User:Milan Horňák/Sandbox 1
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== Function == | == Function == | ||
| - | KCNE1 and KVLQT1 protein products coassemble to form the slow delayed rectifier current I(Ks) . <ref>PMID:8900283</ref> Through the formation of heteromeric channel complexes, KCNE1 is central to the control of the heart rate and rhythm. <ref>PMID:9230439</ref> KCNE1 modifies the KCNQ1 potassium channel by slowing activation and enhancing channel conductance. Experiments suggest that this is carried out by restricting the movement of the S4–S5 linker of KCNQ1. This interaction must be first disrupted before the channel can be opened. | + | [[https://www.uniprot.org/uniprot/KCNE1_HUMAN KCNE1_HUMAN]] KCNE1 and KVLQT1 protein products coassemble to form the slow delayed rectifier current I(Ks) . <ref>PMID:8900283</ref> Through the formation of heteromeric channel complexes, KCNE1 is central to the control of the heart rate and rhythm. <ref>PMID:9230439</ref> KCNE1 modifies the KCNQ1 potassium channel by slowing activation and enhancing channel conductance. Experiments suggest that this is carried out by restricting the movement of the S4–S5 linker of KCNQ1. This interaction must be first disrupted before the channel can be opened. |
== Disease == | == Disease == | ||
=== LQT5=== | === LQT5=== | ||
| - | + | Mutations in KCNE1 cause long QT syndrome type 5 (LQT5) [MIM:[http://omim.org/entry/613695 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. <ref> PMID: 10220144 </ref> | + | 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. <ref> PMID: 10220144 </ref> <ref>PMID:9354802</ref> <ref>PMID:9445165</ref> <ref>PMID:10973849</ref> <ref>PMID:11692163 </ref> <ref>PMID:19716085</ref> |
===JLNS2=== | ===JLNS2=== | ||
Mutations in KCNE1 are also the cause of Jervell and Lange-Nielsen syndrome type 2 (JLNS2)[MIM:[http://omim.org/entry/612347 612347]]. | Mutations in KCNE1 are also the cause of Jervell and Lange-Nielsen syndrome type 2 (JLNS2)[MIM:[http://omim.org/entry/612347 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. <ref> PMID:13435203 </ref> | + | 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. <ref> PMID:13435203 </ref> <ref>PMID:9354783</ref> <ref>PMID:9328483</ref> <ref>PMID:9445165</ref> |
=== N5Q and T7I mutants === | === N5Q and T7I mutants === | ||
| - | These mutations inhibit the ability of KCNE1 to form fully functional IKs channels. Mutations that disrupt the proper glycosylation of KCNE1 ( | + | These mutations inhibit the ability of KCNE1 to form fully functional IKs channels. Mutations that disrupt the proper glycosylation of KCNE1 (i.e. N5Q and T7I) lead to the formation of channels that are unable of proper cell surface expression due to defect in anterograde trafficking. WT subunits are glycosylated both co-translationally and post-translationally, whereas the N5Q and T7I mutants lack the co-translational gylcosylation, which in turn severely lowers their proclivity to be glycosylated post-translationally and therefore their proper function. <ref>PMID:21676880</ref> |
=== P127T mutants === | === P127T mutants === | ||
| - | It has been shown that KCNE1 P127T mutation led to decrease in IKs currents by impairing their stimulation by cAMP. Specifically, it prevented the phosphorylation of KCNQ1 at S27 following cAMP stimulation. | + | It has been shown that KCNE1 P127T mutation led to decrease in IKs currents by impairing their stimulation by cAMP. Specifically, it prevented the phosphorylation of KCNQ1 at S27 following cAMP stimulation. <ref>PMID:25037568</ref> |
| - | <ref>PMID: | + | |
=== Other === | === Other === | ||
Mutations in KCNE1 may be a cause for hightened susceptibility to the Noise-Induced Hearing Loss. <ref>PMID:16823764</ref> | Mutations in KCNE1 may be a cause for hightened susceptibility to the Noise-Induced Hearing Loss. <ref>PMID:16823764</ref> | ||
Current revision
NMR structure of human KCNE1 in LMPG micelles at pH 6.0 and 40 degree C
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Categories: Human | George, A L | Kang, C | Kim, H | Meiler, J | Sanders, C R | Smith, J A | Sonnichsen, F D | Tian, C | Vanoye, C G | Auxilliary subunit | Ion transport | Ionic channel | Kcne1 | Membrane protein | Micelle | Mink | Potassium channel | Potassium transport | Transmembrane | Transport | Voltage-gated channel
