KCMA1_PIG
ID KCMA1_PIG Reviewed; 1152 AA.
AC O18866;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 144.
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 Flags: Fragment;
GN Name=KCNMA1; Synonyms=KCNMA;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lens epithelium;
RX PubMed=9678416; DOI=10.1080/02713689808951247;
RA Shepard A.R., Rae J.L.;
RT "Ion transporters and receptors in cDNA libraries from lens and cornea
RT epithelia.";
RL Curr. Eye Res. 17:708-719(1998).
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}.
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:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=May be partially controlled by hormonal stress. A number of
CC isoforms are produced.;
CC Name=1;
CC IsoId=O18866-1; Sequence=Displayed;
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}.
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DR EMBL; AF026000; AAB88803.2; -; mRNA.
DR RefSeq; NP_999384.1; NM_214219.1. [O18866-1]
DR AlphaFoldDB; O18866; -.
DR BMRB; O18866; -.
DR SMR; O18866; -.
DR STRING; 9823.ENSSSCP00000011011; -.
DR PaxDb; O18866; -.
DR PRIDE; O18866; -.
DR GeneID; 397434; -.
DR KEGG; ssc:397434; -.
DR CTD; 3778; -.
DR eggNOG; KOG1420; Eukaryota.
DR InParanoid; O18866; -.
DR OrthoDB; 124461at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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:1902632; P:positive regulation of membrane hyperpolarization; IMP:AgBase.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0060087; P:relaxation of vascular associated smooth muscle; IMP:AgBase.
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; 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..1152
FT /note="Calcium-activated potassium channel subunit alpha-1"
FT /id="PRO_0000054135"
FT TOPO_DOM <1..60
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical; Name=Segment S0"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..152
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..213
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 235..238
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 296..309
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 310..332
FT /note="Pore-forming; Name=P region"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..341
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..1152
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 389..532
FT /note="RCK N-terminal"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 530..550
FT /note="Segment S7"
FT REGION 587..607
FT /note="Segment S8"
FT REGION 651..655
FT /note="Heme-binding motif"
FT REGION 675..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 753..773
FT /note="Segment S9"
FT REGION 948..968
FT /note="Segment S10"
FT REGION 1102..1152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 326..329
FT /note="Selectivity for potassium"
FT /evidence="ECO:0000250"
FT MOTIF 919..941
FT /note="Calcium bowl"
FT COMPBIAS 682..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1102..1133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1134..1152
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 413
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 436
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 438
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 928
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 931
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 934
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 936
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 679
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 694
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 886
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 894
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 1137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT MOD_RES 1140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT LIPID 92
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 93
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 95
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 1152 AA; 129006 MW; F656770B0C031806 CRC64;
MSSNIHANHL SLDASSSSSS SSSSSSSSSS SSSSVHEPKM DALIIPVTME VPCDSRGQRM
WWAFLASSMV TFFGGLFIIL LWRTLKYLWT VCCHCGGKTK EAQKINNGAS QADGTLKPVD
EKEEVVAAEV GWMTSVKDWA GVMISAQTLT GRVLVVLVFA LSIGALVIYF IDSSNPIESC
QNFYKDFTLQ IDMAFNVFFL LYFGLRFIAA NDKLWFWLEV NSVVDFFTVP PVFVSVYLNR
SWLGLRFLRA LRLIQFSEIL QFLNILKTSN SIKLVNLLSI FISTWLTAAG FIHLVENSGD
PWENFQNNQA LTYWECVYLL MVTMSTVGYG DVYAKTTLGR LFMVFFILGG LAMFASYVPE
IIELIGNRKK YGGSYSAVSG RKHIVVCGHI TLESVSNFLK DFLHKDRDDV NVEIVFLHNI
SPNLELEALF KRHFTQVEFY QGSVLNPHDL ARVKIESADA CLILANKYCA DPDAEDASNI
MRVISIKNYH PKIRIITQML QYHNKAHLLN IPSWNWKEGD DAICLAELKL GFIAQSCLAQ
GLSTMLANLF SMRSFIKIEE DTWQKYYLEG VSNEMYTEYL SSAFVGLSFP TVCELCFVKL
KLLMIAIEYK SANRESRILI NPGNHLKIQE GTLGFFIASD AKEVKRAFFY CKACHDDITD
PKRIKKCGCK RLEDEQPSTL SPKKKQRNGG MRNSPSSSPK LMRHDPLLIP GNDQIDNMDS
NVKKYDSTGM FHWCAPKEIE KVILTRSEAA MTVLSGHVVV CIFGDVSSAL IGLRNLVMPL
RASNFHYHEL KHIVFVGSIE YLKREWETLH NFPKVSILPG TPLSRADLRA VNINLCDMCV
ILSANQNNID DTSLQDKECI LASLNIKSMQ FDDSIGVLQA NSQGFTPPGM DRSSPDNSPV
HGMLRQPSIT TGVNIPIITE LVNDTNVQFL DQDDDDDPDT ELYLTQPFAC GTAFAVSVLD
SLMSATYFND NILTLIRTLV TGGATPELEA LIAEENALRG GYSTPQTLAN RDRCRVAQLA
LLDGPFADLG DGGCYGDLFC KALKTYNMLC FGIYRLRDAH LSTPSQCTKR YVITNPPYEF
ELVPTDLIFC LMQFDHNAGQ SRASLSHSSH SSQSSSKKSS SVHSIPSTAN RQNRPKSRES
RDKQKYVQEE RL
