Affinage

KCNA5

Potassium voltage-gated channel subfamily A member 5 · UniProt P22460

Round 2 corrected
Length
613 aa
Mass
67.2 kDa
Annotated
2026-04-28
130 papers in source corpus 44 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNA5 encodes the Kv1.5 voltage-gated potassium channel α-subunit, which forms Shaker-family delayed-rectifier channels (IKur) that regulate membrane potential in human atrial myocytes, pulmonary artery smooth muscle cells (PASMC), macrophages, and coronary vascular smooth muscle. Surface density and gating of Kv1.5 are tuned by a network of post-translational modifications—SUMOylation selectively shifts inactivation (PMID:17261810), S-acylation serves as a quality-control checkpoint for ER-to-surface trafficking (PMID:17344312), Src-mediated tyrosine phosphorylation suppresses current (PMID:8953041), and Kvβ subunit association confers pyridine-nucleotide-dependent inactivation modulation (PMID:22426702)—while scaffolding by SAP97 immobilizes channels at plasma membrane contact sites (PMID:18245566), dynein/Rab-GTPase-dependent endosomal recycling and proteasomal degradation set the channel's half-life (PMID:16185660, PMID:18755741), and cholesterol-rich microdomain targeting via caveolin modulates gating (PMID:18045854). In PASMC, Kv1.5 acts as the principal O₂-sensitive K⁺ channel mediating hypoxic pulmonary vasoconstriction; its loss—through loss-of-function mutations, Polycomb/DNA-methylation-mediated epigenetic silencing, or miR-1-directed repression—reduces K⁺ efflux, depolarizes the membrane, inhibits apoptosis, and drives the proliferative vascular remodeling of pulmonary arterial hypertension (PMID:15217912, PMID:18083891, PMID:36917789, PMID:25435365, PMID:29717493). Both gain- and loss-of-function KCNA5 mutations are associated with atrial fibrillation (PMID:23264583).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Molecular cloning of KCNA5 from human heart and insulinoma tissue and reconstitution in Xenopus oocytes established that the gene encodes a Shaker-family, 4-AP-sensitive delayed-rectifier K⁺ channel, answering the fundamental question of its molecular identity and basic electrophysiology.

    Evidence cDNA cloning and two-electrode voltage clamp in Xenopus oocytes, two independent groups

    PMID:1986382 PMID:2001794

    Open questions at the time
    • Tetrameric stoichiometry and heteromeric partner compatibility not yet determined
    • Native tissue current identity not established
  2. 1995 High

    Immunolocalization of Kv1.5 to intercalated disks in human atrial and ventricular myocytes, and to vascular smooth muscle, established the channel's native tissue distribution and suggested distinct functional roles in cardiac conduction and vascular tone.

    Evidence Epitope-specific immunofluorescence with confocal colocalization in explanted human cardiac tissue

    PMID:7615797

    Open questions at the time
    • Functional contribution of Kv1.5 to the native IKur current not yet proven by loss-of-function
    • Subcellular microdomain localization not resolved
  3. 1996 High

    Discovery that Src tyrosine kinase directly binds the Kv1.5 N-terminal proline-rich SH3-binding domain and that Kvβ2.1 co-assembles with Kv1.5 to shift gating revealed that the channel operates as a signaling complex rather than an autonomous pore, opening the question of how multiple interactors coordinately regulate IKur.

    Evidence Co-immunoprecipitation from transfected cells and native human myocardium; Kvβ2.1 cloning and co-expression electrophysiology in HEK293 cells

    PMID:8576199 PMID:8953041

    Open questions at the time
    • Identity of the tyrosine phosphatase opposing Src not known
    • In vivo significance of Kvβ modulation untested
  4. 2001 High

    Identification of SAP97 as a PDZ-domain scaffold that clusters and immobilizes Kv1.5 at the plasma membrane, augmenting IKur, established a membrane-retention mechanism; subsequent work showed the functional effect depends on the Kv1.5 N-terminus and may be partially indirect.

    Evidence Co-immunoprecipitation, C-terminal mutagenesis, oocyte electrophysiology; later FRAP mobility measurements and N-terminal deletion analysis

    PMID:11709425 PMID:12860415 PMID:18245566

    Open questions at the time
    • Whether the N-terminal dependence reflects an intermediary bridging protein is unknown
    • SAP97-Kv1.5 stoichiometry and structure unresolved
  5. 2004 High

    Demonstration that Kv1.5 is the predominant O₂-sensitive Kv channel in resistance PASMCs—and that K⁺ efflux through it promotes apoptotic volume decrease and caspase activation—linked the channel directly to hypoxic pulmonary vasoconstriction and to apoptosis regulation.

    Evidence Intracellular anti-Kv1.5 antibody application in native PASMCs plus KCNA5 overexpression with caspase-3 and apoptosis assays

    PMID:15140747 PMID:15217912

    Open questions at the time
    • Molecular identity of the PASMC-specific hypoxia sensor upstream of Kv1.5 not defined
    • Contribution of Kv1.5 versus Kv2.1 to HPV quantitatively uncertain
  6. 2005 High

    Characterization of dynein-dependent retrograde trafficking and ubiquitin-proteasomal degradation of Kv1.5 revealed that channel surface density is dynamically controlled by motor-mediated internalization and protein turnover, not solely by biosynthetic delivery.

    Evidence Dominant-negative dynein/dynamin experiments, nocodazole, proteasome inhibitors (MG132/ALLN), pulse-chase with functional electrophysiology

    PMID:16051887 PMID:16185660

    Open questions at the time
    • E3 ubiquitin ligase targeting Kv1.5 not identified
    • Signals triggering accelerated internalization in disease states unknown
  7. 2007 High

    Three post-translational regulatory axes were defined: SUMOylation selectively shifts Kv1.5 inactivation, S-acylation acts as an ER quality-control checkpoint for surface delivery, and caveolin directs Kv1.5 to cholesterol-rich microdomains that modulate gating—collectively showing that multiple lipid and protein modifications independently tune channel function.

