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KCNE1

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KCNE1
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesKCNE1, ISK, JLNS, JLNS2, LQT2/5, LQT5, MinK, potassium voltage-gated channel subfamily E regulatory subunit 1
External IDsOMIM: 176261; GeneCards: KCNE1; OMA:KCNE1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3753

n/a

Ensembl

ENSG00000180509

n/a

UniProt

P15382
Q6FHJ6

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 21: 34.45 – 34.51 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Potassium voltage-gated channel subfamily E member 1 is a protein that in humans is encoded by the KCNE1 gene.[3][4]

Voltage-gated potassium channels (Kv) represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume.

KCNE1 is one of five members of the KCNE family of Kv channel ancillary or β subunits. It is also known as minK (minimal potassium channel subunit).

Function

KCNE1 is primarily known for modulating the cardiac and epithelial Kv channel α subunit, KCNQ1. KCNQ1 and KCNE1 form a complex in human ventricular cardiomyocytes that generates the slowly activating K+ current, IKs. Together with the rapidly activating K+ current (IKr), IKs is important for human ventricular repolarization.[5][6] KCNQ1 is also essential for the normal function of many different epithelial tissues, but in these non-excitable cells it is thought to be predominantly regulated by KCNE2 or KCNE3.[7]

KCNE1 slows the activation of KCNQ1 5-10 fold, increases its unitary conductance 4-fold, eliminates its inactivation, and alters the manner in which KCNQ1 is regulated by other proteins, lipids and small molecules. The association of KCNE1 with KCNQ1 was discovered 8 years after Takumi and colleagues reported the isolation of a fraction of RNA from rat kidney that, when injected into Xenopus oocytes, produced an unusually slow-activating, voltage-dependent, potassium-selective current. Takumi et al discovered the KCNE1 gene[8] and it was correctly predicted to encode a single-transmembrane domain protein with an extracellular N-terminal domain and a cytosolic C-terminal domain. The ability of KCNE1 to generate this current was confusing because of its simple primary structure and topology, contrasting with the 6-transmembrane domain topology of other known Kv α subunits such as Shaker from Drosophila, cloned 2 years earlier. The mystery was solved when KCNQ1 was cloned and found to co-assemble with KCNE1, and it was shown that Xenopus laevis oocytes endogenously express KCNQ1, which is upregulated by exogenous expression of KCNE1 to generate the characteristic slowly activating current.,[5][6] KCNQ1 is also essential for the normal function of many different epithelial tissues, but in these non-excitable cells it is thought to be predominantly regulated by KCNE2 or KCNE3.[7]

KCNE1 is also reported to regulate two other KCNQ family α subunits, KCNQ4 and KCNQ5. KCNE1 increased both their peak currents in oocyte expression studies, and slowed the activation of the latter.,[9][10]

KCNE1 also regulates hERG, which is the Kv α subunit that generates ventricular IKr. KCNE1 doubled hERG current when the two were expressed in mammalian cells, although the mechanism for this remains unknown.[11]

Although KCNE1 had no effect when co-expressed with the Kv1.1 α subunit in Chinese Hamster ovary (CHO) cells, KCNE1 traps the N-type (rapidly inactivating) Kv1.4 α subunit in the ER/Golgi when co-expressed with it. KCNE1 (and KCNE2) also has this effect on the two other canonical N-type Kv α subunits, Kv3.3 and Kv3.4. This appears to be a mechanism for ensuring that homomeric N-type channels do not reach the cell surface, as this mode of suppression by KCNE1 or KCNE2 is relieved by co-expression of same-subfamily delayed rectifier (slowly inactivating) α subunits. Thus, Kv1.1 rescued Kv1.4, Kv3.1 rescued Kv3.4; in each of these cases the resultant channels at the membrane were heteromers (e.g., Kv3.1-Kv3.4) and displayed intermediate inactivation kinetics to those of either α subunit alone.,[12][13]

