Affinage

KCNE4

Potassium voltage-gated channel subfamily E member 4 · UniProt Q8WWG9

Length
221 aa
Mass
23.8 kDa
Annotated
2026-06-10
35 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNE4 is a single-pass transmembrane ancillary subunit that modulates the gating and trafficking of multiple voltage-gated potassium channels, acting predominantly as an inhibitor and thereby shaping cardiac repolarization, vascular smooth-muscle excitability, and leukocyte function (PMID:12096056, PMID:19773357, PMID:26399785). It directly associates with KCNQ1 and completely suppresses KCNQ1 current through a biophysical, gating-based mechanism rather than by reducing α-subunit surface expression, and can co-assemble with KCNE1 and KCNQ1 in a triple-subunit complex (PMID:12096056, PMID:18279388). Its channel partners extend to Kv1.1 and Kv1.3, BK channels in renal intercalated cells, Kv4.2 in cardiac transverse tubules, and Kv7.4/Kv7.5 in vascular myocytes, with effects ranging from gating shifts to changes in protein stability and membrane abundance (PMID:12944270, PMID:18463315, PMID:20498229, PMID:26503181, PMID:33093272). The inhibitory action requires cooperation between the KCNE4 C-terminus and its native transmembrane domain, with a juxtamembrane tetraleucine motif serving as a shared competitive binding platform for the Kv1.3 C-terminus, Ca2+/calmodulin, and KCNE4 itself (PMID:19029186, PMID:21118809, PMID:30969795). For Kv1.3, KCNE4 enforces intracellular retention by masking the YMVIEE forward-trafficking motif and contributing its own ER-retention signal, while CaM-dependent KCNE4 dimerization permits its own escape from the ER along a COP-II anterograde route (PMID:27802162, PMID:30969795, PMID:34234241). KCNE4 expression is transcriptionally upregulated by 5α-dihydrotestosterone, making it a hormone-regulated determinant of sex-specific ventricular potassium currents and cardioprotective signalling (PMID:26399785, PMID:29844497).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Established KCNE4 as a functional channel regulator by showing it completely and specifically inhibits KCNQ1 current through a post-membrane biophysical mechanism rather than by blocking trafficking.

    Evidence Two-electrode voltage clamp and patch clamp in oocytes and CHO-K1 cells, with delayed-mRNA expression and surface immunocytochemistry

    PMID:12096056

    Open questions at the time
    • Molecular basis of gating suppression not defined
    • Physiological tissue context not addressed
  2. 2003 High

    Broadened the KCNE4 target repertoire to Kv1-family channels, demonstrating selective inhibition of Kv1.1 and Kv1.3 with the α-subunit retained at the surface.

    Evidence Voltage clamp in oocytes and HEK293, confocal microscopy and Western blotting across multiple Kv1 partners

    PMID:12944270

    Open questions at the time
    • Interaction interface not mapped
    • Mechanism distinguishing inhibited vs. unaffected Kv1 subtypes unknown
  3. 2008 High

    Confirmed direct physical association of KCNE4 with KCNQ1, capacity to form a triple subunit complex with KCNE1, and mapped the C-terminus plus transmembrane domain as cooperatively required for inhibition.

    Evidence Co-immunoprecipitation, surface biotinylation, and chimeric subunit electrophysiology

    PMID:18279388 PMID:19029186

    Open questions at the time
    • Specific residues mediating C-terminal/KCNQ1 contact not resolved
    • Stoichiometry of triple complex undefined
  4. 2008 High

    Extended KCNE4 to native renal physiology, showing apical co-localization with and calcium-dependent inhibition of BK channels via gating shift and accelerated complex degradation.

    Evidence Immunohistochemistry in rabbit kidney, co-IP, patch clamp, and degradation assays

    PMID:18463315

    Open questions at the time
    • In vivo renal consequence of BK modulation not tested
    • Degradation pathway not identified
  5. 2009 High

    Defined KCNE4 as an inhibitory Kv1.3 partner in leukocytes that retains the channel in the ER and impairs lipid-raft targeting, linking it to immune-cell potassium signalling.

