Affinage

KCNJ2

Inward rectifier potassium channel 2 · UniProt P63252

Length
427 aa
Mass
48.3 kDa
Annotated
2026-06-10
100 papers in source corpus 52 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNJ2 encodes Kir2.1, a strong inwardly rectifying potassium channel that sets resting membrane potential and shapes the terminal repolarization phase of the cardiac action potential, with broader roles in vascular tone, development, and immune cell function (PMID:11371347, PMID:12163457, PMID:10904001). Inward rectification is an intrinsic biophysical property requiring intracellular Mg2+ and voltage-dependent polyamine block within a long, narrow pore whose kinetics depend on permeant external K+; the H5 pore residue Arg148 controls cationic blocker access, while a cytoplasmic G-loop diffusion barrier and a distal di-aspartate cluster are structural determinants of rectification (PMID:15723059, PMID:8189383, PMID:8854340, PMID:9382895). Channel gating and surface density are heavily regulated: PKA phosphorylation at S425 and PKC, tyrosine-kinase phosphorylation at Y242, AMPK (acting through Nedd4-2), SGK3, and cholesterol/lipid-raft partitioning all tune Kir2.1 activity and abundance (PMID:7993632, PMID:8650176, PMID:8609894, PMID:9852063, PMID:15465867, PMID:21501591, PMID:23188060). Forward trafficking proceeds through a C-terminal tyrosine-based YxxΦ Golgi-export motif and is promoted by filamin-A and α-arrestins, while degradation occurs via lysosomal, ESCRT, ERAD, and ubiquitin-proteasome routes (PMID:12923176, PMID:15827083, PMID:24227888, PMID:29784874). In cardiomyocytes Kir2.1 pre-assembles with the sodium channel Nav1.5 at the trans-Golgi through the AP1 adaptor, forming a reciprocally trafficked macromolecular complex with distinct CaMKII- and 14-3-3-dependent regulation and Nedd4-2-mediated degradation (PMID:29514831, PMID:29184507, PMID:30232268). Loss-of-function KCNJ2 mutations cause Andersen-Tawil syndrome through dominant-negative co-assembly or trafficking-defective haploinsufficiency, whereas gain-of-function mutations that abolish inward rectification cause short QT syndrome type 3 and familial atrial fibrillation (PMID:11371347, PMID:14522976, PMID:15761194, PMID:15922306, PMID:23440193, PMID:22155372). Beyond excitable tissue, Kir2.1 controls bioelectric membrane potential governing craniofacial neural-crest morphogenesis and BMP signaling, K+-induced vasodilation in arterial smooth muscle and endothelium, macrophage polarization and nutrient acquisition, and through non-conducting interactions promotes cancer invasion and drug resistance (PMID:26864374, PMID:29571612, PMID:35729093, PMID:35694964, PMID:26840527, PMID:29549164, PMID:25880778).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 High

    Established that Kir2.1 inward rectification is not purely intrinsic to the protein but requires defined intracellular conditions, settling how the channel achieves voltage-dependent gating.

    Evidence Whole-cell and single-channel recording in MEL cells and giant inside-out patches with Mg2+, ATP, and kinase manipulation

    PMID:7993632 PMID:8189383

    Open questions at the time
    • Did not identify the polyamine blockers later shown to mediate rectification
    • Structural basis of the Mg2+/ATP requirement not resolved
  2. 1996 High

    Defined how permeant ions and intracellular blockers cooperate to produce rectification, and identified specific kinase phosphorylation sites controlling channel activity.

    Evidence Patch-clamp polyamine block kinetics across K+ concentrations; PKA/PKC pharmacology and S425N mutagenesis in COS-7/tsA cells

    PMID:8609894 PMID:8650176 PMID:8854340

    Open questions at the time
    • Did not resolve the pore structure accommodating multiple blocker binding sites
    • Physiological receptor inputs driving phosphorylation in native tissue not fully mapped
  3. 1997 High

    Localized a specific pore residue (Arg148) acting as an external barrier governing cationic blocker and divalent access, refining the rectification mechanism at atomic resolution.

    Evidence R148H mutagenesis, single-channel recording, ion selectivity and block analysis in Xenopus oocytes

    PMID:9382895

    Open questions at the time
    • Charge effect inferred functionally without structure at the time
    • Relationship to cytoplasmic blocker sites not integrated
  4. 1998 High

    Identified an additional regulatory layer through tyrosine-kinase suppression at Y242 and characterized the basal transcriptional control of KCNJ2.

    Evidence Y242F mutagenesis with growth-factor receptor coexpression; promoter deletion and transcription-factor cotransfection assays

    PMID:9712915 PMID:9852063

    Open questions at the time
    • In vivo relevance of growth-factor suppression in heart/muscle unquantified
    • Tissue-selective repressor elements not molecularly identified
  5. 2000 High

    Demonstrated through genetic knockout that Kir2.1 is required for inward rectifier currents and K+-induced vasodilation in arterial smooth muscle, establishing a physiological role outside cardiac excitability.

