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Kv2.2

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Target not currently curated in GtoImmuPdb

Target id: 547

Nomenclature: Kv2.2

Family: Voltage-gated potassium channels (Kv)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 911 8q21.11 KCNB2 potassium voltage-gated channel subfamily B member 2 19
Mouse 6 1 907 1 4.5 cM Kcnb2 potassium voltage gated channel, Shab-related subfamily, member 2
Rat 6 1 907 5q11 Kcnb2 potassium voltage-gated channel subfamily B member 2
Previous and Unofficial Names Click here for help
CDRK | potassium voltage-gated channel subfamily B member 2 | potassium voltage-gated channel, Shab-related subfamily, member 2 | potassium channel, voltage gated Shab related subfamily B, member 2 | potassium channel, voltage gated Shab-related subfamily B, member 2 | potassium voltage gated channel
Database Links Click here for help
Alphafold Q92953 (Hs), A6H8H5 (Mm), Q63099 (Rn)
ChEMBL Target CHEMBL2321618 (Hs)
DrugBank Target Q92953 (Hs)
Ensembl Gene ENSG00000182674 (Hs), ENSMUSG00000092083 (Mm), ENSRNOG00000028991 (Rn)
Entrez Gene 9312 (Hs), 98741 (Mm), 117105 (Rn)
Human Protein Atlas ENSG00000182674 (Hs)
KEGG Gene hsa:9312 (Hs), mmu:98741 (Mm), rno:117105 (Rn)
OMIM 607738 (Hs)
Pharos Q92953 (Hs)
RefSeq Nucleotide NM_004770 (Hs), NM_001098528 (Mm), NM_054000 (Rn)
RefSeq Protein NP_004761 (Hs), NP_001091998 (Mm), NP_446452 (Rn)
UniProtKB Q92953 (Hs), A6H8H5 (Mm), Q63099 (Rn)
Wikipedia KCNB2 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Kv8.1 17
Kv9.1 18
Kv2.1 1,13
Kv9.2 18
Auxiliary Subunits
Name References
Kvβ4 5
Other Associated Proteins
Name References
KChaP 21
Ion Selectivity and Conductance Click here for help
Species:  Dog
Rank order:  K+ [15.0 pS]
References:  19
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - 97.0 19 Xenopus laevis oocyte Dog
Inactivation  - -
Comments  A slowly activating K+ current, non-inactivating
Associated subunits (Human)
Kv5.1, Kv6.1-6.4, Kv8.1-8.2 and Kv9.1-9.3