    Evidence In vitro and in vivo SUMOylation assays with mutagenesis and electrophysiology; hydroxylamine sensitivity and acylation inhibitor studies; caveolin co-expression with sucrose fractionation and patch clamp

    PMID:17261810 PMID:17344312 PMID:17525113 PMID:18045854

    Open questions at the time
    • SUMO E3 ligase and stimulus-dependent regulation of channel SUMOylation not identified
    • Specific palmitoyl acyltransferase for Kv1.5 unknown
    • Relative contribution of each modification to native IKur regulation untested
  8. 2008 High

    Mapping the post-endocytic itinerary through Rab5→Rab4 (rapid recycling) and Rab7 (degradation) compartments, and identification of FHL1 as a Kv1.5 C-terminal interactor that enhances current density and modulates gating, completed a picture of both vesicular and scaffolding control of channel availability.

    Evidence Dominant-negative Rab GTPase colocalization and electrophysiology; GST pull-down/mass spectrometry from human atrium with co-IP and patch clamp

    PMID:18281375 PMID:18755741

    Open questions at the time
    • Whether FHL1 and SAP97 form a ternary complex at the channel is unknown
    • Recycling kinetics in native cardiomyocytes not measured
  9. 2012 High

    Discovery that Kvβ-subunit interaction with the Kv1.5 C-terminus is redox-tuned by NADPH/NADP⁺, and that both gain- and loss-of-function KCNA5 mutations associate with atrial fibrillation, connected channel redox sensing and genetic variation to cardiac arrhythmia.

    Evidence C-terminal deletion mutagenesis with intracellular nucleotide dialysis and GST pull-down; biophysical characterization of AF-associated Kv1.5 mutants

    PMID:22426702 PMID:23264583

    Open questions at the time
    • Clinical penetrance and population frequency of AF-associated KCNA5 variants not established
    • Structural basis for pyridine nucleotide selectivity at the Kvβ–C-terminus interface unresolved
  10. 2015 High

    In vivo knockout and smooth-muscle-specific rescue showed Kv1.5 is required for redox-dependent coronary metabolic dilation; concurrently, Polycomb- and DNA-methylation-mediated epigenetic silencing of KCNA5 was shown to promote cancer cell survival by disabling apoptosis, broadening the channel's functional roles beyond excitable-cell electrophysiology.

    Evidence Kv1.5-null mice with inducible SM-specific rescue, isolated artery pharmacology; ChIP for H3K27me3, EZH2/BMI-1 inhibition, decitabine demethylation with proliferation assays

    PMID:25435365 PMID:26224794 PMID:26573141

    Open questions at the time
    • Whether coronary metabolic dilation phenotype relates to PASMC O₂-sensing pathway is unclear
    • Whether epigenetic silencing of KCNA5 occurs in PAH patient lungs not shown
  11. 2018 High

    Validation of miR-1 as a direct KCNA5 3′-UTR targeting miRNA that is elevated in PAH lungs and suppresses Kv1.5 expression, with antagomiR rescue, established post-transcriptional repression as another layer of Kv1.5 downregulation in pulmonary vascular disease.

    Evidence Luciferase 3′-UTR reporter, miR-1 transfection in PASMC with patch clamp, antagomiR-1 in PAH rat model

    PMID:29717493

    Open questions at the time
    • Relative contribution of miR-1 versus epigenetic silencing versus transcriptional repression in human PAH not quantified
    • Upstream signals inducing miR-1 in PAH lungs not defined
  12. 2023 High

    Functional characterization of PAH-associated KCNA5 variants (Arg184Pro, Gly384Arg) as loss-of-function mutations that impair both channel activity and PASMC apoptosis provided the strongest genetic evidence that KCNA5 deficiency directly contributes to PAH pathogenesis.

    Evidence Patch-clamp electrophysiology in HEK293, apoptosis assays in human PASMC, Western blot, molecular modeling

