User:Lukáš Hodboď

Structural highlights

Disease

[KCNE1_HUMAN] Mutations in KCNE1 cause long QT syndrome type 5 (LQT5) [MIM:613695]. Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death. ^[1] Mutations in KCNE1 are the cause of Jervell and Lange-Nielsen syndrome type 2 (JLNS2)[MIM:612347]. The Jervell and Lange-Nielsen syndrome is an autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. ^[2] These mutations inhibit the ability of KCNE1 to form fully functional IKs channels. Mutation that disrupts the N5 sequon of KCNE1 protein hinders its glycosylation, leading to the formation of channels that are unable of proper cell surface expression due to defect in anterograde trafficking. ^{[3] [4] [5] [6] [7] [8] [9] [10][11]} Mutations in KCNE1 may be a cause for hightened susceptibility to the Noise-Induced Hearing Loss. ^[12]

Function

KCNE1 and KVLQT1 protein products coassemble to form the cardiac I(Ks) channel. ^[13] Through the formation of heteromeric channel complexes, KCNE1 is central to the control of the heart rate and rhythm. ^[14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Jongbloed RJ, Wilde AA, Geelen JL, Doevendans P, Schaap C, Van Langen I, van Tintelen JP, Cobben JM, Beaufort-Krol GC, Geraedts JP, Smeets HJ. Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999;13(4):301-10. PMID:10220144 doi:<301::AID-HUMU7>3.0.CO;2-V 10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V
2. ↑ JERVELL A, LANGE-NIELSEN F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J. 1957 Jul;54(1):59-68. PMID:13435203
3. ↑ Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hordt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, Funke H. KCNE1 mutations cause jervell and Lange-Nielsen syndrome. Nat Genet. 1997 Nov;17(3):267-8. doi: 10.1038/ng1197-267. PMID:9354783 doi:http://dx.doi.org/10.1038/ng1197-267
4. ↑ Tyson J, Tranebjaerg L, Bellman S, Wren C, Taylor JF, Bathen J, Aslaksen B, Sorland SJ, Lund O, Malcolm S, Pembrey M, Bhattacharya S, Bitner-Glindzicz M. 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. 1997 Nov;6(12):2179-85. PMID:9328483
5. ↑ Bas T, Gao GY, Lvov A, Chandrasekhar KD, Gilmore R, Kobertz WR. Post-translational N-glycosylation of type I transmembrane KCNE1 peptides: implications for membrane protein biogenesis and disease. J Biol Chem. 2011 Aug 12;286(32):28150-9. doi: 10.1074/jbc.M111.235168. Epub 2011, Jun 15. PMID:21676880 doi:http://dx.doi.org/10.1074/jbc.M111.235168
6. ↑ Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet. 1997 Nov;17(3):338-40. doi: 10.1038/ng1197-338. PMID:9354802 doi:http://dx.doi.org/10.1038/ng1197-338
7. ↑ Duggal P, Vesely MR, Wattanasirichaigoon D, Villafane J, Kaushik V, Beggs AH. Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome. Circulation. 1998 Jan 20;97(2):142-6. PMID:9445165
8. ↑ Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. PMID:10973849
9. ↑ Schulze-Bahr E, Schwarz M, Hauenschild S, Wedekind H, Funke H, Haverkamp W, Breithardt G, Pongs O, Isbrandt D. A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype. J Mol Med. 2001 Sep;79(9):504-9. PMID:11692163 doi:http://dx.doi.org/10.1007/s001090100249
10. ↑ Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 Sep;6(9):1297-303. doi: 10.1016/j.hrthm.2009.05.021. Epub 2009, Jun 23. PMID:19716085 doi:http://dx.doi.org/10.1016/j.hrthm.2009.05.021
11. ↑ . PMID:216315890657
12. ↑ Van Laer L, Carlsson PI, Ottschytsch N, Bondeson ML, Konings A, Vandevelde A, Dieltjens N, Fransen E, Snyders D, Borg E, Raes A, Van Camp G. The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss. Hum Mutat. 2006 Aug;27(8):786-95. PMID:16823764 doi:http://dx.doi.org/10.1002/humu.20360
13. ↑ Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT. Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature. 1996 Nov 7;384(6604):80-3. doi: 10.1038/384080a0. PMID:8900283 doi:http://dx.doi.org/10.1038/384080a0
14. ↑ McDonald TV, Yu Z, Ming Z, Palma E, Meyers MB, Wang KW, Goldstein SA, Fishman GI. A minK-HERG complex regulates the cardiac potassium current I(Kr). Nature. 1997 Jul 17;388(6639):289-92. PMID:9230439 doi:http://dx.doi.org/10.1038/40882
15. ↑ Kang C, Tian C, Sonnichsen FD, Smith JA, Meiler J, George AL Jr, Vanoye CG, Kim HJ, Sanders CR. Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel. Biochemistry. 2008 Aug 5;47(31):7999-8006. Epub 2008 Jul 9. PMID:18611041 doi:http://dx.doi.org/10.1021/bi800875q