KCMA1_RABIT
ID KCMA1_RABIT Reviewed; 1179 AA.
AC Q9BG98; O46371; Q9TT88;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 128.
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=RbSlo;
DE Short=Slo homolog;
GN Name=KCNMA1; Synonyms=KCNMA;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=New Zealand white; TISSUE=Corneal epithelium;
RA Rae J.L.;
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-1179 (ISOFORMS 3 AND 4), AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=9362339; DOI=10.1152/ajprenal.1997.273.4.f615;
RA Morita T., Hanaoka K., Morales M.M., Montrose-Rafizadeh C., Guggino W.B.;
RT "Cloning and characterization of maxi K+ channel alpha-subunit in rabbit
RT kidney.";
RL Am. J. Physiol. 273:F615-F624(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-1179 (ISOFORM 2).
RC TISSUE=Skeletal muscle;
RA Sakamoto H., Ide T., Kasai M.;
RT "Rabbit calcium-activated potassium channel (Maxi-K) alpha subunit mRNA,
RT complete CDS.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RX PubMed=12438308; DOI=10.1074/jbc.m208411200;
RA Wang S.-X., Ikeda M., Guggino W.B.;
RT "The cytoplasmic tail of large conductance, voltage- and Ca2+-activated K+
RT (MaxiK) channel is necessary for its cell surface expression.";
RL J. Biol. Chem. 278:2713-2722(2003).
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) (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:9362339}.
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. Interacts with RAB11B (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12438308};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12438308}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Cytoplasmic, and probably remains in the
CC endoplasmic reticulum. {ECO:0000269|PubMed:12438308}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=May be partially controlled by hormonal stress. Additional
CC isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9BG98-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BG98-2; Sequence=VSP_009967;
CC Name=3; Synonyms=rbslo1;
CC IsoId=Q9BG98-3; Sequence=VSP_009966;
CC Name=4; Synonyms=rbslo2;
CC IsoId=Q9BG98-4; Sequence=VSP_009968, VSP_009969;
CC -!- DOMAIN: The S0 segment is essential for the modulation by the accessory
CC beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. {ECO:0000250}.
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. {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
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 regions required for activation of the channel (By similarity).
CC {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250, 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=AAF17562.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA23747.1; 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; AF321818; AAK09380.1; -; mRNA.
DR EMBL; AF201702; AAF17562.1; ALT_INIT; mRNA.
DR EMBL; AB009312; BAA23747.1; ALT_INIT; mRNA.
DR RefSeq; NP_001075539.1; NM_001082070.1.
DR AlphaFoldDB; Q9BG98; -.
DR SMR; Q9BG98; -.
DR STRING; 9986.ENSOCUP00000022693; -.
DR PRIDE; Q9BG98; -.
DR GeneID; 100008745; -.
DR KEGG; ocu:100008745; -.
DR CTD; 3778; -.
DR eggNOG; KOG1420; Eukaryota.
DR InParanoid; Q9BG98; -.
DR OrthoDB; 124461at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0060072; F:large conductance calcium-activated potassium channel activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR InterPro; IPR024939; Ca-act_K_channel_Slo-1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003929; K_chnl_BK_asu.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR10027:SF28; PTHR10027:SF28; 2.