    PMID:36917789

    Open questions at the time
    • Segregation data in PAH families not provided for these variants
    • Whether these variants affect heteromeric channel assembly (e.g., with Kv1.3 or Kv2.1) is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the molecular identity of the PASMC-specific O₂ sensor that inhibits Kv1.5, the E3 ubiquitin ligase responsible for proteasomal targeting, the high-resolution structure of human Kv1.5 in complex with regulatory subunits (Kvβ, SAP97, FHL1), and whether KCNA5 loss-of-function mutations are causative for heritable PAH as demonstrated by family segregation and rescue studies.
  • No PASMC-specific O₂ sensor molecularly identified
  • E3 ligase for Kv1.5 unknown
  • No cryo-EM or X-ray structure of human Kv1.5 reported in timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4
Localization
GO:0005886 plasma membrane 6 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-382551 Transport of small molecules 5 R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9609507 Protein localization 3
Partners
ACTN2CAV1FHL1KCNAB2PTPRESAP97SRCUBC9
Complex memberships
Kv1.3/Kv1.5 heterotetramerKv1.5 homotetramer (IKur)Kv1.5–Kvβ2/Kvβ3 complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 KCNA5 (HK2/hPCN1) was molecularly cloned from human ventricle and insulinoma/islet tissue, and functional expression in Xenopus oocytes demonstrated a voltage-dependent, slowly inactivating outward K+ current sensitive to low concentrations of 4-aminopyridine, establishing it as a Shaker-family delayed rectifier potassium channel. cDNA cloning, Northern blot, functional expression in Xenopus oocytes with two-electrode voltage clamp FASEB journal / Proceedings of the National Academy of Sciences High 1986382 2001794
1993 Stable mammalian cell expression of Kv1.5 (HK2) revealed a rapidly activating, slowly inactivating delayed rectifier current with well-defined gating kinetics (activation midpoint ~−14 mV, slow biexponential inactivation with voltage-independent time constants ~240 ms and ~2,700 ms), K+ selectivity, and 4-AP sensitivity, establishing the channel's intrinsic biophysical properties. Stable transfection in mouse L-cells, whole-cell patch-clamp electrophysiology The Journal of general physiology High 8505626
1995 Kv1.5 protein is highly localized at intercalated disk regions in human atrial and ventricular myocytes, as determined by colocalization with connexin and N-cadherin; NH2-terminal antibodies additionally stained vascular smooth muscle, suggesting epitope accessibility and possibly different channel structure in cardiac versus vascular myocytes. Immunofluorescence with epitope-specific antibodies in explanted human cardiac tissue, confocal colocalization The Journal of clinical investigation High 7615797
1996 Kv1.5 (hKv1.5) directly associates with Src tyrosine kinase via the channel's proline-rich N-terminal sequences and the SH3 domain of Src; this interaction results in tyrosine phosphorylation of hKv1.5 and suppression of channel current in cells co-expressing v-Src, establishing a signaling complex between a potassium channel and a protein tyrosine kinase. Co-immunoprecipitation from transfected cells and human myocardium, SH3 domain pull-down, whole-cell patch clamp in v-Src co-expressing cells Science High 8953041
1996 Endogenous Kvβ2.1 co-assembles with transfected hKv1.5 α-subunit and shifts the midpoints of activation and inactivation by ~14 mV and ~12 mV toward hyperpolarized potentials, respectively, and increases the extent of slow inactivation, explaining cell-line-dependent differences in Kv1.5 current kinetics. Molecular cloning, immunopurification, Western blot detection of endogenous Kvβ2.1; functional co-expression in HEK293 cells with patch clamp The Journal of biological chemistry High 8576199
1998 Ketoconazole directly blocks both HERG and Kv1.5 channels heterologously expressed in Xenopus oocytes, with IC50 values of ~49 µM and ~107 µM, respectively; the mechanism of block differs between the two channels, and combined application with terfenadine at IC50 concentrations produces additive rather than competitive block. Heterologous expression in Xenopus oocytes, two-microelectrode voltage-clamp pharmacology The Journal of pharmacology and experimental therapeutics High 9694927
1999 A 27-kDa Kv1.5 repressor element binding factor (KBF) was identified in GH3 and cardiac nuclear extracts that specifically binds a 52-bp dinucleotide-repetitive silencer element (KRE) in the Kv1.5 promoter; this KBF–KRE interaction may regulate the cardiac- and GH3-specific expression of the Kv1.5 gene. Electromobility gel shift assay (EMSA), magnetic DNA affinity purification, UV cross-linking Circulation research Medium 10222341
2000 α-actinin-2 physically interacts with Kv1.5 via the channel's N-terminus/core region, as shown by in vitro co-immunoprecipitation and co-expression in HEK cells; co-localization at the membrane was observed, and disruption of the actin cytoskeleton or antisense knockdown of α-actinin-2 modulated Kv1.5 ion and gating current density. In vitro translation co-immunoprecipitation, co-expression in HEK cells, confocal colocalization, actin cytoskeleton disruption, antisense knockdown with patch clamp FEBS letters High 10812072
2000 Protein tyrosine phosphatase epsilon (PTP epsilon) dephosphorylates Kv1.5 in sciatic nerve tissue and Schwann cells; loss of PTP epsilon leads to hyperphosphorylation of Kv1.5 (and Kv2.1) and increased delayed-rectifier K+ channel activity, accompanied by hypomyelination, establishing PTP epsilon as a negative regulator of Kv1.5 channel activity in vivo. PTP epsilon knockout mice, Western blot for tyrosine phosphorylation, Xenopus oocyte co-expression electrophysiology, substrate-trapping co-IP with Kv2.1 The EMBO journal High 10921884
2001 SAP97 co-immunoprecipitates with Kv1.5 in COS-7 cells and co-localizes with Kv1.5 at intercalated disks and lateral membranes in cardiac myocytes; SAP97–Kv1.5 interaction requires the three C-terminal residues (TDL) of Kv1.5; co-expression with SAP97 augments Kv1.5-encoded outward K+ currents in Xenopus oocytes. Co-immunoprecipitation from transfected COS-7 cells, immunocytochemistry in cardiac myocytes, C-terminal mutagenesis, Xenopus oocyte functional expression American journal of physiology. Heart and circulatory physiology High 11709425
