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Q12791 (KCMA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium-activated potassium channel subunit alpha-1
Alternative name(s):
BK channel
BKCA alpha
Calcium-activated potassium channel, subfamily M subunit alpha-1
K(VCA)alpha
KCa1.1
Maxi K channel
Short name=MaxiK
Slo-alpha
Slo1
Slowpoke homolog
Short name=Slo homolog
Short name=hSlo
Gene names
Name:KCNMA1
Synonyms:KCNMA, SLO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1236 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Potassium channel activated by both membrane depolarization or increase in cytosolic Ca2+ that mediates export of K+. It is also activated by the concentration of cytosolic Mg2+. Its activation dampens the excitatory events that elevate the cytosolic Ca2+ concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca2+, caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).

Enzyme regulation

Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation. Ref.22

Subunit structure

Homotetramer; which constitutes the calcium-activated potassium channel. Interacts with RAB11B By similarity. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Interacts with gamma subunits LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma subunits are accessory, and modulate its activity. Ref.18 Ref.19 Ref.20 Ref.21 Ref.26 Ref.28 Ref.29

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.24 Ref.25.

Tissue specificity

Widely expressed. Except in myocytes, it is almost ubiquitously expressed. Ref.13

Domain

The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Ref.15 Ref.17

The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor. Ref.15 Ref.17

The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium. Ref.15 Ref.17

The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca2+ and Mg2+ By similarity. Ref.15 Ref.17

The calcium bowl constitutes one of the Ca2+ sensors and probably acts as a Ca2+-binding site. There are however other Ca2+ sensors regions required for activation of the channel. Ref.15 Ref.17

The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation. Ref.15 Ref.17

Post-translational modification

Phosphorylated Probable. Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity.

Palmitoylation by ZDHHC22 and ZDHHC23 within the intracellular linker between the S0 and S1 transmembrane domains regulates localization to the plasma membrane. Depalmitoylated by LYPLA1 and LYPLAL1, leading to retard exit from the trans-Golgi network. Ref.24 Ref.25

Involvement in disease

Generalized epilepsy and paroxysmal dyskinesia (GEPD) [MIM:609446]: Epilepsy is one of the most common and debilitating neurological disorders. Paroxysmal dyskinesias are neurological disorders characterized by sudden, unpredictable, disabling attacks of involuntary movement often requiring life-long treatment. The coexistence of epilepsy and paroxysmal dyskinesia in the same individual or family is an increasingly recognized phenomenon. Patients manifest absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia, involuntary dystonic or choreiform movements. Onset is usually in childhood and patients may have seizures only, dyskinesia only, or both.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30

Miscellaneous

The protein was initially thought to contain two functionally distinct parts: The core channel (from the N-terminus to the S9 segment) that mediates the channel activity, and the cytoplasmic tail (from the S9 segment to the C-terminus) that mediates the calcium sensing. The situation is however more complex, since the core channel also contains binding sites for Ca2+ and Mg2+.

Sequence similarities

Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily. [View classification]

Contains 1 RCK N-terminal domain.

Sequence caution

The sequence AAA50216.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

The sequence AAB65837.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAC50353.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAK91504.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAD06365.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Epilepsy
   DomainTransmembrane
Transmembrane helix
   LigandCalcium
Magnesium
Metal-binding
Potassium
   Molecular functionIon channel
Potassium channel
Voltage-gated channel
   PTMLipoprotein
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from electronic annotation. Source: Ensembl

auditory receptor cell differentiation

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

cell maturation

Inferred from electronic annotation. Source: Ensembl

cellular potassium ion homeostasis

Inferred from direct assay PubMed 11245614. Source: UniProtKB

eye blink reflex

Inferred from electronic annotation. Source: Ensembl

locomotor rhythm

Inferred from electronic annotation. Source: Ensembl

micturition

Inferred from direct assay PubMed 11641143. Source: UniProtKB

negative regulation of cell volume

Inferred from direct assay PubMed 12388065. Source: UniProtKB

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

neuronal action potential

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 11245614. Source: UniProtKB

potassium ion transmembrane transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

potassium ion transport

Inferred from direct assay PubMed 11245614PubMed 12388065PubMed 17706472PubMed 18458941Ref.2Ref.1Ref.6. Source: UniProtKB