KCNE1 also regulates the gating kinetics of Kv2.1, Kv3.1 and Kv3.2, in each case slowing their activation and deactivation, and accelerating inactivation of the latter two.,[14][15] No effects were observed upon oocyte co-expression of KCNE1 and Kv4.2,[16] but KCNE1 was found to slow the gating and increase macroscopic current of Kv4.3 in HEK cells.[17] In contrast, channels formed by Kv4.3 and the cytosolic ancillary subunit KChIP2 exhibited faster activation and altered inactivation when co-expressed with KCNE1 in CHO cells.[18] Finally, KCNE1 inhibited Kv12.2 in Xenopus oocytes.[19]

Structure

The large majority of studies into the structural basis for KCNE1 modulation of Kv channels focus on its interaction with KCNQ1 (previously named KvLQT1). Residues in the transmembrane domain of KCNE1 lies close to the selectivity filter of KCNQ1 within heteromeric KCNQ1-KCNE1 channel complexes.,[20][21] The C-terminal domain of KCNE1, specifically from amino acids 73 to 79 is necessary for stimulation of slow delayed potassium rectifier current by SGK1.[22] The interaction of KCNE1 with an alpha helix in the S6 KvLQT1 domain contributes to the higher affinity this channel has for benzodiazepine L7 and chromanol 293B by repositioning amino acid residues to allow for this. KCNE1 destabilizes the S4-S5 alpha-helix linkage in the KCNQ1 channel protein in addition to destabilizing the S6 alpha helix, leading to slower activation of this channel when associated with KCNE1.[23] Variable stohiometries have been discussed but there are probably 2 KCNE1 subunits and 4 KCNQ1 subunits in a plasma membrane IKs complex.[24]

The transmembrane segment of KCNE1 is α-helical when in a membrane environment.,[25][26] The transmembrane segment of KCNE1 has been suggested to interact with the KCNQ1 pore domain (S5/S6) and with the S4 domain of the KCNQ1 (KvLQT1) channel.[20] KCNE1 may bind to the outer part of the KCNQ1 pore domain, and slide from this position into the “activation cleft” which leads to greater current amplitudes[22]

KCNE1 slows KCNQ1 activation several-fold, and there are ongoing discussions about the precise mechanisms underlying this. In a study in which KCNQ1 voltage sensor movement was monitored by site-directed fluorimetry and also by measuring the charge displacement associated with movement of charges within the S4 segment of the voltage sensor (gating current), KCNE1 was found to slow S4 movement so much that the gating current was no longer measurable. Fluorimetry measurements indicated that KCNQ1-KCNE1 channel S4 movement was 30-fold slower than that of the well-studied Drosophila Shaker Kv channel.[27] Nakajo and Kubo found that KCNE1 either slowed KCNQ1 S4 movement upon membrane depolarization, or altered S4 equilibrium at a given membrane potential.[28] The Kass lab deduced that while homomeric KCNQ1 channels can open after the movement of a single S4 segment, KCNQ1-KCNE1 channels can only open after all four S4 segments have been activated.[29] The intracellular C-terminal domain of KCNE1 is thought to sit on the KCNQ1 S4-S5 linker, a segment of KCNQ1 crucial for communicating S4 status to the pore and thus control activation.[30]

Tissue distribution

KCNE1 is expressed in human heart (atria and ventricles), whereas in adult mouse heart its expression appears limited to the atria and/or conduction system.[31] KCNE1 is also expressed in human and musine inner ear[32] and kidneys.[33] KCNE1 has been detected in mouse brain[34] but this finding is a subject of ongoing debate.