DR Pfam; PF03493; BK_channel_a; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Cell membrane; Endoplasmic reticulum;
KW Ion channel; Ion transport; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Palmitate; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1179
FT /note="Calcium-activated potassium channel subunit alpha-1"
FT /id="PRO_0000054136"
FT TOPO_DOM 1..87
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical; Name=Segment S0"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..179
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..200
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 201..215
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 237..240
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..265
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..286
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..336
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 337..359
FT /note="Pore-forming; Name=P region"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..1179
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 416..559
FT /note="RCK N-terminal"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 557..577
FT /note="Segment S7"
FT REGION 614..634
FT /note="Segment S8"
FT REGION 678..682
FT /note="Heme-binding motif"
FT REGION 702..730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..800
FT /note="Segment S9"
FT REGION 975..995
FT /note="Segment S10"
FT REGION 1129..1179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 353..356
FT /note="Selectivity for potassium"
FT MOTIF 946..968
FT /note="Calcium bowl"
FT COMPBIAS 27..62
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 709..727
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1129..1160
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1161..1179
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 440
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 463
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 465
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 955
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 958
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 961
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 963
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 706
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 708
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 721
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 725
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 913
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 925
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 1164
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT MOD_RES 1167
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT LIPID 119
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 120
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 122
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 699
FT /note="L -> PKMSIYKRMRRACCFGCGRSERDCSCMSGRVRGHVDTLGRAFPLSSV
FT SVSDCCTRFRAF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9362339"
FT /id="VSP_009966"
FT VAR_SEQ 848..862
FT /note="TPLSRADLRAVNINL -> QGMHLGVTQHQIYAV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9362339"
FT /id="VSP_009968"
FT VAR_SEQ 863..1179
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9362339"
FT /id="VSP_009969"
FT VAR_SEQ 1172..1179
FT /note="KYVQEERL -> NEKKWFTDEPDNAYPRNIQIKPMSTHMANQINQYKSTSSL
FT IPPIREVEDEC (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_009967"
FT CONFLICT 42
FT /note="Missing (in Ref. 3; BAA23747)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="F -> S (in Ref. 3; BAA23747)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="V -> F (in Ref. 3; BAA23747)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="K -> M (in Ref. 3; BAA23747)"
FT /evidence="ECO:0000305"
FT CONFLICT 774
FT /note="S -> T (in Ref. 2; AAF17562)"
FT /evidence="ECO:0000305"
FT CONFLICT 874
FT /note="N -> D (in Ref. 3; BAA23747)"
FT /evidence="ECO:0000305"
FT CONFLICT 1075
FT /note="M -> I (in Ref. 2; AAF17562)"
FT /evidence="ECO:0000305"
FT CONFLICT 1111
FT /note="P -> A (in Ref. 3; BAA23747)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1179 AA; 130925 MW; 9354488A6BB3B7E2 CRC64;
MANGGGGGGG SSGGGGGGGG GGSGLRMSSN IHASHLSLDA SSSSSSSSSS SSSSSSSSSS
SVHEPKMDAL IIPVTMEVPC DSRGQRMWWA FLASSMVTFF GGLFIILLWR TLKYLWTVCC
HCGGKAKEAQ KINNGSSQAD GTLKPVDEKE EAVAAEVGWM TSVKDWAGVM ISAQTLTGRV
LVVLVFALSI GALVIYFIDS SNPIESCQNF YKDFTLQIDM AFNVFFLLYF GLRFIAANDK
LWFWLEVNSV VDFFTVPPVF VSVYLNRSWL GLRFLRALRL IQFSEILQFL NILKTSNSIK
LVNLLSIFIS TWLTAAGFIH LVENSGDPWE NFQNNQALTY WECVYLLMVT MSTVGYGDVY
AKTTLGRLFM VFFILGGLAM FASYVPEIIE LIGNRKKYGG SYSAVSGRKH IVVCGHITLE
SVSNFLKDFL HKDRDDVNVE IVFLHNISPN LELEALFKRH FTQVEFYQGS VLNPHDLARV
KIESADACLI LANKYCADPD AEDASNIMRV ISIKNYHPKI RIITQMLQYH NKAHLLNIPS
WNWKEGDDAI CLAELKLGFI AQSCLAQGLS TMLANLFSMR SFIKIEEDTW QKYYLEGVSN
EMYTEYLSSA FVGLSFPTVC ELCFVKLKLL MIAIEYKSAN RESRILINPG NHLKIQEGTL
GFFIASDAKE VKRAFFYCKA CHDDITDPKR IKKCGCKRLE DEQPSTLSPK KKQRNGGMRN
SPNSSPKLMR HDPLLIPGND QIDNMDSNVK KYDSTGMFHW CAPKEIEKVI LTRSEAAMTV
LSGHVVVCIF GDVSSALIGL RNLVMPLRAS NFHYHELKHI VFVGSIEYLK REWETLHNFP
KVSILPGTPL SRADLRAVNI NLCDMCVILS ANQNNIDDTS LQDKECILAS LNIKSMQFDD
SIGVLQANSQ GFTPPGMDRS SPDNSPVHGM LRQPSITTGV NIPIITELVN DTNVQFLDQD
DDDDPDTELY LTQPFACGTA FAVSVLDSLM SATYFNDNIL TLIRTLVTGG ATPELEALIA
EENALRGGYS TPQTLANRDR CRVAQLALLD GPFADLGDGG CYGDLFCKAL KTYNMLCFGI
YRLRDAHLST PSQCTKRYVI TNPPYEFELV PTDLIFCLMQ FDHNAGQSRA SLSHSSHSSQ
SSSKKSSSVH SIPSTANRQN RPKSRESRDK QKYVQEERL
