KCMA1_MACMU
ID KCMA1_MACMU Reviewed; 1151 AA.
AC O18867;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 140.
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 Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
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=O18867-1; 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; AF026001; AAB88804.1; -; mRNA.
DR RefSeq; NP_001027982.1; NM_001032810.1. [O18867-1]
DR AlphaFoldDB; O18867; -.
DR BMRB; O18867; -.
DR SMR; O18867; -.
DR STRING; 9544.ENSMMUP00000024196; -.
DR GeneID; 574103; -.
DR KEGG; mcc:574103; -.
DR CTD; 3778; -.
DR eggNOG; KOG1420; Eukaryota.
DR HOGENOM; CLU_006846_0_0_1; -.
DR InParanoid; O18867; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0060072; F:large conductance calcium-activated potassium channel activity; IBA:GO_Central.
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 GO; GO:0060087; P:relaxation of vascular associated smooth muscle; IBA:GO_Central.
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..1151
FT /note="Calcium-activated potassium channel subunit alpha-1"
FT /id="PRO_0000054133"
FT TOPO_DOM <1..59
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical; Name=Segment S0"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..187
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 209..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..308
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 309..331
FT /note="Pore-forming; Name=P region"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..340
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..361
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..1151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 388..531
FT /note="RCK N-terminal"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..549
FT /note="Segment S7"
FT REGION 586..606
FT /note="Segment S8"
FT REGION 650..654
FT /note="Heme-binding motif"
FT REGION 674..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 752..772
FT /note="Segment S9"
FT REGION 947..967
FT /note="Segment S10"
FT REGION 1101..1151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 325..328
FT /note="Selectivity for potassium"
FT MOTIF 918..940
FT /note="Calcium bowl"
FT COMPBIAS 681..699
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1101..1132
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1133..1151
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 412
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 435
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 437
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 927
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 930
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 933
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 935
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 678
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 680
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 885
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 897
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 1136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT MOD_RES 1139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT LIPID 91
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 92
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 94
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 1151 AA; 128934 MW; 24E62FE0C1D94015 CRC64;
MSSNIHANHL SLDASSSSSS SSSSSSSSSS SSSVHEPKMD ALIIPVTMEV PCDSRGQRMW
WAFLASSMVT FFGGLFIILL WRTLKYLWTV CCHCGGKTKE AQKINNGSSQ ADGTLKPVDE
KEEAVAAEVG WMTSVKDWAG VMISAQTLTG RVLVVLVFAL SIGALVIYFI DSSNPIESCQ
NFYKDFTLQI DMAFNVFFLL YFGLRFIAAN DKLWFWLEVN SVVDFFTVPP VFVSVYLNRS
WLGLRFLRAL RLIQFSEILQ FLNILKTSNS IKLVNLLSIF ISTWLTAAGF IHLVENSGDP
WENFQNNQAL TYWECVYLLM VTMSTVGYGD VYAKTTLGRL FMVFFILGGL AMFASYVPEI
IELIGNRKKY GGSYSAVSGR KHIVVCGHIT LESVSNFLKD FLHKDRDDVN VEIVFLHNIS
PNLELEALFK RHFTQVEFYQ GSVLNPHDLA RVKIESADAC LILANKYCAD PDAEDASNIM
RVISIKNYHP KIRIITQMLQ YHNKAHLLNI PSWNWKEGDD AICLAELKLG FIAQSCLAQG
LSTMLANLFS MRSFIKIEED TWQKYYLEGV SNEMYTEYLS SAFVGLSFPT VCELCFVKLK
LLMIAIEYKS ANRESRILIN PGNHLKIQEG TLGFFIASDA KEVKRAFFYC KACHDDITDP
KRIKKCGCKR LEDEQPSTLS PKKKQRNGGM RNSPNSSPKL MRHDPLLIPG NDQIDNMDSN
VKKYDSTGMF HWCAPKEIEK VILTRSEAAM TVLSGHVVVC IFGDVSSALI GLRNLVMPLR
ASNFHYHELK HIVFVGSIEY LKREWETLHN FPKVSILPGT PLSRADLRAV NINLCDMCVI
LSANQNNIDD TSLQDKECIL ASLNIKSMQF DDSIGVLQAN SQGFTPPGMD RSSPDNSPVH
GMLRQPSITT GVNIPIITEL VNDTNVQFLD QDDDDDPDTE LYLTQPFACG TAFAVSVLDS
LMSATYFNDN ILTLIRTLVT GGATPELEAL IAEENALRGG YSTPQTLANR DRCRVAQLAL
LDGPFADLGD GGCYGDLFCK ALKTYNMLCF GIYRLRDAHL STPSQCTKRY VITNPPYEFE
LVPTDLIFCL MQFDHNAGQS RASLSHSSHS SQSSSKKSSS VHSIPSTANR QNRPKSRESR
DKQKYVQEER L
