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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 127–616, 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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