    Evidence Patch clamp, co-IP, confocal imaging, lipid-raft fractionation, and RT-PCR in leukocytes and transfected cells

    PMID:19773357

    Open questions at the time
    • Trafficking motifs not yet mapped
    • Functional immune consequence not directly tested at this stage
  6. 2010 High

    Identified Ca2+/calmodulin binding to a juxtamembrane tetraleucine motif as mechanistically required for KCNQ1 inhibition, introducing calcium sensing into KCNE4 function.

    Evidence Co-IP, tetraleucine mutagenesis, Ca2+ chelation, and patch clamp

    PMID:21118809

    Open questions at the time
    • Conformational consequence of CaM binding not resolved
    • Generalizability to non-KCNQ1 partners not tested here
  7. 2010 High

    Placed KCNE4 in cardiac transverse tubules as a Kv4.2 modulator and member of a KChIP2-containing ternary complex with a distinct biophysical profile.

    Evidence Immunofluorescence in cardiac myocytes, voltage clamp in tsA201, and ternary-complex co-IP

    PMID:20498229

    Open questions at the time
    • Physiological role of overshoot abolition unknown
    • Stoichiometry of ternary complex undefined
  8. 2015 High

    Demonstrated in vivo that KCNE4 is a Kv7.4 partner supporting channel membrane abundance and vascular tone, with knockdown depolarizing smooth muscle and increasing vasoconstrictor sensitivity.

    Evidence Proximity ligation assay, HEK patch clamp, morpholino knockdown, and wire myography in rat mesenteric artery

    PMID:26503181

    Open questions at the time
    • Contrasts with inhibitory role on other channels; basis for stabilizing effect unclear
    • Direct gating mechanism on Kv7.4 not resolved
  9. 2015 High

    Revealed KCNE4 as a hormone-regulated determinant of sex-specific ventricular potassium currents, with germline deletion abolishing Ito,f and IK,slow1 sex disparities and DHT driving its transcription.

    Evidence Germline KO mice, ventricular myocyte patch clamp, castration/DHT implants, qRT-PCR, and heterologous Kv1.5 assays

    PMID:26399785

    Open questions at the time
    • Transcriptional mechanism of DHT regulation not mapped
    • Human relevance of sex disparity not established
  10. 2016 High

    Dissected the dual additive mechanism of Kv1.3 retention—motif masking plus an intrinsic ER-retention signal—and showed the C-terminal interaction is separable from gating modulation.

    Evidence Co-IP, truncation/deletion mutagenesis, confocal imaging, surface biotinylation, and electrophysiology

    PMID:27802162

    Open questions at the time
    • Identity of the KCNE4 ER-retention signal not pinpointed
    • Gating-determining region distinct from binding region not mapped
  11. 2016 Medium

    Characterized KCNE4 isoform diversity, showing an extended full-length 221-aa form with attenuated KCNQ1 inhibition and altered effects on KCNQ4.

    Evidence Voltage clamp in oocytes and isoform Western blotting in human tissues

    PMID:27162025

    Open questions at the time
    • Tissue-specific isoform expression not quantified
    • Functional role of N-terminal extension not mechanistically explained
  12. 2016 Medium

    Showed sex-specific KCNE4 control of Kv7.4 protein stability and mesenteric vascular contractility, with deletion altering contractile and relaxant responses differentially between sexes.

    Evidence Germline KO mice, wire myography, Western blotting, and qRT-PCR

    PMID:27710966

    Open questions at the time
    • Molecular basis of sex-specific Kv7.4 stability regulation undefined
    • Single lab
  13. 2019 High

    Resolved the tetraleucine motif as a shared competitive binding platform where Kv1.3 and Ca2+/calmodulin compete, coupling channel binding to trafficking-signal masking.

    Evidence Tetraleucine mutagenesis, co-IP, competitive binding assays, co-localization imaging, and in silico modeling

    PMID:30969795

    Open questions at the time
    • Structural model not experimentally validated
    • Quantitative competition affinities not determined
  14. 2020 Medium

    Defined variable KCNE4:Kv1.3 stoichiometry, linking subunit copy number to graded modulation of activation and surface abundance versus a single subunit sufficing for inactivation enhancement.