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

regulation of aldosterone metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of membrane potential

Inferred from direct assay Ref.1Ref.6. Source: UniProtKB

relaxation of vascular smooth muscle

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from direct assay PubMed 12388065PubMed 18458941. Source: UniProtKB

response to carbon monoxide

Inferred from direct assay PubMed 15528406. Source: UniProtKB

response to hypoxia

Inferred from direct assay PubMed 15528406. Source: UniProtKB

response to osmotic stress

Inferred from direct assay PubMed 10840032PubMed 12388065. Source: UniProtKB

saliva secretion

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

smooth muscle contraction involved in micturition

Inferred from direct assay PubMed 11641143. Source: UniProtKB

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 10840032. Source: UniProtKB

caveola

Inferred from direct assay PubMed 15703204. Source: BHF-UCL

endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: Ensembl

terminal bouton

Inferred from electronic annotation. Source: Ensembl

voltage-gated potassium channel complex

Inferred from direct assay Ref.2Ref.1Ref.6. Source: UniProtKB

   Molecular_functionactin binding

Inferred from direct assay PubMed 15703204. Source: BHF-UCL

calcium-activated potassium channel activity

Inferred from direct assay PubMed 11245614PubMed 17706472PubMed 18458941Ref.2Ref.1Ref.6Ref.13. Source: UniProtKB

large conductance calcium-activated potassium channel activity

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

voltage-gated potassium channel activity

Inferred from direct assay PubMed 12388065Ref.1Ref.6Ref.13. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: May be partially controlled by hormonal stress. Additional isoforms seem to exist.
Isoform 1 (identifier: Q12791-1)

Also known as: SAKCA;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q12791-2)

Also known as: BKTM;

The sequence of this isoform differs from the canonical sequence as follows:
     698-756: PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERAFPLSSVSVNDCSTSFRAF → L
     828-828: L → LVTGWMPYLGPRVLMTCLDIGVVCMPTDIQSTSPASIKKFKE
Isoform 3 (identifier: Q12791-3)

The sequence of this isoform differs from the canonical sequence as follows:
     643-643: R → RSRKR
Isoform 4 (identifier: Q12791-4)

Also known as: hbr5;

The sequence of this isoform differs from the canonical sequence as follows:
     698-756: PKMSIYKRMR...NDCSTSFRAF → LKVAARSRYSKDPFEFKKETPNSRLVTEPV
Isoform 5 (identifier: Q12791-5)

The sequence of this isoform differs from the canonical sequence as follows:
     698-756: PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERAFPLSSVSVNDCSTSFRAF → L
Isoform 6 (identifier: Q12791-6)

The sequence of this isoform differs from the canonical sequence as follows:
     127-168: EAQKINNGSS...MTSVKDWAGV → ATHFGSPEMP...ALEVARCRRL
     169-1236: Missing.
Note: No experimental confirmation available.
Isoform 7 (identifier: Q12791-7)

Also known as: gBK;

The sequence of this isoform differs from the canonical sequence as follows:
     698-756: PKMSIYKRMR...NDCSTSFRAF → RWEEHCSLWR...PNSRLVTEPV
Note: Ref.13 (no nucleotide entry) sequence is in conflict in positions: 726-727:SF->FS.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12361236Calcium-activated potassium channel subunit alpha-1
PRO_0000054132