2003 Mutagenesis of residues Thr-479, Thr-480, Val-505, Ile-508, and Val-512 in the pore helix and S6 segment of Kv1.5 drastically reduced affinity for the channel blocker S0100176 (e.g., T480A increased IC50 362-fold), identifying these inner-cavity residues as the drug-binding site and providing a molecular basis for open-channel block of Kv1.5. Ala-scanning mutagenesis, heterologous expression in Xenopus oocytes, voltage-clamp pharmacology, homology modeling based on KcsA crystal structure The Journal of biological chemistry High 14578345
2003 SAP97 increases hKv1.5 currents through an indirect mechanism dependent on the Kv1.5 N-terminus; deletion of the N-terminus abolished SAP97-mediated current increase, whereas deletion of the C-terminal PDZ-binding motif had no effect; no direct physical interaction between SAP97 and Kv1.5 was detected in cardiac myocytes or transfected HEK cells. N- and C-terminal deletion mutants, transfection in HEK cells, co-immunoprecipitation, yeast two-hybrid, confocal microscopy, patch clamp FEBS letters Medium 12860415
2004 Overexpressed human Kv1.5 in pulmonary artery smooth muscle cells (PASMC) generates a 15-pS single-channel current and large whole-cell K+ current; ET-1, nicotine, bepridil, and correolide each significantly and reversibly reduced Kv1.5 currents, and nicotine/bepridil accelerated inactivation kinetics, identifying specific modulators of the channel. Heterologous overexpression (KCNA5) in PASMC and cell lines, single-channel and whole-cell patch clamp, pharmacology American journal of physiology. Cell physiology High 17267549
2004 Overexpression of KCNA5 in COS-7 cells and rat PASMC significantly increases Kv current (IKV) and enhances staurosporine-induced caspase-3 activation and apoptosis; apoptotic volume decrease (AVD) is accelerated, and 4-AP blockade of KCNA5 channels inhibits staurosporine-induced apoptosis, demonstrating that K+ efflux through Kv1.5 channels promotes apoptotic cell shrinkage and apoptosis. Transient transfection of KCNA5, whole-cell patch clamp, caspase-3 activity assay, flow cytometry for apoptosis, pharmacological blockade with 4-AP American journal of physiology. Cell physiology High 15140747
2004 Kv1.5 (along with Kv2.1) accounts for virtually all O2-sensitive current in resistance pulmonary artery smooth muscle cells; intracellular anti-Kv1.5 antibodies inhibit correolide-sensitive IK, and anti-Kv1.5 plus anti-Kv2.1 additively depolarize resistance PASMCs and inhibit hypoxic depolarization, establishing Kv1.5 as the predominant O2-sensitive Kv channel mediating hypoxic pulmonary vasoconstriction. Intracellular antibody application, patch clamp in isolated resistance PASMCs, selective pharmacology (correolide), immunohistochemistry Circulation research High 15217912
2005 Kv1.5 surface expression is regulated by retrograde trafficking via the dynein motor complex: disruption of dynein-dynactin (p50/dynamitin overexpression), inhibition of endocytosis (dynamin inhibitory peptide), or microtubule depolymerization (nocodazole) all increase Kv1.5 current density and plasma membrane localization; co-immunoprecipitation demonstrated direct Kv1.5–dynein interaction requiring an intact SH3-binding domain in the Kv1.5 N-terminus. Dominant-negative dynein overexpression, dynamin inhibitory peptide, nocodazole treatment, co-immunoprecipitation, Proteinase K surface accessibility assay, confocal imaging, patch clamp Circulation research High 16051887
2005 Acute hypoxia selectively inhibits Kv1.5 (KCNA5) channel activity in PASMC but not in mesenteric artery smooth muscle cells (MASMC), HEK-293, or COS-7 cells; overexpression of KCNA5 in rat MASMC did not confer hypoxia sensitivity, whereas overexpression in PASMC did, demonstrating that a PASMC-specific hypoxia-sensitive mechanism is required for Kv1.5 inhibition. Heterologous KCNA5 overexpression in multiple cell types, whole-cell patch clamp under varying PO2 American journal of physiology. Cell physiology High 16236819
2005 Kv1.5 protein is degraded by the ubiquitin-proteasome pathway with a half-life of ~6.7 h; proteasome inhibitors (MG132, ALLN) prolong the half-life, increase Kv1.5 protein levels and ubiquitinated forms, accumulate channel in the ER/Golgi, and increase IKur currents; lysosomal inhibitors have no effect, and this proteasomal degradation pathway was confirmed in rat atrial cells for endogenous Kv1.5. Pulse-chase analysis, immunofluorescence, proteasome/lysosomal inhibitor pharmacology, patch clamp, Western blot for ubiquitinated forms Biochemical and biophysical research communications High 16185660
2005 C-terminal polymorphisms P532L and R578K in KCNA5 produce near-normal channel gating but confer striking resistance to quinidine block (IC50 increased from 8.4 µM to 133 µM and 54 µM, respectively), identifying the C-terminus as a region modulating drug sensitivity. SSCP/direct sequencing for variant identification, patch-clamp pharmacology in transfected CHO cells Clinical pharmacology and therapeutics High 15735608
2006 Kv1.5 does not co-localize with caveolin-3 in rat and canine atrial or ventricular myocytes (co-localization <12%) and does not associate with low-density raft fractions in HEK293 cells, while co-immunoprecipitation shows Kv1.5 associates with α-actinin but not caveolin-3, demonstrating that Kv1.5 resides outside caveolae in cardiac myocytes. Co-immunoprecipitation, sucrose-gradient fractionation, wide-field deconvolution microscopy, immunoelectron microscopy FEBS letters High 17054951
2006 Kv1.3/Kv1.5 heterotetrameric channels are expressed in macrophages with variable Kv1.3/Kv1.5 stoichiometry across mononuclear phagocyte subtypes; the presence of Kv1.5 in the complex confers resistance to Kv1.3-specific pharmacological agents, compromising the efficacy of Kv1.3-targeted treatments for immune modulation. Patch-clamp electrophysiology, pharmacological profiling of heterotetrameric channels in macrophage subsets Biochemical and biophysical research communications Medium 17157812
2007 SUMO-1, -2, and -3 modify Kv1.5 at two membrane-proximal cytoplasmic consensus sites; Kv1.5 interacts with the SUMO-conjugating enzyme Ubc9 in vivo; purified recombinant Kv1.5 is SUMOylated in a minimal in vitro reaction; SUMO-specific proteases SENP2 and Ulp1 deconjugate SUMO from Kv1.5; loss of SUMOylation (site mutations or SENP2 co-expression) causes a ~15 mV hyperpolarizing shift in steady-state inactivation without altering activation, establishing SUMOylation as a post-translational modifier that selectively tunes Kv1.5 inactivation gating. In vivo SUMOylation assays, in vitro reconstituted SUMOylation, co-IP with Ubc9, site-directed mutagenesis of SUMO consensus sites, SENP2 co-expression, whole-cell patch clamp Proceedings of the National Academy of Sciences High 17261810