    Evidence Tandem-linked subunit constructs, co-IP, electrophysiology, and surface biotinylation

    PMID:32370164

    Open questions at the time
    • Native in-cell stoichiometry not measured
    • Single lab
  15. 2020 Medium

    Confirmed KCNE4 interaction with Kv7.4/Kv7.5 and showed it attenuates pharmacological activation, relevant to vascular smooth-muscle responses.

    Evidence FRET, co-IP, patch clamp in HEK293, and smooth-muscle myography

    PMID:33093272

    Open questions at the time
    • Mechanism of activator attenuation not resolved
    • Single lab
  16. 2018 Medium

    Connected KCNE4 to testosterone-dependent cardioprotection, with deletion impairing RISK and SAFE pathway induction and altering post-ischemic arrhythmia susceptibility in male mice.

    Evidence Germline KO mice with castration/DHT manipulation, phospho-kinase Western blotting, IR injury model, and ECG

    PMID:29844497

    Open questions at the time
    • Mechanistic link between channel modulation and kinase signalling unclear
    • Single lab
  17. 2021 High

    Established KCNE4 self-dimerization as unique in the family and CaM-dependent dimerization as the gate controlling its own COP-II-dependent ER exit and membrane targeting.

    Evidence Co-IP, FRET, mutagenesis, confocal imaging, COP-II inhibition, and competitive binding

    PMID:34234241

    Open questions at the time
    • Structural basis of dimer interface not solved
    • Regulation of CaM occupancy in vivo unknown
  18. 2021 Medium

    Demonstrated cellular immune consequences of KCNE4-Kv1.3 regulation, with overexpression reducing immunological-synapse Kv1.3 clustering, IL-2 production, and growth, and ablation augmenting dendritic-cell proliferation.

    Evidence Overexpression/CRISPR knockout in leukocyte cell lines, IL-2 ELISA, synapse imaging, and flow cytometry

    PMID:34272451

    Open questions at the time
    • In vivo immune phenotype not tested
    • Single lab
  19. 2024 Medium

    Provided the first direct biophysical confirmation of KCNE4's folded single-pass membrane topology with defined extracellular, transmembrane, and intracellular regions.