Regions

Topological domain1 – 8686Extracellular Potential
Transmembrane87 – 10721Helical; Name=Segment S0; Potential
Topological domain108 – 17871Cytoplasmic Potential
Transmembrane179 – 19921Helical; Name=Segment S1; Potential
Topological domain200 – 21415Extracellular Potential
Transmembrane215 – 23521Helical; Name=Segment S2; Potential
Topological domain236 – 2394Cytoplasmic Potential
Transmembrane240 – 26021Helical; Name=Segment S3; Potential
Topological domain261 – 2644Extracellular Potential
Transmembrane265 – 28521Helical; Name=Segment S4; Potential
Topological domain286 – 30015Cytoplasmic Potential
Transmembrane301 – 32121Helical; Name=Segment S5; Potential
Topological domain322 – 33514Extracellular Potential
Intramembrane336 – 35823Pore-forming; Name=P region; Potential
Topological domain359 – 3679Extracellular Potential
Transmembrane368 – 38821Helical; Name=Segment S6; Potential
Topological domain389 – 1236848Cytoplasmic Potential
Domain415 – 558144RCK N-terminal
Region556 – 57621Segment S7
Region613 – 63321Segment S8
Region677 – 6815Heme-binding motif
Region837 – 85721Segment S9
Region1032 – 105221Segment S10
Motif352 – 3554Selectivity for potassium
Motif1003 – 102523Calcium bowl
Compositional bias4 – 107Poly-Gly
Compositional bias13 – 208Poly-Gly
Compositional bias39 – 6022Poly-Ser

Sites

Metal binding4391Magnesium By similarity
Metal binding4621Magnesium By similarity
Metal binding4641Magnesium By similarity
Metal binding10121Calcium; via carbonyl oxygen
Metal binding10151Calcium; via carbonyl oxygen
Metal binding10181Calcium
Metal binding10201Calcium

Amino acid modifications

Lipidation1181S-palmitoyl cysteine Ref.24 Ref.25
Lipidation1191S-palmitoyl cysteine Ref.24 Ref.25
Lipidation1211S-palmitoyl cysteine Ref.24 Ref.25

Natural variations

Alternative sequence127 – 16842EAQKI…DWAGV → ATHFGSPEMPPAARSWSGSP PEAAVLRGASSLALEVARCR RL in isoform 6.
VSP_009952
Alternative sequence169 – 12361068Missing in isoform 6.
VSP_009953
Alternative sequence6431R → RSRKR in isoform 3.
VSP_009954
Alternative sequence698 – 75659PKMSI…SFRAF → L in isoform 2 and isoform 5.
VSP_009955
Alternative sequence698 – 75659PKMSI…SFRAF → LKVAARSRYSKDPFEFKKET PNSRLVTEPV in isoform 4.
VSP_009956
Alternative sequence698 – 75659PKMSI…SFRAF → RWEEHCSLWRLESKGNVRRL NYCRGQQTFSVKVKVAARSR YSKDPFEFKKETPNSRLVTE PV in isoform 7.
VSP_009957
Alternative sequence8281L → LVTGWMPYLGPRVLMTCLDI GVVCMPTDIQSTSPASIKKF KE in isoform 2.
VSP_009958
Natural variant4341D → G in GEPD; may have a synergistic effect with ethanol in the triggering of symptoms. Ref.30
VAR_023821

