Q28204 (KCMA1_BOVIN) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 104. History...
Names and origin
|Protein names||Recommended name:|
Calcium-activated potassium channel subunit alpha-1
Calcium-activated potassium channel, subfamily M subunit alpha-1
Maxi K channel
Short name=Slo homolog
|Organism||Bos taurus (Bovine) [Reference proteome]|
|Taxonomic identifier||9913 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos|
|Sequence length||1166 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca2+ that mediates export of K+. It is also activated by 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) By similarity.
Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation By similarity. Phosphorylation of Thr-139 leads to inhibition of channel activity by ethanol. Ref.3
Homotetramer; which constitutes the calcium-activated potassium channel. 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 By similarity.
The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4 By similarity.
The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor By similarity.
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 By similarity.
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.
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 By similarity.
The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation By similarity.
Phosphorylated. Isoform 1 and isoform 2 are stimulated by PKG, but not by PKA. In contrast, isoform 3 is exclusively stimulated by PKA. In smooth muscles, phosphorylation affects its activity. Ref.2 Ref.3
Incremental phosphorylation of Thr-139 of the KCNMA1 tetramer changes the response to ethanol from increased activation to inhibition of channel activity.
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+.
Contains 1 RCK N-terminal domain.
|This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]|
Note: May be partially controlled by hormonal stress. Additional isoforms seem to exist.
|Isoform 1 (identifier: Q28204-1) |
Also known as: A; BKA;
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: Q28204-2) |
Also known as: B; BKB;
The sequence of this isoform differs from the canonical sequence as follows:
1160-1166: YVQEERL → KEMVYL
|Isoform 3 (identifier: Q28204-3) |
Also known as: C; BKC;
The sequence of this isoform differs from the canonical sequence as follows:
1141-1166: STANRQNRPKSRESRDKQKYVQEERL → PQT
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1166||1166||Calcium-activated potassium channel subunit alpha-1||PRO_0000054130|
|Topological domain||1 – 74||74||Extracellular Potential|
|Transmembrane||75 – 95||21||Helical; Name=Segment S0; Potential|
|Topological domain||96 – 166||71||Cytoplasmic Potential|
|Transmembrane||167 – 187||21||Helical; Name=Segment S1; Potential|
|Topological domain||188 – 202||15||Extracellular Potential|
|Transmembrane||203 – 223||21||Helical; Name=Segment S2; Potential|
|Topological domain||224 – 227||4||Cytoplasmic Potential|
|Transmembrane||228 – 248||21||Helical; Name=Segment S3; Potential|
|Topological domain||249 – 252||4||Extracellular Potential|
|Transmembrane||253 – 273||21||Helical; Voltage-sensor; Name=Segment S4; Potential|
|Topological domain||274 – 288||15||Cytoplasmic Potential|
|Transmembrane||289 – 309||21||Helical; Name=Segment S5; Potential|
|Topological domain||310 – 323||14||Extracellular Potential|
|Intramembrane||324 – 346||23||Pore-forming; Name=P region; Potential|
|Topological domain||347 – 355||9||Extracellular Potential|
|Transmembrane||356 – 376||21||Helical; Name=Segment S6; Potential|
|Topological domain||377 – 1166||790||Cytoplasmic Potential|
|Domain||403 – 546||144||RCK N-terminal|
|Region||544 – 564||21||Segment S7|
|Region||601 – 621||21||Segment S8|
|Region||665 – 669||5||Heme-binding motif|
|Region||767 – 787||21||Segment S9|
|Region||962 – 982||21||Segment S10|
|Motif||340 – 343||4||Selectivity for potassium|
|Motif||933 – 955||23||Calcium bowl|
|Compositional bias||4 – 14||11||Poly-Gly|
|Compositional bias||33 – 48||16||Poly-Ser|
|Metal binding||427||1||Magnesium By similarity|
|Metal binding||450||1||Magnesium By similarity|
|Metal binding||452||1||Magnesium By similarity|
|Metal binding||942||1||Calcium; via carbonyl oxygen By similarity|
|Metal binding||945||1||Calcium; via carbonyl oxygen By similarity|
|Metal binding||948||1||Calcium By similarity|
|Metal binding||950||1||Calcium By similarity|
Amino acid modifications
|Modified residue||139||1||Phosphothreonine; by CamK2 Ref.3|
|Modified residue||695||1||Phosphoserine By similarity|
|Modified residue||1018||1||Phosphothreonine By similarity|
|Modified residue||1151||1||Phosphoserine; by PKG Probable|
|Modified residue||1154||1||Phosphoserine; by PKG Probable|
|Alternative sequence||1141 – 1166||26||STANR…QEERL → PQT in isoform 3.||VSP_009950|
|Alternative sequence||1160 – 1166||7||YVQEERL → KEMVYL in isoform 2.||VSP_009951|
|Mutagenesis||139||1||T → V: Loss of phosphorylation by CaMK2 and, therefore, inhibition of channel activity in response to ethanol. Ref.3|
|Mutagenesis||1151||1||S → A: Induces a stimulation by PKA instead of PKG; when associated with A-1154. Ref.2|
|Mutagenesis||1154||1||S → A: Induces a stimulation by PKA instead of PKG; when associated with A-1151. Ref.2|
|Sequence conflict||33 – 35||3||SSS → GST in AAB03663. Ref.2|
|||"A molecular switch for specific stimulation of the BKCa channel by cGMP and cAMP kinase."|
Zhou X.-B., Arntz C., Kamm S., Motejlek K., Sausbier U., Wang G.-X., Ruth P., Korth M.
J. Biol. Chem. 276:43239-43245(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Trachea smooth muscle.
|||"An evolutionarily conserved binding site for serine proteinase inhibitors in large conductance calcium-activated potassium channels."|
Moss G.W.J., Marshall J., Morabito M., Howe J.R., Moczydlowski E.
Biochemistry 35:16024-16035(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-1166 (ISOFORM 1), ALTERNATIVE SPLICING, PHOSPHORYLATION, MUTAGENESIS OF SER-1151 AND SER-1154.
Tissue: Aortic smooth muscle.
|||"CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels."|
Liu J., Asuncion-Chin M., Liu P., Dopico A.M.
Nat. Neurosci. 9:41-49(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-139, MUTAGENESIS OF THR-139.
|AY033472 mRNA. Translation: AAK54352.1.|
AY033473 mRNA. Translation: AAK54353.1.
AY033474 mRNA. Translation: AAK54354.1.
U60105 mRNA. Translation: AAB03663.1.
|RefSeq||NP_777105.1. NM_174680.2. |
3D structure databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSBTAT00000054334; ENSBTAP00000047743; ENSBTAG00000013300. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.1240. 1 hit. |
|InterPro||IPR024939. Ca-act_K_channel_Slo. |
|PANTHER||PTHR10027:SF3. PTHR10027:SF3. 1 hit. |
|Pfam||PF03493. BK_channel_a. 1 hit. |
PF00520. Ion_trans. 1 hit.
PF02254. TrkA_N. 1 hit.
|PRINTS||PR01449. BKCHANNELA. |
|PROSITE||PS51201. RCK_N. False negative. |
|Accession||Primary (citable) accession number: Q28204|
Secondary accession number(s): Q95J89, Q95J90, Q95J91
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families