ID   KCMA1_MOUSE             Reviewed;        1209 AA.
AC   Q08460; Q64703; Q8VHF1; Q9R196;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-APR-2004, sequence version 2.
DT   24-JAN-2024, entry version 212.
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            Short=mSlo1;
DE   AltName: Full=Slowpoke homolog;
DE            Short=Slo homolog;
DE            Short=mSlo;
GN   Name=Kcnma1; Synonyms=Kcnma;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 26-1209 (ISOFORMS 2 AND 5), AND FUNCTION.
RC   TISSUE=Brain;
RX   PubMed=7687074; DOI=10.1126/science.7687074;
RA   Butler A., Tsunoda S., McCobb D.P., Wei A., Salkoff L.;
RT   "mSlo, a complex mouse gene encoding 'maxi' calcium-activated potassium
RT   channels.";
RL   Science 261:221-224(1993).
RN   [3]
RP   MUTAGENESIS OF VAL-151.
RX   PubMed=16341213; DOI=10.1038/nn1602;
RA   Liu J., Asuncion-Chin M., Liu P., Dopico A.M.;
RT   "CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol
RT   responses of BK channels.";
RL   Nat. Neurosci. 9:41-49(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 66-1209 (ISOFORM 4).
RC   TISSUE=Pituitary anterior lobe;
RX   PubMed=10517674; DOI=10.1210/mend.13.10.0355;
RA   Shipston M.J., Duncan R.R., Clark A.G., Antoni F.A., Tian L.;
RT   "Molecular components of large conductance calcium-activated potassium (BK)
RT   channels in mouse pituitary corticotropes.";
RL   Mol. Endocrinol. 13:1728-1737(1999).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 66-1209 (ISOFORM 3).
RC   STRAIN=NIH Swiss; TISSUE=Parotid gland;
RX   PubMed=12388098; DOI=10.1152/ajpcell.00044.2002;
RA   Nehrke K., Quinn C.C., Begenisich T.;
RT   "Molecular identification of Ca2+-activated K+ channels in parotid acinar
RT   cells.";
RL   Am. J. Physiol. 284:C535-C546(2003).
RN   [6]
RP   INTERACTION WITH KCNMB3.
RX   PubMed=10804197; DOI=10.1523/jneurosci.20-10-03563.2000;
RA   Weiger T.M., Holmqvist M.H., Levitan I.B., Clark F.T., Sprague S.,
RA   Huang W.-J., Ge P., Wang C., Lawson D., Jurman M.E., Glucksmann M.A.,
RA   Silos-Santiago I., DiStefano P.S., Curtis R.;
RT   "A novel nervous system beta subunit that downregulates human large
RT   conductance calcium-dependent potassium channels.";
RL   J. Neurosci. 20:3563-3570(2000).
RN   [7]
RP   MUTAGENESIS OF ARG-272; ARG-278; GLU-284 AND GLN-287.
RX   PubMed=11112549; DOI=10.1021/bi001509+;
RA   Cui J., Aldrich R.W.;
RT   "Allosteric linkage between voltage and Ca(2+)-dependent activation of BK-
RT   type mslo1 K(+) channels.";
RL   Biochemistry 39:15612-15619(2000).
RN   [8]
RP   CALCIUM-BINDING, AND MUTAGENESIS OF 992-ASP--ASP-996.
RX   PubMed=12149279; DOI=10.1085/jgp.20028627;
RA   Bao L., Rapin A.M., Holmstrand E.C., Cox D.H.;
RT   "Elimination of the BK(Ca) channel's high-affinity Ca(2+) sensitivity.";
RL   J. Gen. Physiol. 120:173-189(2002).
RN   [9]
RP   MAGNESIUM-BINDING, AND MUTAGENESIS OF GLU-439; HIS-444; THR-461; GLN-462
RP   AND GLU-464.
RX   PubMed=12192410; DOI=10.1038/nature00941;
RA   Shi J., Krishnamoorthy G., Yang Y., Hu L., Chaturvedi N., Harilal D.,
RA   Qin J., Cui J.;
RT   "Mechanism of magnesium activation of calcium-activated potassium
RT   channels.";
RL   Nature 418:876-880(2002).
RN   [10]
RP   CALCIUM-BINDING, MAGNESIUM-BINDING, AND MUTAGENESIS OF ASP-427; ASP-432;
RP   ASP-434 AND GLU-464.