Experimental info

Mutagenesis1181C → A: Decreased localization to the plasma membrane. Abolishes localization to the plasma membrane; when associated with A-119 and A-121. Ref.24 Ref.25
Mutagenesis1191C → A: Decreased localization to the plasma membrane. Abolishes localization to the plasma membrane; when associated with A-118 and A-121. Ref.24 Ref.25
Mutagenesis1211C → A: Decreased localization to the plasma membrane. Abolishes localization to the plasma membrane; when associated with A-119 and A-121. Ref.24 Ref.25
Mutagenesis2691L → R or H: No effect in the coupling between calcium and channel opening. Ref.17
Mutagenesis2721R → E: Induces reduction in the coupling between calcium and channel opening. Ref.17
Mutagenesis2751R → N: Induces reduction in the coupling between calcium and channel opening. Ref.17
Mutagenesis2781R → Q: Induces reduction in the coupling between calcium and channel opening. Ref.17
Mutagenesis2811Q → R: No effect in the coupling between calcium and channel opening. Ref.17
Mutagenesis2841E → K: No effect in the coupling between calcium and channel opening. Ref.17
Mutagenesis3521T → S: Activated at more negative voltages. Slower rate of inactivation. Impaired inhibition by HMIMP. No effect on channel inhibition by Iberiotoxin. Ref.27
Mutagenesis354 – 3563GYG → AAA: Loss of function. Ref.20
Mutagenesis3801F → A: Loss of function. Ref.27
Mutagenesis3811A → S: Activated at more negative voltages. No effect on inhibition by HMIMP. Ref.27
Mutagenesis3841V → I: No effect on activation voltage. No effect on inhibition by HMIMP. Ref.27
Mutagenesis6801C → S: Loss of heme-induced channel inhibition. Ref.22
Mutagenesis6811H → R: Loss of heme-induced channel inhibition. Ref.22
Sequence conflict251M → N in AAA50216. Ref.9
Sequence conflict351S → G in AAA50216. Ref.9
Sequence conflict381A → V in AAA85104. Ref.1
Sequence conflict4491N → D in AAD31173. Ref.12
Sequence conflict8051N → H in AAC50353. Ref.6
Sequence conflict11521T → A in AAD31173. Ref.12
Sequence conflict1230 – 12367YVQEERL → KEMVYR in CAI39730. Ref.3
Sequence conflict1230 – 12367YVQEERL → KEMVYR in CAI40870. Ref.3
Sequence conflict1230 – 12367YVQEERL → KEMVYR in CAI14074. Ref.3
Sequence conflict1230 – 12367YVQEERL → KEMVYR in CAI16162. Ref.3

Secondary structure

...................................................................................................................................... 1236
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (SAKCA) [UniParc].

Last modified April 13, 2004. Version 2.
Checksum: DF9BFEAF374BE553

FASTA1,236137,560
        10         20         30         40         50         60 
MANGGGGGGG SSGGGGGGGG SSLRMSSNIH ANHLSLDASS SSSSSSSSSS SSSSSSSSSS 

        70         80         90        100        110        120 
VHEPKMDALI IPVTMEVPCD SRGQRMWWAF LASSMVTFFG GLFIILLWRT LKYLWTVCCH 

       130        140        150        160        170        180 
CGGKTKEAQK INNGSSQADG TLKPVDEKEE AVAAEVGWMT SVKDWAGVMI SAQTLTGRVL 

       190        200        210        220        230        240 
VVLVFALSIG ALVIYFIDSS NPIESCQNFY KDFTLQIDMA FNVFFLLYFG LRFIAANDKL 

       250        260        270        280        290        300 
WFWLEVNSVV DFFTVPPVFV SVYLNRSWLG LRFLRALRLI QFSEILQFLN ILKTSNSIKL 

       310        320        330        340        350        360 
VNLLSIFIST WLTAAGFIHL VENSGDPWEN FQNNQALTYW ECVYLLMVTM STVGYGDVYA 

       370        380        390        400        410        420 
KTTLGRLFMV FFILGGLAMF ASYVPEIIEL IGNRKKYGGS YSAVSGRKHI VVCGHITLES 

       430        440        450        460        470        480 
VSNFLKDFLH KDRDDVNVEI VFLHNISPNL ELEALFKRHF TQVEFYQGSV LNPHDLARVK 

       490        500        510        520        530        540 
IESADACLIL ANKYCADPDA EDASNIMRVI SIKNYHPKIR IITQMLQYHN KAHLLNIPSW 

       550        560        570        580        590        600 
NWKEGDDAIC LAELKLGFIA QSCLAQGLST MLANLFSMRS FIKIEEDTWQ KYYLEGVSNE 

       610        620        630        640        650        660 
MYTEYLSSAF VGLSFPTVCE LCFVKLKLLM IAIEYKSANR ESRILINPGN HLKIQEGTLG 

       670        680        690        700        710        720 
FFIASDAKEV KRAFFYCKAC HDDITDPKRI KKCGCKRPKM SIYKRMRRAC CFDCGRSERD 

       730        740        750        760        770        780 
CSCMSGRVRG NVDTLERAFP LSSVSVNDCS TSFRAFEDEQ PSTLSPKKKQ RNGGMRNSPN 