Clinical significance

Inherited or sporadic KCNE gene mutations can cause Romano-Ward syndrome (heterozygotes) and Jervell Lange-Nielsens syndrome (homozygotes). Both these syndromes are characterized by Long QT syndrome, a delay in ventricular repolarization. In addition, Jervell and Lange-Nielsen syndrome also involves bilateral sensorineural deafness. Mutation D76N in the KCNE1 protein can lead to long QT syndrome due to structural changes in the KvLQT1/KCNE1 complex, and people with these mutations are advised to avoid triggers of cardiac arrhythmia and prolonged QT intervals, such as stress or strenuous exercise.[22]

While loss-of-function mutations in KCNE1 cause Long QT syndrome, gain-of-function KCNE1 mutations are associated with early-onset atrial fibrillation.[35] A common KCNE1 polymorphism, S38G, is associated with altered predisposition to lone atrial fibrillation[36] and postoperative atrial fibrillation.[37] Atrial KCNE1 expression was downregulated in a porcine model of post-operative atrial fibrillation following lung lobectomy.[38]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000180509 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Chevillard C, Attali B, Lesage F, Fontes M, Barhanin J, Lazdunski M, Mattei MG (Jan 1993). "Localization of a potassium channel gene (KCNE1) to 21q22.1-q22.2 by in situ hybridization and somatic cell hybridization". Genomics. 15 (1): 243–5. doi:10.1006/geno.1993.1051. PMID 8432548.
  4. ^ "Entrez Gene: KCNE1 potassium voltage-gated channel, Isk-related family, member 1".
  5. ^ a b Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT (Nov 1996). "Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel". Nature. 384 (6604): 80–3. doi:10.1038/384080a0. PMID 8900283.
  6. ^ a b Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (Nov 1996). "K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current". Nature. 384 (6604): 78–80. doi:10.1038/384078a0. PMID 8900282.
  7. ^ a b Abbott GW (Jun 2015). "The KCNE2 K(+) channel regulatory subunit: Ubiquitous influence, complex pathobiology". Gene. 569: 162–72. doi:10.1016/j.gene.2015.06.061. PMID 26123744.
  8. ^ Takumi T, Ohkubo H, Nakanishi S (Nov 1988). "Cloning of a membrane protein that induces a slow voltage-gated potassium current". Science. 242 (4881): 1042–5. doi:10.1126/science.3194754. PMID 3194754.
  9. ^ Strutz-Seebohm N, Seebohm G, Fedorenko O, Baltaev R, Engel J, Knirsch M, Lang F (2006). "Functional coassembly of KCNQ4 with KCNE-beta- subunits in Xenopus oocytes". Cellular Physiology and Biochemistry. 18 (1–3): 57–66. doi:10.1159/000095158. PMID 16914890.
  10. ^ Roura-Ferrer M, Etxebarria A, Solé L, Oliveras A, Comes N, Villarroel A, Felipe A (2009). "Functional implications of KCNE subunit expression for the Kv7.5 (KCNQ5) channel". Cellular Physiology and Biochemistry. 24 (5–6): 325–34. doi:10.1159/000257425. PMID 19910673.
  11. ^ McDonald TV, Yu Z, Ming Z, Palma E, Meyers MB, Wang KW, Goldstein SA, Fishman GI (Jul 1997). "A minK-HERG complex regulates the cardiac potassium current I(Kr)". Nature. 388 (6639): 289–92. doi:10.1038/40882. PMID 9230439.
  12. ^ Kanda VA, Lewis A, Xu X, Abbott GW (Sep 2011). "KCNE1 and KCNE2 inhibit forward trafficking of homomeric N-type voltage-gated potassium channels". Biophysical Journal. 101 (6): 1354–63. doi:10.1016/j.bpj.2011.08.015. PMID 21943416.
  13. ^ Kanda VA, Lewis A, Xu X, Abbott GW (Sep 2011). "KCNE1 and KCNE2 provide a checkpoint governing voltage-gated potassium channel α-subunit composition". Biophysical Journal. 101 (6): 1364–75. doi:10.1016/j.bpj.2011.08.014. PMID 21943417.
  14. ^ McCrossan ZA, Lewis A, Panaghie G, Jordan PN, Christini DJ, Lerner DJ, Abbott GW (Sep 2003). "MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain". The Journal of Neuroscience. 23 (22): 8077–91. PMID 12954870.
  15. ^ Lewis A, McCrossan ZA, Abbott GW (Feb 2004). "MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating". The Journal of Biological Chemistry. 279 (9): 7884–92. doi:10.1074/jbc.M310501200. PMID 14679187.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  16. ^ Zhang M, Jiang M, Tseng GN (May 2001). "minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel?". Circulation Research. 88 (10): 1012–9. doi:10.1161/hh1001.090839. PMID 11375270.
  17. ^ Deschênes I, Tomaselli GF (Sep 2002). "Modulation of Kv4.3 current by accessory subunits". FEBS Letters. 528 (1–3): 183–8. doi:10.1016/s0014-5793(02)03296-9. PMID 12297301.
  18. ^ Radicke S, Cotella D, Graf EM, Banse U, Jost N, Varró A, Tseng GN, Ravens U, Wettwer E (Sep 2006). "Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts". Cardiovascular Research. 71 (4): 695–703. doi:10.1016/j.cardiores.2006.06.017. PMID 16876774.
  19. ^ Clancy SM, Chen B, Bertaso F, Mamet J, Jegla T (22 July 2009). "KCNE1 and KCNE3 beta-subunits regulate membrane surface expression of Kv12.2 K(+) channels in vitro and form a tripartite complex in vivo". PLOS ONE. 4 (7): e6330. doi:10.1371/journal.pone.0006330. PMC 2710002. PMID 19623261.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  20. ^ a b Tristani-Firouzi M, Sanguinetti MC (Jul 1998). "Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits". The Journal of Physiology. 510 (Pt 1): 37–45. doi:10.1111/j.1469-7793.1998.037bz.x. PMC 2231024. PMID 9625865.
  21. ^ Tai KK, Goldstein SA (Feb 1998). "The conduction pore of a cardiac potassium channel". Nature. 391 (6667): 605–8. doi:10.1038/35416. PMID 9468141.
  22. ^ a b c Seebohm G, Strutz-Seebohm N, Ureche ON, Henrion U, Baltaev R, Mack AF, Korniychuk G, Steinke K, Tapken D, Pfeufer A, Kääb S, Bucci C, Attali B, Merot J, Tavare JM, Hoppe UC, Sanguinetti MC, Lang F (Dec 2008). "Long QT syndrome-associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of IKs channels". Circulation Research. 103 (12): 1451–7. doi:10.1161/CIRCRESAHA.108.177360. PMID 19008479.
  23. ^ Strutz-Seebohm N, Pusch M, Wolf S, Stoll R, Tapken D, Gerwert K, Attali B, Seebohm G (2011). "Structural basis of slow activation gating in the cardiac I Ks channel complex". Cellular Physiology and Biochemistry. 27 (5): 443–52. doi:10.1159/000329965. PMID 21691061.
  24. ^ Plant LD, Xiong D, Dai H, Goldstein SA (Apr 2014). "Individual IKs channels at the surface of mammalian cells contain two KCNE1 accessory subunits". Proceedings of the National Academy of Sciences of the United States of America. 111 (14): E1438-46. doi:10.1073/pnas.1323548111. PMID 24591645.
  25. ^ Mercer EA, Abbott GW, Brazier SP, Ramesh B, Haris PI, Srai SK (Jul 1997). "Synthetic putative transmembrane region of minimal potassium channel protein (minK) adopts an alpha-helical conformation in phospholipid membranes". The Biochemical Journal. 325 (2): 475–9. doi:10.1042/bj3250475. PMID 9230130.
  26. ^ Tian C, Vanoye CG, Kang C, Welch RC, Kim HJ, George AL, Sanders CR (Oct 2007). "Preparation, functional characterization, and NMR studies of human KCNE1, a voltage-gated potassium channel accessory subunit associated with deafness and long QT syndrome". Biochemistry. 46 (41): 11459–72. doi:10.1021/bi700705j. PMID 17892302.