RX   PubMed=12192411; DOI=10.1038/nature00956;
RA   Xia X.-M., Zeng X., Lingle C.J.;
RT   "Multiple regulatory sites in large-conductance calcium-activated potassium
RT   channels.";
RL   Nature 418:880-884(2002).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-709; SER-711; SER-724;
RP   SER-728; THR-916; SER-924 AND SER-928, PHOSPHORYLATION [LARGE SCALE
RP   ANALYSIS] AT THR-670 AND SER-672 (ISOFORM 2), AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [12]
RP   INTERACTION WITH RAB11B.
RX   PubMed=22935415; DOI=10.1016/j.bbrc.2012.08.067;
RA   Sokolowski S., Harvey M., Sakai Y., Jordan A., Sokolowski B.;
RT   "The large conductance calcium-activated K(+) channel interacts with the
RT   small GTPase Rab11b.";
RL   Biochem. Biophys. Res. Commun. 426:221-225(2012).
CC   -!- FUNCTION: Potassium channel activated by both membrane depolarization
CC       or increase in cytosolic Ca(2+) that mediates export of K(+). It is
CC       also activated by the concentration of cytosolic Mg(2+). Its activation
CC       dampens the excitatory events that elevate the cytosolic Ca(2+)
CC       concentration and/or depolarize the cell membrane. It therefore
CC       contributes to repolarization of the membrane potential. Plays a key
CC       role in controlling excitability in a number of systems, such as
CC       regulation of the contraction of smooth muscle, the tuning of hair
CC       cells in the cochlea, regulation of transmitter release, and innate
CC       immunity. In smooth muscles, its activation by high level of Ca(2+),
CC       caused by ryanodine receptors in the sarcoplasmic reticulum, regulates
CC       the membrane potential. In cochlea cells, its number and kinetic
CC       properties partly determine the characteristic frequency of each hair
CC       cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1
CC       channels are determined by alternative splicing, phosphorylation status
CC       and its combination with modulating beta subunits. Highly sensitive to
CC       both iberiotoxin (IbTx) and charybdotoxin (CTX).
CC       {ECO:0000269|PubMed:7687074}.
CC   -!- ACTIVITY REGULATION: Ethanol and carbon monoxide-bound heme increase
CC       channel activation. Heme inhibits channel activation (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Homotetramer; which constitutes the calcium-activated
CC       potassium channel. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3
CC       and KCNMB4. Interacts with gamma subunits LRRC26, LRRC38, LRRC52 and
CC       LRRC55. Beta and gamma subunits are accessory, and modulate its
CC       activity (By similarity). Interacts with RAB11B. {ECO:0000250,
CC       ECO:0000269|PubMed:10804197, ECO:0000269|PubMed:22935415}.
CC   -!- INTERACTION:
CC       Q08460; P63260: Actg1; NbExp=4; IntAct=EBI-1633915, EBI-351301;
CC       Q08460; P48036: Anxa5; NbExp=4; IntAct=EBI-1633915, EBI-1184119;
CC       Q08460; Q00623: Apoa1; NbExp=4; IntAct=EBI-1633915, EBI-1634106;
CC       Q08460; P62204: Calm3; NbExp=4; IntAct=EBI-1633915, EBI-397460;
CC       Q08460; Q60598: Cttn; NbExp=2; IntAct=EBI-1633915, EBI-397955;
CC       Q08460; P16858: Gapdh; NbExp=3; IntAct=EBI-1633915, EBI-444871;
CC       Q08460; P84075: Hpca; NbExp=3; IntAct=EBI-1633915, EBI-2128343;
CC       Q08460; O88952: Lin7c; NbExp=4; IntAct=EBI-1633915, EBI-821316;
CC       Q08460; P27573: Mpz; NbExp=4; IntAct=EBI-1633915, EBI-1634589;
CC       Q08460; P61982: Ywhag; NbExp=4; IntAct=EBI-1633915, EBI-359843;
CC       Q08460; P08251: ATP1B1; Xeno; NbExp=5; IntAct=EBI-1633915, EBI-7206371;
CC       Q08460; P46109: CRKL; Xeno; NbExp=5; IntAct=EBI-1633915, EBI-910;
CC       Q08460; Q14247: CTTN; Xeno; NbExp=3; IntAct=EBI-1633915, EBI-351886;
CC       Q08460; O75791: GRAP2; Xeno; NbExp=3; IntAct=EBI-1633915, EBI-740418;
CC       Q08460-4; Q8CAE3: Kcnmb1; NbExp=2; IntAct=EBI-15575817, EBI-15575793;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC         Comment=May be partially controlled by hormonal stress. Additional
CC         isoforms seem to exist.;
CC       Name=1;
CC         IsoId=Q08460-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q08460-2; Sequence=VSP_009960, VSP_009961, VSP_009962,
CC                                  VSP_009964, VSP_009965;
CC       Name=3;
CC         IsoId=Q08460-3; Sequence=VSP_009961, VSP_009964;
CC       Name=4; Synonyms=STREX-1;
CC         IsoId=Q08460-4; Sequence=VSP_009961, VSP_009963, VSP_009964;
CC       Name=5;
CC         IsoId=Q08460-5; Sequence=VSP_009959;
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+).
