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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
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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low loss of function
    in pulmonary artery smooth muscle cells and endothelial cell
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularrythm 
    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