  27. ^ Ruscic KJ, Miceli F, Villalba-Galea CA, Dai H, Mishina Y, Bezanilla F, Goldstein SA (Feb 2013). "IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits". Proceedings of the National Academy of Sciences of the United States of America. 110 (7): E559-66. doi:10.1073/pnas.1222616110. PMID 23359697.
  28. ^ Nakajo K, Kubo Y (Sep 2007). "KCNE1 and KCNE3 stabilize and/or slow voltage sensing S4 segment of KCNQ1 channel". The Journal of General Physiology. 130 (3): 269–81. doi:10.1085/jgp.200709805. PMID 17698596.
  29. ^ Osteen JD, Gonzalez C, Sampson KJ, Iyer V, Rebolledo S, Larsson HP, Kass RS (Dec 2010). "KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate". Proceedings of the National Academy of Sciences of the United States of America. 107 (52): 22710–5. doi:10.1073/pnas.1016300108. PMID 21149716.
  30. ^ Kang C, Tian C, Sönnichsen FD, Smith JA, Meiler J, George AL, Vanoye CG, Kim HJ, Sanders CR (Aug 2008). "Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel". Biochemistry. 47 (31): 7999–8006. doi:10.1021/bi800875q. PMID 18611041.
  31. ^ Temple J, Frias P, Rottman J, Yang T, Wu Y, Verheijck EE, Zhang W, Siprachanh C, Kanki H, Atkinson JB, King P, Anderson ME, Kupershmidt S, Roden DM (Jul 2005). "Atrial fibrillation in KCNE1-null mice". Circulation Research. 97 (1): 62–9. doi:10.1161/01.RES.0000173047.42236.88. PMID 15947250.
  32. ^ Nicolas M, Demêmes D, Martin A, Kupershmidt S, Barhanin J (Mar 2001). "KCNQ1/KCNE1 potassium channels in mammalian vestibular dark cells". Hearing Research. 153 (1–2): 132–45. doi:10.1016/s0378-5955(00)00268-9. PMID 11223304.
  33. ^ Sugimoto T, Tanabe Y, Shigemoto R, Iwai M, Takumi T, Ohkubo H, Nakanishi S (Jan 1990). "Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation: its localization in the apical membrane portion of epithelial cells". The Journal of Membrane Biology. 113 (1): 39–47. doi:10.1007/bf01869604. PMID 2154581.
  34. ^ Goldman AM, Glasscock E, Yoo J, Chen TT, Klassen TL, Noebels JL (Oct 2009). "Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death". Science Translational Medicine. 1 (2): 2ra6. doi:10.1126/scitranslmed.3000289. PMID 20368164.
  35. ^ Olesen MS, Bentzen BH, Nielsen JB, Steffensen AB, David JP, Jabbari J, Jensen HK, Haunsø S, Svendsen JH, Schmitt N (3 April 2012). "Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation". BMC Medical Genetics. 13: 24. doi:10.1186/1471-2350-13-24. PMID 22471742.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  36. ^ Han HG, Wang HS, Yin Z, Jiang H, Fang M, Han J (20 October 2014). "KCNE1 112G>a polymorphism and atrial fibrillation risk: a meta-analysis". Genetics and Molecular Research. 13 (4): 8367–77. doi:10.4238/2014.October.20.12. PMID 25366730.
  37. ^ Voudris KV, Apostolakis S, Karyofillis P, Doukas K, Zaravinos A, Androutsopoulos VP, Michalis A, Voudris V, Spandidos DA (Feb 2014). "Genetic diversity of the KCNE1 gene and susceptibility to postoperative atrial fibrillation". American Heart Journal. 167 (2): 274–280.e1. doi:10.1016/j.ahj.2013.09.020. PMID 24439990.
  38. ^ Heerdt PM, Kant R, Hu Z, Kanda VA, Christini DJ, Malhotra JK, Abbott GW (Sep 2012). "Transcriptomic analysis reveals atrial KCNE1 down-regulation following lung lobectomy". Journal of Molecular and Cellular Cardiology. 53 (3): 350–3. doi:10.1016/j.yjmcc.2012.05.010. PMID 22641150.

