Q08460 (KCMA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 16, 2012.
Version 119.
History...
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Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 Short name=mSlo1 Slowpoke homolog Short name=Slo homolog Short name=mSlo | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus |
Protein attributes
| Sequence length | 1209 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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). Ref.2 |
| Enzyme regulation | Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation By similarity. |
| Subunit structure | Interacts with LRRC26 By similarity. Homotetramer; which constitutes the calcium-activated potassium channel. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Beta subunits are accessory, and modulate its activity. Ref.6 |
| Subcellular location | Membrane; Multi-pass membrane protein By similarity. |
| Domain | The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor. 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. 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+. 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. The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation By similarity. |
| Post-translational modification | Phosphorylated Probable. Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity. Ref.11 |
| 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 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 AAA50215.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Ion transport Potassium transport Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing |
| Domain | Transmembrane Transmembrane helix |
| Ligand | Calcium Magnesium Metal-binding Potassium |
| Molecular function | Ionic channel Potassium channel Voltage-gated channel |
| PTM | Phosphoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Cellular component | voltage-gated potassium channel complex Inferred from electronic annotation. Source: InterPro |
| Molecular function | large conductance calcium-activated potassium channel activity Inferred from electronic annotation. Source: InterPro metal ion bindingInferred from electronic annotation. Source: UniProtKB-KW nucleotide bindingInferred from electronic annotation. Source: InterPro protein bindingInferred from physical interaction PubMed 19423573. Source: IntAct voltage-gated potassium channel activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Actg1 | P63260 | 4 | EBI-1633915,EBI-351301 | |
| Anxa5 | P48036 | 4 | EBI-1633915,EBI-1184119 | |
| Apoa1 | Q00623 | 4 | EBI-1633915,EBI-1634106 | |
| Calm3 | P62204 | 4 | EBI-1633915,EBI-397460 | |
| Gapdh | P16858 | 3 | EBI-1633915,EBI-444871 | |
| Hpca | P84075 | 3 | EBI-1633915,EBI-2128343 | |
| Lin7c | O88952 | 4 | EBI-1633915,EBI-821316 | |
| Mpz | P27573 | 4 | EBI-1633915,EBI-1634589 | |
| Ywhag | P61982 | 4 | EBI-1633915,EBI-359843 |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] Note: May be partially controlled by hormonal stress. Additional isoforms seem to exist. | ||||||
| Isoform 1 (identifier: Q08460-1) 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: Q08460-2) The sequence of this isoform differs from the canonical sequence as follows: 1-50: MANGGGGGGGSSGGGGGGGGGSGLRMSSNIHANNLSLDASSSSSSSSSSS → MELEHPKSPPYP 643-646: Missing. 702-702: L → LIYF 948-974: Missing. 1203-1209: RKEMVYR → ATRMTRMGQAEKKWFTDEPDNAYPRNIQIKPMSTHMANQINQYKSTSSLIPPIREVEDEC | ||||||