2007 Membrane cholesterol depletion by methyl-β-cyclodextrin (MCD) causes redistribution of Kv1.5 from cholesterol-enriched clusters into larger clusters dispersed across the plasma membrane, increasing IKur current density; Kv1.5 subunits co-fractionate with low-density sucrose gradient fractions distinct from caveolae, indicating that Kv1.5 localizes to non-caveolar cholesterol-rich microdomains whose disruption augments channel activity. Methyl-β-cyclodextrin cholesterol depletion, sucrose-gradient fractionation, live-cell confocal imaging of GFP-Kv1.5, whole-cell patch clamp in atrial myocytes and neonatal cardiomyocytes The Journal of physiology High 17525113
2007 S-acylation (palmitoylation) of Kv1.5 via hydroxylamine-sensitive thioester bonds on both N- and C-terminal cysteines is required for normal channel surface expression; pharmacological inhibition of S-acylation reduces surface expression, accumulates channel in intracellular compartments, and targets it for proteasomal degradation; C-terminal cysteines govern S-acylation, and mutation of intracellular cysteines paradoxically increases surface expression, suggesting that fatty acylation acts as a quality-control step. Hydroxylamine sensitivity assay for thioester bonds, pharmacological S-acylation inhibition, proteasome inhibitor rescue, time-course surface expression analysis, confocal imaging American journal of physiology. Cell physiology High 17344312
2007 Caveolin-1 and -3 are required for targeting Kv1.5 to low-density detergent-resistant lipid raft fractions; in cells lacking endogenous caveolin, Kv1.5 association with rafts requires exogenous caveolin co-expression; caveolin-trafficking mutants sequester Kv1.5 in intracellular compartments; wild-type caveolin-1 co-expression induces depolarizing shifts in Kv1.5 activation and inactivation analogous to high membrane cholesterol, indicating caveolin modulates Kv1.5 function by regulating its trafficking to cholesterol-rich microdomains. Sucrose density gradient fractionation, co-immunoprecipitation (channel-caveolin complex), dominant-negative caveolin trafficking mutants, patch-clamp electrophysiology Molecular pharmacology High 18045854
2007 The mitochondria-ROS-HIF-1α-Kv1.5 pathway constitutes an O2-sensing mechanism in PASMCs; decreased mitochondrial ROS in PAH creates a pseudohypoxic state that activates HIF-1α and down-regulates Kv1.5 expression, contributing to PASMC depolarization, Ca2+ influx, and the proliferative/apoptosis-resistant phenotype; dichloroacetate (PDK inhibitor) corrects mitochondrial abnormalities and restores Kv1.5 expression in experimental PAH. Fawn-hooded rat model of PAH, dichloroacetate treatment, ROS measurement, HIF-1α manipulation, Kv1.5 expression analysis, patch clamp American journal of physiology. Heart and circulatory physiology High 18083891
2008 After internalization, Kv1.5 is rapidly trafficked through Rab5-positive early endosomes and Rab4-positive recycling endosomes; dominant-negative Rab5, Rab4, Rab7, and Rab11 constructs all increase Kv1.5 current density; a fraction of internalized channels traffics to Rab7-positive late endosomes for degradation; Rab4 mediates rapid recycling back to the plasma membrane, establishing a post-internalization trafficking itinerary for the channel. Dominant-negative Rab GTPase expression, colocalization with Rab-positive endosome markers, whole-cell patch clamp The Journal of physiology High 18755741
2008 SAP97 overexpression in cardiac myocytes clusters endogenous Kv1.5 subunits at myocyte–myocyte contacts, reduces lateral mobility of GFP-Kv1.5 as measured by FRAP, and increases IKur current density (~74% increase) and single-channel number; in CHO cells, SAP97 organizes freely mobile Kv1.5 into poorly mobile plaque-like clusters, establishing that SAP97 retains and immobilizes Kv1.5 in the plasma membrane to increase functional channel expression. Adenovirus-mediated SAP97 overexpression in neonatal cardiomyocytes, FRAP of GFP-Kv1.5, cell-attached patch clamp, whole-cell patch clamp, immunocytochemistry American journal of physiology. Heart and circulatory physiology High 18245566
2008 Kv1.5 in macrophages does not target to lipid rafts, whereas Kv1.3/Kv1.5 heteromers in transfected HEK-293 cells do associate with rafts; LPS-induced macrophage activation increases the Kv1.3/Kv1.5 ratio and caveolin expression, redirecting Kv1.5 to lipid rafts; Kvβ2.1 co-expression impairs Kv1.5 raft targeting, and a Cav3(DGV) mutant sequesters Kv1.5 in intracellular vesicles, demonstrating that Kv1.5 membrane microdomain targeting is regulated by partner protein stoichiometry. Sucrose density gradient fractionation, cholesterol-depletion experiments, confocal microscopy, dominant-negative caveolin-3 mutant expression, LPS macrophage activation Journal of cellular physiology Medium 18668522
2008 FHL1 (four-and-a-half LIM protein 1) was identified as a Kv1.5 binding partner by GST-KCNA5 C-terminal pull-down from human atrium followed by mass spectrometry; co-immunoprecipitation confirmed the interaction in human atrium and CHO cells; FHL1 co-expression markedly increased Kv1.5 current density, shifted activation to more positive potentials, and enhanced slow inactivation extent and speed, identifying FHL1 as a key regulatory component of the IKur complex. GST pull-down from human atrium, mass spectrometry identification, co-immunoprecipitation, confocal colocalization, whole-cell patch clamp in CHO cells Cardiovascular research High 18281375
2008 Hypoxia suppresses Kv1.5 channel expression in rat pulmonary artery smooth muscle cells via the 15-lipoxygenase/15-HETE pathway; pharmacological inhibition of 15-LOX rescued Kv1.5 mRNA and protein expression under hypoxia and partially restored IKV; exogenous 15-HETE mimicked hypoxia-induced Kv1.5 downregulation and current inhibition, establishing a lipid-mediated mechanism for hypoxic Kv1.5 suppression. 15-LOX inhibitor pharmacology, Kv1.5 mRNA/protein expression analysis, whole-cell patch clamp in PASMC, exogenous 15-HETE application Prostaglandins & other lipid mediators Medium 18984061
2009 T1 domain mutations G182R and E211D in KCNA5 (found in IPAH patients) produce functional channels with accelerated inactivation at more hyperpolarized potentials; mutant channel protein is present predominantly in immature glycosylated form, reduced in expression, and retained intracellularly rather than trafficked to the plasma membrane, demonstrating that the T1 domain regulates both Kv1.5 inactivation kinetics and subcellular localization. Site-directed mutagenesis, whole-cell patch clamp in HEK-293 and COS-1 cells, Western blot for glycosylation state, immunofluorescence for subcellular localization American journal of physiology. Cell physiology High 20018952
