Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Functional Characteristics
- Ion Selectivity and Conductance
- Voltage Dependence
- Activators
- Inhibitors
- Channel Blockers
- Allosteric Modulators
- Tissue Distribution
- Physiological Functions
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- General Comments
- 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 | 872 | 20q13.33 | KCNQ2 | potassium voltage-gated channel subfamily Q member 2 | 32 |
| Mouse | 6 | 1 | 759 | 2 103.57 cM | Kcnq2 | potassium voltage-gated channel, subfamily Q, member 2 | 23 |
| Rat | 6 | 1 | 852 | 3q43 | Kcnq2 | potassium voltage-gated channel subfamily Q member 2 | 16 |
| Previous and Unofficial Names |
| BFNC | EBN1 | ENB1 | HNSPC | KCNA11 | potassium channel subunit alpha KvLQT2 | KQT2 | potassium channel, voltage gated KQT-like subfamily Q, member 2 | potassium channel, voltage-gated KQT-like subfamily Q, member 2 | potassium voltage-gated channel |
| Database Links |
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| Alphafold | O43526 (Hs), Q9Z351 (Mm), O88943 (Rn) |
| ChEMBL Target | CHEMBL2476 (Hs), CHEMBL2985 (Mm), CHEMBL5530 (Rn) |
| DrugBank Target | O43526 (Hs) |
| Ensembl Gene | ENSG00000075043 (Hs), ENSMUSG00000016346 (Mm), ENSRNOG00000011624 (Rn) |
| Entrez Gene | 3785 (Hs), 16536 (Mm), 170848 (Rn) |
| Human Protein Atlas | ENSG00000075043 (Hs) |
| KEGG Gene | hsa:3785 (Hs), mmu:16536 (Mm), rno:170848 (Rn) |
| OMIM | 602235 (Hs) |
| Orphanet | ORPHA122808 (Hs) |
| Pharos | O43526 (Hs) |
| RefSeq Nucleotide | NM_172107 (Hs), NM_010611 (Mm), NM_133322 (Rn) |
| RefSeq Protein | NP_742105 (Hs), NP_034741 (Mm), NP_579856 (Rn) |
| UniProtKB | O43526 (Hs), Q9Z351 (Mm), O88943 (Rn) |
| Wikipedia | KCNQ2 (Hs) |
| Associated Proteins |
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| Associated Protein Comments | ||||||||||||||||||||||||
| Gating and modulation: PIP2 exhibits low affinity to KCNQ2 (≈205 µM) and stabilizes the channel in the open state by increasing the open probability [8,19]. KCNQ2 subunit tethers PIP2, CaM, AKAP79/150, and PKC. Activation of PLC by muscarinic stimulation depletes PIP2 and activates PKC, which phosphorylates KCNQ2 subunit. The phosphorylation of KCNQ2 at S541 located in the distal segment of the CaM-binding site induces dissociation of CaM from the KCNQ2 channel, which lowers affinity towards PIP2. This produces profound suppression of the M-channel activity [17]. Ca2+-Calmodulin reduces the currents produced by KCNQ2, KCNQ4 and KCNQ5, but not those of KCNQ1 and KCNQ3 [8]. | ||||||||||||||||||||||||
| Functional Characteristics |
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| M current as a heteromer between KV7.2 and KV7.3 | |
| Ion Selectivity and Conductance |
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| Ion Selectivity and Conductance Comments | ||||||
| Voltage Dependence |
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Download all structure-activity data for this target as a CSV file 
| Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific activator tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Tissue Distribution
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| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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| General Comments |
| The M current is a slowly activating and deactivating potassium conductance that plays a critical role in determining the sub-threshold excitability of neurones as well as the responsiveness to synaptic inputs. The M current was first described in peripheral sympathetic neurones, and differential expression of this conductance produces subtypes of sympathetic neurones with distinct firing patterns. The M current is also expressed in many neurons in the central nervous system. The M-current is mediated by members of the Kv7 family, which form a heterotetrameric channel consisting of KCNQ3 subunits associated with either KCNQ2 or KCNQ5 subunits. Expression of KCNQ2, KCNQ3 and KCNQ5 proteins mostly overlaps with distribution of M current. The activation mechanism of KCNQ2 has been elicidated using high-resolution structures of the channel generated by cryo-electron microscopy [18]. Retigabine binds at the pore domain and activates the channel by an allosteric modulation, whereas ztz240 binds at the voltage-sensing domain and directly stabilizes the channel in the activated state [18]. |
References
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