KCNE2
Potassium voltage-gated channel subfamily E member 2 (KCNE2), also known as MinK-related peptide 1 (MiRP1), is a
Discovery
Steve Goldstein (then at Yale University) used a BLAST search strategy, focusing on KCNE1 sequence stretches known to be important for function, to identify related expressed sequence tags (ESTs) in the NCBI database. Using sequences from these ESTs, KCNE2, 3 and 4 were cloned.[5]
Tissue distribution
KCNE2 protein is most readily detected in the
Structure
Gene
The KCNE2 gene resides on chromosome 21 at the band 21q22.11 and contains 2
Protein
This protein belongs to the potassium channel KCNE family and is one five single
Like other KCNEs, KCNE2 forms a
Function
Choroid plexus epithelium
KCNE2 protein is most readily detected in the
Gastric epithelium
KCNE2 is also highly expressed in parietal cells of the
Thyroid epithelium
KCNE2 forms constitutively active K+ channels with KCNQ1 in the basolateral membrane of thyroid epithelial cells. Kcne2-/- mice exhibit
Heart
KCNE2 was originally discovered to regulate
In mice, mERG and KCNQ1, another Kv α subunit regulated by KCNE2, are neither influential nor highly expressed in adult ventricles. However, Kcne2-/- mice exhibit QT prolongation at baseline at 7 months of age, or earlier if provoked with a QT-prolonging agent such as sevoflurane. This is because KCNE2 is a promiscuous regulatory subunit that forms complexes with Kv1.5 and with Kv4.2 in adult mouse ventricular myocytes. KCNE2 increases currents though Kv4.2 channels and slows their inactivation. KCNE2 is required for Kv1.5 to localize to the intercalated discs of mouse ventricular myocytes. Kcne2 deletion in mice reduces the native currents generated in ventricular myocytes by Kv4.2 and Kv1.5, namely Ito and IKslow, respectively.[23]
Clinical Significance
Gastric epithelium
Kcne2-/- mice exhibit
Thyroid epithelium
Heart
As observed for hERG mutations, KCNE2 loss-of-function mutations are associated with inherited long QT syndrome, and hERG-KCNE2 channels carrying the mutations show reduced activity compared to wild-type channels. In addition, some KCNE2 mutations and also more common
Recently, a battery of extracardiac effects were discovered in Kcne2-/- mice that may contribute to cardiac arrhythmogenesis in Kcne2-/- mice and could potentially contribute to human cardiac arrhythmias if similar effects are observed in human populations. Kcne2 deletion in mice causes anemia, glucose intolerance, dyslipidemia, hyperkalemia and elevated serum angiotensin II. Some or all of these might contribute to predisposition to sudden cardiac death in Kcne2-/- mice in the context of myocardial ischemia and post-ischemic arrhythmogenesis.[27]
Clinical Marker
A multi-locus genetic risk score study based on a combination of 27 loci, including the KCNE2 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from
See also
Notes
Wikidata Q21710689 . |
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000159197 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039672 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ S2CID 8507168.
- ^ a b "KCNE2 potassium voltage-gated channel subfamily E regulatory subunit 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-10.
- ^ "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-10.
- PMID 22513486.
- ^ PMID 25748612.
- S2CID 8386123.
- ^ PMID 26123744.
- ^ "KCNE2 - Potassium voltage-gated channel subfamily E member 2 - Homo sapiens (Human) - KCNE2 gene & protein". www.uniprot.org. Retrieved 2016-10-10.
- ^ PMID 18221016.
- PMID 24595108.
- PMID 21859894.
- ^ PMID 16754665.
- ^ PMID 20625512.
- ^ PMID 21084694.
- ^ PMID 19767733.
- ^ PMID 22549510.
- ^ PMID 23631727.
- S2CID 7271200.
- PMID 18603586.
- PMID 10984545.
- PMID 15368194.
- PMID 24796621.
- PMID 24403551.
Further reading
- Gouas L, Nicaud V, Chaouch S, Berthet M, Forhan A, Tichet J, Tiret L, Balkau B, Guicheney P (September 2007). "Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects". European Journal of Human Genetics. 15 (9): 974–9. PMID 17534376.
- McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW (March 2009). "Regulation of the Kv2.1 potassium channel by MinK and MiRP1". The Journal of Membrane Biology. 228 (1): 1–14. PMID 19219384.
- Millat G, Kugener B, Chevalier P, Chahine M, Huang H, Malicier D, Rodriguez-Lafrasse C, Rousson R (May 2009). "Contribution of long-QT syndrome genetic variants in sudden infant death syndrome". Pediatric Cardiology. 30 (4): 502–9. S2CID 7473579.
- Abbott GW, Ramesh B, Srai SK (2008). "Secondary structure of the MiRP1 (KCNE2) potassium channel ancillary subunit". Protein and Peptide Letters. 15 (1): 63–75. PMID 18221016.
