ID KCMA1_HUMAN Reviewed; 1236 AA.
AC Q12791; F8WA96; Q12886; Q12917; Q12921; Q12960; Q13150; Q5JQ23; Q5SQR9;
AC Q96LG8; Q9UBB0; Q9UCX0; Q9UQK6;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 27-MAR-2024, entry version 217.
DE RecName: Full=Calcium-activated potassium channel subunit alpha-1;
DE AltName: Full=BK channel;
DE AltName: Full=BKCA alpha;
DE AltName: Full=Calcium-activated potassium channel, subfamily M subunit alpha-1;
DE AltName: Full=K(VCA)alpha;
DE AltName: Full=KCa1.1;
DE AltName: Full=Maxi K channel;
DE Short=MaxiK;
DE AltName: Full=Slo-alpha;
DE AltName: Full=Slo1;
DE AltName: Full=Slowpoke homolog;
DE Short=Slo homolog;
DE Short=hSlo;
GN Name=KCNMA1 {ECO:0000312|HGNC:HGNC:6284}; Synonyms=KCNMA, SLO;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Substantia nigra;
RX PubMed=7877450; DOI=10.1016/0169-328x(94)90203-8;
RA Dworetzky S.I., Trojnacki J.T., Gribkoff V.K.;
RT "Cloning and expression of a human large-conductance calcium-activated
RT potassium channel.";
RL Brain Res. Mol. Brain Res. 27:189-193(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Aortic smooth muscle, and Umbilical smooth muscle;
RX PubMed=7573516; DOI=10.1152/ajpheart.1995.269.3.h767;
RA McCobb D.P., Fowler N.L., Featherstone T., Lingle C.J., Saito M.,
RA Krause J.E., Salkoff L.;
RT "A human calcium-activated potassium channel gene expressed in vascular
RT smooth muscle.";
RL Am. J. Physiol. 269:H767-H777(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6).
RC TISSUE=Cerebellum, Neuroectoderm, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-1236 (ISOFORM 5).
RX PubMed=7993625; DOI=10.1016/0896-6273(94)90418-9;
RA Tseng-Crank J., Foster C.D., Krause J.D., Mertz R., Godinot N.,
RA DiChiara T.J., Reinhart P.H.;
RT "Cloning, expression, and distribution of functionally distinct Ca(2+)-
RT activated K+ channel isoforms from human brain.";
RL Neuron 13:1315-1330(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-1236 (ISOFORM 5).
RC TISSUE=Myometrium;
RX PubMed=12434576;
RA Mazzone J.N., Kaiser R.A., Buxton I.L.O.;
RT "Calcium-activated potassium channel expression in human myometrium: effect
RT of pregnancy.";
RL Proc. West. Pharmacol. Soc. 45:184-186(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-1236 (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 25-1236 (ISOFORM 2).
RC TISSUE=Heart;
RA Naruse K.;
RT "BK variant from human heart.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-670 (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 323-1236 (ISOFORM 4).
RC TISSUE=Muscle;
RX PubMed=7987297; DOI=10.1093/hmg/3.8.1239;
RA Pallanck L., Ganetzky B.;
RT "Cloning and characterization of human and mouse homologs of the Drosophila
RT calcium-activated potassium channel gene, slowpoke.";
RL Hum. Mol. Genet. 3:1239-1243(1994).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-1236 (ISOFORM 5).
RC TISSUE=Lens epithelium;
RA Rae J.L., Shepard A.R.;
RT "Identification of potassium channels in human lens epithelium.";
RL (In) Civan M.M. (eds.);
RL Current topics in membranes. The eye's aqueous humor - from secretion to
RL glaucoma, pp.45:69-104, Academic Press, San Diego (1998).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-1236 (ISOFORM 5), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 693-764 (ISOFORM 4).
RC TISSUE=Myometrium;
RX PubMed=8821792;
RA Wallner M., Meera P., Ottolia M., Kaczorowski G.J., Latorre R.,
RA Garcia M.L., Stefani E., Toro L.;
RT "Characterization of and modulation by a beta-subunit of a human maxi KCa
RT channel cloned from myometrium.";
RL Recept. Channels 3:185-199(1995).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 66-1236 (ISOFORM 5).
RC TISSUE=Pulmonary artery;
RA Cairns V.R., Aebly M.R., Rusch N.J.;
RT "Cloning and characterization of BKCA alpha subunit from human pulmonary
RT artery.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP ALTERNATIVE SPLICING (ISOFORM 7), AND TISSUE SPECIFICITY.
RC TISSUE=Glioblastoma;
RX PubMed=11880513; DOI=10.1523/jneurosci.22-05-01840.2002;
RA Liu X., Chang Y., Reinhart P.H., Sontheimer H., Chang Y.;
RT "Cloning and characterization of glioma BK, a novel BK channel isoform
RT highly expressed in human glioma cells.";
RL J. Neurosci. 22:1840-1849(2002).
RN [14]
RP ERRATUM OF PUBMED:11880513.
RA Liu X., Chang Y., Reinhart P.H., Sontheimer H., Chang Y.;
RL J. Neurosci. 22:1B-1B(2002).
RN [15]
RP DOMAIN S0.
RX PubMed=8962157; DOI=10.1073/pnas.93.25.14922;
RA Wallner M., Meera P., Toro L.;
RT "Determinant for beta-subunit regulation in high-conductance voltage-
RT activated and Ca(2+)-sensitive K+ channels: an additional transmembrane
RT region at the N-terminus.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14922-14927(1996).
RN [16]
RP MEMBRANE TOPOLOGY.
RX PubMed=9391153; DOI=10.1073/pnas.94.25.14066;
RA Meera P., Wallner M., Song M., Toro L.;
RT "Large conductance voltage- and calcium-dependent K+ channel, a distinct
RT member of voltage-dependent ion channels with seven N-terminal
RT transmembrane segments (S0-S6), an extracellular N-terminus, and an
RT intracellular (S9-S10) C-terminus.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14066-14071(1997).
RN [17]
RP DOMAIN S4, AND MUTAGENESIS OF LEU-269; ARG-272; ARG-275; ARG-278; GLN-281
RP AND GLU-284.