    Evidence Kir2.1-/- mice, myocyte patch-clamp, pressurized cerebral artery dilation

    PMID:10904001

    Open questions at the time
    • Endothelial versus smooth-muscle contribution not separated at this stage
    • Downstream coupling to dilatory effectors not defined
  6. 2001 High

    Identified KCNJ2 as the causative gene for Andersen's syndrome and showed mutations act through loss-of-function with dominant-negative suppression, defining the disease mechanism.

    Evidence Genetic mapping and two-electrode voltage-clamp of mutants in Xenopus oocytes; AKAP79 co-IP/pulldown linking PKA anchoring

    PMID:11287423 PMID:11371347

    Open questions at the time
    • Did not distinguish trafficking versus assembly defects among mutations
    • Tissue-specific phenotype variability unexplained
  7. 2002 High

    Connected reduced Kir2.1 current to specific arrhythmogenic action-potential changes and broadened the picture with subtype heteromerization, subcellular distribution, and Ras-MAPK regulation.

    Evidence Voltage-clamp of 10 ATS mutants with computational myocyte modeling; Kir2.4 co-assembly pulldowns; cardiomyocyte immunocytochemistry; Ras-L61/MEK-inhibitor localization studies

    PMID:11809752 PMID:12045162 PMID:12148092 PMID:12163457 PMID:12181143 PMID:12381809

    Open questions at the time
    • Heteromer stoichiometry in native tissue not quantified
    • Mechanistic link between MAPK and trafficking machinery incomplete
  8. 2003 High

    Resolved that distinct ATS mutations cause dysfunction by mechanistically separable routes — dominant-negative co-assembly, trafficking failure, or haploinsufficiency — and identified filamin-A as a trafficking-promoting partner.

    Evidence HEK293 patch-clamp with confocal/FRET trafficking analysis of multiple mutants; yeast two-hybrid, reciprocal pulldown, and co-IP for filamin-A

    PMID:12689820 PMID:12923176 PMID:14522976

    Open questions at the time
    • Determinants selecting which mutation follows which route not predictive
    • Filamin-A interaction interface not mapped to atomic detail
  9. 2005 High

    Provided structural grounding for rectification via the cytoplasmic G-loop and di-aspartate cluster, and established that gain-of-function mutations produce a clinically distinct short-QT/atrial-fibrillation phenotype.

    Evidence X-ray crystallography of cytoplasmic domains with mutagenesis; D172N and V93I gain-of-function patch-clamp with ventricular modeling; YxxΦ Golgi-export chimera analysis

    PMID:15723059 PMID:15761194 PMID:15827083 PMID:15922306

    Open questions at the time
    • Full-length channel structure in membrane not solved
    • How export motif sets heteromer surface stoichiometry mechanistically unresolved
  10. 2006 High

    Pinpointed the G-loop residue V302 as critical for both K+ conduction and PIP2 gating, linking a trafficking-normal ATS mutation directly to a permeation defect.

    Evidence Systematic V302 substitution mutagenesis with patch-clamp, surface assays, and structure-guided interpretation

    PMID:17166852

    Open questions at the time
    • Coupling between PIP2 binding and G-loop conduction not kinetically dissected
    • T192 PIP2-site contribution addressed separately and incompletely
  11. 2011 Medium

    Established kinase-controlled degradation by showing AMPK reduces Kir2.1 surface abundance through Nedd4-2, embedding the channel in metabolic-stress signaling.

    Evidence Xenopus oocyte coexpression, voltage-clamp, confocal surface imaging, Nedd4-2 S795A mutagenesis

    PMID:21501591

    Open questions at the time
    • Direct Kir2.1 ubiquitination by Nedd4-2 not demonstrated here
    • Native-tissue relevance not tested
  12. 2013 High

    Mapped the degradation and surface-trafficking machinery (lysosome, ESCRT, ERAD, α-arrestins) and characterized additional gain-of-function mutations disrupting rectification through heteromerization.

    Evidence Yeast synthetic gene array screens with human-cell validation and surface-quantification fusions; E299V patch-clamp, co-IP, and modeling; zacopride PKA-dependent activation via S425

    PMID:23440193 PMID:23929001 PMID:24227888 PMID:29784874

    Open questions at the time
    • Relative flux through ESCRT versus ERAD in native cardiomyocytes unknown
    • Mammalian orthologs of α-arrestin effects not fully validated
  13. 2014 High

    Connected charge-dependent loss of rectification to disease and showed SQT3 mutations gain function additionally by altering ubiquitylation, lipid-raft partitioning, and caveolin interactions.

