Gene Symbol: Hk
Description: Hyperkinetic
Alias: CG17779, CG2287, CG32688, CG34319, CG43388, Dm_X:51771, Dmel\CG43388, Dmel_CG32688, Dmel_CG34319, lincRNA.975, hyperkinetic, CG43388-PD, CG43388-PE, CG43388-PF, CG43388-PG, CG43388-PH, CG43388-PI, CG43388-PK, CG43388-PL, CG43388-PM, Hk-PD, Hk-PE, Hk-PF, Hk-PG, Hk-PH, Hk-PI, Hk-PK, Hk-PL, Hk-PM, hyperk, kvbeta channel subunit
Species: fruit fly

Top Publications

  1. Bushey D, Huber R, Tononi G, Cirelli C. Drosophila Hyperkinetic mutants have reduced sleep and impaired memory. J Neurosci. 2007;27:5384-93 pubmed
    ..The Sh current is potentiated by a beta modulatory subunit coded by Hyperkinetic (Hk)...
  2. Koh K, Joiner W, Wu M, Yue Z, Smith C, Sehgal A. Identification of SLEEPLESS, a sleep-promoting factor. Science. 2008;321:372-6 pubmed publisher
    ..Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability. ..
  3. Chouinard S, Wilson G, Schlimgen A, Ganetzky B. A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus. Proc Natl Acad Sci U S A. 1995;92:6763-7 pubmed
    Genetic and physiological studies of the Drosophila Hyperkinetic (Hk) mutant revealed defects in the function or regulation of K+ channels encoded by the Shaker (Sh) locus...
  4. Rogina B, Helfand S. Regulation of gene expression is linked to life span in adult Drosophila. Genetics. 1995;141:1043-8 pubmed
    ..Genetic mutations, Hyperkinetic and Shaker, which are known to shorten life span through an acceleration of the aging process, were used to ..
  5. Kaplan W, Trout W. The behavior of four neurological mutants of Drosophila. Genetics. 1969;61:399-409 pubmed
  6. Trout W, Kaplan W. A relation between longevity, metabolic rate, and activity in shaker mutants of Drosophila melanogaster. Exp Gerontol. 1970;5:83-92 pubmed
  7. Singh S, Kumar P, Ramachandra N, Nongthomba U. Roles of the troponin isoforms during indirect flight muscle development in Drosophila. J Genet. 2014;93:379-88 pubmed
    ..Moreover, rescue experiments conducted with troponin-I embryonic isoform in the IFMs, where flies were rendered flightless, show developmental and functional differences of TnI isoforms and importance of maintaining the right isoform. ..
  8. Rogina B, Vaupel J, Partridge L, Helfand S. Regulation of gene expression is preserved in aging Drosophila melanogaster. Curr Biol. 1998;8:475-8 pubmed
    ..Although regulation of gene expression is a central feature of life, a global decline in the control of gene expression does not appear to be either a cause or a consequence of the process of aging. ..
  9. Pavlidis P, Tanouye M. Seizures and failures in the giant fiber pathway of Drosophila bang-sensitive paralytic mutants. J Neurosci. 1995;15:5810-9 pubmed
    ..This hypothesis is supported by the finding that, in double mutant combination with mlenapts, which suppresses behavioral bang sensitivity, DLM failures, but not seizures, were reduced. ..

More Information


  1. Wang J, Wu C. Modulation of the frequency response of Shaker potassium channels by the quiver peptide suggesting a novel extracellular interaction mechanism. J Neurogenet. 2010;24:67-74 pubmed publisher
    ..Correspondingly, qvr mutant larvae exhibit multiple synaptic discharges following individual nerve stimuli during repetitive activity. ..
  2. Ueda A, Wu C. Effects of social isolation on neuromuscular excitability and aggressive behaviors in Drosophila: altered responses by Hk and gsts1, two mutations implicated in redox regulation. J Neurogenet. 2009;23:378-94 pubmed publisher
    ..We found that mutations of two genes, Hyperkinetic (Hk) and glutathione S-transferase-S1 (gsts1), alter the response to social isolation in Drosophila...