RX PubMed=9829973; DOI=10.1074/jbc.273.49.32430;
RA Diaz L., Meera P., Amigo J., Stefani E., Alvarez O., Toro L., Latorre R.;
RT "Role of the S4 segment in a voltage-dependent calcium-sensitive potassium
RT (hSlo) channel.";
RL J. Biol. Chem. 273:32430-32436(1998).
RN [18]
RP INTERACTION WITH KCNMB2.
RX PubMed=10097176; DOI=10.1073/pnas.96.7.4137;
RA Wallner M., Meera P., Toro L.;
RT "Molecular basis of fast inactivation in voltage and Ca2+-activated K+
RT channels: a transmembrane beta-subunit homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4137-4142(1999).
RN [19]
RP INTERACTION WITH KCNMB3 AND KCNMB4.
RX PubMed=10692449; DOI=10.1074/jbc.275.9.6453;
RA Brenner R., Jegla T.J., Wickenden A., Liu Y., Aldrich R.W.;
RT "Cloning and functional characterization of novel large conductance
RT calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.";
RL J. Biol. Chem. 275:6453-6461(2000).
RN [20]
RP HOMOTETRAMERIZATION, AND MUTAGENESIS OF 354-GLY--GLY-356.
RX PubMed=11604135; DOI=10.1016/s0896-6273(01)00444-5;
RA Quirk J.C., Reinhart P.H.;
RT "Identification of a novel tetramerization domain in large conductance
RT K(ca) channels.";
RL Neuron 32:13-23(2001).
RN [21]
RP INTERACTION WITH KCNMB1; KCNMB2; KCNMB3 AND KCNMB4.
RX PubMed=11880485; DOI=10.1523/jneurosci.22-05-01550.2002;
RA Wang Y.-W., Ding J.-P., Xia X.-M., Lingle C.J.;
RT "Consequences of the stoichiometry of Slo1 alpha and auxiliary beta
RT subunits on functional properties of large-conductance Ca2+-activated K+
RT channels.";
RL J. Neurosci. 22:1550-1561(2002).
RN [22]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF CYS-680 AND HIS-681.
RX PubMed=14523450; DOI=10.1038/nature02003;
RA Tang X.D., Xu R., Reynolds M.F., Garcia M.L., Heinemann S.H., Hoshi T.;
RT "Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK
RT channels.";
RL Nature 425:531-535(2003).
RN [23]
RP REVIEW.
RX PubMed=12566537; DOI=10.1085/jgp.20028721;
RA Magleby K.L.;
RT "Gating mechanism of BK (Slo1) channels: so near, yet so far.";
RL J. Gen. Physiol. 121:81-96(2003).
RN [24]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-118; CYS-119 AND CYS-121, AND
RP MUTAGENESIS OF CYS-118; CYS-119 AND CYS-121.
RX PubMed=20693285; DOI=10.1074/jbc.m110.153940;
RA Jeffries O., Geiger N., Rowe I.C., Tian L., McClafferty H., Chen L., Bi D.,
RA Knaus H.G., Ruth P., Shipston M.J.;
RT "Palmitoylation of the S0-S1 linker regulates cell surface expression of
RT voltage- and calcium-activated potassium (BK) channels.";
RL J. Biol. Chem. 285:33307-33314(2010).
RN [25]
RP SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-118; CYS-119 AND CYS-121,
RP DEPALMITOYLATION, AND MUTAGENESIS OF CYS-118; CYS-119 AND CYS-121.
RX PubMed=22399288; DOI=10.1074/jbc.m111.335547;
RA Tian L., McClafferty H., Knaus H.G., Ruth P., Shipston M.J.;
RT "Distinct acyl protein transferases and thioesterases control surface
RT expression of calcium-activated potassium channels.";
RL J. Biol. Chem. 287:14718-14725(2012).
RN [26]
RP INTERACTION WITH LRRC26.
RX PubMed=20613726; DOI=10.1038/nature09162;
RA Yan J., Aldrich R.W.;
RT "LRRC26 auxiliary protein allows BK channel activation at resting voltage
RT without calcium.";
RL Nature 466:513-516(2010).
RN [27]
RP MUTAGENESIS OF THR-352; PHE-380; ALA-381 AND VAL-384.
RX PubMed=20430843; DOI=10.1124/jpet.110.166017;
RA Gordon E., Semus S.F., Lozinskaya I.M., Lin Z., Xu X.;
RT "Characterizing the role of Thr352 in the inhibition of the large
RT conductance Ca2+-activated K+ channels by 1-[1-Hexyl-6-(methyloxy)-1H-
RT indazol-3-yl]-2-methyl-1-propanone.";
RL J. Pharmacol. Exp. Ther. 334:402-409(2010).
RN [28]
RP INTERACTION WITH GAMMA SUBUNITS LRRC26; LRRC38; LRRC52 AND LRRC55.
RX PubMed=22547800; DOI=10.1073/pnas.1205435109;
RA Yan J., Aldrich R.W.;
RT "BK potassium channel modulation by leucine-rich repeat-containing
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7917-7922(2012).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 406-1179, CALCIUM-BINDING SITES,
RP AND SUBUNIT.
RX PubMed=20508092; DOI=10.1126/science.1190414;
RA Yuan P., Leonetti M.D., Pico A.R., Hsiung Y., MacKinnon R.;
RT "Structure of the human BK channel Ca2+-activation apparatus at 3.0 A
RT resolution.";
RL Science 329:182-186(2010).
RN [30]
RP INVOLVEMENT IN PNKD3, AND VARIANT PNKD3 GLY-434.
RX PubMed=15937479; DOI=10.1038/ng1585;
RA Du W., Bautista J.F., Yang H., Diez-Sampedro A., You S.-A., Wang L.,
RA Kotagal P., Lueders H.O., Shi J., Cui J., Richerson G.B., Wang Q.K.;
RT "Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal
RT movement disorder.";
RL Nat. Genet. 37:733-738(2005).
RN [31]
RP INVOLVEMENT IN PNKD3, AND VARIANTS PNKD3 LYS-884 AND SER-1053.