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 regions 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 (By similarity). {ECO:0000250}.
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 (By
CC       similarity). {ECO:0000250}.
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       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=AAA50215.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U09383; AAA50215.1; ALT_INIT; mRNA.
DR   EMBL; L16912; AAA39746.1; -; mRNA.
DR   EMBL; AF156674; AAD49225.1; -; mRNA.
DR   EMBL; AF465244; AAL69971.1; -; mRNA.
DR   CCDS; CCDS79275.1; -. [Q08460-3]
DR   CCDS; CCDS79276.1; -. [Q08460-4]
DR   CCDS; CCDS79277.1; -. [Q08460-1]
DR   PIR; A48206; A48206.
DR   PIR; I49017; I49017.
DR   RefSeq; NP_001240294.1; NM_001253365.1.
DR   RefSeq; NP_001240298.1; NM_001253369.1.
DR   RefSeq; NP_034740.2; NM_010610.3.
DR   AlphaFoldDB; Q08460; -.
DR   BMRB; Q08460; -.
DR   SMR; Q08460; -.
DR   BioGRID; 200913; 185.
DR   DIP; DIP-42413N; -.
DR   IntAct; Q08460; 200.
DR   MINT; Q08460; -.
DR   STRING; 10090.ENSMUSP00000140275; -.
DR   ChEMBL; CHEMBL2800; -.
DR   DrugBank; DB08837; Tetraethylammonium.
DR   GuidetoPHARMACOLOGY; 380; -.
DR   GlyGen; Q08460; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q08460; -.
DR   PhosphoSitePlus; Q08460; -.
DR   SwissPalm; Q08460; -.
DR   MaxQB; Q08460; -.
DR   PaxDb; 10090-ENSMUSP00000140275; -.
DR   PeptideAtlas; Q08460; -.
DR   ProteomicsDB; 269190; -. [Q08460-1]
DR   ProteomicsDB; 269191; -. [Q08460-2]
DR   ProteomicsDB; 269192; -. [Q08460-3]
DR   ProteomicsDB; 269193; -. [Q08460-4]
DR   ProteomicsDB; 269194; -. [Q08460-5]
DR   ABCD; Q08460; 3 sequenced antibodies.
DR   DNASU; 16531; -.
DR   GeneID; 16531; -.
DR   KEGG; mmu:16531; -.
DR   UCSC; uc029sfy.1; mouse. [Q08460-2]
DR   AGR; MGI:99923; -.
DR   CTD; 3778; -.
DR   MGI; MGI:99923; Kcnma1.
DR   eggNOG; KOG1420; Eukaryota.
DR   InParanoid; Q08460; -.
DR   OrthoDB; 2902976at2759; -.
DR   PhylomeDB; Q08460; -.
DR   Reactome; R-MMU-1296052; Ca2+ activated K+ channels.
DR   BioGRID-ORCS; 16531; 0 hits in 72 CRISPR screens.
DR   ChiTaRS; Kcnma1; mouse.
DR   PRO; PR:Q08460; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q08460; Protein.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR   GO; GO:0005901; C:caveola; ISO:MGI.
DR   GO; GO:0030425; C:dendrite; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0045211; C:postsynaptic membrane; IDA:MGI.
DR   GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0016528; C:sarcoplasm; IDA:MGI.
DR   GO; GO:0043195; C:terminal bouton; IDA:MGI.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IGI:MGI.
DR   GO; GO:0003779; F:actin binding; ISO:MGI.
DR   GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR   GO; GO:0060072; F:large conductance calcium-activated potassium channel activity; IDA:MGI.
DR   GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005267; F:potassium channel activity; IMP:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:MGI.
DR   GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR   GO; GO:0097746; P:blood vessel diameter maintenance; ISO:MGI.
DR   GO; GO:0007268; P:chemical synaptic transmission; IMP:MGI.
DR   GO; GO:0007623; P:circadian rhythm; IMP:MGI.
DR   GO; GO:0002069; P:columnar/cuboidal epithelial cell maturation; IMP:MGI.