2009 Acute hypoxia selectively inhibits Kv1.5 (KCNA5) current in PASMC but not MASMC; KCNA5 overexpression in PASMC confers hypoxia sensitivity to the overexpressed current, whereas overexpression in MASMC, HEK, or COS cells does not, confirming that a PASMC-specific hypoxia-sensing mechanism is required and contributes to intracellular Ca2+ homeostasis regulation during hypoxia. KCNA5 overexpression, whole-cell patch clamp at varying PO2, comparison across cell types Annals of the New York Academy of Sciences Medium 19845612
2010 A novel KCNA5 mutation deleting 11 amino acids in the N-terminal proline-rich SH3-binding domain causes ~60% loss-of-function in IKur and exerts dominant-negative effects on wild-type Kv1.5 current; pretreatment with the Src inhibitor PP2 prevented v-Src tyrosine kinase from suppressing wild-type Kv1.5 current by ~90%, whereas the mutant channel was unresponsive to v-Src, implicating tyrosine kinase signaling through the SH3-binding domain as a regulatory mechanism. Site-directed mutagenesis, whole-cell patch clamp in transfected cells, Src kinase inhibitor (PP2) pharmacology, dominant-negative analysis Heart rhythm High 20638934
2012 Mutations E48G, A305T, and D322H in Kv1.5 (found in lone AF patients) display preserved surface expression and gain-of-function in patch-clamp studies; mutations Y155C, D469E, and P488S display decreased surface expression and loss-of-function; establishing that both gain- and loss-of-function mutations in KCNA5 are associated with atrial fibrillation. Confocal microscopy for surface expression, whole-cell patch-clamp electrophysiology in transfected cells European heart journal High 23264583
2012 The C-terminal domain of Kv1.5 (residues Arg543–Val583) is required for interaction with Kvβ-subunits in a pyridine nucleotide-dependent manner: NADPH accelerates Kv1.5-Kvβ3-mediated inactivation while NADP+ decreases inactivation and reverses the Kvβ2 activation shift; deletion of the C-terminus abolishes these nucleotide-dependent effects; a GST-C-terminal fusion protein binds Kvβ2:NADPH with higher affinity than Kvβ2:NADP+. C-terminal deletion mutagenesis, co-expression with Kvβ2/Kvβ3, whole-cell patch clamp with intracellular NADPH/NADP+ in pipette solution, GST pull-down from mouse brain lysates, structural analysis Pflugers Archiv High 22426702
2015 Kv1.5 channel function is required for coronary metabolic dilation: Kv1.5-null mice show impaired myocardial blood flow increase during cardiac stress despite higher cardiac work, and isolated arteries from null mice have impaired relaxation to H2O2 (a reactive oxygen species involved in redox-dependent vasodilation) but normal responses to adenosine and acetylcholine; smooth-muscle-specific rescue of Kv1.5 in null mice restores metabolic dilation, directly linking Kv1.5 in vascular smooth muscle to redox-sensitive coronary flow regulation. Kv1.5 knockout mice, inducible smooth-muscle-specific Kv1.5 re-expression, in vivo myocardial blood flow measurement, tissue O2 tension, isolated artery pharmacology Circulation research High 26224794
2015 PKC activation reduces Kv1.5 membrane expression and current in Xenopus oocytes and MDCK cells; AMPK activation decreases Kv1.5 membrane expression in MDCK cells but not in atrial HL-1 cells, and this AMPK effect requires co-expression of Nedd4-2 in oocytes, demonstrating that both PKC and AMPK regulate Kv1.5 surface expression through distinct mechanisms. Xenopus oocyte expression, MDCK and HL-1 cell transfection, confocal microscopy, patch clamp, kinase activators and Nedd4-2 co-expression Channels (Austin, Tex.) Medium 26043299
2015 Polycomb group (PcG) proteins BMI-1 and EZH2 repress KCNA5 expression in Ewing sarcoma and neuroblastoma cells; the KCNA5 promoter bears H3K27me3 repressive marks that increase under hypoxia; genetic/pharmacological inhibition of BMI-1/EZH2 restores KCNA5 expression; ectopic Kv1.5 channel expression induces apoptotic cell death under hypoxic stress, establishing PcG-mediated epigenetic silencing of KCNA5 as a mechanism promoting cancer cell survival. Chromatin immunoprecipitation for H3K27me3, pharmacological EZH2 inhibition, genetic BMI-1 inhibition, ectopic KCNA5 overexpression, cell death assays under hypoxia Oncogene High 25435365
2015 DNA methylation of the KCNA5 CpG island promoter in Ewing sarcoma stably silences Kv1.5 channel expression; treatment with the DNA methylation inhibitor decitabine reverses KCNA5 methylation, restores Kv1.5 channel function, and inhibits Ewing sarcoma cell proliferation, demonstrating that epigenetic KCNA5 silencing contributes functionally to tumor cell proliferation. Methylation array and bisulfite sequencing, decitabine treatment, flow cytometry/electrophysiology to confirm Kv1.5 restoration, proliferation assays Molecular cancer research High 26573141
2018 miR-1 directly targets the KCNA5 3'-UTR as confirmed by luciferase reporter assay; miR-1 transfection in pulmonary artery smooth muscle cells reduces Kv1.5 current and induces membrane depolarization; miR-1 is elevated in lungs from a PAH rat model, and Kv1.5 is correspondingly decreased; antagomiR-1 prevents Kv1.5 downregulation and depolarization induced by hypoxia/Su5416. Luciferase 3'-UTR reporter assay, miR-1 transfection in PASMC, patch clamp (DPO-1-sensitive current), antagomiR-1 treatment in PAH rat model The Journal of physiology High 29717493
2020 miR-3940-5p promotes granulosa cell proliferation by directly targeting KCNA5; luciferase reporter assay validated KCNA5 as a miR-3940-5p target; functional analysis confirmed that miR-3940-5p-driven proliferation is KCNA5-dependent, identifying KCNA5 as a downstream effector of miR-3940-5p in polycystic ovary syndrome-associated granulosa cell biology. Luciferase 3'-UTR reporter assay, miR-3940-5p overexpression, KCNA5 knockdown rescue experiment, proliferation assays Biochemical and biophysical research communications Medium 32019676
2023 KCNA5 variants Arg184Pro and Gly384Arg found in PAH patients produce clear loss-of-function as assessed by patch clamp in HEK293 cells; Arg184Pro also reduces Kv1.5 protein expression; transfection with either variant decreases apoptosis in human PASMC compared to wild-type, demonstrating that loss-of-function KCNA5 variants impair both channel activity and the apoptotic response in vascular smooth muscle cells. Patch-clamp electrophysiology in HEK293, flow cytometry for apoptosis in human PASMC, Western blot, confocal microscopy, molecular modeling American journal of respiratory cell and molecular biology High 36917789