    Evidence Recombinant expression, CD spectroscopy, and CW-EPR/power saturation

    PMID:39780724

    Open questions at the time
    • No functional validation of the purified protein
    • Channel-bound conformation not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KCNE4 mechanistically switches between inhibiting (KCNQ1, Kv1.3, BK) and stabilizing/promoting (Kv7.4 membrane abundance) different channel partners, and the high-resolution structure of any KCNE4-channel complex, remain unresolved.
  • No experimental structure of a KCNE4-channel complex
  • Determinants of inhibitory vs. stabilizing outcome unknown
  • Transcriptional mechanism of DHT regulation unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 4
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 4
Pathway
R-HSA-9609507 Protein localization 3 R-HSA-112316 Neuronal System 2
Partners
CALM (CALMODULIN)KCNE1KCNIP2KCNQ1KV1.1KV1.3KV4.2KV7.4
Complex memberships
KCNQ1-KCNE1-KCNE4 triple-subunit complexKv1.3-KCNE4 complexKv4.2-KCNE4-KChIP2 ternary complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 KCNE4 acts as an inhibitory subunit to KCNQ1 channels; co-expression in Xenopus oocytes and CHO-K1 cells completely inhibits KCNQ1 current. The inhibition occurs on channels already expressed in the plasma membrane, as delayed KCNE4 mRNA expression still suppressed current. Immunocytochemistry and Western blotting showed no significant difference in plasma membrane KCNQ1 expression, indicating a biophysical rather than trafficking mechanism. The effect was specific: no inhibition of KCNQ2-5 or hERG1. Two-electrode voltage clamp (Xenopus oocytes), whole-cell patch clamp (CHO-K1), immunocytochemistry, Western blotting, delayed mRNA expression experiment The Journal of physiology High 12096056
2003 KCNE4 inhibits Kv1.1 and Kv1.3 but not Kv1.2, Kv1.4, Kv1.5, or Kv4.3 homomeric channels; it also reduces current through Kv1.1/Kv1.2 and Kv1.2/Kv1.3 heteromeric complexes. Confocal microscopy and Western blotting showed Kv1.1 present at the cell surface together with KCNE4, indicating the inhibition is not due to retention of the α-subunit. Two-electrode voltage clamp (Xenopus oocytes), whole-cell patch clamp (HEK293), confocal microscopy, Western blotting Biophysical journal High 12944270
2008 KCNE4 directly associates with KCNQ1 by co-immunoprecipitation and can form a 'triple subunit' complex with KCNE1 and KCNQ1 simultaneously. Cell-surface biotinylation demonstrated that KCNE4 does not impair plasma membrane expression of KCNQ1 or the triple-subunit complex, indicating that biophysical (gating) mechanisms underlie KCNE4-dependent inhibition. Co-immunoprecipitation, Western blotting, cell-surface biotinylation in heterologous expression The FEBS journal High 18279388
2008 KCNE4 (MiRP3) localizes to the apical membrane of renal intercalated cells by immunohistochemistry, co-localizing with BK channels. MiRP3 and BK subunits form detergent-stable complexes in tissue culture. MiRP3 reduces BK current density by shifting the current-voltage relationship ~10 mV toward depolarization in a calcium-dependent fashion and by accelerating degradation of MiRP3-BK complexes. Immunohistochemistry (rabbit kidney), co-immunoprecipitation, electrophysiology (whole-cell patch clamp), biochemical degradation assay American journal of physiology. Renal physiology High 18463315
2008 The KCNE4 C-terminus is necessary and cooperative with its transmembrane domain for inhibition of KCNQ1. Chimeras replacing KCNE1 or KCNE3 C-termini with that of KCNE4 conferred strong KCNQ1 inhibition. The transmembrane tripeptide motif critical for KCNE1/KCNE3 functional differences does not account for KCNE4 activity. The KCNE4 C-terminus directly interacts with KCNQ1, and a surrogate transmembrane domain (from CD8) cannot substitute for the native KCNE4 transmembrane domain, indicating that both domains cooperate. Chimeric subunit construction, two-electrode voltage clamp (Xenopus oocytes), co-immunoprecipitation The Journal of physiology High 19029186
2009 KCNE4, but not KCNE2, acts as an inhibitory Kv1.3 partner in leukocytes. KCNE4 associates with Kv1.3 in the ER, retains Kv1.3 intracellularly, decreases cell-surface Kv1.3 number, impairs targeting to lipid raft microdomains, decreases current density, slows activation, accelerates inactivation, and increases cumulative inactivation. LPS activation increases both Kv1.3 and KCNE4 mRNA, while dexamethasone decreases Kv1.3 without changing KCNE4. Whole-cell patch clamp, co-immunoprecipitation, confocal immunofluorescence, lipid-raft fractionation, RT-PCR, Western blotting in leukocytes and transfected cells Journal of cell science High 19773357
2010 KCNE4 physically interacts with calmodulin (CaM) in a Ca2+-dependent manner via a tetraleucine motif in its juxtamembrane C-terminal region. KCNE1 does not interact with CaM. Mutagenesis of the tetraleucine motif or acute Ca2+ chelation disrupts the KCNE4-CaM interaction and impairs KCNE4's ability to inhibit KCNQ1, establishing CaM binding as mechanistically required for KCNQ1 suppression. Co-immunoprecipitation, mutagenesis of tetraleucine motif, Ca2+ chelation, whole-cell patch clamp The Journal of biological chemistry High 21118809
2010 MiRP3 (KCNE4) localizes to the transverse tubules of murine cardiac myocytes by immunofluorescence and co-localizes with Kv4.2. Co-expression of MiRP3 with Kv4.2 in tsA201 cells modulates activation (shifts V1/2 ~20 mV), slows inactivation ~100%, speeds recovery from inactivation ~30%, and causes current overshoot. The cytoplasmic subunit KChIP2 also assembles with Kv4.2-MiRP3 to form a biochemically isolable ternary complex with a distinct biophysical profile that abolishes the MiRP3-induced overshoot. Immunofluorescence microscopy (cardiac myocytes), whole-cell voltage clamp (tsA201), co-immunoprecipitation of ternary complex The Journal of physiology High 20498229
2007 The KCNE4 E145D polymorphism reverses the functional effect on KCNQ1: wild-type KCNE4 inhibits KCNQ1 current, whereas the 145D variant augments it and shifts V1/2 of activation toward depolarization, also altering activation and deactivation kinetics ('gain of function'). Whole-cell patch clamp in CHO-K1 cells transiently co-transfected with KCNQ1 and KCNE4 variants Chinese medical journal Medium 17335661
2015 KCNE4 co-localizes with Kv7.4 in mesenteric artery myocytes (proximity ligation assay). In HEK cells, KCNE4 co-expression increases Kv7.4 membrane expression and alters Kv7.4 current properties. Morpholino-induced knockdown of KCNE4 in rat mesenteric arteries reduces Kv7.4 membrane abundance, depolarizes smooth muscle cells, increases sensitivity to vasoconstrictors, and impairs effects of Kv7 modulators. Proximity ligation assay, patch clamp (HEK), morpholino knockdown, wire myography, Western blotting The Journal of physiology High 26503181
2015 Germline Kcne4 deletion eliminates the sex-specific disparity in ventricular fast transient outward current (Ito,f) and slowly activating K+ current (IK,slow1) in mice. Ventricular Kcne4 expression is ~8-fold higher in young adult males vs. females and is upregulated by 5α-dihydrotestosterone (DHT); castration reduces male Kcne4 expression and DHT implants restore it, demonstrating DHT-dependent transcriptional regulation. KCNE4 functionally regulated heterologously expressed Kv1.5 (IKslow1 subunit). Germline knockout mice, patch clamp (ventricular myocytes), castration/DHT implant experiments, qRT-PCR, heterologous expression electrophysiology FASEB journal High 26399785
2016 The C-terminal domain of Kv1.3 is necessary and sufficient for interaction with KCNE4 (pulldown/co-IP), but this domain is not involved in modulating Kv1.3 gating. KCNE4-dependent intracellular retention of Kv1.3 operates via two additive mechanisms: (1) masking the YMVIEE forward-trafficking motif at the Kv1.3 C-terminus, and (2) an ER retention motif intrinsic to KCNE4. Co-immunoprecipitation, truncation/deletion mutagenesis, confocal imaging, surface biotinylation, electrophysiology Journal of cell science High 27802162