  3. Scantlebury N, Sajic R, Campos A. Kinematic analysis of Drosophila larval locomotion in response to intermittent light pulses. Behav Genet. 2007;37:513-24 pubmed
  4. Xu K, Bogert B, Li W, Su K, Lee A, Gao F. The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG/ENaC protein pickpocket1. Curr Biol. 2004;14:1025-34 pubmed
    ..Our finding that the level of ppk1 mRNA is regulated by DFMR1 and Ago2 reveals a genetic pathway that controls sensory input-modulated locomotion behavior. ..
  5. Lee J, Wu C. Genetic modifications of seizure susceptibility and expression by altered excitability in Drosophila Na(+) and K(+) channel mutants. J Neurophysiol. 2006;96:2465-78 pubmed
    ..Altered transient K(+) currents in Sh(133) and Hk mutants promoted ID induction...
  6. Ganetzky B, Wu C. Indirect Suppression Involving Behavioral Mutants with Altered Nerve Excitability in DROSOPHILA MELANOGASTER. Genetics. 1982;100:597-614 pubmed
    ..Genetic interactions of this type help reveal functional relationships between different behavioral mutants and suggest ways of isolating new mutants with altered excitable membranes. ..
  7. Budnik V. Synapse maturation and structural plasticity at Drosophila neuromuscular junctions. Curr Opin Neurobiol. 1996;6:858-67 pubmed
    ..The manipulation of the genes encoding ion channels, components of second-messenger cascades, and cell adhesion molecules is beginning to tease apart the mechanisms underlying structural synaptic plasticity. ..
  8. Bushey D, Hughes K, Tononi G, Cirelli C. Sleep, aging, and lifespan in Drosophila. BMC Neurosci. 2010;11:56 pubmed publisher
    ..We compared 3 short sleeping mutant lines (Hk1, HkY and Hk2) carrying a mutation in Hyperkinetic, which codes for the beta subunit of the Shaker channel, to wild-type siblings throughout their entire lifespan ..
  9. Stern M, Ganetzky B. Identification and characterization of inebriated, a gene affecting neuronal excitability in Drosophila. J Neurogenet. 1992;8:157-72 pubmed
    ..Application of DDF to ine mutants had no effects either in the presence or absence of quinidine. We conclude that ine mutations increase neuronal membrane excitability and perhaps block a DDF-sensitive potassium channel. ..
  10. Tolar L, Pallanck L. NSF function in neurotransmitter release involves rearrangement of the SNARE complex downstream of synaptic vesicle docking. J Neurosci. 1998;18:10250-6 pubmed
  11. Iyengar A, Wu C. Flight and seizure motor patterns in Drosophila mutants: simultaneous acoustic and electrophysiological recordings of wing beats and flight muscle activity. J Neurogenet. 2014;28:316-28 pubmed publisher
    ..K(+) channels (slowpoke, slo), and 3) voltage-gated K(+) channels (Shaker, Sh) and their auxiliary subunits (Hyperkinetic, Hk and quiver, qvr)...
  12. Weber U, Eroglu C, Mlodzik M. Phospholipid membrane composition affects EGF receptor and Notch signaling through effects on endocytosis during Drosophila development. Dev Cell. 2003;5:559-70 pubmed
    ..A further link between PC/PI content, endocytosis, and signaling is supported by genetic interactions of dCCT1 with Egfr, Notch, and genes affecting endosomal traffic. ..
  13. Trimmer J. Regulation of ion channel expression by cytoplasmic subunits. Curr Opin Neurobiol. 1998;8:370-4 pubmed
    ..The mechanisms by which these effects occur are now being elucidated through a combined approach that employs biophysical, pharmacological, cell biological and biochemical techniques. ..
  14. Ruan H, Wu C. Social interaction-mediated lifespan extension of Drosophila Cu/Zn superoxide dismutase mutants. Proc Natl Acad Sci U S A. 2008;105:7506-10 pubmed publisher
    ..Our results provide a definitive case of beneficial social interaction on lifespan and a useful entry point for analyzing the underlying molecular networks and physiological mechanisms. ..