| Isoform 3 (identifier: Q08460-3) The sequence of this isoform differs from the canonical sequence as follows: 643-646: Missing. 948-974: Missing. | ||||||
| Isoform 4 (identifier: Q08460-4) Also known as: STREX-1; The sequence of this isoform differs from the canonical sequence as follows: 643-646: Missing. 702-702: L → PKMSIYKRMRRACCFDCGRSERDCSCMSGRVRGNVDTLERTFPLSSVSVNDCSTSFRAF 948-974: Missing. | ||||||
| Isoform 5 (identifier: Q08460-5) The sequence of this isoform differs from the canonical sequence as follows: 1-65: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1209 | 1209 | Calcium-activated potassium channel subunit alpha-1 | PRO_0000054134 | |||||
Regions | |||||||||
| Topological domain | 1 – 86 | 86 | Extracellular Potential | ||||||
| Transmembrane | 87 – 107 | 21 | Helical; Name=Segment S0; Potential | ||||||
| Topological domain | 108 – 178 | 71 | Cytoplasmic Potential | ||||||
| Transmembrane | 179 – 199 | 21 | Helical; Name=Segment S1; Potential | ||||||
| Topological domain | 200 – 214 | 15 | Extracellular Potential | ||||||
| Transmembrane | 215 – 235 | 21 | Helical; Name=Segment S2; Potential | ||||||
| Topological domain | 236 – 239 | 4 | Cytoplasmic Potential | ||||||
| Transmembrane | 240 – 260 | 21 | Helical; Name=Segment S3; Potential | ||||||
| Topological domain | 261 – 264 | 4 | Extracellular Potential | ||||||
| Transmembrane | 265 – 285 | 21 | Helical; Voltage-sensor; Name=Segment S4; Potential | ||||||
| Topological domain | 286 – 300 | 15 | Cytoplasmic Potential | ||||||
| Transmembrane | 301 – 321 | 21 | Helical; Name=Segment S5; Potential | ||||||
| Topological domain | 322 – 335 | 14 | Extracellular Potential | ||||||
| Intramembrane | 336 – 358 | 23 | Pore-forming; Name=P region; Potential | ||||||
| Topological domain | 359 – 367 | 9 | Extracellular Potential | ||||||
| Transmembrane | 368 – 388 | 21 | Helical; Name=Segment S6; Potential | ||||||
| Topological domain | 389 – 1209 | 821 | Cytoplasmic Potential | ||||||
| Domain | 415 – 558 | 144 | RCK N-terminal | ||||||
| Region | 556 – 576 | 21 | Segment S7 | ||||||
| Region | 613 – 633 | 21 | Segment S8 | ||||||
| Region | 681 – 685 | 5 | Heme-binding motif | ||||||
| Region | 783 – 803 | 21 | Segment S9 | ||||||
| Region | 1005 – 1025 | 21 | Segment S10 | ||||||
| Motif | 352 – 355 | 4 | Selectivity for potassium | ||||||
| Motif | 976 – 998 | 23 | Calcium bowl | ||||||
| Compositional bias | 4 – 10 | 7 | Poly-Gly | ||||||
| Compositional bias | 13 – 23 | 11 | Poly-Gly | ||||||
| Compositional bias | 40 – 60 | 21 | Poly-Ser | ||||||
Sites | |||||||||
| Metal binding | 439 | 1 | Magnesium Probable | ||||||
| Metal binding | 462 | 1 | Magnesium Probable | ||||||
| Metal binding | 464 | 1 | Magnesium Probable | ||||||
Amino acid modifications | |||||||||
| Modified residue | 569 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 711 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 1059 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 1061 | 1 | Phosphothreonine Ref.11 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 65 | 65 | Missing in isoform 5. | VSP_009959 | |||||
| Alternative sequence | 1 – 50 | 50 | MANGG…SSSSS → MELEHPKSPPYP in isoform 2. | VSP_009960 | |||||
| Alternative sequence | 643 – 646 | 4 | Missing in isoform 2, isoform 3 and isoform 4. | VSP_009961 | |||||
| Alternative sequence | 702 | 1 | L → LIYF in isoform 2. | VSP_009962 | |||||
| Alternative sequence | 702 | 1 | L → PKMSIYKRMRRACCFDCGRS ERDCSCMSGRVRGNVDTLER TFPLSSVSVNDCSTSFRAF in isoform 4. | VSP_009963 | |||||
| Alternative sequence | 948 – 974 | 27 | Missing in isoform 2, isoform 3 and isoform 4. | VSP_009964 | |||||
| Alternative sequence | 1203 – 1209 | 7 | RKEMVYR → ATRMTRMGQAEKKWFTDEPD NAYPRNIQIKPMSTHMANQI NQYKSTSSLIPPIREVEDEC in isoform 2. | VSP_009965 | |||||
Experimental info | |||||||||
| Mutagenesis | 151 | 1 | V → T: Loss of phosphorylation-independent activation of channel activity by ethanol. CaMK2-dependent phosphorylation leads to populations of partially phosphorylated tetramers with a range of responses to ethanol from activation to inhibition. Ref.3 | ||||||
| Mutagenesis | 272 | 1 | R → Q: Alters the voltage-dependent gating. Ref.7 | ||||||
| Mutagenesis | 278 | 1 | R → Q: Alters the voltage-dependent gating. Ref.7 | ||||||
| Mutagenesis | 284 | 1 | E → R: Alters the voltage-dependent gating; when associated with R-287. Ref.7 | ||||||
| Mutagenesis | 287 | 1 | Q → R: Alters the voltage-dependent gating; when associated with K-284. Ref.7 | ||||||
| Mutagenesis | 427 | 1 | D → A: Does not affect sensitivity to Ca(2+). Ref.10 | ||||||
| Mutagenesis | 432 | 1 | D → A: Reduced sensitivity to Ca(2+). Ref.10 | ||||||
| Mutagenesis | 434 | 1 | D → A: Does not affect sensitivity to Ca(2+). Ref.10 | ||||||
| Mutagenesis | 439 | 1 | E → A: Abolishes sensitivity to Mg(2+), but not sensitivity to Ca(2+). Ref.9 | ||||||
| Mutagenesis | 444 | 1 | H → G: Reduces sensitivity to Mg(2+), but not sensitivity to Ca(2+). Ref.9 | ||||||
| Mutagenesis | 461 | 1 | T → A: Reduces sensitivity to Mg(2+), but not sensitivity to Ca(2+). Ref.9 | ||||||
| Mutagenesis | 462 | 1 | Q → C: Reduces sensitivity to Mg(2+), but not sensitivity to Ca(2+). Ref.9 | ||||||
| Mutagenesis | 464 | 1 | E → D or A: Remains sensitive to Mg(2+). Ref.9 Ref.10 | ||||||
| Mutagenesis | 464 | 1 | E → N: Abolishes sensitivity to Mg(2+), but not sensitivity to Ca(2+). Ref.9 Ref.10 | ||||||
| Mutagenesis | 992 – 996 | 5 | DDDPD → AAAAA: Alters calcium binding. Ref.8 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "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: 7987297] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain. |
| [2] | "mSlo, a complex mouse gene encoding 'maxi' calcium-activated potassium channels." Butler A., Tsunoda S., McCobb D.P., Wei A., Salkoff L. Science 261:221-224(1993) [PubMed: 7687074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 26-1209 (ISOFORMS 2 AND 5), FUNCTION. Tissue: Brain. |
| [3] | "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: 16341213] [Abstract] Cited for: MUTAGENESIS OF VAL-151. |
| [4] | "Molecular components of large conductance calcium-activated potassium (BK) channels in mouse pituitary corticotropes." Shipston M.J., Duncan R.R., Clark A.G., Antoni F.A., Tian L. Mol. Endocrinol. 13:1728-1737(1999) [PubMed: 10517674] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 66-1209 (ISOFORM 4). Tissue: Pituitary anterior lobe. |
| [5] | "Molecular identification of Ca2+-activated K+ channels in parotid acinar cells." Nehrke K., Quinn C.C., Begenisich T. Am. J. Physiol. 284:C535-C546(2003) [PubMed: 12388098] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 66-1209 (ISOFORM 3). Strain: NIH Swiss. Tissue: Parotid gland. |
| [6] | "A novel nervous system beta subunit that downregulates human large conductance calcium-dependent potassium channels." Weiger T.M., Holmqvist M.H., Levitan I.B., Clark F.T., Sprague S., Huang W.-J., Ge P., Wang C., Lawson D., Jurman M.E., Glucksmann M.A., Silos-Santiago I., DiStefano P.S., Curtis R. J. Neurosci. 20:3563-3570(2000) [PubMed: 10804197] [Abstract] Cited for: INTERACTION WITH KCNMB3. |
| [7] | "Allosteric linkage between voltage and Ca(2+)-dependent activation of BK-type mslo1 K(+) channels." Cui J., Aldrich R.W. Biochemistry 39:15612-15619(2000) [PubMed: 11112549] [Abstract] Cited for: MUTAGENESIS OF ARG-272; ARG-278; GLU-284 AND GLN-287. |
| [8] | "Elimination of the BK(Ca) channel's high-affinity Ca(2+) sensitivity." Bao L., Rapin A.M., Holmstrand E.C., Cox D.H. J. Gen. Physiol. 120:173-189(2002) [PubMed: 12149279] [Abstract] Cited for: CALCIUM-BINDING, MUTAGENESIS OF 992-ASP--ASP-996. |
| [9] | "Mechanism of magnesium activation of calcium-activated potassium channels." Shi J., Krishnamoorthy G., Yang Y., Hu L., Chaturvedi N., Harilal D., Qin J., Cui J. Nature 418:876-880(2002) [PubMed: 12192410] [Abstract] Cited for: MAGNESIUM-BINDING, MUTAGENESIS OF GLU-439; HIS-444; THR-461; GLN-462 AND GLU-464. |
| [10] | "Multiple regulatory sites in large-conductance calcium-activated potassium channels." Xia X.-M., Zeng X., Lingle C.J. Nature 418:880-884(2002) [PubMed: 12192411] [Abstract] Cited for: CALCIUM-BINDING, MAGNESIUM-BINDING, MUTAGENESIS OF ASP-427; ASP-432; ASP-434 AND GLU-464. |
| [11] | "Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-711 AND THR-1061, MASS SPECTROMETRY. Tissue: Brain cortex. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U09383 mRNA. Translation: AAA50215.1. Different initiation. L16912 mRNA. Translation: AAA39746.1. AF156674 mRNA. Translation: AAD49225.1. AF465244 mRNA. Translation: AAL69971.1. |
| IPI | IPI00120643. IPI00410901. IPI00410903. IPI00410904. IPI00975115. |
| PIR | A48206. I49017. |
| RefSeq | NP_001240294.1. NM_001253365.1. NP_001240298.1. NM_001253369.1. NP_034740.2. NM_010610.3. |
| UniGene | Mm.343607. Mm.483319. Mm.486347. |
3D structure databases | |
| ProteinModelPortal | Q08460. |
| SMR | Q08460. Positions 257-284, 310-391, 396-1155. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q08460. 165 interactions. |
| MINT | MINT-1203219. |
| STRING | Q08460. |
PTM databases | |
| PhosphoSite | Q08460. |
Proteomic databases | |
| PRIDE | Q08460. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| GeneID | 16531. |
| KEGG | mmu:16531. |
| UCSC | uc007sme.2. mouse. uc007smh.1. mouse. uc007smi.1. mouse. |
Organism-specific databases | |
| MGI | MGI:99923. Kcnma1. |
Phylogenomic databases | |
| eggNOG | COG1226. |
| HOGENOM | HOG000019856. |
| HOVERGEN | HBG052222. |
| KO | K04936. |
| OrthoDB | EOG4QFWCD. |
Gene expression databases | |
| ArrayExpress | Q08460. |
| Genevestigator | Q08460. |
| GermOnline | ENSMUSG00000063142. Mus musculus. |
Family and domain databases | |
| Gene3D | G3DSA:3.40.50.720. NAD(P)-bd. 1 hit. |
| InterPro | IPR024939. Ca-act_K_channel_Slo. IPR005821. Ion_trans. IPR003091. K_chnl. IPR003929. K_chnl_Ca-activ_BK_asu. IPR016040. NAD(P)-bd_dom. IPR003148. RCK_N. [Graphical view] |
| PANTHER | PTHR10027. PTHR10027. 1 hit. PTHR10027:SF3. PTHR10027:SF3. 1 hit. |
| Pfam | PF03493. BK_channel_a. 1 hit. PF00520. Ion_trans. 1 hit. PF02254. TrkA_N. 1 hit. [Graphical view] |
| PRINTS | PR01449. BKCHANNELA. PR00169. KCHANNEL. |
| PROSITE | PS51201. RCK_N. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 289945. |
| SOURCE | Search... |
Entry information
| Entry name | KCMA1_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q08460 Secondary accession number(s): Q64703, Q8VHF1, Q9R196 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |