KCNA5

Summary

Gene Symbol: KCNA5
Description: potassium voltage-gated channel subfamily A member 5
Alias: ATFB7, HCK1, HK2, HPCN1, KV1.5, PCN1, potassium voltage-gated channel subfamily A member 5, cardiac potassium channel, insulinoma and islet potassium channel, potassium channel 1, potassium channel, voltage gated shaker related subfamily A, member 5, potassium voltage-gated channel, shaker-related subfamily, member 5, voltage-gated potassium channel HK2, voltage-gated potassium channel protein Kv1.5, voltage-gated potassium channel subunit Kv1.5
Species: human
Products:     KCNA5

Top Publications

  1. Tamkun M, Knoth K, Walbridge J, Kroemer H, Roden D, Glover D. Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J. 1991;5:331-7 pubmed
    ..These two cDNAs, designated HK1 and HK2, encode proteins of 653 and 605 amino acids, respectively...
  2. Yang Z, Browning C, Hallaq H, Yermalitskaya L, Esker J, Hall M, et al. Four and a half LIM protein 1: a partner for KCNA5 in human atrium. Cardiovasc Res. 2008;78:449-57 pubmed publisher
    ..In human heart, the Shaker-related voltage-gated K(+) channel KCNA5 alpha-subunit forms the major basis of an atrial-specific, ultra-rapid delayed rectifier K(+) current, I(Kur)...
  3. Vicente R, Villalonga N, Calvo M, Escalada A, Solsona C, Soler C, et al. Kv1.5 association modifies Kv1.3 traffic and membrane localization. J Biol Chem. 2008;283:8756-64 pubmed publisher
    ..3 and Kv1.5 targeting to rafts. Our results implicate the traffic and localization of Kv1.3/Kv1.5 heteromers in the complex regulation of immune system cells. ..
  4. Schumacher S, McEwen D, Zhang L, Arendt K, Van Genderen K, Martens J. Antiarrhythmic drug-induced internalization of the atrial-specific k+ channel kv1.5. Circ Res. 2009;104:1390-8 pubmed publisher
    ....
  5. Remillard C, Tigno D, Platoshyn O, Burg E, Brevnova E, Conger D, et al. Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension. Am J Physiol Cell Physiol. 2007;292:C1837-53 pubmed
    ..Here, we report that overexpression of the Kv1.5 channel gene (KCNA5) in human PASMC and other cell lines produced a 15-pS single channel current and a large whole cell current that ..
  6. Kurata H, Soon G, Eldstrom J, Lu G, Steele D, Fedida D. Amino-terminal determinants of U-type inactivation of voltage-gated K+ channels. J Biol Chem. 2002;277:29045-53 pubmed
    ..1. These data suggest that intersubunit T1 domain interactions influence U-type inactivation in Kv1 channels, and suggest a generalized influence of the T1 domain on U-type inactivation between Kv channel subfamilies. ..
  7. Christophersen I, Olesen M, Liang B, Andersen M, Larsen A, Nielsen J, et al. Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. Eur Heart J. 2013;34:1517-25 pubmed publisher
    Genetic factors may be important in the development of atrial fibrillation (AF) in the young. KCNA5 encodes the potassium channel α-subunit KV1.5, which underlies the voltage-gated atrial-specific potassium current IKur...
  8. Abi Char J, El Haou S, Balse E, Neyroud N, Vranckx R, Coulombe A, et al. The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes. Am J Physiol Heart Circ Physiol. 2008;294:H1851-61 pubmed publisher
    ..In conclusion, SAP97 regulates the K(+) current in cardiac myocytes by retaining and immobilizing Kv1.5 subunits in the plasma membrane. This new regulatory mechanism may contribute to the targeting of Kv channels in cardiac myocytes. ..
  9. Yang Y, Li J, Lin X, Yang Y, Hong K, Wang L, et al. Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation. J Hum Genet. 2009;54:277-83 pubmed publisher
    ..However, the molecular defects in most patients with AF remain to be identified. Here, we report on three novel KCNA5 mutations that were identified in 4 of 120 unrelated AF families...
  10. Peretz A, Gil Henn H, Sobko A, Shinder V, Attali B, Elson A. Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon. EMBO J. 2000;19:4036-45 pubmed
    ..In all, PTP epsilon antagonizes activation of Kv channels by tyrosine kinases in vivo, and affects Schwann cell function during a critical period of Schwann cell growth and myelination. ..

Detail Information

Publications62

  1. Tamkun M, Knoth K, Walbridge J, Kroemer H, Roden D, Glover D. Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J. 1991;5:331-7 pubmed
    ..These two cDNAs, designated HK1 and HK2, encode proteins of 653 and 605 amino acids, respectively...
  2. Yang Z, Browning C, Hallaq H, Yermalitskaya L, Esker J, Hall M, et al. Four and a half LIM protein 1: a partner for KCNA5 in human atrium. Cardiovasc Res. 2008;78:449-57 pubmed publisher
    ..In human heart, the Shaker-related voltage-gated K(+) channel KCNA5 alpha-subunit forms the major basis of an atrial-specific, ultra-rapid delayed rectifier K(+) current, I(Kur)...
  3. Vicente R, Villalonga N, Calvo M, Escalada A, Solsona C, Soler C, et al. Kv1.5 association modifies Kv1.3 traffic and membrane localization. J Biol Chem. 2008;283:8756-64 pubmed publisher
    ..3 and Kv1.5 targeting to rafts. Our results implicate the traffic and localization of Kv1.3/Kv1.5 heteromers in the complex regulation of immune system cells. ..
  4. Schumacher S, McEwen D, Zhang L, Arendt K, Van Genderen K, Martens J. Antiarrhythmic drug-induced internalization of the atrial-specific k+ channel kv1.5. Circ Res. 2009;104:1390-8 pubmed publisher
    ....
  5. Remillard C, Tigno D, Platoshyn O, Burg E, Brevnova E, Conger D, et al. Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension. Am J Physiol Cell Physiol. 2007;292:C1837-53 pubmed
    ..Here, we report that overexpression of the Kv1.5 channel gene (KCNA5) in human PASMC and other cell lines produced a 15-pS single channel current and a large whole cell current that ..
  6. Kurata H, Soon G, Eldstrom J, Lu G, Steele D, Fedida D. Amino-terminal determinants of U-type inactivation of voltage-gated K+ channels. J Biol Chem. 2002;277:29045-53 pubmed
    ..1. These data suggest that intersubunit T1 domain interactions influence U-type inactivation in Kv1 channels, and suggest a generalized influence of the T1 domain on U-type inactivation between Kv channel subfamilies. ..
  7. Christophersen I, Olesen M, Liang B, Andersen M, Larsen A, Nielsen J, et al. Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. Eur Heart J. 2013;34:1517-25 pubmed publisher
    Genetic factors may be important in the development of atrial fibrillation (AF) in the young. KCNA5 encodes the potassium channel α-subunit KV1.5, which underlies the voltage-gated atrial-specific potassium current IKur...
  8. Abi Char J, El Haou S, Balse E, Neyroud N, Vranckx R, Coulombe A, et al. The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes. Am J Physiol Heart Circ Physiol. 2008;294:H1851-61 pubmed publisher
    ..In conclusion, SAP97 regulates the K(+) current in cardiac myocytes by retaining and immobilizing Kv1.5 subunits in the plasma membrane. This new regulatory mechanism may contribute to the targeting of Kv channels in cardiac myocytes. ..
  9. Yang Y, Li J, Lin X, Yang Y, Hong K, Wang L, et al. Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation. J Hum Genet. 2009;54:277-83 pubmed publisher
    ..However, the molecular defects in most patients with AF remain to be identified. Here, we report on three novel KCNA5 mutations that were identified in 4 of 120 unrelated AF families...
  10. Peretz A, Gil Henn H, Sobko A, Shinder V, Attali B, Elson A. Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon. EMBO J. 2000;19:4036-45 pubmed
    ..In all, PTP epsilon antagonizes activation of Kv channels by tyrosine kinases in vivo, and affects Schwann cell function during a critical period of Schwann cell growth and myelination. ..