       790        800        810        820        830        840 
TSPKLMRHDP LLIPGNDQID NMDSNVKKYD STGMFHWCAP KEIEKVILTR SEAAMTVLSG 

       850        860        870        880        890        900 
HVVVCIFGDV SSALIGLRNL VMPLRASNFH YHELKHIVFV GSIEYLKREW ETLHNFPKVS 

       910        920        930        940        950        960 
ILPGTPLSRA DLRAVNINLC DMCVILSANQ NNIDDTSLQD KECILASLNI KSMQFDDSIG 

       970        980        990       1000       1010       1020 
VLQANSQGFT PPGMDRSSPD NSPVHGMLRQ PSITTGVNIP IITELVNDTN VQFLDQDDDD 

      1030       1040       1050       1060       1070       1080 
DPDTELYLTQ PFACGTAFAV SVLDSLMSAT YFNDNILTLI RTLVTGGATP ELEALIAEEN 

      1090       1100       1110       1120       1130       1140 
ALRGGYSTPQ TLANRDRCRV AQLALLDGPF ADLGDGGCYG DLFCKALKTY NMLCFGIYRL 

      1150       1160       1170       1180       1190       1200 
RDAHLSTPSQ CTKRYVITNP PYEFELVPTD LIFCLMQFDH NAGQSRASLS HSSHSSQSSS 

      1210       1220       1230 
KKSSSVHSIP STANRQNRPK SRESRDKQKY VQEERL 

« Hide

Isoform 2 (BKTM) [UniParc].

Checksum: 932986BE30E0D409
Show »

FASTA1,219135,495
Isoform 3 [UniParc].

Checksum: 83DA8EC8C379A3D9
Show »

FASTA1,240138,087
Isoform 4 (hbr5) [UniParc].

Checksum: 7B9C03A8BFA5055B
Show »

FASTA1,207134,362
Isoform 5 [UniParc].

Checksum: AD3C9634F8A21EEC
Show »

FASTA1,178130,999
Isoform 6 [UniParc].

Checksum: 101980B6E7017A03
Show »

FASTA16817,191
Isoform 7 (gBK) [UniParc].

Checksum: CE8B6449D8C7B9CC
Show »

FASTA1,239138,297

References

« Hide 'large scale' references
[1]"Cloning and expression of a human large-conductance calcium-activated potassium channel."
Dworetzky S.I., Trojnacki J.T., Gribkoff V.K.
Brain Res. Mol. Brain Res. 27:189-193(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
Tissue: Substantia nigra.
[2]"A human calcium-activated potassium channel gene expressed in vascular smooth muscle."
McCobb D.P., Fowler N.L., Featherstone T., Lingle C.J., Saito M., Krause J.E., Salkoff L.
Am. J. Physiol. 269:H767-H777(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
Tissue: Aortic smooth muscle and Umbilical smooth muscle.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6).
Tissue: Cerebellum, Neuroectoderm and Testis.
[6]"Cloning, expression, and distribution of functionally distinct Ca(2+)-activated K+ channel isoforms from human brain."
Tseng-Crank J., Foster C.D., Krause J.D., Mertz R., Godinot N., DiChiara T.J., Reinhart P.H.
Neuron 13:1315-1330(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-1236 (ISOFORM 5).
[7]"Calcium-activated potassium channel expression in human myometrium: effect of pregnancy."
Mazzone J.N., Kaiser R.A., Buxton I.L.O.
Proc. West. Pharmacol. Soc. 45:184-186(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-1236 (ISOFORM 5).
Tissue: Myometrium.
[8]"BK variant from human heart."
Naruse K.
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-1236 (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 25-1236 (ISOFORM 2).
Tissue: Heart.
[9]"Cloning and characterization of human and mouse homologs of the Drosophila calcium-activated potassium channel gene, slowpoke."
Pallanck L., Ganetzky B.
Hum. Mol. Genet. 3:1239-1243(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 24-670 (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF 323-1236 (ISOFORM 4).
Tissue: Muscle.
[10]"Identification of potassium channels in human lens epithelium."
Rae J.L., Shepard A.R.
(In) Civan M.M. (eds.); Current topics in membranes. The eye's aqueous humor - from secretion to glaucoma, pp.45:69-104, Academic Press, San Diego (1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-1236 (ISOFORM 5).
Tissue: Lens epithelium.
[11]"Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium."
Wallner M., Meera P., Ottolia M., Kaczorowski G.J., Latorre R., Garcia M.L., Stefani E., Toro L.
Recept. Channels 3:185-199(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 38-1236 (ISOFORM 5), NUCLEOTIDE SEQUENCE [MRNA] OF 693-764 (ISOFORM 4).
Tissue: Myometrium.
[12]"Cloning and characterization of BKCA alpha subunit from human pulmonary artery."
Cairns V.R., Aebly M.R., Rusch N.J.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 66-1236 (ISOFORM 5).
Tissue: Pulmonary artery.
[13]"Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells."
Liu X., Chang Y., Reinhart P.H., Sontheimer H., Chang Y.
J. Neurosci. 22:1840-1849(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 7), TISSUE SPECIFICITY.
Tissue: Glioblastoma.
[14]Erratum
Liu X., Chang Y., Reinhart P.H., Sontheimer H., Chang Y.
J. Neurosci. 22:1B-1B(2002)
[15]"Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N-terminus."
Wallner M., Meera P., Toro L.
Proc. Natl. Acad. Sci. U.S.A. 93:14922-14927(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN S0.
[16]"Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N-terminus, and an intracellular (S9-S10) C-terminus."
Meera P., Wallner M., Song M., Toro L.
Proc. Natl. Acad. Sci. U.S.A. 94:14066-14071(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: MEMBRANE TOPOLOGY.
[17]"Role of the S4 segment in a voltage-dependent calcium-sensitive potassium (hSlo) channel."
Diaz L., Meera P., Amigo J., Stefani E., Alvarez O., Toro L., Latorre R.
J. Biol. Chem. 273:32430-32436(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN S4, MUTAGENESIS OF LEU-269; ARG-272; ARG-275; ARG-278; GLN-281 AND GLU-284.
[18]"Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog."
Wallner M., Meera P., Toro L.
Proc. Natl. Acad. Sci. U.S.A. 96:4137-4142(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCNMB2.
[19]"Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4."
Brenner R., Jegla T.J., Wickenden A., Liu Y., Aldrich R.W.
J. Biol. Chem. 275:6453-6461(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCNMB3 AND KCNMB4.
[20]"Identification of a novel tetramerization domain in large conductance K(ca) channels."
Quirk J.C., Reinhart P.H.
Neuron 32:13-23(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMOTETRAMERIZATION, MUTAGENESIS OF 354-GLY--GLY-356.
[21]"Consequences of the stoichiometry of Slo1 alpha and auxiliary beta subunits on functional properties of large-conductance Ca2+-activated K+ channels."
Wang Y.-W., Ding J.-P., Xia X.-M., Lingle C.J.
J. Neurosci. 22:1550-1561(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KCNMB1; KCNMB2; KCNMB3 AND KCNMB4.