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2005 International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacological reviews 721 16382104
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2006 Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 367 17060380
1998 Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 321 9760292
2007 Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. American journal of physiology. Heart and circulatory physiology 308 18083891
1998 Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Critical reviews in clinical laboratory sciences 267 9759557
2020 Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2. Cell death & disease 257 32094325
1993 A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. The Journal of general physiology 246 8505626
1996 Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science (New York, N.Y.) 235 8953041
2015 HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection. Autophagy 228 26075878
1991 Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 221 2001794
1995 Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue. The Journal of clinical investigation 177 7615797
2019 Unlocking the Potential of HK2 in Cancer Metabolism and Therapeutics. Current medicinal chemistry 168 30543165
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2004 Preferential expression and function of voltage-gated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells. Circulation research 149 15217912
2005 Substrate-trapping techniques in the identification of cellular PTP targets. Methods (San Diego, Calif.) 146 15588985
2012 PPARγ contributes to PKM2 and HK2 expression in fatty liver. Nature communications 132 22334075
2007 Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension. American journal of physiology. Cell physiology 131 17267549
2007 SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5. Proceedings of the National Academy of Sciences of the United States of America 124 17261810
2012 Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. European heart journal 123 23264583
1996 Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv beta 2.1 subunits. The Journal of biological chemistry 117 8576199
2023 STING is a cell-intrinsic metabolic checkpoint restricting aerobic glycolysis by targeting HK2. Nature cell biology 116 37443289
2021 Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nature genetics 116 34857952
2014 Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes. Proceedings of the National Academy of Sciences of the United States of America 114 24550280
2015 Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death. The Journal of cell biology 109 26323688
2003 Voltage-gated K+ channels in rat small cerebral arteries: molecular identity of the functional channels. The Journal of physiology 109 12815189
2009 Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation. Journal of human genetics 104 19343045
2003 Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas. Neuroscience letters 97 12850541
2003 Molecular basis for Kv1.5 channel block: conservation of drug binding sites among voltage-gated K+ channels. The Journal of biological chemistry 95 14578345
2022 The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis. Cellular & molecular immunology 93 34983946
2016 Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth. Cancer cell international 88 26884725
1998 Blockade of HERG and Kv1.5 by ketoconazole. The Journal of pharmacology and experimental therapeutics 88 9694927
1991 Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proceedings of the National Academy of Sciences of the United States of America 87 1986382
2004 Overexpression of human KCNA5 increases IK V and enhances apoptosis. American journal of physiology. Cell physiology 85 15140747
2005 Kv1.5 surface expression is modulated by retrograde trafficking of newly endocytosed channels by the dynein motor. Circulation research 84 16051887
2022 Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer. Cancer research 80 35255118
2022 Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis. Cell death and differentiation 80 35296795
2000 alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS letters 79 10812072
2004 Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus. Circulation 78 15353504
2007 Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes. The Journal of physiology 77 17525113
2000 Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon. The EMBO journal 75 10921884
2015 Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation. Circulation research 74 26224794
2017 TNFα-YAP/p65-HK2 axis mediates breast cancer cell migration. Oncogenesis 72 28945218
2022 UBR7 inhibits HCC tumorigenesis by targeting Keap1/Nrf2/Bach1/HK2 and glycolysis. Journal of experimental & clinical cancer research : CR 68 36419136
2018 Ketoconazole and Posaconazole Selectively Target HK2-expressing Glioblastoma Cells. Clinical cancer research : an official journal of the American Association for Cancer Research 68 30322879
2022 HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways. Cell communication and signaling : CCS 65 36042519
2021 Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2. Cell death & disease 62 34741026
2006 Kv1.3/Kv1.5 heteromeric channels compromise pharmacological responses in macrophages. Biochemical and biophysical research communications 62 17157812
2010 Novel KCNA5 mutation implicates tyrosine kinase signaling in human atrial fibrillation. Heart rhythm 58 20638934
2005 Acute hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. American journal of physiology. Cell physiology 52 16236819
2010 Association of a KCNA5 gene polymorphism with systemic sclerosis-associated pulmonary arterial hypertension in the European Caucasian population. Arthritis and rheumatism 51 20556823
2018 miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries. The Journal of physiology 50 29717493
2022 Glutamate from nerve cells promotes perineural invasion in pancreatic cancer by regulating tumor glycolysis through HK2 mRNA-m6A modification. Pharmacological research 49 36403721
2019 An HK2 Antisense Oligonucleotide Induces Synthetic Lethality in HK1-HK2+ Multiple Myeloma. Cancer research 49 30885978
2017 Roles of claudin-2, ZO-1 and occludin in leaky HK-2 cells. PloS one 46 29252987
2001 SAP97 interacts with Kv1.5 in heterologous expression systems. American journal of physiology. Heart and circulatory physiology 46 11709425
2007 S-acylation regulates Kv1.5 channel surface expression. American journal of physiology. Cell physiology 42 17344312
2023 Gastric cancer mesenchymal stem cells via the CXCR2/HK2/PD-L1 pathway mediate immunosuppression. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 40 37300724
2019 The Roles of HK2 on Tumorigenesis of Cervical Cancer. Technology in cancer research & treatment 40 31530094
2008 The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes. American journal of physiology. Heart and circulatory physiology 40 18245566
2008 Internalized Kv1.5 traffics via Rab-dependent pathways. The Journal of physiology 40 18755741
2020 CSN5 upregulates glycolysis to promote hepatocellular carcinoma metastasis via stabilizing the HK2 protein. Experimental cell research 39 31991125
2003 SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism. FEBS letters 39 12860415
2019 Novel xanthine oxidase-based cell model using HK-2 cell for screening antihyperuricemic functional compounds. Free radical biology & medicine 38 30980888
2019 Genes CEP55, FOXD3, FOXF2, GNAO1, GRIA4, and KCNA5 as potential diagnostic biomarkers in colorectal cancer. BMC medical genomics 38 30987631
2006 Localization of Kv1.5 channels in rat and canine myocyte sarcolemma. FEBS letters 36 17054951
2020 TRIM59 knockdown blocks cisplatin resistance in A549/DDP cells through regulating PTEN/AKT/HK2. Gene 35 32165307