DR   GO; GO:0060082; P:eye blink reflex; IMP:MGI.
DR   GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IMP:MGI.
DR   GO; GO:0030007; P:intracellular potassium ion homeostasis; ISO:MGI.
DR   GO; GO:0045475; P:locomotor rhythm; IMP:MGI.
DR   GO; GO:0060073; P:micturition; IMP:MGI.
DR   GO; GO:0045794; P:negative regulation of cell volume; IMP:MGI.
DR   GO; GO:1904348; P:negative regulation of small intestine smooth muscle contraction; ISO:MGI.
DR   GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
DR   GO; GO:0042551; P:neuron maturation; IMP:MGI.
DR   GO; GO:0019228; P:neuronal action potential; IMP:MGI.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006813; P:potassium ion transport; IDA:MGI.
DR   GO; GO:0032344; P:regulation of aldosterone metabolic process; IMP:MGI.
DR   GO; GO:0042391; P:regulation of membrane potential; IDA:MGI.
DR   GO; GO:0060087; P:relaxation of vascular associated smooth muscle; IMP:MGI.
DR   GO; GO:0051592; P:response to calcium ion; ISO:MGI.
DR   GO; GO:0034465; P:response to carbon monoxide; ISO:MGI.
DR   GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR   GO; GO:0001666; P:response to hypoxia; IDA:MGI.
DR   GO; GO:0006970; P:response to osmotic stress; ISO:MGI.
DR   GO; GO:0009268; P:response to pH; ISO:MGI.
DR   GO; GO:0046541; P:saliva secretion; IGI:MGI.
DR   GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR   GO; GO:0060083; P:smooth muscle contraction involved in micturition; IMP:MGI.
DR   GO; GO:0042311; P:vasodilation; IMP:MGI.
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   Alternative splicing; Calcium; Cell membrane; Ion channel; Ion transport;
KW   Lipoprotein; Magnesium; Membrane; Metal-binding; Palmitate; Phosphoprotein;
KW   Potassium; Potassium channel; Potassium transport; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..1209
FT                   /note="Calcium-activated potassium channel subunit alpha-1"
FT                   /id="PRO_0000054134"
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; Voltage-sensor; 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..1209
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          681..685
FT                   /note="Heme-binding motif"
FT   REGION          703..733
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          783..803
FT                   /note="Segment S9"
FT   REGION          1005..1025
FT                   /note="Segment S10"
FT   REGION          1159..1209
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           352..355
FT                   /note="Selectivity for potassium"
FT   MOTIF           976..998
FT                   /note="Calcium bowl"
FT   COMPBIAS        26..61
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        712..730
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1159..1190
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1191..1209
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|PubMed:12192410"
FT   BINDING         462
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000305|PubMed:12192410"
FT   BINDING         464
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000305|PubMed:12192410"
FT   BINDING         985
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT   BINDING         988
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT   BINDING         991
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT   BINDING         993
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:B7ZC96"
FT   MOD_RES         709
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         711
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         724
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         728
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         916
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         924
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         928
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1194
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q28204"
FT   MOD_RES         1197
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q28204"
FT   LIPID           118
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           119
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           121
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..65
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:7687074"
FT                   /id="VSP_009959"
FT   VAR_SEQ         1..50
FT                   /note="MANGGGGGGGSSGGGGGGGGGSGLRMSSNIHANNLSLDASSSSSSSSSSS
FT                   -> MELEHPKSPPYP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7687074"
FT                   /id="VSP_009960"
FT   VAR_SEQ         643..646
FT                   /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:10517674,
FT                   ECO:0000303|PubMed:12388098, ECO:0000303|PubMed:7687074"
FT                   /id="VSP_009961"
FT   VAR_SEQ         702
FT                   /note="L -> LIYF (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7687074"
FT                   /id="VSP_009962"
FT   VAR_SEQ         702
FT                   /note="L -> PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERTFPLSSV
FT                   SVNDCSTSFRAF (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:10517674"
FT                   /id="VSP_009963"
FT   VAR_SEQ         948..974
FT                   /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:10517674,
FT                   ECO:0000303|PubMed:12388098, ECO:0000303|PubMed:7687074"
FT                   /id="VSP_009964"
FT   VAR_SEQ         1203..1209
FT                   /note="RKEMVYR -> ATRMTRMGQAEKKWFTDEPDNAYPRNIQIKPMSTHMANQIN
FT                   QYKSTSSLIPPIREVEDEC (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7687074"
FT                   /id="VSP_009965"
FT   MUTAGEN         151
FT                   /note="V->T: Loss of phosphorylation-independent activation
FT                   of channel activity by ethanol. CaMK2-dependent
FT                   phosphorylation leads to populations of partially
FT                   phosphorylated tetramers with a range of responses to
FT                   ethanol from activation to inhibition."