  11. Guerrico A, Hillman D, Karnes J, Davis B, Gaston S, Klee G. Roles of kallikrein-2 biomarkers (free-hK2 and pro-hK2) for predicting prostate cancer progression-free survival. J Circ Biomark. 2017;6:1849454417720151 pubmed publisher
    Free human kallikrein 2 (free-hK2) and hK2 pro-form (pro-hK2) have been found to be increased in tumor tissues and serum from patients with prostate cancer...
  12. Philipson L, Hice R, Schaefer K, LaMendola J, Bell G, Nelson D, et al. Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc Natl Acad Sci U S A. 1991;88:53-7 pubmed
    ..This K+ channel isoform, designated hPCN1, with a deduced amino acid sequence of 613 residues (Mr = 67,097), is related to the Shaker family of Drosophila K+..
  13. Zhang X, Zhang M, Cong Q, Zhang M, Zhang M, Lu Y, et al. Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy. Int J Biochem Cell Biol. 2017;: pubmed publisher
    ..Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis...
  14. Ruben J, García Romo G, Breman E, van der Kooij S, Redeker A, Arens R, et al. Human plasmacytoid dendritic cells acquire phagocytic capacity by TLR9 ligation in the presence of soluble factors produced by renal epithelial cells. Kidney Int. 2017;: pubmed publisher
    ..Maturation and interferon alpha production by pDCs was enhanced when cells were activated in the presence of viable HK2 renal epithelial cells...
  15. Kim S, Ao Z, Warnock G, McIntosh C. Incretin-stimulated interaction between β-cell Kv1.5 and Kvβ2 channel proteins involves acetylation/deacetylation by CBP/SirT1. Biochem J. 2013;451:227-34 pubmed publisher
    ..5 in response to GIP or GLP-1. Incretin regulation of β-cell function therefore involves the acetylation of multiple Kvα and Kvβ subunits. ..
  16. Gupta P, Sheikh T, Sen E. SIRT6 regulated nucleosomal occupancy affects Hexokinase 2 expression. Exp Cell Res. 2017;357:98-106 pubmed publisher
    ..association between inflammation and dysregulated metabolism in glioblastoma, the effect of IL-1β on Hexokinase 2 (HK2) expression was investigated. IL-1β induced HK2 expression was accompanied by heightened SIRT6 and MZF1 levels...
  17. Park S, Lee Y, Ma T, Park J, Han M, Lee H, et al. hKv1.5 channels play a pivotal role in the functions of human alveolar macrophages. Biochem Biophys Res Commun. 2006;346:567-71 pubmed
    ..5 channel was lowered by the antisense hKv1.5 oligodeoxynucleotides. These results suggest that hKv1.5 channel is expressed in human alveolar macrophages and it plays a role in phagocytosis and migration of the human alveolar macrophage. ..
  18. Overturf K, Russell S, Carl A, Vogalis F, Hart P, Hume J, et al. Cloning and characterization of a Kv1.5 delayed rectifier K+ channel from vascular and visceral smooth muscles. Am J Physiol. 1994;267:C1231-8 pubmed
    ..5 in smooth muscles of the gastrointestinal tract and abundant expression in several vascular smooth muscles. We propose that cKv1.5 represents a component of the delayed rectifier current in both vascular and visceral smooth muscles...
  19. Kuryshev Y, Wible B, Gudz T, Ramirez A, Brown A. KChAP/Kvbeta1.2 interactions and their effects on cardiac Kv channel expression. Am J Physiol Cell Physiol. 2001;281:C290-9 pubmed
    ..2 may alter both sustained and transient cardiac Kv currents. The interaction of these two different classes of modulatory proteins may constitute a novel mechanism for regulating cardiac K+ currents...
  20. Mia S, Munoz C, Pakladok T, Siraskar G, Voelkl J, Alesutan I, et al. Downregulation of Kv1.5 K channels by the AMP-activated protein kinase. Cell Physiol Biochem. 2012;30:1039-50 pubmed publisher
    ..5-mediated currents. AMPK is a potent regulator of Kv1.5. AMPK inhibits Kv1.5 presumably in part by activation of Nedd4- 2 with subsequent clearance of channel protein from the cell membrane. ..
