KCMA1_CANLF
ID KCMA1_CANLF Reviewed; 1159 AA.
AC Q28265;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 149.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Colon smooth muscle;
RX PubMed=8897882; DOI=10.1152/ajpgi.1996.271.4.g629;
RA Vogalis F., Vincent T., Qureshi I., Schmalz F.M., Ward M.W., Sanders K.M.,
RA Horowitz B.;
RT "Cloning and expression of the large-conductance Ca(2+)-activated K+
RT channel from colonic smooth muscle.";
RL Am. J. Physiol. 271:G629-G639(1996).
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:8897882}.
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=Q28265-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Expressed in all vascular and smooth muscles.
CC {ECO:0000269|PubMed:8897882}.
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; U41001; AAA84000.1; -; mRNA.
DR RefSeq; NP_001003300.2; NM_001003300.2.
DR AlphaFoldDB; Q28265; -.
DR SMR; Q28265; -.
DR STRING; 9615.ENSCAFP00000022780; -.
DR iPTMnet; Q28265; -.
DR PaxDb; Q28265; -.
DR PRIDE; Q28265; -.
DR GeneID; 403984; -.
DR KEGG; cfa:403984; -.
DR CTD; 3778; -.
DR eggNOG; KOG1420; Eukaryota.
DR InParanoid; Q28265; -.
DR OrthoDB; 124461at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISA:AgBase.
DR GO; GO:0005901; C:caveola; ISA:AgBase.
DR GO; GO:0005737; C:cytoplasm; ISA:AgBase.
DR GO; GO:0005783; C:endoplasmic reticulum; ISA:AgBase.
DR GO; GO:0009897; C:external side of plasma membrane; ISA:AgBase.
DR GO; GO:0070062; C:extracellular exosome; ISA:AgBase.
DR GO; GO:0016021; C:integral component of membrane; ISA:AgBase.
DR GO; GO:0005886; C:plasma membrane; ISA:AgBase.
DR GO; GO:0045211; C:postsynaptic membrane; ISA:AgBase.
DR GO; GO:0043195; C:terminal bouton; ISA:AgBase.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISA:AgBase.
DR GO; GO:0003779; F:actin binding; ISA:AgBase.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; ISA:AgBase.
DR GO; GO:0060072; F:large conductance calcium-activated potassium channel activity; ISA:AgBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005267; F:potassium channel activity; ISA:AgBase.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISA:AgBase.
DR GO; GO:0007628; P:adult walking behavior; ISA:AgBase.
DR GO; GO:0048469; P:cell maturation; ISA:AgBase.
DR GO; GO:0030007; P:cellular potassium ion homeostasis; ISA:AgBase.
DR GO; GO:0007268; P:chemical synaptic transmission; ISA:AgBase.
DR GO; GO:0007623; P:circadian rhythm; ISA:AgBase.
DR GO; GO:0060082; P:eye blink reflex; ISA:AgBase.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; ISA:AgBase.
DR GO; GO:0045475; P:locomotor rhythm; ISA:AgBase.
DR GO; GO:0060073; P:micturition; ISA:AgBase.
DR GO; GO:0045794; P:negative regulation of cell volume; ISA:AgBase.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISA:AgBase.
DR GO; GO:0019228; P:neuronal action potential; ISA:AgBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISA:AgBase.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISA:AgBase.
DR GO; GO:0006813; P:potassium ion transport; ISA:AgBase.
DR GO; GO:0051260; P:protein homooligomerization; ISA:AgBase.
DR GO; GO:0032344; P:regulation of aldosterone metabolic process; ISA:AgBase.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0042391; P:regulation of membrane potential; ISA:AgBase.
DR GO; GO:0060087; P:relaxation of vascular associated smooth muscle; ISA:AgBase.
DR GO; GO:0051592; P:response to calcium ion; ISA:AgBase.
DR GO; GO:0034465; P:response to carbon monoxide; ISA:AgBase.
DR GO; GO:0001666; P:response to hypoxia; ISA:AgBase.
DR GO; GO:0006970; P:response to osmotic stress; ISA:AgBase.
DR GO; GO:0046541; P:saliva secretion; ISA:AgBase.
DR GO; GO:0007605; P:sensory perception of sound; ISA:AgBase.