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

Gating inhibitors Click here for help
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
GxTx-1E Peptide Click here for species-specific activity table Hs - 8.6 pKd - - 9
⤷ pKd 8.6 (Kd 2.6x10-9 M) [9]
ScTx1 Peptide Click here for species-specific activity table Rn - 7.7 pIC50 - - 4
⤷ pIC50 7.7 (IC50 2.14x10-8 M) [4]
RY796 Small molecule or natural product Click here for species-specific activity table Hs - 7.1 pIC50 - - 8
⤷ pIC50 7.1 (IC50 9x10-8 M) [8]
RY785 Small molecule or natural product Click here for species-specific activity table Hs - 6.7 pIC50 - - 8
⤷ pIC50 6.7 (IC50 2x10-7 M) [8]
View species-specific gating inhibitor tables
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
quinine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Hs - 4.9 pIC50 - - 19
⤷ pIC50 4.9 [19]
fampridine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs - 2.8 pIC50 - - 19
⤷ pIC50 2.8 (IC50 1.5x10-3 M) [19]
tetraethylammonium Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - 2.6 pIC50 - - 19
⤷ pIC50 2.6 (IC50 2.6x10-3 M) [19]
Channel Blocker Comments
Phencyclidine (PCP) also inhbits human Kv2.2 from human colonic circular smooth muscle (pIC50 roughly 4.3) [6]
Tissue Distribution Click here for help
Gastric cancer cells
Species:  Human
Technique:  RT-PCR
References:  14
Pancreatic islet delta cells
Species:  Human
Technique:  Immunohistochemistry
References:  23
Brain: neocortical neurons with partial overlap with Kv2.1, basal forebrain, medial nucleus of the trapezoid body
Species:  Mouse
Technique:  Immunohistochemistry
References:  7,12
Gastrointestinal smooth muscle, mesenteric artery smooth muscle
Species:  Rat
Technique:  RT-PCR
References:  22
Brain neocortical neurons with partial overlap with Kv2.1, basal forebrain, medial nucleus of the trapezoid body
Species:  Rat
Technique:  Immunohistochemistry
References:  7,13
Tissue Distribution Comments
Also: Rabbit myocytes from corpus cavernosum (RT-PCR, [16]), Ferret cardiac myocytes (In situ hybridisation, [3]).
Functional Assays Click here for help
Gene cloning and voltage clamp
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  slowly activating K+ current
References:  19
Physiological Functions Click here for help
Maintaining membrane potential, modulating electrical excitability in neurons
Species:  Rat
Tissue:  Superior cervical ganglion (SCG)
References:  15
Maintaining membrane potential, modulating electrical excitability in spinal chord neurons
Species:  None
Tissue:  Xenopus laevis spinal chord neurons
References:  2
Maintain high frequency action potential firing
Species:  Mouse
Tissue:  MNTB neurons
References:  12
Physiological Functions Comments
Species ([2]): Xenopus laevis embryonic spinal neurons
Gene Expression and Pathophysiology Click here for help
KV2.2 expression in DRG neurons decreased after peripheral axotomy.
Tissue or cell type:  Dorsal root ganglion neurones
Pathophysiology:  Repetitive firing and peripheral hyperexcitability
Species:  Rat
Technique:  In situ hybridisation
References:  20
Biologically Significant Variant Comments
A total of 7585 SNPs have been identified in human KCNB2. For more information, please see the entry on GeneCards.
General Comments
The angiotensin II type 1 receptor mediates inhibition of Kv2.2 in the brainstem and hypothalamic neurons. It is a member of the mammalian Shab-related family. Some immunohistochemical studies performed with antibodies that were generated against an incorrect sequence of rat Kv2.2 [10], some studies on recombinant Kv2.2 channels using the rat cDNA may be confounded by incorrect sequence, as published in [11]. See [13] for correction.

References

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1. Blaine JT, Ribera AB. (1998) Heteromultimeric potassium channels formed by members of the Kv2 subfamily. J Neurosci, 18 (23): 9585-93. [PMID:9822719]

2. Blaine JT, Taylor AD, Ribera AB. (2004) Carboxyl tail region of the Kv2.2 subunit mediates novel developmental regulation of channel density. J Neurophysiol, 92 (6): 3446-54. [PMID:15306626]

3. Brahmajothi MV, Morales MJ, Liu S, Rasmusson RL, Campbell DL, Strauss HC. (1996) In situ hybridization reveals extensive diversity of K+ channel mRNA in isolated ferret cardiac myocytes. Circ Res, 78 (6): 1083-9. [PMID:8635239]

4. Escoubas P, Diochot S, Célérier ML, Nakajima T, Lazdunski M. (2002) Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Mol Pharmacol, 62 (1): 48-57. [PMID:12065754]

5. Fink M, Duprat F, Lesage F, Heurteaux C, Romey G, Barhanin J, Lazdunski M. (1996) A new K+ channel beta subunit to specifically enhance Kv2.2 (CDRK) expression. J Biol Chem, 271 (42): 26341-8. [PMID:8824288]

6. Frey BW, Lynch FT, Kinsella JM, Horowitz B, Sanders KM, Carl A. (2000) Blocking of cloned and native delayed rectifier K channels from visceral smooth muscles by phencyclidine. Neurogastroenterol Motil, 12 (6): 509-16. [PMID:11123705]

7. Hermanstyne TO, Kihira Y, Misono K, Deitchler A, Yanagawa Y, Misonou H. (2010) Immunolocalization of the voltage-gated potassium channel Kv2.2 in GABAergic neurons in the basal forebrain of rats and mice. J Comp Neurol, 518 (21): 4298-310. [PMID:20853508]

8. Herrington J, Solly K, Ratliff KS, Li N, Zhou YP, Howard A, Kiss L, Garcia ML, McManus OB, Deng Q et al.. (2011) Identification of novel and selective Kv2 channel inhibitors. Mol Pharmacol, 80 (6): 959-64. [PMID:21948463]

9. Herrington J, Zhou YP, Bugianesi RM, Dulski PM, Feng Y, Warren VA, Smith MM, Kohler MG, Garsky VM, Sanchez M et al.. (2006) Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion. Diabetes, 55 (4): 1034-42. [PMID:16567526]

10. Hwang PM, Fotuhi M, Bredt DS, Cunningham AM, Snyder SH. (1993) Contrasting immunohistochemical localizations in rat brain of two novel K+ channels of the Shab subfamily. J Neurosci, 13 (4): 1569-76. [PMID:8463836]

11. Hwang PM, Glatt CE, Bredt DS, Yellen G, Snyder SH. (1992) A novel K+ channel with unique localizations in mammalian brain: molecular cloning and characterization. Neuron, 8 (3): 473-81. [PMID:1550672]

12. Johnston J, Griffin SJ, Baker C, Skrzypiec A, Chernova T, Forsythe ID. (2008) Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons. J Physiol (Lond.), 586 (14): 3493-509. [PMID:18511484]

13. Kihira Y, Hermanstyne TO, Misonou H. (2010) Formation of heteromeric Kv2 channels in mammalian brain neurons. J Biol Chem, 285 (20): 15048-55. [PMID:20202934]

14. Lan M, Shi Y, Han Z, Hao Z, Pan Y, Liu N, Guo C, Hong L, Wang J, Qiao T et al.. (2005) Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells. Cancer Biol Ther, 4 (12): 1342-7. [PMID:16258262]

15. Malin SA, Nerbonne JM. (2002) Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons. J Neurosci, 22 (23): 10094-105. [PMID:12451110]

16. Malysz J, Farrugia G, Ou Y, Szurszewski JH, Nehra A, Gibbons SJ. (2002) The Kv2.2 alpha subunit contributes to delayed rectifier K(+) currents in myocytes from rabbit corpus cavernosum. J Androl, 23 (6): 899-910. [PMID:12399537]

17. Salinas M, de Weille J, Guillemare E, Lazdunski M, Hugnot JP. (1997) Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. J Biol Chem, 272 (13): 8774-80. [PMID:9079713]

18. Salinas M, Duprat F, Heurteaux C, Hugnot JP, Lazdunski M. (1997) New modulatory alpha subunits for mammalian Shab K+ channels. J Biol Chem, 272 (39): 24371-9. [PMID:9305895]

19. Schmalz F, Kinsella J, Koh SD, Vogalis F, Schneider A, Flynn ER, Kenyon JL, Horowitz B. (1998) Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles. Am J Physiol, 274 (5 Pt 1): G901-11. [PMID:9612272]

20. Tsantoulas C, Zhu L, Yip P, Grist J, Michael GJ, McMahon SB. (2014) Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input. Exp Neurol, 251: 115-26. [PMID:24252178]

21. Wible BA, Yang Q, Kuryshev YA, Accili EA, Brown AM. (1998) Cloning and expression of a novel K+ channel regulatory protein, KChAP. J Biol Chem, 273 (19): 11745-51. [PMID:9565597]

22. 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]

23. Yan L, Figueroa DJ, Austin CP, Liu Y, Bugianesi RM, Slaughter RS, Kaczorowski GJ, Kohler MG. (2004) Expression of voltage-gated potassium channels in human and rhesus pancreatic islets. Diabetes, 53 (3): 597-607. [PMID:14988243]

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