  21. He W, Fang N, Wang R, Wu Y, Zeng G, Guan C, et al. Fine Mapping of a New Race-Specific Blast Resistance Gene, Pi-hk2, in Japonica Heikezijing from Taihu Region of China. Phytopathology. 2017;107:84-91 pubmed
    ..10 and phenotypic variance of 46.19% and might be a major QTL, named Pi-hk2. The line RIL84 with Pi-hk2 derived from a cross between Heikezijing and Suyunuo was selected as Pi-hk2 gene donor ..
  22. Yokoyama N, Miller W. Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck. J Biol Chem. 2003;278:47713-23 pubmed
    ..Our data suggest that Hck is a novel binding partner for ACK1 that can regulate ACK1 activity by phosphorylation. ..
  23. Zadeh A, Cheng Y, Xu H, Wong N, Wang Z, Goonasekara C, et al. Kif5b is an essential forward trafficking motor for the Kv1.5 cardiac potassium channel. J Physiol. 2009;587:4565-74 pubmed publisher
    ..5 in a tetracycline inducible system blocked surface expression of the channel in both HEK293 cells and H9c2 cardiomyoblasts. Thus, Kif5b is essential to anterograde trafficking of a cardiac voltage-gated potassium channel. ..
  24. Munoz C, Tóvolli R, Sopjani M, Alesutan I, Lam R, Seebohm G, et al. Activation of voltage gated K⁺ channel Kv1.5 by β-catenin. Biochem Biophys Res Commun. 2012;417:692-6 pubmed publisher
    ..5 requires the same protein domains that are required for association of β-catenin with cadherin. The experiments disclose a completely novel function of β-catenin, i.e. the regulation of Kv1.5 channel activity. ..
  25. Pérez Verdaguer M, Capera J, Martínez Mármol R, Camps M, Comes N, Tamkun M, et al. Caveolin interaction governs Kv1.3 lipid raft targeting. Sci Rep. 2016;6:22453 pubmed publisher
    ..Our results identify a caveolin-binding domain in Kv1 channels and highlight the mechanisms that govern the regulation of channel surface localization during cellular processes. ..
  26. Ma J, Fan Y, Feng T, Chen F, Xu Z, Li S, et al. HOTAIR regulates HK2 expression by binding endogenous miR-125 and miR-143 in oesophageal squamous cell carcinoma progression. Oncotarget. 2017;8:86410-86422 pubmed publisher
    ..We highlight the molecular mechanisms by which HOTAIR could influence the expression of Hexokinase 2 (HK2) in ESCC through binding miR-125 and miR-143 directly...
  27. Cao J, Liu L, Zhang Y, Xiao J, Wang Y. The influence of HK2 blood group antigen on human B cell activation for ABOi-KT conditions. BMC Immunol. 2017;18:49 pubmed publisher
    ..The main barrier for ABOi-KT is how to keep host B cell activation and blood group antibody titer in low levels. Moreover, the mechanism of B cell activation induced by blood group antigen was unclear in ABOi-KT...
  28. Thebaud B, Michelakis E, Wu X, Moudgil R, Kuzyk M, Dyck J, et al. Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus. Circulation. 2004;110:1372-9 pubmed
    ..Modulation of Kv channels may have therapeutic potential in diseases associated with impaired O2 responsiveness, including persistent DA. ..
  29. Vatta M, Ackerman M, Ye B, Makielski J, Ughanze E, Taylor E, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation. 2006;114:2104-12 pubmed
    ..The present study reports the first CAV3 mutations in subjects with LQTS, and we provide functional data demonstrating a gain-of-function increase in late sodium current. ..
  30. Yan J, Du F, Li S, Yuan Y, Jiang J, Li S, et al. AUF1 modulates TGF-β signal in renal tubular epithelial cells via post-transcriptional regulation of Nedd4L expression. Biochim Biophys Acta. 2018;1865:48-56 pubmed publisher
    ..While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion ..
  31. Kou B, Liu W, Tang X, Kou Q. HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-β/Smad2 signaling pathway. Oncol Rep. 2018;39:101-108 pubmed publisher
    ..highly expressed in five renal cell carcinoma cell lines compared with that in the normal renal tubular epithelial HK2 cell line...
