium channel, subfamily K

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	potassium non voltage-gated heat activated background channel outwardly rectifying
	acting as an outward rectifier when external potassium concentration is low; when external potassium concentration is high, current is inward
	playing an important role in mediating pulmonary vascular responses to changes in extracellular pH, and in the regulation of pulmonary vascular tone
	play a key role in modulating effector functions of T lymphocytes
	may serve as molecular sensors for central chemoreception because they are highly expressed in multiple neuronal populations in the respiratory pathway and contribute to their pH sensitivity
	controls the resting membrane potential in humanpulmonary artery smooth muscle cells (PASMCs), and renders these cells sensitive to a variety of vasoactive factors
	regulate neuronal firing and may contribute to the specialized responses of orexin neurons to glucose and pH
	role in enhancing neuronal excitability and promoting high-frequency firing, but KCNK3/KCNK9 subunits are not essential for orexin cell responses to glucose and pH
	plays a functional role in the repolarization of the cardiac action potential and contributes to the maintenance of heart rate variability (HRV)
	is vital for setting the resting membrane potential and is the primary target for volatile anesthetics
	plays a major role in a number of physiological functions throughout the CNS and periphery, and mechanisms that alter KCNK3 function and availability are likely to have a significant systemic impact
	role potential for KCNK3 to uniquely contribute to synaptic plasticity
	acid-sensitive KCNK1, KCNK3, KCNK9 change ion selectivity and become permeable to sodium in extracellular acidification
	K(+) leak channel that mediates hypoxic depolarisation in neurons
	oligodendrocytes express functional KCNK3 channels which contribute to oligodendrocyte damage in hypoxia
	is an important modulator of membrane voltage and Ca(2+) entry
	important role for KCNK3 channels in limiting pancreatic alpha-cell excitability and glucagon secretion during glucose stimulation
	controls the thermogenic activity in brown adipocytes through modulation of ADRB signaling

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	ion transport

PATHWAY

metabolism

signaling

a component

heterodimerizing with KCNK9

INTERACTION

DNA

RNA

small molecule

protein	cooperative action of KCNK3 and NADPH oxidase-4 (NOX4) mediated the O2-sensitive K+ current response
	interacting with EDN1 (may exert its vasoconstrictive effects in part by targeting KCNK3, which might represent a novel pathologic mechanism related to pulmonary arterial hypertension)
	YWHAB is absolutely required for KCNK3 internalization, a role heretofore not described for a 14-3-3 protein
	is subject to dynamic PRKCA-regulated endocytic trafficking that is YWHAB-dependent
	STX8 interacts with the acid-sensitive potassium channel KCNK3, and regulates the endocytosis of KCNK3

cell & other

REGULATION

Other

controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels

ASSOCIATED DISORDERS

corresponding disease(s)

PPH4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low loss of function in pulmonary artery smooth muscle cells and endothelial cell

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular rythm   promising drug targets against atrial fibrillation, the most common arrhythmia in the elderly

ANIMAL & CELL MODELS

	disruption of the TASK1 gene in mice resulted in an autonomous aldosterone production and caused a remarkable aberrant expression of aldosterone synthase in zona fasciculata cells that normally produce glucocorticoids
	Task1-null mice, compared with their controls, became overweight, mainly because of an increase in white adipose tissue mass and BAT whitening