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Kv1.6

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Not curated in GtoImmuPdb

Target id: 543

Nomenclature: Kv1.6

Family: Voltage-gated potassium channels (Kv)

Annotation status:  image of a blue circle Annotated and reviewed, awaiting update  » Email us

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 529 12p13.32 KCNA6 potassium voltage-gated channel subfamily A member 6 1,5
Mouse 6 1 529 6 61.72 cM Kcna6 potassium voltage-gated channel, shaker-related, subfamily, member 6 11
Rat 6 1 530 4q42 Kcna6 potassium voltage-gated channel subfamily A member 6 11
Previous and Unofficial Names Click here for help
HBK2 | RCK2 | potassium voltage-gated channel subfamily A member 6 | potassium voltage gated channel, shaker related subfamily, member 6 | potassium voltage-gated channel, shaker-related subfamily, member 6 | potassium channel, voltage gated shaker related subfamily A, member 6 | potassium voltage-gated channel, shaker-related, subfamily, member 6 | potassium voltage-gated channel
Database Links Click here for help
Alphafold P17658 (Hs), Q61923 (Mm), P17659 (Rn)
ChEMBL Target CHEMBL5279 (Hs), CHEMBL4105906 (Rn)
DrugBank Target P17658 (Hs)
Ensembl Gene ENSG00000151079 (Hs), ENSMUSG00000038077 (Mm), ENSRNOG00000052486 (Rn)
Entrez Gene 3742 (Hs), 16494 (Mm), 64358 (Rn)
Human Protein Atlas ENSG00000151079 (Hs)
KEGG Gene hsa:3742 (Hs), mmu:16494 (Mm), rno:64358 (Rn)
OMIM 176257 (Hs)
Pharos P17658 (Hs)
RefSeq Nucleotide NM_002235 (Hs), NM_013568 (Mm), NM_023954 (Rn)
RefSeq Protein NP_002226 (Hs), NP_038596 (Mm), NP_076444 (Rn)
UniProtKB P17658 (Hs), Q61923 (Mm), P17659 (Rn)
Wikipedia KCNA6 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Kv1.1 3
Kv1.2 3
Auxiliary Subunits
Name References
Kvβ1 14-15
Kvβ2 14-15
Other Associated Proteins
Name References
Caspr2 12
Functional Characteristics Click here for help
KV
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  K+ [9.0 pS]
References:  5
Species:  Human
Macroscopic current rectification:  Ik: Delayed Rectifier K+ current
References:  5
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -20.0 - 5 Xenopus laevis oocyte Human
Inactivation  - 3200.0 5
Associated subunits (Human)
Kv β1 and Kv β2

Download all structure-activity data for this target as a CSV file go icon to follow link

Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
[125I]BgK (W5Y / Y26F) Peptide Ligand is labelled Ligand is radioactive Rn - 11.4 pKd - - 13
⤷ pKd 11.4 [13]
hongotoxin-1 Peptide Click here for species-specific activity table Rn - 11.0 pKd - - 9
⤷ pKd 11.0 [9]
[125I]α-DTX Peptide Ligand is labelled Ligand is radioactive Rn - 10.4 pKd - - 13
⤷ pKd 10.4 [13]
ShK Toxin Peptide Click here for species-specific activity table Rn - 9.8 pIC50 - - 7
⤷ pIC50 9.8 [7]
charybdotoxin Peptide Click here for species-specific activity table Hs - 9.0 pIC50 - - 5
⤷ pIC50 9.0 [5]
mast cell degranulating peptide Peptide Hs - 8.0 pIC50 - - 5
⤷ pIC50 8.0 [5]
α-dendrotoxin Peptide Hs - 7.7 pIC50 - - 5
⤷ pIC50 7.7 (IC50 1.99x10-8 M) [5]
conopeptide Y-PI1 Peptide Rn Pore blocker 6.8 pIC50 - - 6
⤷ pIC50 6.8 (IC50 1.7x10-7 M) [6]
tetraethylammonium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - 2.2 pIC50 - - 5
⤷ pIC50 2.2 (IC50 7x10-3 M) [5]
View species-specific channel blocker tables
Channel Blocker Comments
β-bungarotoxin (pIC50 6.7), 10-N-methylcarbamoyl-3, 7 -bis(dimethylamino)phenothiazine (pIC50 6.7), 4-AP (pIC50 6.7), p114a (pIC50 5.8) [5,18].
Tissue Distribution Click here for help
Astrocytes.
Species:  Mouse
Technique:  Immunocytochemistry
References:  17
Spinal cord.
Species:  Rat
Technique:  In situ hybridisation
References:  10
Distal pulmonary artery, aorta, pulmonary artery smooth muscle cells.
Species:  Rat
Technique:  RT-PCR
References:  19,21
Oligodendrocytes, progenitor cells.
Species:  Rat
Technique:  In situ hybridisation
References:  2
Brain (medulla-pons, inferior colliculus > colliculus, midbrain > corpus striatum, cerebral cortex, hippocampus > cerebellum > olfactory bulb).
Species:  Rat
Technique:  Northern blot
References:  5
Myelinated adult optic nerve, murine colonic smooth muscle.
Species:  Rat
Technique:  RT-PCR, immunohistochemistry
References:  8,14
Functional Assays Click here for help
Molecular clone and voltage clamp.
Species:  Human
Tissue:  Xenopus laevis oocytes.
Response measured:  Delayed rectifier current.
References:  5
Physiological Functions Click here for help
Regulator of membrane potential neurons.
Species:  Rat
Tissue:  Nodose ganglia.
References:  4
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna6tm1Lex Kcna6tm1Lex/Kcna6tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J		 MGI:96663  MP:0001552 increased circulating triglyceride level
Kcna6tm1Lex Kcna6tm1Lex/Kcna6tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J		 MGI:96663  MP:0001973 increased thermal nociceptive threshold
Gene Expression and Pathophysiology Click here for help
Decrease of Kv1.6 mRNA and protein expression
Tissue or cell type:  Distal pulmonary artery
Pathophysiology:  The mRNA and protein levels of Kv1.6 α-subunits reduced by 34.4% and 39.2% separately exposed to chronic hypoxia
Species:  Rat
Technique:  RT-PCR, Western Blotting
References:  20
Biologically Significant Variant Comments
A total of 1034 SNPs have been identified in human KCNA6. For more information please see the entry on GeneCards.
General Comments
Kv1.6 may co-assemble with other Kv1 family members in heteromultimers. It cannot, however, co-assemble with members of other Kv families. It has an intronless coding region. The N-terminus of the protein contains an N-terminus inactivation prevention (NIP) domain [16]

References

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1. Albrecht B, Weber K, Pongs O. (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Recept Channels, 3 (3): 213-20. [PMID:8821794]

2. Attali B, Wang N, Kolot A, Sobko A, Cherepanov V, Soliven B. (1997) Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells. J Neurosci, 17 (21): 8234-45. [PMID:9334399]

3. Dodson PD, Barker MC, Forsythe ID. (2002) Two heteromeric Kv1 potassium channels differentially regulate action potential firing. J Neurosci, 22 (16): 6953-61. [PMID:12177193]

4. Glazebrook PA, Ramirez AN, Schild JH, Shieh CC, Doan T, Wible BA, Kunze DL. (2002) Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons. J Physiol (Lond.), 541 (Pt 2): 467-82. [PMID:12042352]

5. Grupe A, Schröter KH, Ruppersberg JP, Stocker M, Drewes T, Beckh S, Pongs O. (1990) Cloning and expression of a human voltage-gated potassium channel. A novel member of the RCK potassium channel family. EMBO J, 9 (6): 1749-56. [PMID:2347305]

6. Imperial JS, Chen P, Sporning A, Terlau H, Daly NL, Craik DJ, Alewood PF, Olivera BM. (2008) Tyrosine-rich conopeptides affect voltage-gated K+ channels. J Biol Chem, 283 (34): 23026-32. [PMID:18505731]

7. Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA et al.. (1998) ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem, 273 (49): 32697-707. [PMID:9830012]

8. Koh SD, Ward SM, Dick GM, Epperson A, Bonner HP, Sanders KM, Horowitz B, Kenyon JL. (1999) Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle. J Physiol (Lond.), 515 ( Pt 2): 475-87. [PMID:10050014]

9. Koschak A, Bugianesi RM, Mitterdorfer J, Kaczorowski GJ, Garcia ML, Knaus HG. (1998) Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom. J Biol Chem, 273 (5): 2639-44. [PMID:9446567]

10. Matus-Leibovitch N, Vogel Z, Ezra-Macabee V, Etkin S, Nevo I, Attali B. (1996) Chronic morphine administration enhances the expression of Kv1.5 and Kv1.6 voltage-gated K+ channels in rat spinal cord. Brain Res Mol Brain Res, 40 (2): 261-70. [PMID:8872310]

11. Migeon MB, Street VA, Demas VP, Tempel BL. (1992) Cloning, sequence and chromosomal localization of MK6, a murine potassium channel gene. Epilepsy Res Suppl, 9: 173-80; discussion 180-1. [PMID:1285906]

12. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E. (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron, 24 (4): 1037-47. [PMID:10624965]

13. Racapé J, Lecoq A, Romi-Lebrun R, Liu J, Kohler M, Garcia ML, Ménez A, Gasparini S. (2002) Characterization of a novel radiolabeled peptide selective for a subpopulation of voltage-gated potassium channels in mammalian brain. J Biol Chem, 277 (6): 3886-93. [PMID:11707459]

14. Rasband MN, Trimmer JS, Peles E, Levinson SR, Shrager P. (1999) K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve. J Neurocytol, 28 (4-5): 319-31. [PMID:10739574]

15. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, Trimmer JS. (1997) Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes. J Neurosci, 17 (21): 8246-58. [PMID:9334400]

16. Roeper J, Sewing S, Zhang Y, Sommer T, Wanner SG, Pongs O. (1998) NIP domain prevents N-type inactivation in voltage-gated potassium channels. Nature, 391 (6665): 390-3. [PMID:9450755]

17. Smart SL, Bosma MM, Tempel BL. (1997) Identification of the delayed rectifier potassium channel, Kv1.6, in cultured astrocytes. Glia, 20 (2): 127-34. [PMID:9179597]

18. Swanson R, Marshall J, Smith JS, Williams JB, Boyle MB, Folander K, Luneau CJ, Antanavage J, Oliva C, Buhrow SA. (1990) Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron, 4 (6): 929-39. [PMID:2361015]

19. Wang J, Juhaszova M, Rubin LJ, Yuan XJ. (1997) Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells. J Clin Invest, 100 (9): 2347-53. [PMID:9410914]

20. Wang J, Weigand L, Wang W, Sylvester JT, Shimoda LA. (2005) Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery. Am J Physiol Lung Cell Mol Physiol, 288 (6): L1049-58. [PMID:15665041]

21. Yuan XJ, Wang J, Juhaszova M, Golovina VA, Rubin LJ. (1998) Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells. Am J Physiol, 274 (4 Pt 1): L621-35. [PMID:9575881]

Contributors

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Citation information

K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Michael C. Sanguinetti, Walter Stühmer, James S. Trimmer, Xiaoliang Wang.

Last modified on 14/10/2014.

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