  15. Humphreys J, Duyf B, Joiner M, Phillips J, Hilliker A. Genetic analysis of oxygen defense mechanisms in Drosophila melanogaster and identification of a novel behavioural mutant with a Shaker phenotype. Genome. 1996;39:749-57 pubmed
    ..This mutation is similar in phenotype to the Shaker (Sh), ether-a-gogo (eag), and Hyperkinetic (Hk) mutations, all of which affect potassium channel function in D. melanogaster.
  16. Iyengar A, Imoehl J, Ueda A, Nirschl J, Wu C. Automated quantification of locomotion, social interaction, and mate preference in Drosophila mutants. J Neurogenet. 2012;26:306-16 pubmed publisher
    ..We report altered motor activity in the K(+) and Na(+) channel mutants, Hk(1) and para(ts1), which had previously been shown to display abnormal larval locomotion...
  17. Fogle K, Baik L, Houl J, Tran T, Roberts L, Dahm N, et al. CRYPTOCHROME-mediated phototransduction by modulation of the potassium ion channel β-subunit redox sensor. Proc Natl Acad Sci U S A. 2015;112:2245-50 pubmed publisher
    ..via a well conserved redox sensor of the voltage-gated potassium (K(+)) channel β-subunit (Kvβ) Hyperkinetic (Hk)...
  18. Huang Q, Wu Y, Wei X, He W, Liu X, Ye J. Evolutionary analysis of voltage-gated potassium channels by Bayes method. J Mol Neurosci. 2014;53:41-9 pubmed publisher
  19. Parrish J, Kim C, Tang L, Bergquist S, Wang T, Derisi J, et al. Krüppel mediates the selective rebalancing of ion channel expression. Neuron. 2014;82:537-44 pubmed publisher
    ..Thus, homeostatic signaling systems responsible for rebalancing ion channel expression can be selectively induced after the loss or impairment of a specific ion channel. ..
  20. Haddrill P, Thornton K, Charlesworth B, Andolfatto P. Multilocus patterns of nucleotide variability and the demographic and selection history of Drosophila melanogaster populations. Genome Res. 2005;15:790-9 pubmed
    ..Demographic departures from equilibrium expectations in both ancestral and derived populations thus represent a serious challenge to detecting positive selection in genome-wide scans using current methodologies. ..
  21. Pimentel D, Donlea J, Talbot C, Song S, Thurston A, Miesenbock G. Operation of a homeostatic sleep switch. Nature. 2016;536:333-337 pubmed publisher
    ..Biophysical changes in a small population of neurons are thus linked to the control of sleep-wake state. ..
  22. Budnik V, Zhong Y, Wu C. Morphological plasticity of motor axons in Drosophila mutants with altered excitability. J Neurosci. 1990;10:3754-68 pubmed
    ..We examined motor axon terminals of (1) hyperexcitable mutants Shaker (Sh), ether a go-go (eag), Hyperkinetic (Hk), and Duplication of para+ (Dp para+); and (2) mutants with reduced excitability, no action potential (..
  23. Engel J, Wu C. Genetic dissection of functional contributions of specific potassium channel subunits in habituation of an escape circuit in Drosophila. J Neurosci. 1998;18:2254-67 pubmed
    ..Our results show that mutations altering each of four K+ channel subunits (Sh, slo, eag, and Hk) have distinct effects on habituation at least as strong as those of dunce and rutabaga, memory mutants with ..
  24. McCormack T. Comparison of K+-channel genes within the genomes of Anopheles gambiae and Drosophila melanogaster. Genome Biol. 2003;4:R58 pubmed
  25. Rogina B, Helfand S. Spatial and temporal pattern of expression of the wingless and engrailed genes in the adult antenna is regulated by age-dependent mechanisms. Mech Dev. 1997;63:89-97 pubmed
    ..These studies suggest that the expression of wg and en in the adult antenna is controlled by age-dependent mechanisms. ..
