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Target not currently curated in GtoImmuPdb
Target id: 380
Nomenclature: KCa1.1
Family: Calcium- and sodium-activated potassium channels (KCa, KNa)
Gene and Protein Information | |||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 1 | 1236 | 10q22.3 | KCNMA1 | potassium calcium-activated channel subfamily M alpha 1 | 17 |
Mouse | 7 | 1 | 1209 | 14 A3 | Kcnma1 | potassium large conductance calcium-activated channel, subfamily M, alpha member 1 | |
Rat | 7 | 1 | 1209 | 15p16 | Kcnma1 | potassium calcium-activated channel subfamily M alpha 1 |
Database Links | |
Alphafold | Q12791 (Hs), Q08460 (Mm), Q62976 (Rn) |
ChEMBL Target | CHEMBL4304 (Hs), CHEMBL2800 (Mm), CHEMBL5505 (Rn) |
DrugBank Target | Q12791 (Hs) |
Ensembl Gene | ENSG00000156113 (Hs), ENSMUSG00000063142 (Mm), ENSRNOG00000005985 (Rn) |
Entrez Gene | 3778 (Hs), 16531 (Mm), 83731 (Rn) |
Human Protein Atlas | ENSG00000156113 (Hs) |
KEGG Gene | hsa:3778 (Hs), mmu:16531 (Mm), rno:83731 (Rn) |
OMIM | 600150 (Hs) |
Orphanet | ORPHA122795 (Hs) |
Pharos | Q12791 (Hs) |
RefSeq Nucleotide | NM_001014797 (Hs), NM_010610 (Mm), NM_031828 (Rn) |
RefSeq Protein | NP_001014797 (Hs), NP_034740 (Mm), NP_114016 (Rn) |
UniProtKB | Q12791 (Hs), Q08460 (Mm), Q62976 (Rn) |
Wikipedia | KCNMA1 (Hs) |
Associated Proteins | ||||||||||||||||||||||
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Functional Characteristics | |
Maxi KCa |
Ion Selectivity and Conductance | ||||||
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Download all structure-activity data for this target as a CSV file
Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mg2+ has also been reported as an activator for the KCa1.1 |
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific channel blocker tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Other channel blockers include: charybdotoxin, iberiotoxin and tetraethylammonium. |
Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Tissue Distribution | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||
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General Comments |
Channel openers may have applications in stroke, epilepsy, bladder over-reactivity, asthma, hypertension, gastric hypermotility and psychoses [5,7,10]. Crystal Structures have been solved for the Intracellular Gating Rings [22,26-27]. A gene therapy plasmid vector that expresses human KCa1.1 (URO-902) is in clinical development as a novel therapeutic approach for the treament of overactive bladder syndrome associated with detrusor overactivity [14]. URO-902 is delivered either by a single intravesical instillation or by direct injections into bladder detrusor muscle, thus limting effects to bladder tissue. |
1. Amrutkar DVm Foster K, Jacobsen TA, Jefson MR, Keaney GF, Larsen JS, Nielsen KS. (2018) Potassium channel modulators. Patent number: US9975886B1. Assignee: Cadent Therapeutics Inc. Priority date: 23/01/2018. Publication date: 22/04/2018.
2. Bentzen BH, Nardi A, Calloe K, Madsen LS, Olesen SP, Grunnet M. (2007) The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels. Mol Pharmacol, 72 (4): 1033-44. [PMID:17636045]
3. Brenner R, Jegla TJ, Wickenden A, Liu Y, Aldrich RW. (2000) Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J Biol Chem, 275 (9): 6453-61. [PMID:10692449]
4. Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L. (1993) mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels. Science, 261 (5118): 221-4. [PMID:7687074]
5. Coghlan MJ, Carroll WA, Gopalakrishnan M. (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J Med Chem, 44 (11): 1627-53. [PMID:11356099]
6. Garcia-Valdes J, Zamudio FZ, Toro L, Possani LD, Possan LD. (2001) Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between alpha and alpha+beta (beta1 or beta4) complexes. FEBS Lett, 505 (3): 369-73. [PMID:11576530]
7. Gribkoff VK, Starrett Jr JE, Dworetzky SI, Hewawasam P, Boissard CG, Cook DA, Frantz SW, Heman K, Hibbard JR, Huston K et al.. (2001) Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels. Nat Med, 7 (4): 471-7. [PMID:11283675]
8. Jiang Z, Wallner M, Meera P, Toro L. (1999) Human and rodent MaxiK channel beta-subunit genes: cloning and characterization. Genomics, 55 (1): 57-67. [PMID:9888999]
9. Joiner WJ, Tang MD, Wang LY, Dworetzky SI, Boissard CG, Gan L, Gribkoff VK, Kaczmarek LK. (1998) Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci, 1 (6): 462-9. [PMID:10196543]
10. Kaczorowski GJ, Knaus HG, Leonard RJ, McManus OB, Garcia ML. (1996) High-conductance calcium-activated potassium channels; structure, pharmacology, and function. J Bioenerg Biomembr, 28 (3): 255-67. [PMID:8807400]
11. Liu G, Shi J, Yang L, Cao L, Park SM, Cui J, Marx SO. (2004) Assembly of a Ca2+-dependent BK channel signaling complex by binding to beta2 adrenergic receptor. EMBO J, 23 (11): 2196-205. [PMID:15141163]
12. Meera P, Wallner M, Song M, Toro L. (1997) 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. Proc Natl Acad Sci USA, 94 (25): 14066-71. [PMID:9391153]
13. Persohn E, Malherbe P, Richards JG. (1992) Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS. J Comp Neurol, 326 (2): 193-216. [PMID:1336019]
14. Rovner E, Chai TC, Jacobs S, Christ G, Andersson KE, Efros M, Nitti V, Davies K, McCullough AR, Melman A. (2020) Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials. Neurourol Urodyn, 39 (2): 744-753. [PMID:31945197]
15. Sanchez M, McManus OB. (1996) Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel. Neuropharmacology, 35 (7): 963-8. [PMID:8938726]
16. Strøbaek D, Christophersen P, Holm NR, Moldt P, Ahring PK, Johansen TE, Olesen SP. (1996) Modulation of the Ca(2+)-dependent K+ channel, hslo, by the substituted diphenylurea NS 1608, paxilline and internal Ca2+. Neuropharmacology, 35 (7): 903-14. [PMID:8938721]
17. Tseng-Crank J, Foster CD, Krause JD, Mertz R, Godinot N, DiChiara TJ, Reinhart PH. (1994) Cloning, expression, and distribution of functionally distinct Ca(2+)-activated K+ channel isoforms from human brain. Neuron, 13 (6): 1315-30. [PMID:7993625]
18. Valverde MA, Rojas P, Amigo J, Cosmelli D, Orio P, Bahamonde MI, Mann GE, Vergara C, Latorre R. (1999) Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science, 285 (5435): 1929-31. [PMID:10489376]
19. Wei A, Solaro C, Lingle C, Salkoff L. (1994) Calcium sensitivity of BK-type KCa channels determined by a separable domain. Neuron, 13 (3): 671-81. [PMID:7917297]
20. Weiger TM, Holmqvist MH, Levitan IB, Clark FT, Sprague S, Huang WJ, Ge P, Wang C, Lawson D, Jurman ME, Glucksmann MA, Silos-Santiago I, DiStefano PS, Curtis R. (2000) A novel nervous system beta subunit that downregulates human large conductance calcium-dependent potassium channels. J Neurosci, 20 (10): 3563-70. [PMID:10804197]
21. Wisden W, Laurie DJ, Monyer H, Seeburg PH. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci, 12 (3): 1040-62. [PMID:1312131]
22. Wu Y, Yang Y, Ye S, Jiang Y. (2010) Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel. Nature, 466 (7304): 393-7. [PMID:20574420]
23. Yan J, Aldrich RW. (2010) LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium. Nature, 466 (7305): 513-6. [PMID:20613726]
24. Yan J, Aldrich RW. (2012) BK potassium channel modulation by leucine-rich repeat-containing proteins. Proc Natl Acad Sci USA, 109 (20): 7917-22. [PMID:22547800]
25. Yao J, Chen X, Li H, Zhou Y, Yao L, Wu G, Chen X, Zhang N, Zhou Z, Xu T et al.. (2005) BmP09, a "long chain" scorpion peptide blocker of BK channels. J Biol Chem, 280 (15): 14819-28. [PMID:15695820]
26. Yuan P, Leonetti MD, Hsiung Y, MacKinnon R. (2012) Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel. Nature, 481 (7379): 94-7. [PMID:22139424]
27. Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R. (2010) Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution. Science, 329 (5988): 182-6. [PMID:20508092]