RX PubMed=26195193; DOI=10.1002/mds.26216;
RA Zhang Z.B., Tian M.Q., Gao K., Jiang Y.W., Wu Y.;
RT "De novo KCNMA1 mutations in children with early-onset paroxysmal
RT dyskinesia and developmental delay.";
RL Mov. Disord. 30:1290-1292(2015).
RN [32]
RP INVOLVEMENT IN CADEDS.
RX PubMed=27567911; DOI=10.1007/s00439-016-1726-y;
RA Tabarki B., AlMajhad N., AlHashem A., Shaheen R., Alkuraya F.S.;
RT "Homozygous KCNMA1 mutation as a cause of cerebellar atrophy, developmental
RT delay and seizures.";
RL Hum. Genet. 135:1295-1298(2016).
RN [33]
RP FUNCTION, INVOLVEMENT IN EIG16, VARIANT EIG16 SER-1053, CHARACTERIZATION OF
RP VARIANT EIG16 SER-1053, VARIANTS ASN-518; ALA-656 AND SER-1217, AND
RP CHARACTERIZATION OF VARIANTS ASN-518; ALA-656 AND SER-1217.
RX PubMed=29330545; DOI=10.1038/s41431-017-0073-3;
RA Li X., Poschmann S., Chen Q., Fazeli W., Oundjian N.J.,
RA Snoeijen-Schouwenaars F.M., Fricke O., Kamsteeg E.J., Willemsen M.,
RA Wang Q.K.;
RT "De novo BK channel variant causes epilepsy by affecting voltage gating but
RT not Ca2+ sensitivity.";
RL Eur. J. Hum. Genet. 26:220-229(2018).
RN [34]
RP INVOLVEMENT IN LIWAS, VARIANT LIWAS ARG-375, CHARACTERIZATION OF VARIANT
RP LIWAS ARG-375, AND FUNCTION.
RX PubMed=31152168; DOI=10.1093/hmg/ddz117;
RA Liang L., Li X., Moutton S., Schrier Vergano S.A., Cogne B.,
RA Saint-Martin A., Hurst A.C.E., Hu Y., Bodamer O., Thevenon J., Hung C.Y.,
RA Isidor B., Gerard B., Rega A., Nambot S., Lehalle D., Duffourd Y.,
RA Thauvin-Robinet C., Faivre L., Bezieau S., Dure L.S., Helbling D.C.,
RA Bick D., Xu C., Chen Q., Mancini G.M.S., Vitobello A., Wang Q.K.;
RT "De novo loss-of-function KCNMA1 variants are associated with a new
RT multiple malformation syndrome and a broad spectrum of developmental and
RT neurological phenotypes.";
RL Hum. Mol. Genet. 28:2937-2951(2019).
RN [35]
RP VARIANT CADEDS 458-ARG--LEU-1236 DEL.
RX PubMed=29545233; DOI=10.4274/balkanmedj.2017.0986;
RA Yesil G., Aralasmak A., Akyuez E., Icagasioglu D., Uygur Sahin T.,
RA Bayram Y.;
RT "Expanding the phenotype of homozygous KCNMA1 mutations; dyskinesia,
RT epilepsy, intellectual disability, cerebellar and corticospinal tract
RT atrophy.";
RL Balkan Med. J. 35:336-339(2018).
CC -!- FUNCTION: Potassium channel activated by both membrane depolarization
CC or increase in cytosolic Ca(2+) that mediates export of K(+)
CC (PubMed:29330545, PubMed:31152168). It is also activated by the
CC concentration of cytosolic Mg(2+). Its activation dampens the
CC excitatory events that elevate the cytosolic Ca(2+) concentration
CC and/or depolarize the cell membrane. It therefore contributes to
CC repolarization of the membrane potential. Plays a key role in
CC controlling excitability in a number of systems, such as regulation of
CC the contraction of smooth muscle, the tuning of hair cells in the
CC cochlea, regulation of transmitter release, and innate immunity. In
CC smooth muscles, its activation by high level of Ca(2+), caused by
CC ryanodine receptors in the sarcoplasmic reticulum, regulates the
CC membrane potential. In cochlea cells, its number and kinetic properties
CC partly determine the characteristic frequency of each hair cell and
CC thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels
CC are determined by alternative splicing, phosphorylation status and its
CC combination with modulating beta subunits. Highly sensitive to both
CC iberiotoxin (IbTx) and charybdotoxin (CTX).
CC {ECO:0000269|PubMed:29330545, ECO:0000269|PubMed:31152168}.
CC -!- ACTIVITY REGULATION: Ethanol and carbon monoxide-bound heme increase
CC channel activation. Heme inhibits channel activation.
CC {ECO:0000269|PubMed:14523450}.
CC -!- SUBUNIT: Homotetramer; which constitutes the calcium-activated
CC potassium channel. Interacts with RAB11B (By similarity). Interacts
CC with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Interacts with
CC gamma subunits LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma
CC subunits are accessory, and modulate its activity. {ECO:0000250,
CC ECO:0000269|PubMed:10097176, ECO:0000269|PubMed:10692449,
CC ECO:0000269|PubMed:11880485, ECO:0000269|PubMed:20508092,
CC ECO:0000269|PubMed:20613726, ECO:0000269|PubMed:22547800}.