  26. Ueda A, Wu C. Effects of hyperkinetic, a beta subunit of Shaker voltage-dependent K+ channels, on the oxidation state of presynaptic nerve terminals. J Neurogenet. 2008;22:1-13 pubmed publisher
    The Drosophila Hyperkinetic (Hk) gene encodes a beta subunit of Shaker (Sh) K+ channels and shows high sequence homology to aldoketoreductase...
  27. Roeper J, Pongs O. Presynaptic potassium channels. Curr Opin Neurobiol. 1996;6:338-41 pubmed
  28. Wang J, Wu C. In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels. Biophys J. 1996;71:3167-76 pubmed
    ..Drosophila Hyperkinetic (Hk) mutations alter a gene encoding a homolog of the mammalian K+ channel beta subunit, providing a unique ..
  29. Kerscher S, Albert S, Wucherpfennig D, Heisenberg M, Schneuwly S. Molecular and genetic analysis of the Drosophila mas-1 (mannosidase-1) gene which encodes a glycoprotein processing alpha 1,2-mannosidase. Dev Biol. 1995;168:613-26 pubmed
    ..These findings illustrate that the processing of N-linked glycans plays a functional role in Drosophila development. There is, however, ample evidence for genetic and biochemical redundancy in the mannose-trimming steps of this pathway. ..
  30. Trout W, Kaplan W. Mosaic mapping of foci associated with longevity in the neurological mutants Hk1 and Sh5 of Drosophila melanogaster. Exp Gerontol. 1981;16:461-74 pubmed
  31. Deak I, Bellamy P, Bienz M, Dubuis Y, Fenner E, Gollin M, et al. Mutations affecting the indirect flight muscles of Drosophila melanogaster. J Embryol Exp Morphol. 1982;69:61-81 pubmed
    ..The absence of reduction of the 54 K protein was strongly correlated with aberrant Z-bands. ..
  32. Yoshihara M, Ito K. Acute genetic manipulation of neuronal activity for the functional dissection of neural circuits-a dream come true for the pioneers of behavioral genetics. J Neurogenet. 2012;26:43-52 pubmed publisher
    ..This methodology opened a new avenue to dissect functions of neural circuits to make dreams of the pioneers into reality. ..
  33. Joiner M, Asztalos Z, Jones C, Tully T, Wu C. Effects of mutant Drosophila K+ channel subunits on habituation of the olfactory jump response. J Neurogenet. 2007;21:45-58 pubmed
    ..Habituation in the olfactory jump assay in Hyperkinetic and Shaker mutants was drastically different from the degree of defect in the giant fiber-mediated escape ..
  34. Stern M, Ganetzky B. Altered synaptic transmission in Drosophila hyperkinetic mutants. J Neurogenet. 1989;5:215-28 pubmed
    ..Here we show that mutations in the Hyperkinetic (Hk) gene also affect the properties of synaptic transmission at the neuromuscular junction...
  35. Lee A, Li W, Xu K, Bogert B, Su K, Gao F. Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1. Development. 2003;130:5543-52 pubmed
    ..These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect. ..
  36. Rogina B, Helfand S. Indy mutations and Drosophila longevity. Front Genet. 2013;4:47 pubmed publisher
    ..Here we report that several Indy alleles in a diverse array of genetic backgrounds confer increased longevity. ..
  37. Stern M, Kreber R, Ganetzky B. Dosage effects of a Drosophila sodium channel gene on behavior and axonal excitability. Genetics. 1990;124:133-43 pubmed
    ..We conclude that the number of sodium channels present in at least some Drosophila neurons can be affected by changes in para+ gene dosage, and that the level of para+ expression can strongly influence neuronal excitability. ..
  38. Ingleby L, Maloney R, Jepson J, Horn R, Reenan R. Regulated RNA editing and functional epistasis in Shaker potassium channels. J Gen Physiol. 2009;133:17-27 pubmed publisher
    ..Our results unmask allosteric communication across disparate regions of the channel protein and between evolved and regulated amino acid changes introduced by RNA editing. ..