2016 Previously undiscovered N-terminal protein-coding regions in exon 1 extend KCNE4 by 51 residues (full-length = 221 aa). Full-length KCNE4 partially inhibits KCNQ1 (~40% vs. ~80% for short isoform) and abolishes KCNE4-dependent augmentation of KCNQ4; the short isoform slowing of Kv4.2 inactivation is preserved in the full-length form. Two-electrode voltage clamp (Xenopus oocytes), Western blotting for isoform detection in human tissues FASEB journal Medium 27162025
2016 Kcne4 deletion in male but not female mice increased mesenteric artery contractility to methoxamine and decreased responses to Kv7.2-7.5 activator ML213; Kcne4 deletion decreased isoprenaline-induced vasorelaxation in both sexes. Kv7.4 protein expression was twice as high in female vs. male mesenteric artery and was reduced by Kcne4 deletion in both sexes, establishing KCNE4 as a sex-specific regulator of Kv7.4 protein stability and vascular function. Germline Kcne4 knockout mice, wire myography, Western blotting, qRT-PCR Journal of vascular research Medium 27710966
2019 The tetraleucine motif in the KCNE4 C-terminal juxtamembrane domain mediates direct association with Kv1.3. Ca2+/calmodulin and Kv1.3 compete for this same tetraleucine motif on KCNE4. Structural modeling suggests KCNE4 binding hides the forward-trafficking YMVIEE signature of Kv1.3 and adds an ER retention signal to the Kv1.3-KCNE4 complex. Mutagenesis of tetraleucine motif, co-immunoprecipitation, co-localization imaging, competitive binding assays, in silico structural modeling FASEB journal High 30969795
2021 KCNE4 dimerizes (unique among KCNE family members) via the tetraleucine juxtamembrane domain; CaM-dependent dimerization controls KCNE4 membrane targeting. Kv1.3, Ca2+/CaM, and dimerizing KCNE4 compete for the tetraleucine motif. KCNE4 escapes ER retention in a CaM-dependent manner and follows a COP-II-dependent anterograde trafficking route. Co-immunoprecipitation, FRET, mutagenesis, confocal imaging, COP-II inhibition assay, competitive binding Scientific reports High 34234241
2021 KCNE4 overexpression in T cells (Jurkat) reduces Kv1.3 clustering at the immunological synapse, decreases cell growth, alters apoptosis, and reduces IL-2 production; KCNE4 ablation in dendritic cells augments proliferation. LPS activation of CY15 dendritic cells induces Kv1.3 but not KCNE4, increasing the Kv1.3:KCNE4 ratio and free (unassociated) Kv1.3 surface expression. KCNE4 overexpression/CRISPR knockout in leukocyte cell lines, IL-2 ELISA, confocal imaging of immunological synapse, flow cytometry Scientific reports Medium 34272451
2020 Up to four KCNE4 subunits can associate with a single Kv1.3 tetramer (variable stoichiometry). Increasing KCNE4 copy number progressively slows Kv1.3 activation and decreases surface abundance, while a single KCNE4 subunit is sufficient for cooperative enhancement of channel inactivation. Tandem-linked subunit constructs, co-immunoprecipitation, electrophysiology, surface biotinylation Cells Medium 32370164
2018 Kcne4 deletion in aged male mice impairs both baseline and post-ischemia/reperfusion induction of cardioprotective RISK (Akt/ERK) and SAFE (STAT3) pathways in a testosterone-dependent manner; castration of Kcne4-/- males eliminates sex-specific differences in RISK/SAFE induction and in ventricular tachyarrhythmia predisposition after IR. Germline KO mice, castration/DHT manipulation, Western blotting for phospho-kinases, IR injury model, ECG Scientific reports Medium 29844497
2024 KCNE4 protein was successfully expressed, purified from E. coli, and characterized by CD spectroscopy (confirming folded secondary structure) and CW-EPR/power saturation (confirming extracellular, transmembrane, and intracellular topological regions), validating a single-pass membrane topology. Recombinant expression, SDS-PAGE, CD spectroscopy, CW-EPR, EPR power saturation The journal of physical chemistry. B Medium 39780724
2020 KCNE4 co-expression with Kv7.4 and Kv7.5 attenuates the agonistic action of the Kv7 activator URO-K10. Strong in vitro interactions between Kv7.4/Kv7.5 and KCNE4 were confirmed by FRET and co-immunoprecipitation in HEK293 cells. FRET, co-immunoprecipitation, whole-cell patch clamp (HEK293), smooth muscle strip myography The Korean journal of physiology & pharmacology Medium 33093272