Further reading

  • Murai T, Kakizuka A, Takumi T, Ohkubo H, Nakanishi S (May 1989). "Molecular cloning and sequence analysis of human genomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity". Biochemical and Biophysical Research Communications. 161 (1): 176–81. doi:10.1016/0006-291X(89)91577-5. PMID 2730656.
  • Malo MS, Srivastava K, Ingram VM (Jul 1995). "Gene assignment by polymerase chain reaction: localization of the human potassium channel IsK gene to the Down's syndrome region of chromosome 21q22.1-q22.2". Gene. 159 (2): 273–5. doi:10.1016/0378-1119(95)00102-C. PMID 7622063.
  • Lai LP, Deng CL, Moss AJ, Kass RS, Liang CS (Dec 1994). "Polymorphism of the gene encoding a human minimal potassium ion channel (minK)". Gene. 151 (1–2): 339–40. doi:10.1016/0378-1119(94)90685-8. PMID 7828904.
  • Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J, Fauré S, Gary F, Coumel P, Petit C, Schwartz K, Guicheney P (Feb 1997). "A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome". Nature Genetics. 15 (2): 186–9. doi:10.1038/ng0297-186. PMID 9020846.
  • Chouabe C, Neyroud N, Guicheney P, Lazdunski M, Romey G, Barhanin J (Sep 1997). "Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias". The EMBO Journal. 16 (17): 5472–9. doi:10.1093/emboj/16.17.5472. PMC 1170178. PMID 9312006.
  • Tyson J, Tranebjaerg L, Bellman S, Wren C, Taylor JF, Bathen J, Aslaksen B, Sørland SJ, Lund O, Malcolm S, Pembrey M, Bhattacharya S, Bitner-Glindzicz M (Nov 1997). "IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome". Human Molecular Genetics. 6 (12): 2179–85. doi:10.1093/hmg/6.12.2179. PMID 9328483.
  • Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hördt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, Funke H (Nov 1997). "KCNE1 mutations cause jervell and Lange-Nielsen syndrome". Nature Genetics. 17 (3): 267–8. doi:10.1038/ng1197-267. PMID 9354783.
  • Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT (Nov 1997). "Mutations in the hminK gene cause long QT syndrome and suppress IKs function". Nature Genetics. 17 (3): 338–40. doi:10.1038/ng1197-338. PMID 9354802.
  • Duggal P, Vesely MR, Wattanasirichaigoon D, Villafane J, Kaushik V, Beggs AH (Jan 1998). "Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome". Circulation. 97 (2): 142–6. doi:10.1161/01.cir.97.2.142. PMID 9445165.
  • Bianchi L, Shen Z, Dennis AT, Priori SG, Napolitano C, Ronchetti E, Bryskin R, Schwartz PJ, Brown AM (Aug 1999). "Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome". Human Molecular Genetics. 8 (8): 1499–507. doi:10.1093/hmg/8.8.1499. PMID 10400998.
  • Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT (Sep 2000). "Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2". Circulation. 102 (10): 1178–85. doi:10.1161/01.cir.102.10.1178. PMID 10973849.
  • Melman YF, Domènech A, de la Luna S, McDonald TV (Mar 2001). "Structural determinants of KvLQT1 control by the KCNE family of proteins". The Journal of Biological Chemistry. 276 (9): 6439–44. doi:10.1074/jbc.M010713200. PMID 11104781.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  • Schulze-Bahr E, Schwarz M, Hauenschild S, Wedekind H, Funke H, Haverkamp W, Breithardt G, Pongs O, Isbrandt D, Hoffman S (Sep 2001). "A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype". Journal of Molecular Medicine. 79 (9): 504–9. doi:10.1007/s001090100249. PMID 11692163.
  • Furukawa T, Ono Y, Tsuchiya H, Katayama Y, Bang ML, Labeit D, Labeit S, Inagaki N, Gregorio CC (Nov 2001). "Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system". Journal of Molecular Biology. 313 (4): 775–84. doi:10.1006/jmbi.2001.5053. PMID 11697903.
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