  39. Wu C, Chen M. Co-assembly of potassium channel subunits in Drosophila: the combinatorial hypothesis revisited. Chin J Physiol. 1995;38:131-8 pubmed
    ..Various lines of evidence from in situ experiments in Drosophila and heterologous channel expression in Xenopus oocytes will be reviewed. ..
  40. Wang J, Humphreys J, Phillips J, Hilliker A, Wu C. A novel leg-shaking Drosophila mutant defective in a voltage-gated K(+)current and hypersensitive to reactive oxygen species. J Neurosci. 2000;20:5958-64 pubmed
    ..One mutant so isolated, named quiver(1) (qvr(1)), has a leg-shaking phenotype. Mutants of the Shaker (Sh), Hyperkinetic (Hk), and ether a go-go (eag) genes, which encode different K(+) channel subunits that regulate the A-type K(+) ..
  41. Barros A, Sierra L, Comendador M. Decreased metabolic rate as an acrolein resistance mechanism in Drosophila melanogaster. Behav Genet. 1991;21:445-51 pubmed
    ..The results agree with this prediction. ..
  42. Wang J, Soll D, Wu C. Morphometric description of the wandering behavior in Drosophila larvae: a phenotypic analysis of K+ channel mutants. J Neurogenet. 2002;16:45-63 pubmed
    ..Mutations of the Shaker (Sh), Hyperkinetic (Hk), ether a go-go (eag) and quiver (qvr) genes have been found to affect the IAK+ channel in different ways...
  43. Helfand S, Rogina B. Genetics of aging in the fruit fly, Drosophila melanogaster. Annu Rev Genet. 2003;37:329-48 pubmed
  44. Burnet B, Connolly K, Mallinson M. Activity and sexual behavior of neurological mutants in Drosophila melanogaster. Behav Genet. 1974;4:227-35 pubmed
  45. Wilson G, Wang Z, Chouinard S, Griffith L, Ganetzky B. Interaction of the K channel beta subunit, Hyperkinetic, with eag family members. J Biol Chem. 1998;273:6389-94 pubmed
    ..Xu, J., and Li, M. (1996) Neuron 16, 441-453). Here we show that the Drosophila beta subunit homologue Hyperkinetic (Hk) associates with members of the ether go-go (eag), as well as Sh, families...
  46. Rogina B, Helfand S. Timing of expression of a gene in the adult Drosophila is regulated by mechanisms independent of temperature and metabolic rate. Genetics. 1996;143:1643-51 pubmed
    ..Varying the ambient temperature and using hyperactivity mutants (Hyperkinetic, Shaker) demonstrates that the rate of this decline is independent of temperature and metabolic rate...
  47. Lorbeck M, Singh N, Zervos A, Dhatta M, Lapchenko M, Yang C, et al. The histone demethylase Dmel\Kdm4A controls genes required for life span and male-specific sex determination in Drosophila. Gene. 2010;450:8-17 pubmed publisher
    ..Our results have implications for the role of the epigenetic regulator Dmel\Kdm4A in the control of genes involved in life span and male-specific sex determination in the fly. ..
  48. Dissel S, Melnattur K, Shaw P. Sleep, Performance, and Memory in Flies. Curr Sleep Med Rep. 2015;1:47-54 pubmed publisher
    ..We conclude that as Drosophila sleep researchers expand their analysis beyond sleep time, the opportunities to discover the function of sleep will be enhanced. ..
  49. Pan L, Xie W, Li K, Yang Z, Xu J, Zhang W, et al. Heterochromatin remodeling by CDK12 contributes to learning in Drosophila. Proc Natl Acad Sci U S A. 2015;112:13988-93 pubmed publisher
    ..Taken together, these results define a previously unidentified role of CDK12 in controlling the epigenetic transition between euchromatin and heterochromatin and suggest a chromatin regulatory mechanism in neuronal behaviors. ..
  50. Livingstone M, Sziber P, Quinn W. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell. 1984;37:205-15 pubmed
    ..The mutation possibly affects the catalytic subunit directly. We postulate that there is at least one other type of adenylate cyclase activity that is unaffected by the mutation and insensitive to calcium/calmodulin. ..