FT                   /evidence="ECO:0000269|PubMed:16341213"
FT   MUTAGEN         272
FT                   /note="R->Q: Alters the voltage-dependent gating."
FT                   /evidence="ECO:0000269|PubMed:11112549"
FT   MUTAGEN         278
FT                   /note="R->Q: Alters the voltage-dependent gating."
FT                   /evidence="ECO:0000269|PubMed:11112549"
FT   MUTAGEN         284
FT                   /note="E->R: Alters the voltage-dependent gating; when
FT                   associated with R-287."
FT                   /evidence="ECO:0000269|PubMed:11112549"
FT   MUTAGEN         287
FT                   /note="Q->R: Alters the voltage-dependent gating; when
FT                   associated with K-284."
FT                   /evidence="ECO:0000269|PubMed:11112549"
FT   MUTAGEN         427
FT                   /note="D->A: Does not affect sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192411"
FT   MUTAGEN         432
FT                   /note="D->A: Reduced sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192411"
FT   MUTAGEN         434
FT                   /note="D->A: Does not affect sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192411"
FT   MUTAGEN         439
FT                   /note="E->A: Abolishes sensitivity to Mg(2+), but not
FT                   sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192410"
FT   MUTAGEN         444
FT                   /note="H->G: Reduces sensitivity to Mg(2+), but not
FT                   sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192410"
FT   MUTAGEN         461
FT                   /note="T->A: Reduces sensitivity to Mg(2+), but not
FT                   sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192410"
FT   MUTAGEN         462
FT                   /note="Q->C: Reduces sensitivity to Mg(2+), but not
FT                   sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192410"
FT   MUTAGEN         464
FT                   /note="E->D,A: Remains sensitive to Mg(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192410,
FT                   ECO:0000269|PubMed:12192411"
FT   MUTAGEN         464
FT                   /note="E->N: Abolishes sensitivity to Mg(2+), but not
FT                   sensitivity to Ca(2+)."
FT                   /evidence="ECO:0000269|PubMed:12192410,
FT                   ECO:0000269|PubMed:12192411"
FT   MUTAGEN         992..996
FT                   /note="DDDPD->AAAAA: Alters calcium binding."
FT                   /evidence="ECO:0000269|PubMed:12149279"
FT   MOD_RES         Q08460-2:670
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         Q08460-2:672
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
SQ   SEQUENCE   1209 AA;  134396 MW;  9E07ABF5DCFA62DF CRC64;
     MANGGGGGGG SSGGGGGGGG GSGLRMSSNI HANNLSLDAS SSSSSSSSSS SSSSSSSSSS
     VHEPKMDALI IPVTMEVPCD SRGQRMWWAF LASSMVTFFG GLFIILLWRT LKYLWTVCCH
     CGGKTKEAQK INNGSSQADG TLKPVDEKEE VVAAEVGWMT 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 ESRSRKRILI NPGNHLKIQE
     GTLGFFIASD AKEVKRAFFY CKACHDDVTD PKRIKKCGCR RLEDEQPPTL SPKKKQRNGG
     MRNSPNTSPK LMRHDPLLIP GNDQIDNMDS NVKKYDSTGM FHWCAPKEIE KVILTRSEAA
     MTVLSGHVVV CIFGDVSSAL IGLRNLVMPL RASNFHYHEL KHIVFVGSIE YLKREWETLH
     NFPKVSILPG TPLSRADLRA VNINLCDMCV ILSANQNNID DTSLQDKECI LASLNIKSMQ
     FDDSIGVLQA NSQGFTPPGM DRSSPDNSPV HGMLRQPSIT TGVNIPIITE LAKPGKLPLV
     SVNQEKNSGT HILMITELVN DTNVQFLDQD DDDDPDTELY LTQPFACGTA FAVSVLDSLM
     SATYFNDNIL TLIRTLVTGG ATPELEALIA EENALRGGYS TPQTLANRDR CRVAQLALLD
     GPFADLGDGG CYGDLFCKAL KTYNMLCFGI YRLRDAHLST PSQCTKRYVI TNPPYEFELV
     PTDLIFCLMQ FDHNAGQSRA SLSHSSHSSQ SSSKKSSSVH SIPSTANRPN RPKSRESRDK
     QNRKEMVYR
//