CC -!- INTERACTION:
CC Q12791; Q2I0M4: LRRC26; NbExp=3; IntAct=EBI-1220676, EBI-15863320;
CC Q12791; Q6NXK8-1: Asic1; Xeno; NbExp=2; IntAct=EBI-1220676, EBI-15686410;
CC Q12791-5; Q12791-5: KCNMA1; NbExp=2; IntAct=EBI-15861807, EBI-15861807;
CC Q12791-5; Q2I0M4: LRRC26; NbExp=2; IntAct=EBI-15861807, EBI-15863320;
CC Q12791-5; P21731-3: TBXA2R; NbExp=7; IntAct=EBI-15861807, EBI-15885629;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20693285,
CC ECO:0000269|PubMed:22399288}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:20693285, ECO:0000269|PubMed:22399288}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=May be partially controlled by hormonal stress. Additional
CC isoforms seem to exist.;
CC Name=1; Synonyms=SAKCA;
CC IsoId=Q12791-1; Sequence=Displayed;
CC Name=2; Synonyms=BKTM;
CC IsoId=Q12791-2; Sequence=VSP_009955, VSP_009958;
CC Name=3;
CC IsoId=Q12791-3; Sequence=VSP_009954;
CC Name=4; Synonyms=hbr5;
CC IsoId=Q12791-4; Sequence=VSP_009956;
CC Name=5;
CC IsoId=Q12791-5; Sequence=VSP_009955;
CC Name=6;
CC IsoId=Q12791-6; Sequence=VSP_009952, VSP_009953;
CC Name=7; Synonyms=gBK;
CC IsoId=Q12791-7; Sequence=VSP_009957;
CC -!- TISSUE SPECIFICITY: Widely expressed. Except in myocytes, it is almost
CC ubiquitously expressed. {ECO:0000269|PubMed:11880513}.
CC -!- DOMAIN: The S0 segment is essential for the modulation by the accessory
CC beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4.
CC -!- DOMAIN: The S4 segment, which is characterized by a series of
CC positively charged amino acids at every third position, is part of the
CC voltage-sensor.
CC -!- DOMAIN: The pore-forming domain (also referred as P region) is imbedded
CC into the membrane, and forms the selectivity filter of the pore. It
CC contains the signature sequence of potassium channels that displays
CC selectivity to potassium.
CC -!- DOMAIN: The RCK N-terminal domain mediates the homotetramerization,
CC thereby promoting the assembly of monomers into functional potassium
CC channel. It includes binding sites for Ca(2+) and Mg(2+) (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The calcium bowl constitutes one of the Ca(2+) sensors and
CC probably acts as a Ca(2+)-binding site. There are however other Ca(2+)
CC sensors region required for activation of the channel.
CC {ECO:0000250|UniProtKB:B7ZC96}.
CC -!- DOMAIN: The heme-binding motif mediates inhibition of channel
CC activation by heme. Carbon monoxide-bound heme leads to increased
CC channel activation.
CC -!- PTM: Phosphorylated (Probable). Phosphorylation by kinases such as PKA
CC and/or PKG. In smooth muscles, phosphorylation affects its activity.
CC {ECO:0000305}.
CC -!- PTM: Palmitoylation by ZDHHC22 and ZDHHC23 within the intracellular
CC linker between the S0 and S1 transmembrane domains regulates
CC localization to the plasma membrane. Depalmitoylated by LYPLA1 and
CC LYPLAL1, leading to retard exit from the trans-Golgi network.
CC {ECO:0000269|PubMed:20693285, ECO:0000269|PubMed:22399288}.
CC -!- DISEASE: Paroxysmal nonkinesigenic dyskinesia, 3, with or without
CC generalized epilepsy (PNKD3) [MIM:609446]: An autosomal dominant
CC neurologic disorder characterized by absence seizures, generalized
CC tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia and
CC involuntary dystonic or choreiform movements. Onset is usually in
CC childhood. Patients may have seizures only, dyskinesia only, or both.
CC {ECO:0000269|PubMed:15937479, ECO:0000269|PubMed:26195193}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Epilepsy, idiopathic generalized 16 (EIG16) [MIM:618596]: An
CC autosomal dominant form of idiopathic generalized epilepsy, a disorder
CC characterized by recurring generalized seizures in the absence of
CC detectable brain lesions and/or metabolic abnormalities. Generalized
CC seizures arise diffusely and simultaneously from both hemispheres of
CC the brain. Seizure types include juvenile myoclonic seizures, absence
CC seizures, and generalized tonic-clonic seizures. EIG16 is characterized
CC by onset of seizures soon after birth or in the first years of life.
CC {ECO:0000269|PubMed:29330545}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Cerebellar atrophy, developmental delay, and seizures (CADEDS)
CC [MIM:617643]: An autosomal recessive disease characterized by epilepsy,
CC developmental delay and severe cerebellar atrophy.
CC {ECO:0000269|PubMed:27567911, ECO:0000269|PubMed:29545233}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Liang-Wang syndrome (LIWAS) [MIM:618729]: An autosomal
CC dominant syndrome characterized by a highly variable phenotype and
CC severity. The broad spectrum of clinical features includes
CC developmental delay, intellectual disability, ataxia, axial hypotonia,
CC and poor or absent speech, visceral and cardiac malformations,
CC connective tissue presentations with arterial involvement, bone
CC dysplasia and characteristic craniofacial dysmorphism. About half of
CC patients have cerebral and cerebellar atrophy, and thin corpus
CC callosum. {ECO:0000269|PubMed:31152168}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The protein was initially thought to contain two
CC functionally distinct parts: The core channel (from the N-terminus to
CC the S9 segment) that mediates the channel activity, and the cytoplasmic
CC tail (from the S9 segment to the C-terminus) that mediates the calcium
CC sensing. The situation is however more complex, since the core channel
CC also contains binding sites for Ca(2+) and Mg(2+).
CC -!- SIMILARITY: Belongs to the potassium channel family. Calcium-activated
CC (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA50216.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=AAB65837.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC50353.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK91504.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD06365.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; U13913; AAA85104.1; -; mRNA.
DR EMBL; U23767; AAA92290.1; -; mRNA.
DR EMBL; AC011439; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC021032; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627447; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC067745; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL607069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54599.1; -; Genomic_DNA.
DR EMBL; BC062659; AAH62659.1; -; mRNA.
DR EMBL; BC137115; AAI37116.1; -; mRNA.
DR EMBL; BC137137; AAI37138.1; -; mRNA.
DR EMBL; U11717; AAC50353.1; ALT_INIT; mRNA.
DR EMBL; AY040849; AAK91504.1; ALT_INIT; mRNA.
DR EMBL; AB113575; BAD06397.1; -; mRNA.
DR EMBL; AB113382; BAD06365.1; ALT_INIT; mRNA.
DR EMBL; U02632; AAA50173.1; -; mRNA.
DR EMBL; U09384; AAA50216.1; ALT_SEQ; mRNA.