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 KCNE4 is an inhibitory subunit to the KCNQ1 channel. The Journal of physiology 136 12096056
2009 KCNE4 suppresses Kv1.3 currents by modulating trafficking, surface expression and channel gating. Journal of cell science 68 19773357
2003 KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels. Biophysical journal 66 12944270
2015 Fundamental role for the KCNE4 ancillary subunit in Kv7.4 regulation of arterial tone. The Journal of physiology 62 26503181
2008 KCNE4 can co-associate with the I(Ks) (KCNQ1-KCNE1) channel complex. The FEBS journal 40 18279388
2016 KCNE4 and KCNE5: K(+) channel regulation and cardiac arrhythmogenesis. Gene 39 27484720
2016 Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity. Journal of vascular research 37 27710966
2010 KCNE4 juxtamembrane region is required for interaction with calmodulin and for functional suppression of KCNQ1. The Journal of biological chemistry 30 21118809
2015 Kcne4 deletion sex- and age-specifically impairs cardiac repolarization in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 26399785
2016 The C-terminal domain of Kv1.3 regulates functional interactions with the KCNE4 subunit. Journal of cell science 22 27802162
2007 Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism. Chinese medical journal 20 17335661
2008 MiRP3 acts as an accessory subunit with the BK potassium channel. American journal of physiology. Renal physiology 19 18463315
2010 The membrane protein MiRP3 regulates Kv4.2 channels in a KChIP-dependent manner. The Journal of physiology 17 20498229
2008 KCNE4 domains required for inhibition of KCNQ1. The Journal of physiology 17 19029186
2016 Novel exon 1 protein-coding regions N-terminally extend human KCNE3 and KCNE4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 27162025
2019 The calmodulin-binding tetraleucine motif of KCNE4 is responsible for association with Kv1.3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 30969795
2021 KCNE4-dependent functional consequences of Kv1.3-related leukocyte physiology. Scientific reports 12 34272451
2016 Regulation of human cardiac potassium channels by full-length KCNE3 and KCNE4. Scientific reports 12 27922120
2021 Calmodulin-dependent KCNE4 dimerization controls membrane targeting. Scientific reports 11 34234241
2020 Functional Consequences of the Variable Stoichiometry of the Kv1.3-KCNE4 Complex. Cells 10 32370164
2022 KCNE4 expression is correlated with the pathological characteristics of colorectal cancer patients and associated with the radioresistance of cancer cells. Pathology, research and practice 8 36459833
2018 Kcne4 deletion sex-specifically predisposes to cardiac arrhythmia via testosterone-dependent impairment of RISK/SAFE pathway induction in aged mice. Scientific reports 8 29844497
2013 [Association of single nucleotide polymorphism of KCNE1 and KCNE4 gene with atrial fibrillation in Xinjiang Uygur and Han population]. Zhonghua xin xue guan bing za zhi 8 24370217
2019 Kcne4 deletion sex dependently inhibits the RISK pathway response and exacerbates hepatic ischemia-reperfusion injury in mice. American journal of physiology. Regulatory, integrative and comparative physiology 7 30758982
2024 Influential upregulation of KCNE4: Propelling cancer associated fibroblasts-driven colorectal cancer progression. Cancer cell international 6 38462626
2017 [Association of KCNE1 and KCNE4 gene polymorphisms with atrial fibrillation among Uygur and Han Chinese populations in Xinjiang]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 5 28981946
2024 KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry. Virology journal 4 39118175
2023 The novel KV7 channel activator URO-K10 exerts enhanced pulmonary vascular effects independent of the KCNE4 regulatory subunit. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 4 37295249
2013 [Effect of additional disease (comorbidity) on association of allergic rhinitis with KCNE4 gene rs12621643 variant]. Genetika 4 23866632
2020 The agonistic action of URO-K10 on Kv7.4 and 7.5 channels is attenuated by co-expression of KCNE4 ancillary subunit. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 3 33093272
2024 The Expression, Purification, Spectroscopic Characterization, and Membrane Topology Classification of KCNE4 from Recombinant E. coli. The journal of physical chemistry. B 2 39780724
2022 Induction of potassium channel regulator KCNE4 in a submandibular lymph node metastasis model. Scientific reports 2 35915077
2025 A missense mutation in the KCNE4 gene is not predictive of equine anhidrosis. Animal genetics 1 39953936
2024 Molecular and structural analysis of Hdh-MIRP3 and its impact on reproductive regulation in female Pacific abalone, Haliotis discus hannai. International journal of biological macromolecules 1 38403211
2026 Additional Evidence Fails to Associate Variation in KCNE4 With Equine Anhidrosis. Animal genetics 0 42035749

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