2016 Regulation of HK2 expression through alterations in CpG methylation of the HK2 promoter during progression of hepatocellular carcinoma. Oncotarget 35 27260001
2014 Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic parameters in patients with pulmonary arterial hypertension. PloS one 35 24936649
2007 Caveolin regulates kv1.5 trafficking to cholesterol-rich membrane microdomains. Molecular pharmacology 35 18045854
2003 TGF-beta1-mediated inhibition of HK-2 cell migration. Journal of the American Society of Nephrology : JASN 34 12595498
1998 Expression of Kv1.5 K+ channels in activated microglia in vivo. Glia 34 9814821
2022 Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway. Cellular and molecular gastroenterology and hepatology 33 35863742
2022 A pan-cancer analysis of the role of hexokinase II (HK2) in human tumors. Scientific reports 33 36335239
2019 PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2. Biochemistry and cell biology = Biochimie et biologie cellulaire 32 31742425
2012 Interactions between the C-terminus of Kv1.5 and Kvβ regulate pyridine nucleotide-dependent changes in channel gating. Pflugers Archiv : European journal of physiology 32 22426702
2005 Evidence for proteasomal degradation of Kv1.5 channel protein. Biochemical and biophysical research communications 32 16185660
2018 Zinc and p53 disrupt mitochondrial binding of HK2 by phosphorylating VDAC1. Experimental cell research 30 30528266
2008 Multiple Kv1.5 targeting to membrane surface microdomains. Journal of cellular physiology 30 18668522
2022 ZNF281 drives hepatocyte senescence in alcoholic liver disease by reducing HK2-stabilized PINK1/Parkin-mediated mitophagy. Cell proliferation 28 36514923
2021 NR2F1-AS1/miR-140/HK2 Axis Regulates Hypoxia-Induced Glycolysis and Migration in Hepatocellular Carcinoma. Cancer management and research 28 33488124
2020 FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer. Cell communication and signaling : CCS 28 31918722
2020 FoxA2 inhibits the proliferation of hepatic progenitor cells by reducing PI3K/Akt/HK2-mediated glycolysis. Journal of cellular physiology 28 32495363
2015 PKC and AMPK regulation of Kv1.5 potassium channels. Channels (Austin, Tex.) 28 26043299
2005 Polymorphism screening in the cardiac K+ channel gene KCNA5. Clinical pharmacology and therapeutics 28 15735608
2024 CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis. Journal of translational medicine 26 38750462
2022 Exosome-delivered circular RNA DLGAP4 induces chemoresistance via miR-143-HK2 axis in neuroblastoma. Cancer biomarkers : section A of Disease markers 23 35068445
2013 Decreased Kv1.5 expression in intrauterine growth retardation rats with exaggerated pulmonary hypertension. American journal of physiology. Lung cellular and molecular physiology 23 24077947
2020 Hsa_circ_0069094 accelerates cell malignancy and glycolysis through regulating the miR-591/HK2 axis in breast cancer. Cellular signalling 22 33309838
2015 Involvement of PPARγ in emodin-induced HK-2 cell apoptosis. Toxicology in vitro : an international journal published in association with BIBRA 22 25448808
2015 Promoter Methylation Analysis Reveals That KCNA5 Ion Channel Silencing Supports Ewing Sarcoma Cell Proliferation. Molecular cancer research : MCR 22 26573141
2008 Modeling the binding modes of Kv1.5 potassium channel and blockers. Journal of molecular graphics & modelling 22 18485768
2024 Impaired microglial glycolysis promotes inflammatory responses after intracerebral haemorrhage via HK2-dependent mitochondrial dysfunction. Journal of advanced research 21 39142439
2021 Methylation-associated silencing of miR-9-1 promotes nasopharyngeal carcinoma progression and glycolysis via HK2. Cancer science 21 34382305
2022 E6E7 regulates the HK2 expression in cervical cancer via GSK3β/FTO signal. Archives of biochemistry and biophysics 20 36075458
2020 FAT10 promotes the progression of bladder cancer by upregulating HK2 through the EGFR/AKT pathway. Experimental cell research 20 33253711
2019 Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics. Theranostics 20 31149033
2019 Chemical and biological study of aplysiatoxin derivatives showing inhibition of potassium channel Kv1.5. RSC advances 20 35521179
2018 5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary arterial hypertension: A meta-analysis. Gene 20 30218748
2014 Pharmacology of voltage-gated potassium channel Kv1.5--impact on cardiac excitability. Current opinion in pharmacology 20 24632326
2008 Hypoxia suppresses KV1.5 channel expression through endogenous 15-HETE in rat pulmonary artery. Prostaglandins & other lipid mediators 20 18984061
2022 CDK6 increases glycolysis and suppresses autophagy by mTORC1-HK2 pathway activation in cervical cancer cells. Cell cycle (Georgetown, Tex.) 19 35167417
2022 miR-532-3p suppresses proliferation and invasion of ovarian cancer cells via GPNMB/HIF-1α/HK2 axis. Pathology, research and practice 19 35914373
2020 MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome. Biochemical and biophysical research communications 19 32019676
2016 Blockade of Kv1.5 channels by the antidepressant drug sertraline. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 19 26937216
2008 Four and a half LIM protein 1: a partner for KCNA5 in human atrium. Cardiovascular research 19 18281375
2021 Leptin promotes glycolytic metabolism to induce dendritic cells activation via STAT3-HK2 pathway. Immunology letters 18 34480980
2014 Polycomb-dependent repression of the potassium channel-encoding gene KCNA5 promotes cancer cell survival under conditions of stress. Oncogene 18 25435365
2024 AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated glycolysis. Molecular medicine (Cambridge, Mass.) 17 39217289
2023 Role of mitochondria-bound HK2 in rheumatoid arthritis fibroblast-like synoviocytes. Frontiers in immunology 16 37529037
2010 Kv1.5 in the immune system: the good, the bad, or the ugly? Frontiers in physiology 16 21423392
2019 Fubp1 supports the lactate-Akt-mTOR axis through the upregulation of Hk1 and Hk2. Biochemical and biophysical research communications 15 30871777
2009 Hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. Annals of the New York Academy of Sciences 15 19845612
2009 Tetramerization domain mutations in KCNA5 affect channel kinetics and cause abnormal trafficking patterns. American journal of physiology. Cell physiology 15 20018952
2001 Functional expression of a GFP-tagged Kv1.5 alpha-subunit in mouse ventricle. American journal of physiology. Heart and circulatory physiology 15 11668056
2023 Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension. American journal of respiratory cell and molecular biology 14 36917789
2021 Long Noncoding RNA LINC01410 Suppresses Tumorigenesis and Enhances Radiosensitivity in Neuroblastoma Cells Through Regulating miR-545-3p/HK2 Axis. OncoTargets and therapy 14 34040388
2021 Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells. International journal of molecular sciences 14 34576046
2016 Suppression of Kv1.5 protects against endothelial apoptosis induced by palmitate and in type 2 diabetes mice. Life sciences 14 26764232
2025 The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products. International journal of medical sciences 13 39991762
2023 HK2 in microglia and macrophages contribute to the development of neuropathic pain. Glia 13 37909251
2021 Hsa_circ_0001806 promotes glycolysis and cell progression in hepatocellular carcinoma through miR-125b/HK2. Journal of clinical laboratory analysis 13 34664737
1999 Purification and preliminary characterization of a cardiac Kv1.5 repressor element binding factor. Circulation research 13 10222341
2024 Therapeutic efficacy of ECs Foxp1 targeting Hif1α-Hk2 glycolysis signal to restrict angiogenesis. Redox biology 12 39083899