DR GO; GO:0060083; P:smooth muscle contraction involved in micturition; ISA:AgBase.
DR GO; GO:0042311; P:vasodilation; ISA: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..1159
FT /note="Calcium-activated potassium channel subunit alpha-1"
FT /id="PRO_0000054131"
FT TOPO_DOM <1..24
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Name=Segment S0"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..152
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..202
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 224..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 274..296
FT /note="Pore-forming; Name=P region"
FT /evidence="ECO:0000255"
FT TOPO_DOM 297..305
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..1159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 353..496
FT /note="RCK N-terminal"
FT REGION 494..514
FT /note="Segment S7"
FT REGION 551..571
FT /note="Segment S8"
FT REGION 615..619
FT /note="Heme-binding motif"
FT REGION 639..668
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 717..737
FT /note="Segment S9"
FT REGION 912..932
FT /note="Segment S10"
FT REGION 1066..1124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 290..293
FT /note="Selectivity for potassium"
FT MOTIF 883..905
FT /note="Calcium bowl"
FT COMPBIAS 646..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1066..1097
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1098..1118
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 377
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 400
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 402
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 892
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 895
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 898
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 900
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 643
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 645
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 850
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 858
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 862
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08460"
FT MOD_RES 1101
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT MOD_RES 1104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28204"
FT LIPID 56
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 57
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 59
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 1159 AA; 130296 MW; D8CF38C32971BB64 CRC64;
EPNMDALIIP VTMEVPCDSR GQRMWWAFLA SSMVTFFGGL FIILLWRTLK YLWTVCCHCG
DKTKEAQKIN NGSSQADGTL KPVDEKEEAV AAEVGWMTSV KDWAGVMISA QTLTGRVLVV
LVFALSIGAL VIYFIDSSNP IESCQNFYKD FTLQIDMAFN VFFLLYFGLR FIAANDNLWF
WLEVNSVVDF FTVPPVFVSV YLNRSWLGLR FLRALRLIQF SEILQFLNIL KTSNSIKLVN
LLSIFISTWL TAAGFIHLVE NSGDPWENFQ NSQALTYWEC VYLLMVTMST VGYGDVYAKT
TPGGLFIVFF ILGGLAMFAS YVPEIIEIIG NRKKYGGSYS AVSGRKHIVV CGHITLESVS
HFLKDFLHKD RDDVNVEIVF LHNISPNLEL EALFKRHFTQ VEFYQGSVLN PHDLARVKIE
SADACLILAN KYCDDPDAED ASNIMRVISI KNYHPKIRII TQMLQYHNKA HLLNIPSWNW
KEGDDAICLA ELRLGFIAQS CLAQGLSTML ANLFSIGSFI KIEEDTWHKY YLEGVSNEMY
TEYLSSAFVG LSFPTVCELC FVKLKLLMIA IEYKSANRES RILINPGNHL KIQEGTSGFF
IASDAKEVKR AFFYCKACHN DITDPKRIKK CGCKRLEDEQ PSTLSPKKKQ RNGGMRNSPS
SSPKLMRHDP LLIPGNDQID NMDSNVKKYD STGMFHWCAP KEIEKVISTR SEAAMTVLSG
HVVVCIFGHV SSALIGLRNL VMPLRASNFH YHELKHIVFV GSIEYLKREW ETLHNFPKVS
ILPGTPLTRA DLRAVNINLC DMCVILSANQ NNIDDTSLQD KECILASLNI KSMQFDDSIG
VLQANSQGFT PPGMDKSSPD NSPVHGMLRQ PSITTGVNIP IITELVNDTN VQFLDQDDDD
DPDTELYLTQ PFACGTAFAV SVLDSLMSAT YFNDNILTLI RTLVTGGATP ELEALIAEEN
ALRGGYSTPQ TLANRDRCRV AQLALLDGPF ADLGDGGCYG DLFCKALKTY NMLCFGIYRL
RDAHLSTPSQ CTKRYVITNP PYRFELVPTD LIFCLMQFDH NAGQSRASLS HSSHSSQSSS
KKSSSVHSIP STANRQNRPK SRESRDKQTE KKWFTDEPDN AYPRNIQIEP MSTHMANQIN
QYKSTSSLIP PIREVEDEC