- Jiang M, Xu X, Wang Y, Toyoda F, Liu XS, Zhang M, Robinson RB, Tseng GN (June 2009). "Dynamic partnership between KCNQ1 and KCNE1 and influence on cardiac IKs current amplitude by KCNE2". The Journal of Biological Chemistry. 284 (24): 16452–62. PMID 19372218.
- Nyholt DR, LaForge KS, Kallela M, Alakurtti K, Anttila V, Färkkilä M, Hämaläinen E, Kaprio J, Kaunisto MA, Heath AC, Montgomery GW, Göbel H, Todt U, Ferrari MD, Launer LJ, Frants RR, Terwindt GM, de Vries B, Verschuren WM, Brand J, Freilinger T, Pfaffenrath V, Straube A, Ballinger DG, Zhan Y, Daly MJ, Cox DR, Dichgans M, van den Maagdenberg AM, Kubisch C, Martin NG, Wessman M, Peltonen L, Palotie A (November 2008). "A high-density association screen of 155 ion transport genes for involvement with common migraine". Human Molecular Genetics. 17 (21): 3318–31. PMID 18676988.
- Chevalier P, Bellocq C, Millat G, Piqueras E, Potet F, Schott JJ, Baró I, Lemarec H, Barhanin J, Rousson R, Rodriguez-Lafrasse C (February 2007). "Torsades de pointes complicating atrioventricular block: evidence for a genetic predisposition". Heart Rhythm. 4 (2): 170–4. PMID 17275752.
- Kurokawa J, Bankston JR, Kaihara A, Chen L, Furukawa T, Kass RS (2009). "KCNE variants reveal a critical role of the beta subunit carboxyl terminus in PKA-dependent regulation of the IKs potassium channel". Channels. 3 (1): 16–24. PMID 19077539.
- Lehtinen AB, Daniel KR, Shah SA, Nelson MR, Ziegler JT, Freedman BI, Carr JJ, Herrington DM, Langefeld CD, Bowden DW (January 2009). "Relationship between genetic variants in myocardial sodium and potassium channel genes and QT interval duration in diabetics: the Diabetes Heart Study". Annals of Noninvasive Electrocardiology. 14 (1): 72–9. PMID 19149796.
- Heitzmann D, Koren V, Wagner M, Sterner C, Reichold M, Tegtmeier I, Volk T, Warth R (2007). "KCNE beta subunits determine pH sensitivity of KCNQ1 potassium channels". Cellular Physiology and Biochemistry. 19 (1–4): 21–32. PMID 17310097.
- Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, Vege A, Wang DW, Rhodes TE, George AL, Schwartz PJ (January 2007). "Prevalence of long-QT syndrome gene variants in sudden infant death syndrome". Circulation. 115 (3): 361–7. PMID 17210839.
- Liu XS, Zhang M, Jiang M, Wu DM, Tseng GN (April 2007). "Probing the interaction between KCNE2 and KCNQ1 in their transmembrane regions". The Journal of Membrane Biology. 216 (2–3): 117–27. S2CID 12153552.
- Um SY, McDonald TV (2007). Valdivia R (ed.). "Differential association between HERG and KCNE1 or KCNE2". PLOS ONE. 2 (9): e933. PMID 17895974.
- Liu WJ, Wang HT, Chen WW, Deng JX, Jiang Y, Liu J (June 2008). "Co-expression of KCNE2 and KChIP2c modulates the electrophysiological properties of Kv4.2 current in COS-7 cells". Acta Pharmacologica Sinica. 29 (6): 653–60. PMID 18501111.
- Berge KE, Haugaa KH, Früh A, Anfinsen OG, Gjesdal K, Siem G, Oyen N, Greve G, Carlsson A, Rognum TO, Hallerud M, Kongsgård E, Amlie JP, Leren TP (2008). "Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers". Scandinavian Journal of Clinical and Laboratory Investigation. 68 (5): 362–8. S2CID 25777418.
- Chung SK, MacCormick JM, McCulley CH, Crawford J, Eddy CA, Mitchell EA, Shelling AN, French JK, Skinner JR, Rees MI (October 2007). "Long QT and Brugada syndrome gene mutations in New Zealand". Heart Rhythm. 4 (10): 1306–14. PMID 17905336.
- Tester DJ, Cronk LB, Carr JL, Schulz V, Salisbury BA, Judson RS, Ackerman MJ (July 2006). "Allelic dropout in long QT syndrome genetic testing: a possible mechanism underlying false-negative results". Heart Rhythm. 3 (7): 815–21. PMID 16818214.
- Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, Wilde AA, Ackerman MJ (September 2009). "Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test". Heart Rhythm. 6 (9): 1297–303. PMID 19716085.
External links
- GeneReviews/NIH/NCBI/UW entry on Romano-Ward Syndrome
- KCNE2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- KCNE2 human gene location in the UCSC Genome Browser.
- KCNE2 human gene details in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q9Y6J6 (Potassium voltage-gated channel subfamily E member 2) at the PDBe-KB.