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FLASH GENE
Symbol KCNMA1 contributors: mct/npt - updated : 23-06-2014
HGNC name potassium large conductance calcium-activated channel, subfamily M, alpha member 1
HGNC id 6284
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
  • N-terminal seven transmembrane domains (S0 to S6)
  • two functional domains, a core consisting of four voltage sensors controlling an ion-conducting pore, and a larger tail that forms an intracellular gating ring thought to confer Ca(2+) and Mg(2+) sensitivity
  • a RCK1 domain between S6 and S8, that is a high-affinity Ca(2+) sensor that transduces Ca(2+) binding into structural rearrangements, likely representing elementary steps in the Ca(2+)-dependent activation of KCNMA1 channels
  • a calcium bowl
  • CRAC motifs, cholesterol-binding motifs
  • an extensive C-terminus with four hydrophobic segments (S7 to S10), and a motif required for surface targeting
  • mono polymer homomer , tetramer
    HOMOLOGY
    interspecies homolog to Drosophila slowpoke
    Homologene
    FAMILY
  • potassium channel family
  • calcium-activated subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • control of smooth muscle tone and neuronal excitability
  • constituting the calcium-activated potassium channel and playing a key role in controlling excitability in a number of systems, such as regulation of the contraction
  • of smooth muscle, the tuning of hair cells in the cochlea,
    regulation of transmitter release, and innate immunity
  • play a fundamental role in cellular function by integrating information from their voltage and Ca(2+) sensors to control membrane potential and Ca(2+) homeostasis
  • role of endothelial KCNM1A channels in altered vasoreactivity following hypoxia
  • mediate cholinergic inhibition of high frequency cochlear hair cells
  • play important roles in regulating vascular contractility
  • (egulate neuronal functions such as spike frequency adaptation and transmitter release
  • modulate visual responses in vivo at the bipolar cell level at intermediate stimulus conditions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling neurotransmission , signal transduction
    a component
  • pore constituent (forming alpha member 1) complexing with alternative beta subunits
  • composed of four KCNMA1 subunits, which contain the voltage-sensing and pore-gate domains in the membrane and Ca(2+) binding sites in the cytoplasmic domain, and accessory beta subunits
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4
  • interaction with caveolin-1 (interaction facilitating the tethering of the KCNMA1 C-terminal end to the membrane)
  • binds MAGI1
  • WNK4 inhibits KCNMA1 activity by reducing KCNMA1 protein at the membrane, but the inhibition is not due to an increase in clathrin-mediated endocytosis of KCNMA1, but likely due to enhancing its lysosomal degradation
  • insulin stimulation of KCNMA1 channels in podocytes may prepare podocytes to adapt to changes in pressure gradients that occur during postprandial hyperfiltration
  • RAB11B has a moderate association with a region of KCNMA1 that includes AA 127616, and this interaction of RAB11B and KCNMA1 is in cochlea
  • lack of TMPRSS3 leads to a decrease in KCNMA1 potassium channels expression in inner hair cells (IHCs)
  • CRBN inactivation releases deubiquitinated KCNMA1 channels from the ER to the plasma membrane, leading to markedly enhanced channel activity
  • LRRC26 associates with KCNMA1 subunits, and elevates channel voltage- and apparent Ca2+-sensitivity in arterial myocytes to induce vasodilation (PMID;
  • cell & other
    REGULATION
    activated by intracellular Zn(2+) that potently and reversibly activates large-conductance voltage- and Ca(2+)-activated KCNMA1
    ASSOCIATED DISORDERS
    corresponding disease(s) GEPD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in late-stage prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target promising diagnostic and therapeutic target in patients with prostate cancer
    ANIMAL & CELL MODELS