{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:43:33Z","timestamp":1791078213791,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2002,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>KCNE<\/jats:italic>\n                    genes encode single transmembrane\u2010domain subunits, the MinK\u2010related peptides (MiRPs), which assemble with pore\u2010forming \u03b1 subunits to establish the attributes of potassium channels in vivo. To investigate whether MinK, MiRP1, and MiRP2 operate similarly with their known native a subunit partners (KCNQ1, HERG, and Kv3.4, respectively) two conserved residues associated with human disease and influential in channel function were evaluated. As MiRPs assemble with a variety of \u03b1 subunits in experimental cells and may do so in vivo, each peptide was also assessed with the other two \u03b1 subunits. Inherited mutation of aspartate to asparagine (D \u2192 N) to yield D76N\u2010MinK is linked to cardiac arrhythmia and deafness;the analogs D82N\u2010MiRP1 and D90N\u2010MiRP2 were studied. Mutation of arginine to histidine (R \u2192 H) to yield R83H\u2010MiRP2 is associated with periodic paralysis; the analogs K69H\u2010MinK and K75H\u2010MiRP1 were also studied. Macroscopic and single\u2010channel currents showed that D \u2192 N mutations suppressed a subset of functions whereas R\/K \u2192 H changes altered the activity of MinK, MiRP1, and MiRP2 with all three \u03b1 subunits. The findings indicate that the KCNE peptides interact similarly with different \u03b1 subunits and suggest a hypothesis: that clinical manifestations of inherited\n                    <jats:italic>KCNE<\/jats:italic>\n                    point mutations result from disruption of multiple native currents via promiscuous interactions.\u2014Abbott, G. W., Goldstein, S. A. N. Disease\u2010associated mutations in\n                    <jats:italic>KCNE<\/jats:italic>\n                    potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    16, 390\u2013400 (2002)\n                  <\/jats:p>","DOI":"10.1096\/fj.01-0520hyp","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:24Z","timestamp":1027710204000},"page":"390-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Disease\u2010associated mutations in\n                    <i>KCNE<\/i>\n                    potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism"],"prefix":"10.1096","volume":"16","author":[{"given":"Geoffrey W.","family":"Abbott","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Cellular and Molecular Physiology Boyer Center for Molecular Medicine Yale University School of Medicine  New Haven Connecticut 06536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve A. 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