DR EMBL; AF025999; AAB88802.1; -; mRNA.
DR EMBL; U11058; AAB65837.1; ALT_INIT; mRNA.
DR EMBL; AF118141; AAD31173.1; -; mRNA.
DR CCDS; CCDS53545.1; -. [Q12791-2]
DR CCDS; CCDS60569.1; -. [Q12791-1]
DR CCDS; CCDS60571.1; -. [Q12791-6]
DR CCDS; CCDS7352.1; -. [Q12791-5]
DR PIR; I38596; I38596.
DR PIR; S62904; S62904.
DR RefSeq; NP_001014797.1; NM_001014797.2.
DR RefSeq; NP_001154824.1; NM_001161352.1. [Q12791-1]
DR RefSeq; NP_001154825.1; NM_001161353.1. [Q12791-2]
DR RefSeq; NP_001258447.1; NM_001271518.1.
DR RefSeq; NP_001258451.1; NM_001271522.1. [Q12791-6]
DR RefSeq; NP_002238.2; NM_002247.3. [Q12791-5]
DR PDB; 2K44; NMR; -; A=257-284.
DR PDB; 3MT5; X-ray; 3.00 A; A=406-1179.
DR PDB; 3NAF; X-ray; 3.10 A; A=395-681, A=782-1182.
DR PDB; 6ND0; EM; 3.50 A; A/B/C/D=292-1175.
DR PDB; 6V22; EM; 3.20 A; A/B/C/D=66-1179.
DR PDB; 6V35; EM; 3.50 A; A/B/C/D=66-1179.
DR PDB; 6V38; EM; 3.80 A; A/B/C/D=66-1179.
DR PDB; 6V3G; EM; 4.00 A; A/B/C/D=66-1179.
DR PDB; 6V5A; X-ray; 2.00 A; A=406-1179.
DR PDB; 8GH9; EM; 3.80 A; A/B/C/D=67-1179.
DR PDB; 8GHF; EM; 2.70 A; A/B/C/D=67-1179.
DR PDB; 8GHG; EM; 3.30 A; A/B/C/D=67-1179.
DR PDBsum; 2K44; -.
DR PDBsum; 3MT5; -.
DR PDBsum; 3NAF; -.
DR PDBsum; 6ND0; -.
DR PDBsum; 6V22; -.
DR PDBsum; 6V35; -.
DR PDBsum; 6V38; -.
DR PDBsum; 6V3G; -.
DR PDBsum; 6V5A; -.
DR PDBsum; 8GH9; -.
DR PDBsum; 8GHF; -.
DR PDBsum; 8GHG; -.
DR AlphaFoldDB; Q12791; -.
DR BMRB; Q12791; -.
DR EMDB; EMD-0439; -.
DR EMDB; EMD-21025; -.
DR EMDB; EMD-21028; -.
DR EMDB; EMD-21029; -.
DR EMDB; EMD-21036; -.
DR EMDB; EMD-40038; -.
DR EMDB; EMD-40044; -.
DR EMDB; EMD-40045; -.
DR SMR; Q12791; -.
DR BioGRID; 109979; 19.
DR CORUM; Q12791; -.
DR DIP; DIP-29729N; -.
DR IntAct; Q12791; 6.
DR MINT; Q12791; -.
DR STRING; 9606.ENSP00000286628; -.
DR BindingDB; Q12791; -.
DR ChEMBL; CHEMBL4304; -.
DR DrugBank; DB00436; Bendroflumethiazide.
DR DrugBank; DB00356; Chlorzoxazone.
DR DrugBank; DB02587; Colforsin.
DR DrugBank; DB04209; Dequalinium.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB00999; Hydrochlorothiazide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB00867; Ritodrine.
DR DrugBank; DB09089; Trimebutine.
DR DrugCentral; Q12791; -.
DR GuidetoPHARMACOLOGY; 380; -.
DR TCDB; 1.A.1.3.10; the voltage-gated ion channel (vic) superfamily.
DR GlyConnect; 1058; 1 N-Linked glycan (1 site).
DR GlyCosmos; Q12791; 1 site, 1 glycan.
DR GlyGen; Q12791; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; Q12791; -.
DR MetOSite; Q12791; -.
DR PhosphoSitePlus; Q12791; -.
DR SwissPalm; Q12791; -.
DR BioMuta; KCNMA1; -.
DR DMDM; 46396283; -.
DR EPD; Q12791; -.
DR jPOST; Q12791; -.
DR MassIVE; Q12791; -.
DR MaxQB; Q12791; -.
DR PaxDb; 9606-ENSP00000286628; -.
DR PeptideAtlas; Q12791; -.
DR ProteomicsDB; 30456; -.
DR ProteomicsDB; 58926; -. [Q12791-1]
DR ProteomicsDB; 58927; -. [Q12791-2]
DR ProteomicsDB; 58928; -. [Q12791-3]
DR ProteomicsDB; 58929; -. [Q12791-4]
DR ProteomicsDB; 58930; -. [Q12791-5]
DR ProteomicsDB; 58931; -. [Q12791-6]
DR ProteomicsDB; 58932; -. [Q12791-7]
DR ABCD; Q12791; 1 sequenced antibody.
DR Antibodypedia; 29733; 381 antibodies from 37 providers.
DR DNASU; 3778; -.
DR Ensembl; ENST00000286627.10; ENSP00000286627.5; ENSG00000156113.25. [Q12791-5]
DR Ensembl; ENST00000286628.14; ENSP00000286628.8; ENSG00000156113.25. [Q12791-1]
DR Ensembl; ENST00000434208.6; ENSP00000402150.2; ENSG00000156113.25. [Q12791-4]
DR Ensembl; ENST00000480683.2; ENSP00000474686.1; ENSG00000156113.25. [Q12791-6]
DR Ensembl; ENST00000626620.3; ENSP00000485867.1; ENSG00000156113.25. [Q12791-2]
DR Ensembl; ENST00000638575.1; ENSP00000492049.1; ENSG00000156113.25. [Q12791-7]
DR Ensembl; ENST00000638759.1; ENSP00000492632.1; ENSG00000156113.25. [Q12791-3]
DR Ensembl; ENST00000640969.1; ENSP00000492200.1; ENSG00000156113.25. [Q12791-4]
DR GeneID; 3778; -.