[22]"Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels."
Tang X.D., Xu R., Reynolds M.F., Garcia M.L., Heinemann S.H., Hoshi T.
Nature 425:531-535(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, MUTAGENESIS OF CYS-680 AND HIS-681.
[23]"Gating mechanism of BK (Slo1) channels: so near, yet so far."
Magleby K.L.
J. Gen. Physiol. 121:81-96(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[24]"Palmitoylation of the S0-S1 linker regulates cell surface expression of voltage- and calcium-activated potassium (BK) channels."
Jeffries O., Geiger N., Rowe I.C., Tian L., McClafferty H., Chen L., Bi D., Knaus H.G., Ruth P., Shipston M.J.
J. Biol. Chem. 285:33307-33314(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-118; CYS-119 AND CYS-121, MUTAGENESIS OF CYS-118; CYS-119 AND CYS-121.
[25]"Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels."
Tian L., McClafferty H., Knaus H.G., Ruth P., Shipston M.J.
J. Biol. Chem. 287:14718-14725(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-118; CYS-119 AND CYS-121, DEPALMITOYLATION, MUTAGENESIS OF CYS-118; CYS-119 AND CYS-121.
[26]"LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium."
Yan J., Aldrich R.W.
Nature 466:513-516(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRRC26.
[27]"Characterizing the role of Thr352 in the inhibition of the large conductance Ca2+-activated K+ channels by 1-[1-Hexyl-6-(methyloxy)-1H-indazol-3-yl]-2-methyl-1-propanone."
Gordon E., Semus S.F., Lozinskaya I.M., Lin Z., Xu X.
J. Pharmacol. Exp. Ther. 334:402-409(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-352; PHE-380; ALA-381 AND VAL-384.
[28]"BK potassium channel modulation by leucine-rich repeat-containing proteins."
Yan J., Aldrich R.W.
Proc. Natl. Acad. Sci. U.S.A. 109:7917-7922(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GAMMA SUBUNITS LRRC26; LRRC38; LRRC52 AND LRRC55.
[29]"Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution."
Yuan P., Leonetti M.D., Pico A.R., Hsiung Y., MacKinnon R.
Science 329:182-186(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 406-1179, CALCIUM-BINDING SITES, SUBUNIT.
[30]"Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder."
Du W., Bautista J.F., Yang H., Diez-Sampedro A., You S.-A., Wang L., Kotagal P., Lueders H.O., Shi J., Cui J., Richerson G.B., Wang Q.K.
Nat. Genet. 37:733-738(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GEPD GLY-434.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U13913 mRNA. Translation: AAA85104.1.
U23767 mRNA. Translation: AAA92290.1.
AL157833 expand/collapse EMBL AC list , AL731560, AL731556, AL627447, AC021032, AC011439 Genomic DNA. Translation: CAI39730.1.
AL157833 expand/collapse EMBL AC list , AC011439, AC021032, AL627447, AL731556, AL731560 Genomic DNA. Translation: CAI39736.1.
AL627447 expand/collapse EMBL AC list , AL731560, AL731556, AC021032, AC011439, AL157833 Genomic DNA. Translation: CAI16162.1.
AL627447 expand/collapse EMBL AC list , AC011439, AC021032, AL157833, AL731556, AL731560 Genomic DNA. Translation: CAI16171.1.
AL731556 expand/collapse EMBL AC list , AC011439, AL157833, AC021032, AL731560, AL627447 Genomic DNA. Translation: CAI14074.1.
AL731556 expand/collapse EMBL AC list , AC011439, AC021032, AL157833, AL627447, AL731560 Genomic DNA. Translation: CAI14082.1.
AL731560 expand/collapse EMBL AC list , AL157833, AL731556, AC021032, AC011439, AL627447 Genomic DNA. Translation: CAI40870.1.
AL731560 expand/collapse EMBL AC list , AC011439, AC021032, AL157833, AL627447, AL731556 Genomic DNA. Translation: CAI40877.1.
AC067745 Genomic DNA. No translation available.
AL607069 Genomic DNA. No translation available.
AL731575 Genomic DNA. No translation available.
CH471083 Genomic DNA. Translation: EAW54599.1.
BC062659 mRNA. Translation: AAH62659.1.
BC137115 mRNA. Translation: AAI37116.1.
BC137137 mRNA. Translation: AAI37138.1.
U11717 mRNA. Translation: AAC50353.1. Different initiation.
AY040849 mRNA. Translation: AAK91504.1. Different initiation.
AB113575 mRNA. Translation: BAD06397.1.
AB113382 mRNA. Translation: BAD06365.1. Different initiation.
U02632 mRNA. Translation: AAA50173.1.
U09384 mRNA. Translation: AAA50216.1. Sequence problems.
AF025999 mRNA. Translation: AAB88802.1.
U11058 mRNA. Translation: AAB65837.1. Different initiation.
AF118141 mRNA. Translation: AAD31173.1.
PIRI38596.
S62904.
RefSeqNP_001014797.1. NM_001014797.2.
NP_001154824.1. NM_001161352.1.
NP_001154825.1. NM_001161353.1.
NP_001258447.1. NM_001271518.1.
NP_001258451.1. NM_001271522.1.
NP_002238.2. NM_002247.3.
UniGeneHs.144795.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2K44NMR-A257-284[»]
3MT5X-ray3.00A406-1179[»]
3NAFX-ray3.10A395-1178[»]
ProteinModelPortalQ12791.
SMRQ12791. Positions 223-392, 396-1179.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109979. 9 interactions.
DIPDIP-29729N.
IntActQ12791. 2 interactions.
MINTMINT-4825316.