  32. Tian C, Yuan Z, Xu D, Ding P, Wang T, Zhang L, et al. Inhibition of glycolysis by a novel EGFR/HER2 inhibitor KU004 suppresses the growth of HER2+ cancer. Exp Cell Res. 2017;357:211-221 pubmed publisher
    ..KU004, inhibited the Warburg effect by suppressing hexokinase II (HK2) expression at the transcriptional and post-translational levels...
  33. Marampon F, Antinozzi C, Corinaldesi C, Vannelli G, Sarchielli E, Migliaccio S, et al. The phosphodiesterase 5 inhibitor tadalafil regulates lipidic homeostasis in human skeletal muscle cell metabolism. Endocrine. 2017;: pubmed publisher
    ..to cellular energy control, glycolitic activity or microtubule formation/vesicle transport, as GLUT4, PPARγ, HK2, IRS-1, KIF1C, and KIFAP3; (ii) GLUT4, Flotillin-1, and Caveolin-1 localization, all proteins involved in energy-..
  34. Schwetz T, Norring S, Bennett E. N-glycans modulate K(v)1.5 gating but have no effect on K(v)1.4 gating. Biochim Biophys Acta. 2010;1798:367-75 pubmed publisher
    ..Such modulation is relevant to changes in action potential repolarization that occur as ion channel expression and glycosylation are regulated. ..
  35. An M, Li S, Yao H, Li C, Wang J, Sun J, et al. BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells. J Cell Biol. 2017;: pubmed publisher
    ..Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
  36. Marczenke M, Piccini I, Mengarelli I, Fell J, Röpke A, Seebohm G, et al. Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells. Front Physiol. 2017;8:469 pubmed publisher
    ..5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF)...
  37. Liu Y, Murray Stewart T, Casero R, Kagiampakis I, Jin L, Zhang J, et al. Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol. 2017;50:2011-2023 pubmed publisher
    In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells...
  38. Bielanska J, Hernandez Losa J, Pérez Verdaguer M, Moline T, Somoza R, Ramon Y Cajal S, et al. Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human cancer. Curr Cancer Drug Targets. 2009;9:904-14 pubmed
    ..The concept of Kv channels as therapeutic targets or prognostic biomarkers attracts increasing interest and warrants further investigation. ..
  39. Luo R, Kakizoe Y, Wang F, Fan X, Hu S, Yang T, et al. Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction. Am J Physiol Renal Physiol. 2017;312:F121-F133 pubmed publisher
    ..CAY10598 prevented the activation of NLRP3 inflammasomes induced by angiotensin II in human proximal tubule cells (HK2)...
  40. Liu H, Liu N, Cheng Y, Jin W, Zhang P, Wang X, et al. Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway. PLoS ONE. 2017;12:e0189353 pubmed publisher
    ..The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor...
  41. Guo N, Tan J, Wu J, Xu Y. Isoflurane promotes glucose metabolism through upregulation of miR-21 and suppresses mitochondrial oxidative phosphorylation of ovarian cancer cells. Biosci Rep. 2017;: pubmed publisher
    ..The glycolysis enzymes, HK2, PKM2 and LDHA were upregulated by isoflurane...
  42. Houtmann S, Schombert B, Sanson C, Partiseti M, Bohme G. Automated Patch-Clamp Methods for the hERG Cardiac Potassium Channel. Methods Mol Biol. 2017;1641:187-199 pubmed publisher
    ..We also show that the sensitivity of the assay can be improved by adding a surfactant to the extracellular medium. ..
  43. Song L, Tang H, Liao W, Luo X, Li Y, Chen T, et al. FOXC2 positively regulates YAP signaling and promotes the glycolysis of nasopharyngeal carcinoma. Exp Cell Res. 2017;357:17-24 pubmed publisher
    ..Furthermore, FOXC2-YAP signaling positively regulated the expression of Hexokinase 2 (HK2) and promoted the glycolysis...
  44. Zheng X, Han H, Liu G, Ma Y, Pan R, Sang L, et al. LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. EMBO J. 2017;36:3325-3335 pubmed publisher
    ..BCAR4, which subsequently coordinates the Hedgehog signaling to enhance the transcription of glycolysis activators HK2 and PFKFB3...