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FLASH GENE

Symbol

KCNK2

contributors: mct/npt - updated : 22-10-2014

HGNC name	potassium channel, subfamily K, member 2
HGNC id	6277

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	231.55 kb     7 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001017424 7 - 3597 NP_001017424 - 422 - 2010 20605797 NM_014217 7 - 3274 NP_055032 - 411 - 2010 20605797 NM_001017425 7 - 3398 NP_001017425 - 426 - 2010 20605797 TREK1deltaEx4 6 - 2496 - 370 . in the brain . retained in the intracellular compartment 2010 20605797 truncated protein, retaining a single transmembrane domain has no channel activity itself but reduced KCNK2 whole cell current amplitude might have some dominant-negative effect on KCNK2 expression

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 Digestive salivary gland       highly Endocrine pancreas       highly   thyroid       highly Nervous brain       highly Homo sapiens Reproductive female system uterus       Homo sapiens   female system ovary     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth myoepithelium   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Homo sapiens Nervous neuron Skeleton osteoblast

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal domain and first transmembrane domain are likely to be important for channel dimerization and trafficking to the plasma membrane
	four transmembrane segments
	two pore forming regions (P domains) with two P-domains arranged like a tandem of outward rectifier channels

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY	two pore domain potassium channel (TC 1.A.1.8) family
	potassium channel, subfamily K
	two-pore domain (K2P)5 K+ channel family

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	localized at the plasma membrane and cytoplasm close to the plasma membrane when coexpressed with each splice variant

basic FUNCTION	potassium non voltage-gated heat activated background channel outwardly rectifying, candidate physiological thermoreceptor
	playing a possible role in mechanotransduction, leading to bone remodelling
	having a role in adrenal glomerulosa cells for their background potassium current (Brenner 2008)
	KCNK2, KCNK10 are potently activated by polyunsaturated fatty acids and are involved in neuroprotection, anesthesia, and pain perception
	role in contributing to uterine quiescence during gestation and hypothesize that dysregulation of this mechanism may underlie certain cases of spontaneous pre-term birth
	may participate in pathophysiologic alteration and electrical remodelling of left ventricular myocardium after MI, which may eventually lead to post-MI ventricular arrhythmias
	could be involved in regulation of alveolar epithelial cell proliferation and cytokine secretion
	may be important to protect disc cells against ischaemic damage, and subsequent disc degeneration, and may also play a role in effecting mechanotransduction
	KCNK2 activity is involved in astrocytic function and neuronal survival
	KCNK2 and BEST1 mediate fast and slow glutamate release in acutely dissociated astrocytes
	eukaryotic mechanosensitive channel, directly sensitive to a modification of membrane tension
	endothelial KCNK2 regulates immune-cell trafficking into the CNS

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

formed by two homodimers that create a channel that leaks potassium out of the cell to control resting membrane potential

INTERACTION

DNA

RNA

small molecule

protein	protein-protein interaction between KCNK2 and COPB2 (
	KCNK2, KCNK4, KCNK10 interact with partner proteins that influence their activity and their plasma membrane expression
	C terminus of GNG4 showed strong interaction with KCNK2, whereas N terminus did not

cell & other

REGULATION

activated by	volatile general anaesthetics such as chloroform, halothane and isoflurane
	by fenamates

inhibited by

external acidification

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function KCNK2 deficient cells have less F-actin and are more deformable making them more resistant to stretch-induced injury constitutional     --over   in human endometrium with molecular expression of KCNK2 shown to be higher in proliferative than secretory phase endometrium constitutional     --over   during gestation to term such that it may maintain uterine quiescence by hyperpolarizing the smooth muscle cell membrane

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS