KCa3.1
Target id: 384
Nomenclature: KCa3.1
Family: Calcium- and sodium-activated potassium channels (KCa, KNa)
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Functional Characteristics
- Ion Selectivity and Conductance
- Voltage Dependence
- Activators
- Gating Inhibitors
- Channel Blockers
- Immunopharmacology Comments
- Immuno Cell Type Associations
- Immuno Process Associations
- Tissue Distribution
- Functional Assays
- Physiological Functions
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Gene Expression and Pathophysiology
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 6 | 1 | 427 | 19q13.31 | KCNN4 | potassium calcium-activated channel subfamily N member 4 | 22-23,28,30,40 |
| Mouse | 6 | 1 | 425 | 7 A3 | Kcnn4 | potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 | 68 |
| Rat | 6 | 1 | 425 | 1q21 | Kcnn4 | potassium calcium-activated channel subfamily N member 4 | 70 |
| Previous and Unofficial Names |
| Gardos channel | IKCa1 | Ik1 | KCa4 | intermediate-conductance Ca-activated K channel | SK4 | potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 4 | potassium intermediate/small conductance calcium-activated channel |
| Database Links |
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| Alphafold | O15554 (Hs), O89109 (Mm), Q9QYW1 (Rn) |
| ChEMBL Target | CHEMBL4305 (Hs) |
| DrugBank Target | O15554 (Hs) |
| Ensembl Gene | ENSG00000104783 (Hs), ENSMUSG00000054342 (Mm), ENSRNOG00000019440 (Rn) |
| Entrez Gene | 3783 (Hs), 16534 (Mm), 65206 (Rn) |
| Human Protein Atlas | ENSG00000104783 (Hs) |
| KEGG Gene | hsa:3783 (Hs), mmu:16534 (Mm), rno:65206 (Rn) |
| OMIM | 602754 (Hs) |
| Pharos | O15554 (Hs) |
| RefSeq Nucleotide | NM_002250 (Hs), NM_008433 (Mm), NM_023021 (Rn) |
| RefSeq Protein | NP_002241 (Hs), NP_032459 (Mm), NP_075410 (Rn) |
| UniProtKB | O15554 (Hs), O89109 (Mm), Q9QYW1 (Rn) |
| Wikipedia | KCNN4 (Hs) |
| Associated Proteins |
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| Functional Characteristics |
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| IKCa | |
| Ion Selectivity and Conductance |
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| Voltage Dependence Comments |
| KCa3.1 is voltage independent. |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No species differences described; NS309, DCEBIO, riluzole and EBIO increase the Ca2+ sensitivity of both KCa3.1 and KCa2 channels; see [74-75] for a recent extensive review of KCa3.1 and KCa2 channel pharmacology. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gating Inhibitor Comments | ||
| [1,3-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate) (RA-2) is a negative gating modulator that inhibits KCa3.1 with an IC50 of 17 nM and all three KCa2 channels with similar potency. It right-shifts the Ca2+ activation curve [44]. The inhibitory gating modulator of KCa2 channels NS8593 does not block KCa3.1 [61]. |
| Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Many more blockers have been characterised; see [74-75] for an extensive review of the pharmacology. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| KCa3.1 and KV1.3 are the predominant potassium channels involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation [12,18,41]. KCa3.1 is voltage-independent and is activated by Ca2+ binding to the calmodulin that is always present at the channel's C terminus. In activated T cells, KCa3.1 and KV1.3 localise to the immunological synapse, where interactions with regulatory kinases occurs. In addition to functions in cell cycle progression and cellular proliferation, KCa3.1 channels play an important immunoregulatory role, including participation in pathologic mechanisms that are associated with the inflammatory and proliferative cascades that characterise autoimmune diseases such as rheumatoid arthritis [20,51]. Notably KCa3.1 knockout mice are resistant to experimental collagen‐induced (i.e. autoimmune) arthritis [51]. KCa3.1 is involved in lymphocyte activation, and in the proliferation and migration of T cells, B cells, mast cells, macrophages and fibroblasts. As an inflammation-relevant drug target [72], KCa3.1 modulators are being investigated for potential in the treatment of asthma and fibroproliferative disorders, and for immunosuppressant efficacy [69]. |
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References
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49. Rapetti-Mauss R, Lacoste C, Picard V, Guitton C, Lombard E, Loosveld M, Nivaggioni V, Dasilva N, Salgado D, Desvignes JP et al.. (2015) A mutation in the Gardos channel is associated with hereditary xerocytosis. Blood, 126 (11): 1273-80. [PMID:26148990]
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