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Gene and Protein Information  |
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| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 6 | 1 | 757 | 19q13.33 | KCNC3 | potassium voltage-gated channel subfamily C member 3 | 3,15 |
| Mouse | 6 | 1 | 769 | 7 28.85 cM | Kcnc3 | potassium voltage gated channel, Shaw-related subfamily, member 3 | 15 |
| Rat | 6 | 1 | 889 | 1q22 | Kcnc3 | potassium voltage-gated channel subfamily C member 3 | |
| Previous and Unofficial Names |
| potassium voltage-gated channel subfamily C member 3 | Kcr2-3 | potassium voltage gated channel, Shaw-related subfamily, member 3 | potassium voltage-gated channel, Shaw-related subfamily, member 3 | potassium channel, voltage gated Shaw related subfamily C, member 3 | potassium channel, voltage gated Shaw-related subfamily C, member 3 | potassium voltage gated channel |
| Database Links |
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| Alphafold | Q14003 (Hs), Q63959 (Mm), Q01956 (Rn) |
| DrugBank Target | Q14003 (Hs) |
| Ensembl Gene | ENSG00000131398 (Hs), ENSMUSG00000062785 (Mm), ENSRNOG00000019959 (Rn) |
| Entrez Gene | 3748 (Hs), 16504 (Mm), 117101 (Rn) |
| Human Protein Atlas | ENSG00000131398 (Hs) |
| KEGG Gene | hsa:3748 (Hs), mmu:16504 (Mm), rno:117101 (Rn) |
| OMIM | 176264 (Hs) |
| Orphanet | ORPHA159737 (Hs) |
| Pharos | Q14003 (Hs) |
| RefSeq Nucleotide | NM_004977 (Hs), NM_008422 (Mm), NM_053997 (Rn) |
| RefSeq Protein | NP_004968 (Hs), NP_032448 (Mm), NP_446449 (Rn) |
| UniProtKB | Q14003 (Hs), Q63959 (Mm), Q01956 (Rn) |
| Wikipedia | KCNC3 (Hs) |
| Functional Characteristics |
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| KA | |
| Ion Selectivity and Conductance |
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| Ion Selectivity and Conductance Comments | ||||||
| K+ ion selectivity; details not established |
| Voltage Dependence |
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| Voltage Dependence Comments | ||||||||||||||||
| Also carried out in CHO and HEK293 cells transfected with the teleost homologue of Kv3.3 known as AptKv3.3 [10] |
Download all structure-activity data for this target as a CSV file 
| Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Also detected in rabbit lens and corneal epithelium [21] | ||||||||
| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| General Comments |
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Mice lacking Kv3.3 and Kv3.1 show alcohol hypersensitivity, increased locomotion and myoclonus [8] It is a member of the mammalian Shaw-related family. |
1. Adelman JP, Bond CT, Pessia M, Maylie J. (1995) Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron, 15 (6): 1449-54. [PMID:8845167]
2. Akemann W, Knöpfel T. (2006) Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons. J Neurosci, 26 (17): 4602-12. [PMID:16641240]
3. Brooke RE, Atkinson L, Edwards I, Parson SH, Deuchars J. (2006) Immunohistochemical localisation of the voltage gated potassium ion channel subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord. Brain Res, 1070 (1): 101-15. [PMID:16403474]
4. Brooke RE, Corns L, Edwards IJ, Deuchars J. (2010) Kv3.3 immunoreactivity in the vestibular nuclear complex of the rat with focus on the medial vestibular nucleus: targeting of Kv3.3 neurones by terminals positive for vesicular glutamate transporter 1. Brain Res, 1345: 45-58. [PMID:20471378]
5. Chang SY, Zagha E, Kwon ES, Ozaita A, Bobik M, Martone ME, Ellisman MH, Heintz N, Rudy B. (2007) Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations of mouse brain. J Comp Neurol, 502 (6): 953-72. [PMID:17444489]
6. Duarri A, Nibbeling EA, Fokkens MR, Meijer M, Boerrigter M, Verschuuren-Bemelmans CC, Kremer BP, van de Warrenburg BP, Dooijes D, Boddeke E et al.. (2015) Functional analysis helps to define KCNC3 mutational spectrum in dutch ataxia cases. PLoS ONE, 10 (3): e0116599. [PMID:25756792]
7. Espinosa F, Marks G, Heintz N, Joho RH. (2004) Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels. Genes Brain Behav, 3 (2): 90-100. [PMID:15005717]
8. Espinosa F, McMahon A, Chan E, Wang S, Ho CS, Heintz N, Joho RH. (2001) Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. J Neurosci, 21 (17): 6657-65. [PMID:11517255]
9. Espinosa F, Torres-Vega MA, Marks GA, Joho RH. (2008) Ablation of Kv3.1 and Kv3.3 potassium channels disrupts thalamocortical oscillations in vitro and in vivo. J Neurosci, 28 (21): 5570-81. [PMID:18495891]
10. Fernandez FR, Morales E, Rashid AJ, Dunn RJ, Turner RW. (2003) Inactivation of Kv3.3 potassium channels in heterologous expression systems. J Biol Chem, 278 (42): 40890-8. [PMID:12923191]
11. Figueroa KP, Minassian NA, Stevanin G, Waters M, Garibyan V, Forlani S, Strzelczyk A, Bürk K, Brice A, Dürr A et al.. (2010) KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients. Hum Mutat, 31 (2): 191-6. [PMID:19953606]
12. Figueroa KP, Waters MF, Garibyan V, Bird TD, Gomez CM, Ranum LP, Minassian NA, Papazian DM, Pulst SM. (2011) Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13). PLoS ONE, 6 (3): e17811. [PMID:21479265]
13. Ghanshani S, Pak M, McPherson JD, Strong M, Dethlefs B, Wasmuth JJ, Salkoff L, Gutman GA, Chandy KG. (1992) Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1. Genomics, 12 (2): 190-6. [PMID:1740329]
14. Grigg JJ, Brew HM, Tempel BL. (2000) Differential expression of voltage-gated potassium channel genes in auditory nuclei of the mouse brainstem. Hear Res, 140 (1-2): 77-90. [PMID:10675636]
15. Haas M, Ward DC, Lee J, Roses AD, Clarke V, D'Eustachio P, Lau D, Vega-Saenz de Miera E, Rudy B. (1993) Localization of Shaw-related K+ channel genes on mouse and human chromosomes. Mamm Genome, 4 (12): 711-5. [PMID:8111118]
16. Hurlock EC, Bose M, Pierce G, Joho RH. (2009) Rescue of motor coordination by Purkinje cell-targeted restoration of Kv3.3 channels in Kcnc3-null mice requires Kcnc1. J Neurosci, 29 (50): 15735-44. [PMID:20016089]
17. Hurlock EC, McMahon A, Joho RH. (2008) Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. J Neurosci, 28 (18): 4640-8. [PMID:18448641]
18. Joho RH, Street C, Matsushita S, Knöpfel T. (2006) Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice. Genes Brain Behav, 5 (6): 472-82. [PMID:16923152]
19. Ordög B, Brutyó E, Puskás LG, Papp JG, Varró A, Szabad J, Boldogkoi Z. (2006) Gene expression profiling of human cardiac potassium and sodium channels. Int J Cardiol, 111 (3): 386-93. [PMID:16257073]
20. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Dolan CR, Fong CT, Smith RJH et al.. (1993) Spinocerebellar Ataxia Type 13. GeneReviews(®),. [PMID:20301404]
21. Rae JL, Shepard AR. (2000) Kv3.3 potassium channels in lens epithelium and corneal endothelium. Exp Eye Res, 70 (3): 339-48. [PMID:10712820]
22. Sacco T, De Luca A, Tempia F. (2006) Properties and expression of Kv3 channels in cerebellar Purkinje cells. Mol Cell Neurosci, 33 (2): 170-9. [PMID:16949837]
23. Vega-Saenz de Miera E, Moreno H, Fruhling D, Kentros C, Rudy B. (1992) Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel. Proc Biol Sci, 248 (1321): 9-18. [PMID:1381835]
24. Waters MF, Minassian NA, Stevanin G, Figueroa KP, Bannister JP, Nolte D, Mock AF, Evidente VG, Fee DB, Müller U et al.. (2006) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet, 38 (4): 447-51. [PMID:16501573]
25. Xu C, Lu Y, Tang G, Wang R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am J Physiol, 277 (5): G1055-63. [PMID:10564112]
26. Zagha E, Lang EJ, Rudy B. (2008) Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform. J Neurosci, 28 (6): 1291-300. [PMID:18256249]
27. Zagha E, Manita S, Ross WN, Rudy B. (2010) Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes. J Neurophysiol, 103 (6): 3516-25. [PMID:20357073]