DR KEGG; hsa:3778; -.
DR MANE-Select; ENST00000286628.14; ENSP00000286628.8; NM_001161352.2; NP_001154824.1.
DR UCSC; uc001jxm.4; human. [Q12791-1]
DR AGR; HGNC:6284; -.
DR CTD; 3778; -.
DR DisGeNET; 3778; -.
DR GeneCards; KCNMA1; -.
DR HGNC; HGNC:6284; KCNMA1.
DR HPA; ENSG00000156113; Tissue enhanced (endometrium).
DR MalaCards; KCNMA1; -.
DR MIM; 600150; gene.
DR MIM; 609446; phenotype.
DR MIM; 617643; phenotype.
DR MIM; 618596; phenotype.
DR MIM; 618729; phenotype.
DR neXtProt; NX_Q12791; -.
DR OpenTargets; ENSG00000156113; -.
DR Orphanet; 79137; Generalized epilepsy-paroxysmal dyskinesia syndrome.
DR Orphanet; 3473; Zimmermann-Laband syndrome.
DR PharmGKB; PA220; -.
DR VEuPathDB; HostDB:ENSG00000156113; -.
DR eggNOG; KOG1420; Eukaryota.
DR GeneTree; ENSGT00940000154935; -.
DR InParanoid; Q12791; -.
DR OMA; YWCKQCH; -.
DR OrthoDB; 2902976at2759; -.
DR PhylomeDB; Q12791; -.
DR TreeFam; TF314283; -.
DR PathwayCommons; Q12791; -.
DR Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR Reactome; R-HSA-418457; cGMP effects.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-9667769; Acetylcholine inhibits contraction of outer hair cells.
DR SignaLink; Q12791; -.
DR SIGNOR; Q12791; -.
DR BioGRID-ORCS; 3778; 16 hits in 1158 CRISPR screens.
DR ChiTaRS; KCNMA1; human.
DR EvolutionaryTrace; Q12791; -.
DR GenomeRNAi; 3778; -.
DR Pharos; Q12791; Tclin.
DR PRO; PR:Q12791; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q12791; Protein.
DR Bgee; ENSG00000156113; Expressed in parotid gland and 194 other cell types or tissues.
DR ExpressionAtlas; Q12791; baseline and differential.
DR Genevisible; Q12791; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:BHF-UCL.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0060072; F:large conductance calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0030007; P:intracellular potassium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0060073; P:micturition; IDA:UniProtKB.
DR GO; GO:0045794; P:negative regulation of cell volume; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR GO; GO:0034465; P:response to carbon monoxide; IDA:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0060083; P:smooth muscle contraction involved in micturition; IDA:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IBA:GO_Central.
DR Gene3D; 1.10.287.70; -; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003929; K_chnl_BK_asu.
DR InterPro; IPR047871; K_chnl_Slo-like.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR048735; Slowpoke-like_C.
DR PANTHER; PTHR10027; CALCIUM-ACTIVATED POTASSIUM CHANNEL ALPHA CHAIN; 1.
DR PANTHER; PTHR10027:SF28; CALCIUM-ACTIVATED POTASSIUM CHANNEL SUBUNIT ALPHA-1; 1.
DR Pfam; PF03493; BK_channel_a; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF21014; Slowpoke_C; 1.
DR PRINTS; PR01449; BKCHANNELA.
DR PRINTS; PR00169; KCHANNEL.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Disease variant; Epilepsy; Ion channel; Ion transport; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Palmitate; Phosphoprotein; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1236
FT /note="Calcium-activated potassium channel subunit alpha-1"
FT /id="PRO_0000054132"
FT TOPO_DOM 1..86
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical; Name=Segment S0"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 322..335
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 336..358
FT /note="Pore-forming; Name=P region"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..367
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 368..388
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..1236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 415..558
FT /note="RCK N-terminal"
FT REGION 1..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..576
FT /note="Segment S7"
FT REGION 613..633
FT /note="Segment S8"
FT REGION 677..681
FT /note="Heme-binding motif"
FT REGION 757..787
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 837..857
FT /note="Segment S9"
FT REGION 1032..1052
FT /note="Segment S10"
FT REGION 1186..1236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 352..355
FT /note="Selectivity for potassium"
FT MOTIF 1003..1025
FT /note="Calcium bowl"
FT COMPBIAS 21..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 766..784
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1186..1217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1218..1236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 439
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305"
FT BINDING 462
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305"
FT BINDING 464
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305"
FT BINDING 1012
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT BINDING 1015
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT BINDING 1018
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT BINDING 1020
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT MOD_RES 763
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 765
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 778
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 970
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 982
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 1221
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT MOD_RES 1224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT LIPID 118
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:20693285,
FT ECO:0000269|PubMed:22399288"
FT LIPID 119
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:20693285,
FT ECO:0000269|PubMed:22399288"
FT LIPID 121