Chemistry

BindingDBQ12791.
ChEMBLCHEMBL4304.
DrugBankDB00436. Bendroflumethiazide.
DB00562. Benzthiazide.
DB00880. Chlorothiazide.
DB00356. Chlorzoxazone.
DB01003. Cromoglicate.
DB00606. Cyclothiazide.
DB01119. Diazoxide.
DB00228. Enflurane.
DB00999. Hydrochlorothiazide.
DB00774. Hydroflumethiazide.
DB00232. Methyclothiazide.
DB01325. Quinethazone.
DB01021. Trichlormethiazide.
GuidetoPHARMACOLOGY380.

PTM databases

PhosphoSiteQ12791.

Polymorphism databases

DMDM46396283.

Proteomic databases

PaxDbQ12791.
PRIDEQ12791.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286627; ENSP00000286627; ENSG00000156113. [Q12791-5]
ENST00000286628; ENSP00000286628; ENSG00000156113. [Q12791-1]
ENST00000354353; ENSP00000346321; ENSG00000156113.
ENST00000404857; ENSP00000385806; ENSG00000156113. [Q12791-2]
ENST00000480683; ENSP00000474686; ENSG00000156113. [Q12791-6]
GeneID3778.
KEGGhsa:3778.
UCSCuc001jxj.2. human. [Q12791-5]
uc001jxn.3. human. [Q12791-1]
uc001jxo.3. human. [Q12791-2]
uc001jxs.4. human. [Q12791-6]
uc009xrt.1. human. [Q12791-4]

Organism-specific databases

CTD3778.
GeneCardsGC10M078629.
HGNCHGNC:6284. KCNMA1.
HPAHPA054648.
MIM600150. gene.
609446. phenotype.
neXtProtNX_Q12791.
Orphanet79137. Generalized epilepsy - paroxysmal dyskinesia.
PharmGKBPA220.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOVERGENHBG052222.
InParanoidQ12791.
KOK04936.
PhylomeDBQ12791.
TreeFamTF314283.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ12791.
BgeeQ12791.
GenevestigatorQ12791.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR024939. Ca-act_K_channel_Slo.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
IPR003929. K_chnl_Ca-activ_BK_asu.
IPR016040. NAD(P)-bd_dom.
IPR003148. RCK_N.
[Graphical view]
PANTHERPTHR10027:SF3. PTHR10027:SF3. 1 hit.
PfamPF03493. BK_channel_a. 1 hit.
PF00520. Ion_trans. 1 hit.
PF02254. TrkA_N. 1 hit.
[Graphical view]
PRINTSPR01449. BKCHANNELA.
PR00169. KCHANNEL.
ProtoNetSearch...

Other

ChiTaRSKCNMA1. human.
EvolutionaryTraceQ12791.
GenomeRNAi3778.
NextBio14823.
PROQ12791.
SOURCESearch...

Entry information

Entry nameKCMA1_HUMAN
AccessionPrimary (citable) accession number: Q12791
Secondary accession number(s): F8WA96 expand/collapse secondary AC list , Q12886, Q12917, Q12921, Q12960, Q13150, Q5JQ23, Q5SQR9, Q96LG8, Q9UBB0, Q9UCX0, Q9UQK6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: April 16, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM