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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 | 630 | 7q31.31 | KCND2 | potassium voltage-gated channel subfamily D member 2 | 21,50 |
| Mouse | 6 | 1 | 630 | 6 8.49 cM | Kcnd2 | potassium voltage-gated channel, Shal-related family, member 2 | 18 |
| Rat | 6 | 1 | 630 | 4q22 | Kcnd2 | potassium voltage-gated channel subfamily D member 2 | 4 |
| Previous and Unofficial Names |
| Potassium voltage-gated channel subfamily D member 2 | RK5 | potassium voltage-gated channel, Shal-related subfamily, member 2 | potassium channel, voltage gated Shal related subfamily D, member 2 | potassium channel, voltage-gated Shal-related subfamily D, member 2 | potassium voltage-gated channel, Shal-related family, member 2 | potassium voltage-gated channel |
| Database Links |
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| Alphafold | Q9NZV8 (Hs), Q9Z0V2 (Mm), Q63881 (Rn) |
| ChEMBL Target | CHEMBL5885 (Hs), CHEMBL1075227 (Rn) |
| DrugBank Target | Q9NZV8 (Hs) |
| Ensembl Gene | ENSG00000184408 (Hs), ENSMUSG00000060882 (Mm), ENSRNOG00000067416 (Rn) |
| Entrez Gene | 3751 (Hs), 16508 (Mm), 65180 (Rn) |
| Human Protein Atlas | ENSG00000184408 (Hs) |
| KEGG Gene | hsa:3751 (Hs), mmu:16508 (Mm), rno:65180 (Rn) |
| OMIM | 605410 (Hs) |
| Pharos | Q9NZV8 (Hs) |
| RefSeq Nucleotide | NM_012281 (Hs), NM_019697 (Mm), NM_031730 (Rn) |
| RefSeq Protein | NP_036413 (Hs), NP_062671 (Mm), NP_113918 (Rn) |
| UniProtKB | Q9NZV8 (Hs), Q9Z0V2 (Mm), Q63881 (Rn) |
| Wikipedia | KCND2 (Hs) |
| Associated Proteins |
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| Functional Characteristics |
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| KA | |
| Ion Selectivity and Conductance |
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| Voltage Dependence |
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| Associated subunits (Human) |
| KChIP 1-4, DPP6, DPP10, Kvβ1, NCS-1, Navβ1 |
Download all structure-activity data for this target as a CSV file 
| Gating Inhibitor Comments | ||
| UO126 suppresses rat Kv4.2-mediated K+ currents and accelerates current decay in transfected CHO cells [48]. |
| Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Kv4.2 was relatively insensitive to TEA and also to DABCO (1,4 - Diazabicyclo[2.2.2] octane) derivatives, showing 3% block with 100 µM JE188, 3% block with 1 mM TG27, and 38% block with 0.5 mM JC638.2 [13] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Phenotypes, Alleles and Disease Models
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| Gene Expression and Pathophysiology
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| General Comments |
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Kv4.2 is a member of the mammalian Shal-related family. The Kv4.2 (KCND2) gene, like KCND1 and KCND3, contains six exons, although the introns are significantly longer in KCND2. The kinetic properties depend on the expression system, recording configuration, and the presence of auxiliary subunits (KChIPs). Kv4.2 currents expressed in Xenopus laevis oocytes are suppressed in response to protein kinase C activation. |
1. Adams JP, Anderson AE, Varga AW, Dineley KT, Cook RG, Pfaffinger PJ, Sweatt JD. (2000) The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated protein kinase ERK. J Neurochem, 75 (6): 2277-87. [PMID:11080179]
2. An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS et al.. (2000) Modulation of A-type potassium channels by a family of calcium sensors. Nature, 403 (6769): 553-6. [PMID:10676964]
3. Barry DM, Xu H, Schuessler RB, Nerbonne JM. (1998) Functional knockout of the transient outward current, long-QT syndrome, and cardiac remodeling in mice expressing a dominant-negative Kv4 alpha subunit. Circ Res, 83 (5): 560-7. [PMID:9734479]
4. Blair TA, Roberds SL, Tamkun MM, Hartshorne RP. (1991) Functional characterization of RK5, a voltage-gated K+ channel cloned from the rat cardiovascular system. FEBS Lett, 295 (1-3): 211-3. [PMID:1722463]
5. Brundel BJ, Van Gelder IC, Henning RH, Tuinenburg AE, Wietses M, Grandjean JG, Wilde AA, Van Gilst WH, Crijns HJ. (2001) Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels. J Am Coll Cardiol, 37 (3): 926-32. [PMID:11693772]
6. Bähring R, Boland LM, Varghese A, Gebauer M, Pongs O. (2001) Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels. J Physiol (Lond.), 535 (Pt 1): 65-81. [PMID:11507158]
7. Caballero R, Pourrier M, Schram G, Delpón E, Tamargo J, Nattel S. (2003) Effects of flecainide and quinidine on Kv4.2 currents: voltage dependence and role of S6 valines. Br J Pharmacol, 138 (8): 1475-84. [PMID:12721103]
8. Carrasquillo Y, Burkhalter A, Nerbonne JM. (2012) A-type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons. J Physiol (Lond.), 590 (Pt 16): 3877-90. [PMID:22615428]
9. Chagot B, Escoubas P, Villegas E, Bernard C, Ferrat G, Corzo G, Lazdunski M, Darbon H. (2004) Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus. Protein Sci, 13 (5): 1197-208. [PMID:15096626]
10. Diochot S, Drici MD, Moinier D, Fink M, Lazdunski M. (1999) Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Ito1 in cardiac electrogenesis. Br J Pharmacol, 126 (1): 251-63. [PMID:10051143]
11. Ebbinghaus J, Legros C, Nolting A, Guette C, Celerier ML, Pongs O, Bähring R. (2004) Modulation of Kv4.2 channels by a peptide isolated from the venom of the giant bird-eating tarantula Theraphosa leblondi. Toxicon, 43 (8): 923-32. [PMID:15208026]
12. Foeger NC, Wang W, Mellor RL, Nerbonne JM. (2013) Stabilization of Kv4 protein by the accessory K(+) channel interacting protein 2 (KChIP2) subunit is required for the generation of native myocardial fast transient outward K(+) currents. J Physiol (Lond.), 591 (Pt 17): 4149-66. [PMID:23713033]
13. Gordon E, Cohen JL, Engel R, Abbott GW. (2006) 1,4-Diazabicyclo[2.2.2]octane derivatives: a novel class of voltage-gated potassium channel blockers. Mol Pharmacol, 69 (3): 718-26. [PMID:16317109]
14. Guo W, Jung WE, Marionneau C, Aimond F, Xu H, Yamada KA, Schwarz TL, Demolombe S, Nerbonne JM. (2005) Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical and molecular remodeling, with no evidence of ventricular hypertrophy or myocardial dysfunction. Circ Res, 97 (12): 1342-50. [PMID:16293790]
15. Guo W, Li H, Aimond F, Johns DC, Rhodes KJ, Trimmer JS, Nerbonne JM. (2002) Role of heteromultimers in the generation of myocardial transient outward K+ currents. Circ Res, 90 (5): 586-93. [PMID:11909823]
16. Guo W, Malin SA, Johns DC, Jeromin A, Nerbonne JM. (2002) Modulation of Kv4-encoded K(+) currents in the mammalian myocardium by neuronal calcium sensor-1. J Biol Chem, 277 (29): 26436-43. [PMID:11994284]
17. Han W, Nattel S, Noguchi T, Shrier A. (2006) C-terminal domain of Kv4.2 and associated KChIP2 interactions regulate functional expression and gating of Kv4.2. J Biol Chem, 281 (37): 27134-44. [PMID:16820361]
18. Harrell MD, Harbi S, Hoffman JF, Zavadil J, Coetzee WA. (2007) Large-scale analysis of ion channel gene expression in the mouse heart during perinatal development. Physiol Genomics, 28 (3): 273-83. [PMID:16985003]
19. Holmqvist MH, Cao J, Knoppers MH, Jurman ME, Distefano PS, Rhodes KJ, Xie Y, An WF. (2001) Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins. J Neurosci, 21 (12): 4154-61. [PMID:11404400]
20. Hu HJ, Carrasquillo Y, Karim F, Jung WE, Nerbonne JM, Schwarz TL, Gereau 4th RW. (2006) The kv4.2 potassium channel subunit is required for pain plasticity. Neuron, 50 (1): 89-100. [PMID:16600858]
21. Isbrandt D, Leicher T, Waldschütz R, Zhu X, Luhmann U, Michel U, Sauter K, Pongs O. (2000) Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA). Genomics, 64 (2): 144-54. [PMID:10729221]
22. Jerng HH, Qian Y, Pfaffinger PJ. (2004) Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10). Biophys J, 87 (4): 2380-96. [PMID:15454437]
23. Jin HW, Zhang W, Qu LT, Wang XL. (2003) [Electrophysiological correspondence between Kv4.2 current and transient outward potassium current in the cultured rat hippocampal neuron]. Sheng Li Xue Bao, 55 (6): 711-6. [PMID:14695490]
24. Lee H, Lin MC, Kornblum HI, Papazian DM, Nelson SF. (2014) Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum Mol Genet, 23 (13): 3481-9. [PMID:24501278]
25. Lin YL, Chen CY, Cheng CP, Chang LS. (2004) Protein-protein interactions of KChIP proteins and Kv4.2. Biochem Biophys Res Commun, 321 (3): 606-10. [PMID:15358149]
26. London B, Baker LC, Petkova-Kirova P, Nerbonne JM, Choi BR, Salama G. (2007) Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT. J Physiol (Lond.), 578 (Pt 1): 115-29. [PMID:17110412]
27. Marionneau C, Carrasquillo Y, Norris AJ, Townsend RR, Isom LL, Link AJ, Nerbonne JM. (2012) The sodium channel accessory subunit Navβ1 regulates neuronal excitability through modulation of repolarizing voltage-gated K⁺ channels. J Neurosci, 32 (17): 5716-27. [PMID:22539834]
28. Marionneau C, LeDuc RD, Rohrs HW, Link AJ, Townsend RR, Nerbonne JM. (2009) Proteomic analyses of native brain K(V)4.2 channel complexes. Channels (Austin), 3 (4): 284-94. [PMID:19713751]
29. Nadal MS, Ozaita A, Amarillo Y, Vega-Saenz de Miera E, Ma Y, Mo W, Goldberg EM, Misumi Y, Ikehara Y, Neubert TA et al.. (2003) The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels. Neuron, 37 (3): 449-61. [PMID:12575952]
30. Nakamura TY, Sturm E, Pountney DJ, Orenzoff B, Artman M, Coetzee WA. (2003) Developmental expression of NCS-1 (frequenin), a regulator of Kv4 K+ channels, in mouse heart. Pediatr Res, 53 (4): 554-7. [PMID:12612193]
31. Nerbonne JM. (2000) Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. J Physiol (Lond.), 525 Pt 2: 285-98. [PMID:10835033]
32. Norris AJ, Nerbonne JM. (2010) Molecular dissection of I(A) in cortical pyramidal neurons reveals three distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits. J Neurosci, 30 (14): 5092-101. [PMID:20371829]
33. Plant LD, Webster NJ, Boyle JP, Ramsden M, Freir DB, Peers C, Pearson HA. (2006) Amyloid beta peptide as a physiological modulator of neuronal 'A'-type K+ current. Neurobiol Aging, 27 (11): 1673-83. [PMID:16271805]
34. Pourrier M, Herrera D, Caballero R, Schram G, Wang Z, Nattel S. (2004) The Kv4.2 N-terminal restores fast inactivation and confers KChlP2 modulatory effects on N-terminal-deleted Kv1.4 channels. Pflugers Arch, 449 (3): 235-47. [PMID:15452711]
35. Roberds SL, Tamkun MM. (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc Natl Acad Sci USA, 88 (5): 1798-802. [PMID:1705709]
36. Sanguinetti MC, Johnson JH, Hammerland LG, Kelbaugh PR, Volkmann RA, Saccomano NA, Mueller AL. (1997) Heteropodatoxins: peptides isolated from spider venom that block Kv4.2 potassium channels. Mol Pharmacol, 51 (3): 491-8. [PMID:9058605]
37. Sankaranarayanan A, Raman G, Busch C, Schultz T, Zimin PI, Hoyer J, Köhler R, Wulff H. (2009) Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol, 75 (2): 281-95. [PMID:18955585]
38. Shibata R, Misonou H, Campomanes CR, Anderson AE, Schrader LA, Doliveira LC, Carroll KI, Sweatt JD, Rhodes KJ, Trimmer JS. (2003) A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. J Biol Chem, 278 (38): 36445-54. [PMID:12829703]
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40. Strop P, Bankovich AJ, Hansen KC, Garcia KC, Brunger AT. (2004) Structure of a human A-type potassium channel interacting protein DPPX, a member of the dipeptidyl aminopeptidase family. J Mol Biol, 343 (4): 1055-65. [PMID:15476821]
41. Suzuki T, Takimoto K. (2005) Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy. Am J Physiol Endocrinol Metab, 288 (2): E335-41. [PMID:15454398]
42. Takimoto K, Li D, Hershman KM, Li P, Jackson EK, Levitan ES. (1997) Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats. Circ Res, 81 (4): 533-9. [PMID:9314834]
43. Tsaur ML, Sheng M, Lowenstein DH, Jan YN, Jan LY. (1992) Differential expression of K+ channel mRNAs in the rat brain and down-regulation in the hippocampus following seizures. Neuron, 8 (6): 1055-67. [PMID:1610565]
44. Vacher H, Diochot S, Bougis PE, Martin-Eauclaire MF, Mourre C. (2006) Kv4 channels sensitive to BmTX3 in rat nervous system: autoradiographic analysis of their distribution during brain ontogenesis. Eur J Neurosci, 24 (5): 1325-40. [PMID:16987219]
45. Villarroel A, Schwarz TL. (1996) Inhibition of the Kv4 (Shal) family of transient K+ currents by arachidonic acid. J Neurosci, 16 (8): 2522-32. [PMID:8786428]
46. Wang H, Shi H, Wang Z. (1999) Nicotine depresses the functions of multiple cardiac potassium channels. Life Sci, 65 (12): PL143-9. [PMID:10503950]
47. Wickenden AD, Jegla TJ, Kaprielian R, Backx PH. (1999) Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle. Am J Physiol, 276 (5): H1599-607. [PMID:10330244]
48. Yuan LL, Chen X, Kunjilwar K, Pfaffinger P, Johnston D. (2006) Acceleration of K+ channel inactivation by MEK inhibitor U0126. Am J Physiol, Cell Physiol, 290 (1): C165-71. [PMID:16135544]
49. Zagha E, Ozaita A, Chang SY, Nadal MS, Lin U, Saganich MJ, McCormack T, Akinsanya KO, Qi SY, Rudy B. (2005) DPP10 modulates Kv4-mediated A-type potassium channels. J Biol Chem, 280 (19): 18853-61. [PMID:15671030]
50. Zhu XR, Wulf A, Schwarz M, Isbrandt D, Pongs O. (1999) Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Recept Channels, 6 (5): 387-400. [PMID:10551270]