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:20693285,
FT ECO:0000269|PubMed:22399288"
FT VAR_SEQ 127..168
FT /note="EAQKINNGSSQADGTLKPVDEKEEAVAAEVGWMTSVKDWAGV -> ATHFGS
FT PEMPPAARSWSGSPPEAAVLRGASSLALEVARCRRL (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009952"
FT VAR_SEQ 169..1236
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009953"
FT VAR_SEQ 643
FT /note="R -> RSRKR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7987297"
FT /id="VSP_009954"
FT VAR_SEQ 698..756
FT /note="PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERAFPLSSVSVNDC
FT STSFRAF -> L (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:12434576,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7573516,
FT ECO:0000303|PubMed:7877450, ECO:0000303|PubMed:7993625,
FT ECO:0000303|PubMed:8821792, ECO:0000303|Ref.10,
FT ECO:0000303|Ref.12, ECO:0000303|Ref.8"
FT /id="VSP_009955"
FT VAR_SEQ 698..756
FT /note="PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERAFPLSSVSVNDC
FT STSFRAF -> LKVAARSRYSKDPFEFKKETPNSRLVTEPV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7987297,
FT ECO:0000303|PubMed:8821792"
FT /id="VSP_009956"
FT VAR_SEQ 698..756
FT /note="PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERAFPLSSVSVNDC
FT STSFRAF -> RWEEHCSLWRLESKGNVRRLNYCRGQQTFSVKVKVAARSRYSKDPFEF
FT KKETPNSRLVTEPV (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_009957"
FT VAR_SEQ 828
FT /note="L -> LVTGWMPYLGPRVLMTCLDIGVVCMPTDIQSTSPASIKKFKE (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.8"
FT /id="VSP_009958"
FT VARIANT 375
FT /note="G -> R (in LIWAS; loss of voltage-gated potassium
FT channel activity; dbSNP:rs1554829003)"
FT /evidence="ECO:0000269|PubMed:31152168"
FT /id="VAR_083554"
FT VARIANT 434
FT /note="D -> G (in PNKD3; may have a synergistic effect with
FT ethanol in the triggering of symptoms; dbSNP:rs137853333)"
FT /evidence="ECO:0000269|PubMed:15937479"
FT /id="VAR_023821"
FT VARIANT 458..1236
FT /note="Missing (in CADEDS)"
FT /evidence="ECO:0000269|PubMed:29545233"
FT /id="VAR_083555"
FT VARIANT 518
FT /note="K -> N (found in a patient with epileptic
FT encephalopathy; uncertain significance; no effect on
FT voltage-dependent sensitivity; dbSNP:rs201996416)"
FT /evidence="ECO:0000269|PubMed:29330545"
FT /id="VAR_083204"
FT VARIANT 656
FT /note="E -> A (found in a patient with epilepsy; uncertain
FT significance; no effect on voltage-dependent sensitivity;
FT dbSNP:rs917980352)"
FT /evidence="ECO:0000269|PubMed:29330545"
FT /id="VAR_083205"
FT VARIANT 884
FT /note="E -> K (in PNKD3)"
FT /evidence="ECO:0000269|PubMed:26195193"
FT /id="VAR_079156"
FT VARIANT 1053
FT /note="N -> S (in PNKD3 and EIG16; increased sensitivity to
FT voltage-dependent activation resulting in increased channel
FT activity; no change in calcium sensitivity;
FT dbSNP:rs886039469)"
FT /evidence="ECO:0000269|PubMed:26195193,
FT ECO:0000269|PubMed:29330545"
FT /id="VAR_079157"
FT VARIANT 1217
FT /note="N -> S (found in patient with epilepsy; uncertain
FT significance; dbSNP:rs563967757)"
FT /evidence="ECO:0000269|PubMed:29330545"
FT /id="VAR_083206"
FT MUTAGEN 118
FT /note="C->A: Decreased localization to the plasma membrane.
FT Abolishes localization to the plasma membrane; when
FT associated with A-119 and A-121."
FT /evidence="ECO:0000269|PubMed:20693285,
FT ECO:0000269|PubMed:22399288"
FT MUTAGEN 119
FT /note="C->A: Decreased localization to the plasma membrane.
FT Abolishes localization to the plasma membrane; when
FT associated with A-118 and A-121."
FT /evidence="ECO:0000269|PubMed:20693285,
FT ECO:0000269|PubMed:22399288"
FT MUTAGEN 121
FT /note="C->A: Decreased localization to the plasma membrane.
FT Abolishes localization to the plasma membrane; when
FT associated with A-119 and A-121."
FT /evidence="ECO:0000269|PubMed:20693285,
FT ECO:0000269|PubMed:22399288"
FT MUTAGEN 269
FT /note="L->R,H: No effect in the coupling between calcium
FT and channel opening."
FT /evidence="ECO:0000269|PubMed:9829973"
FT MUTAGEN 272
FT /note="R->E: Induces reduction in the coupling between
FT calcium and channel opening."
FT /evidence="ECO:0000269|PubMed:9829973"
FT MUTAGEN 275
FT /note="R->N: Induces reduction in the coupling between
FT calcium and channel opening."
FT /evidence="ECO:0000269|PubMed:9829973"
FT MUTAGEN 278
FT /note="R->Q: Induces reduction in the coupling between
FT calcium and channel opening."
FT /evidence="ECO:0000269|PubMed:9829973"
FT MUTAGEN 281
FT /note="Q->R: No effect in the coupling between calcium and
FT channel opening."
FT /evidence="ECO:0000269|PubMed:9829973"
FT MUTAGEN 284
FT /note="E->K: No effect in the coupling between calcium and
FT channel opening."
FT /evidence="ECO:0000269|PubMed:9829973"
FT MUTAGEN 352
FT /note="T->S: Activated at more negative voltages. Slower
FT rate of inactivation. Impaired inhibition by HMIMP. No
FT effect on channel inhibition by Iberiotoxin."
FT /evidence="ECO:0000269|PubMed:20430843"
FT MUTAGEN 354..356
FT /note="GYG->AAA: Loss of function."
FT /evidence="ECO:0000269|PubMed:11604135"
FT MUTAGEN 380
FT /note="F->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:20430843"
FT MUTAGEN 381
FT /note="A->S: Activated at more negative voltages. No effect
FT on inhibition by HMIMP."
FT /evidence="ECO:0000269|PubMed:20430843"
FT MUTAGEN 384
FT /note="V->I: No effect on activation voltage. No effect on
FT inhibition by HMIMP."
FT /evidence="ECO:0000269|PubMed:20430843"
FT MUTAGEN 680
FT /note="C->S: Loss of heme-induced channel inhibition."
FT /evidence="ECO:0000269|PubMed:14523450"
FT MUTAGEN 681
FT /note="H->R: Loss of heme-induced channel inhibition."
