KCNE1

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Potassium voltage-gated channel, Isk-related family, member 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KCNE1 ; ISK; JLNS; JLNS2; LQT2/5; LQT5; MinK
External IDs OMIM176261 MGI96673 HomoloGene185 ChEMBL: 4872 GeneCards: KCNE1 Gene
RNA expression pattern
PBB GE KCNE1 208514 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3753 16509
Ensembl ENSG00000180509 ENSMUSG00000039639
UniProt P15382 P23299
RefSeq (mRNA) NM_000219 NM_008424
RefSeq (protein) NP_000210 NP_032450
Location (UCSC) Chr 21:
35.82 – 35.88 Mb
Chr 16:
92.35 – 92.36 Mb
PubMed search [1] [2]

Potassium voltage-gated channel subfamily E member 1 is a protein that in humans is encoded by the KCNE1 gene.[1][2]

KCNE1 is a gene that codes for the KCNE1 protein, which is one of five members of the KCNE family of proteins. It is also known as minK protein (minimal potassium subunits). It can both cause Romano-Ward syndrome (heterozygotes) and Jervell Lange-Nielsens syndrome (homozygotes). 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.[3]

Function[edit]

KCNE1 associates with the pore region of KvLQT1 (KCNQ1), and its transmembrane domain contributes to the selectivity filter of this heteromeric channel complex.[4] 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.[3] 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 KvLQT1 channel protein in addition to destabilizing the S6 alpha helix, leading to slower activation of this channel when associated with KCNE1.[5]

Interaction with KvLQT1[edit]

The alpha-helix of the KCNE1 protein interacts with the pore domain S5/S6 and with the S4 domain of the KCNQ1 (KvLQT1) channel.[4] KCNE1 binds to this outer part of the KvLQT1 pore domain, and slides from this position into the “activation cleft” which leads to greater current amplitudes[3]

See also[edit]

References[edit]

  1. ^ Chevillard C, Attali B, Lesage F, Fontes M, Barhanin J, Lazdunski M, Mattei MG (Mar 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. 
  2. ^ "Entrez Gene: KCNE1 potassium voltage-gated channel, Isk-related family, member 1". 
  3. ^ a b c Seebohm, G.; Strutz-Seebohm, N.; Ureche, O. N.; Henrion, U.; Baltaev, R.; Mack, A. F.; Korniychuk, G.; Steinke, K.; Tapken, D.; Pfeufer, A.; Kääb, S.; Bucci, C.; Attali, B.; Merot, J.; Tavare, J. M.; Hoppe, U. C.; Sanguinetti, M. C.; Lang, F. (2008). "Long QT Syndrome-Associated Mutations in KCNQ1 and KCNE1 Subunits Disrupt Normal Endosomal Recycling of IKs Channels". Circulation Research 103 (12): 1451–1457. doi:10.1161/CIRCRESAHA.108.177360. PMID 19008479.  edit
  4. ^ a b Tristani-Firouzi, M.; Sanguinetti, M. C. (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) (Pt 1): 37–45. doi:10.1111/j.1469-7793.1998.037bz.x. PMC 2231024. PMID 9625865.  edit
  5. ^ 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 IKs Channel Complex". Cellular Physiology and Biochemistry 27 (5): 443–452. doi:10.1159/000329965. PMID 21691061.  edit

Further reading[edit]

  • Murai T, Kakizuka A, Takumi T et al. (1989). "Molecular cloning and sequence analysis of human genomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity". Biochem. Biophys. Res. Commun. 161 (1): 176–81. doi:10.1016/0006-291X(89)91577-5. PMID 2730656. 
  • Malo MS, Srivastava K, Ingram VM (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 et al. (1995). "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. 
  • Tesson F, Donger C, Denjoy I et al. (1997). "Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome". J. Mol. Cell. Cardiol. 28 (9): 2051–5. doi:10.1006/jmcc.1996.0198. PMID 8899564. 
  • Sanguinetti MC, Curran ME, Zou A et al. (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. 
  • Neyroud N, Tesson F, Denjoy I et al. (1997). "A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome". Nat. Genet. 15 (2): 186–9. doi:10.1038/ng0297-186. PMID 9020846. 
  • McDonald TV, Yu Z, Ming Z et al. (1997). "A minK-HERG complex regulates the cardiac potassium current I(Kr)". Nature 388 (6639): 289–92. doi:10.1038/40882. PMID 9230439. 
  • Chouabe C, Neyroud N, Guicheney P et al. (1997). "Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias". EMBO J. 16 (17): 5472–9. doi:10.1093/emboj/16.17.5472. PMC 1170178. PMID 9312006. 
  • Tyson J, Tranebjaerg L, Bellman S et al. (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". Hum. Mol. Genet. 6 (12): 2179–85. doi:10.1093/hmg/6.12.2179. PMID 9328483. 
  • Schulze-Bahr E, Wang Q, Wedekind H et al. (1997). "KCNE1 mutations cause jervell and Lange-Nielsen syndrome". Nat. Genet. 17 (3): 267–8. doi:10.1038/ng1197-267. PMID 9354783. 
  • Splawski I, Tristani-Firouzi M, Lehmann MH et al. (1997). "Mutations in the hminK gene cause long QT syndrome and suppress IKs function". Nat. Genet. 17 (3): 338–40. doi:10.1038/ng1197-338. PMID 9354802. 
  • Duggal P, Vesely MR, Wattanasirichaigoon D et al. (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 et al. (1999). "Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome". Hum. Mol. Genet. 8 (8): 1499–507. doi:10.1093/hmg/8.8.1499. PMID 10400998. 
  • Piccini M, Vitelli F, Seri M et al. (1999). "KCNE1-like gene is deleted in AMME contiguous gene syndrome: identification and characterization of the human and mouse homologs". Genomics 60 (3): 251–7. doi:10.1006/geno.1999.5904. PMID 10493825. 
  • Hattori M, Fujiyama A, Taylor TD et al. (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953. 
  • Splawski I, Shen J, Timothy KW et al. (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 (2001). "Structural determinants of KvLQT1 control by the KCNE family of proteins". J. Biol. Chem. 276 (9): 6439–44. doi:10.1074/jbc.M010713200. PMID 11104781. 
  • Schulze-Bahr E, Schwarz M, Hauenschild S et al. (2002). "A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype". J. Mol. Med. 79 (9): 504–9. doi:10.1007/s001090100249. PMID 11692163. 
  • Furukawa T, Ono Y, Tsuchiya H et al. (2001). "Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system". J. Mol. Biol. 313 (4): 775–84. doi:10.1006/jmbi.2001.5053. PMID 11697903. 

External links[edit]