Calcium-activated potassium channel subunit alpha-1

UniProt Q12791 Organism Homo sapiens Gene KCNMA, KCNMA1, SLO

Also known as: KCNMA, KCNMA1, SLO

Function

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays 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. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX). Possibly induces sleep when activated by melatonin and through melatonin receptor MTNR1A-dependent dissociation of G-beta and G-gamma subunits, leading to increased sensitivity to Ca(2+) and reduced synaptic transmission.

Classification

Family (Pfam): PF03493 BK_channel_a, PF00520 Ion_trans, PF22614 Slo-like_RCK, PF21014 Slowpoke_C
InterPro: Ion_trans_dom, K_chnl_BK_asu, K_chnl_Slo-like, NAD(P)-bd_dom_sf, RCK_N, Slowpoke-like_C
Functional cluster: S-Adenosylmethionine Synthases & related

Experimental structures · PDB · 35

2K44 NMR
3MT5 X-ray 3.00A
3NAF X-ray 3.10A
6ND0 EM 3.50A
6V22 EM 3.20A
6V35 EM 3.50A
6V38 EM 3.80A
6V3G EM 4.00A
6V5A X-ray 2.00A
7YNZ EM 3.50A
7YO0 EM 3.60A
7YO1 EM 3.60A
… and 23 more

A predicted model is available from AlphaFold.

Gene Ontology · 25

Disease associations

generalized epilepsy-paroxysmal dyskinesia syndrome MONDO:0012276
cerebellar atrophy, developmental delay, and seizures MONDO:0060551
epilepsy, idiopathic generalized, susceptibility to, 16 MONDO:0032827
Liang-Wang syndrome MONDO:0032886

Drugs targeting this protein · 3

ANDOLAST activator
BMS-223131 activator
FLINDOKALNER opener

Neighborhood · nearest proteins

Nearest neighbours of Calcium-activated potassium channel subunit alpha-1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Leucine-rich repeat-containing protein 26 2 shared papers
Calcium-activated potassium channel subunit beta-2 2 shared papers
Calcium-activated potassium channel subunit beta-1 1 shared papers
Calcium-activated potassium channel subunit alpha-1 1 shared papers
Leucine-rich repeat-containing protein 38 1 shared papers
Leucine-rich repeat-containing protein 55 1 shared papers
Melatonin receptor pdcr-1 1 shared papers
Melatonin receptor type 1A 1 shared papers
Alpha N-terminal protein methyltransferase 1 1 shared papers
Palmitoyltransferase ZDHHC23 1 shared papers
Leucine-rich repeat-containing protein 52 1 shared papers
Lysophospholipase-like protein 1 1 shared papers

Literature · 31 cited papers

Melatonin promotes sleep by activating the BK channel in C. elegans. Proc. Natl. Acad. Sci. U.S.A. · 2020
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes. Hum. Mol. Genet. · 2019
Expanding the phenotype of homozygous KCNMA1 mutations; dyskinesia, epilepsy, intellectual disability, cerebellar and corticospinal tract atrophy. Balkan Med. J. · 2018
De novo BK channel variant causes epilepsy by affecting voltage gating but not Ca2+ sensitivity. Eur. J. Hum. Genet. · 2018
Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental delay and seizures. Hum. Genet. · 2016
De novo KCNMA1 mutations in children with early-onset paroxysmal dyskinesia and developmental delay. Mov. Disord. · 2015
BK potassium channel modulation by leucine-rich repeat-containing proteins. Proc. Natl. Acad. Sci. U.S.A. · 2012
Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels. J. Biol. Chem. · 2012
Palmitoylation of the S0-S1 linker regulates cell surface expression of voltage- and calcium-activated potassium (BK) channels. J. Biol. Chem. · 2010
LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium. Nature · 2010
Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution. Science · 2010
Characterizing the role of Thr352 in the inhibition of the large conductance Ca2+-activated K+ channels by 1-[1-Hexyl-6-(methyloxy)-1H-indazol-3-yl]-2-methyl-1-propanone. J. Pharmacol. Exp. Ther. · 2010
… and 19 more in the literature graph

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