FT /evidence="ECO:0000269|PubMed:14523450"
FT CONFLICT 25
FT /note="M -> N (in Ref. 9; AAA50216)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="S -> G (in Ref. 9; AAA50216)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="A -> V (in Ref. 1; AAA85104)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="N -> D (in Ref. 12; AAD31173)"
FT /evidence="ECO:0000305"
FT CONFLICT 805
FT /note="N -> H (in Ref. 6; AAC50353)"
FT /evidence="ECO:0000305"
FT CONFLICT 1152
FT /note="T -> A (in Ref. 12; AAD31173)"
FT /evidence="ECO:0000305"
FT HELIX 87..111
FT /evidence="ECO:0007829|PDB:6V22"
FT TURN 112..118
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 159..170
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 175..198
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:6V22"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 213..235
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 239..243
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 246..264
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 272..281
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 282..287
FT /evidence="ECO:0007829|PDB:6V22"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 295..323
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 339..350
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:6V22"
FT HELIX 363..390
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:6ND0"
FT STRAND 409..415
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 418..431
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 439..446
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 453..459
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 463..468
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:3NAF"
FT HELIX 473..478
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 485..490
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 498..515
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 521..527
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 532..536
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:6V35"
FT HELIX 542..544
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 547..550
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 551..564
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 568..574
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:3MT5"
FT HELIX 589..597
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 600..605
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 608..610
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 615..626
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 629..634
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 638..640
FT /evidence="ECO:0007829|PDB:3NAF"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 650..653
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 659..665
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 667..670
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 672..675
FT /evidence="ECO:0007829|PDB:6V5A"
FT TURN 678..681
FT /evidence="ECO:0007829|PDB:6ND0"
FT HELIX 685..689
FT /evidence="ECO:0007829|PDB:3NAF"
FT HELIX 803..805
FT /evidence="ECO:0007829|PDB:3MT5"
FT STRAND 813..816
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 823..825
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 830..835
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 842..847
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 850..852
FT /evidence="ECO:0007829|PDB:3NAF"
FT HELIX 858..861
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 863..865
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 867..869
FT /evidence="ECO:0007829|PDB:3NAF"
FT HELIX 871..873
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 877..881
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 883..889
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 890..892
FT /evidence="ECO:0007829|PDB:6V5A"
FT TURN 893..895
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 896..904
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 909..914
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 917..919
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 921..927
FT /evidence="ECO:0007829|PDB:6V5A"
FT TURN 930..932
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 936..938
FT /evidence="ECO:0007829|PDB:3NAF"
FT HELIX 941..952
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 994..996
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 1001..1007
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1008..1013
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 1016..1018
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1026..1028
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1030..1033
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 1036..1039
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1040..1044
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1045..1052
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1055..1065
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1074..1079
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1089..1093
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1094..1096
FT /evidence="ECO:0007829|PDB:6V22"
FT STRAND 1099..1104
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 1106..1108
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1111..1114
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1119..1130
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 1133..1140
FT /evidence="ECO:0007829|PDB:6V5A"
FT HELIX 1141..1143
FT /evidence="ECO:0007829|PDB:6V35"
FT STRAND 1144..1146
FT /evidence="ECO:0007829|PDB:3NAF"
FT STRAND 1154..1159
FT /evidence="ECO:0007829|PDB:6V5A"
FT STRAND 1171..1176
FT /evidence="ECO:0007829|PDB:6V5A"
FT CONFLICT Q12791-7:726..727
FT /note="FS -> SF (in Ref. 13; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1236 AA; 137560 MW; DF9BFEAF374BE553 CRC64;
MANGGGGGGG SSGGGGGGGG SSLRMSSNIH ANHLSLDASS SSSSSSSSSS SSSSSSSSSS
VHEPKMDALI IPVTMEVPCD SRGQRMWWAF LASSMVTFFG GLFIILLWRT LKYLWTVCCH
CGGKTKEAQK INNGSSQADG TLKPVDEKEE AVAAEVGWMT SVKDWAGVMI SAQTLTGRVL
VVLVFALSIG ALVIYFIDSS NPIESCQNFY KDFTLQIDMA FNVFFLLYFG LRFIAANDKL
WFWLEVNSVV DFFTVPPVFV SVYLNRSWLG LRFLRALRLI QFSEILQFLN ILKTSNSIKL
VNLLSIFIST WLTAAGFIHL VENSGDPWEN FQNNQALTYW ECVYLLMVTM STVGYGDVYA
KTTLGRLFMV FFILGGLAMF ASYVPEIIEL IGNRKKYGGS YSAVSGRKHI VVCGHITLES
VSNFLKDFLH KDRDDVNVEI VFLHNISPNL ELEALFKRHF TQVEFYQGSV LNPHDLARVK
IESADACLIL ANKYCADPDA EDASNIMRVI SIKNYHPKIR IITQMLQYHN KAHLLNIPSW
NWKEGDDAIC LAELKLGFIA QSCLAQGLST MLANLFSMRS FIKIEEDTWQ KYYLEGVSNE
MYTEYLSSAF VGLSFPTVCE LCFVKLKLLM IAIEYKSANR ESRILINPGN HLKIQEGTLG
FFIASDAKEV KRAFFYCKAC HDDITDPKRI KKCGCKRPKM SIYKRMRRAC CFDCGRSERD
CSCMSGRVRG NVDTLERAFP LSSVSVNDCS TSFRAFEDEQ PSTLSPKKKQ RNGGMRNSPN
TSPKLMRHDP LLIPGNDQID NMDSNVKKYD STGMFHWCAP KEIEKVILTR SEAAMTVLSG
HVVVCIFGDV SSALIGLRNL VMPLRASNFH YHELKHIVFV GSIEYLKREW ETLHNFPKVS
ILPGTPLSRA DLRAVNINLC DMCVILSANQ NNIDDTSLQD KECILASLNI KSMQFDDSIG
VLQANSQGFT PPGMDRSSPD NSPVHGMLRQ PSITTGVNIP IITELVNDTN VQFLDQDDDD
DPDTELYLTQ PFACGTAFAV SVLDSLMSAT YFNDNILTLI RTLVTGGATP ELEALIAEEN
ALRGGYSTPQ TLANRDRCRV AQLALLDGPF ADLGDGGCYG DLFCKALKTY NMLCFGIYRL
RDAHLSTPSQ CTKRYVITNP PYEFELVPTD LIFCLMQFDH NAGQSRASLS HSSHSSQSSS
KKSSSVHSIP STANRQNRPK SRESRDKQKY VQEERL
//