    Evidence M301K/R/A mutagenesis with cardiomyocyte overexpression; ubiquitylation, raft fractionation, caveolin co-IP, and patch-clamp

    PMID:22155372 PMID:24794859

    Open questions at the time
    • Whether stability and conduction changes are mechanistically coupled unresolved
    • Caveolin-1 versus caveolin-2 functional division not fully defined
  14. 2016 High

    Revealed a non-excitable, bioelectric role for Kir2.1 in craniofacial development and identified Cdo/p38MAPK as a trafficking-promoting axis in myogenesis.

    Evidence Xenopus optogenetics, voltage-dye imaging, ATS-mutation expression, Kcnj2 KO mouse analysis; Cdo co-IP, surface assays, MKK6(EE) rescue in primary myoblasts

    PMID:26864374 PMID:27380411

    Open questions at the time
    • How membrane voltage is transduced to patterning-gene expression mechanistically unclear
    • Cdo interaction interface not mapped
  15. 2018 High

    Defined the cardiac Kir2.1-Nav1.5 macromolecular complex — co-trafficked from the trans-Golgi via AP1 and reciprocally regulated — establishing channel interdependence relevant to both ATS and Brugada syndrome.

    Evidence Co-IP, FRAP, biotinylation, AP1 silencing in hiPSC-CMs; SCN5A haploinsufficient mice and hiPSC-CMs with trafficking-defective Nav1.5 mutants; PLA and CaMKII/14-3-3 inhibitor analysis

    PMID:29184507 PMID:29514831 PMID:30232268

    Open questions at the time
    • Stoichiometry of the channelosome unresolved
    • GRASP-dependent unconventional rescue route mechanistically incomplete
  16. 2018 Medium

    Demonstrated a conduction-independent oncogenic function of Kir2.1, scaffolding kinase signaling to drive EMT, invasion, and drug resistance in cancer.

    Evidence Co-IP of Stk38 and MRP1, knockdown/overexpression, ubiquitination assays, and invasion/drug-resistance assays in gastric and small-cell lung cancer

    PMID:25880778 PMID:29549164

    Open questions at the time
    • Direct versus indirect nature of interactions not fully resolved
    • In vivo tumor relevance limited to single labs
  17. 2022 Medium

    Extended Kir2.1 into immunometabolism, showing its hyperpolarizing current controls macrophage polarization and nutrient transport, linking membrane bioelectrics to inflammatory and metabolic programs.

    Evidence Genetic and pharmacological inhibition, Ca2+ imaging, phospholipid and epigenetic analysis, in vivo sepsis/peritonitis models

    PMID:35694964 PMID:35729093

    Open questions at the time
    • Direct molecular sensor coupling hyperpolarization to transporter retention not defined
    • Whether channel conduction or scaffolding dominates not separated
  18. 2024 Medium

    Identified Kir2.1 as a tractable node in neural injury, where its inhibition mitigates neurodegenerative hallmarks after mechanical brain injury.

    Evidence Genome-wide CRISPRi screen in iPSC cortical organoids with ultrasound injury and in vivo validation; prior microglial Kir2.1 work in neuropathic pain

    PMID:32220118 PMID:38579683

    Open questions at the time
    • Mechanism linking Kir2.1 activity to tau phosphorylation and TDP-43 mislocalization unknown
    • Cell-type contribution (neuron vs glia) not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Kir2.1's conducting and non-conducting (scaffolding/bioelectric) functions are partitioned across tissues, and how membrane voltage is mechanistically transduced into developmental, immune, and signaling outputs, remain open.
  • No unified model linking ion conduction to scaffolding functions
  • Signal transduction from membrane potential to gene-expression programs undefined
  • Full-length membrane-embedded structure with regulatory partners not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005764 lysosome 2 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-9609507 Protein localization 3 R-HSA-112316 Neuronal System 2 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 2 R-HSA-397014 Muscle contraction 1
Partners
AKAP5CDONFLNAKCNJ14KCNJ16NEDD4LSCN5ASTK38
Complex memberships
Kir2.1-Nav1.5 channelosomeKir2.x heterotetramers (Kir2.4, Kir5.1)

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Loss-of-function mutations in KCNJ2 (Kir2.1) cause Andersen's syndrome. Expression of D71V and other mutations in Xenopus oocytes revealed loss of function and a dominant-negative effect on Kir2.1 current by voltage-clamp, establishing KCNJ2 as the causative gene. Xenopus oocyte expression system, two-electrode voltage-clamp, genetic mapping Cell High 11371347
2002 Ten KCNJ2 mutations associated with Andersen syndrome all resulted in loss of function and dominant-negative suppression of Kir2.1 channel function when assessed by two-microelectrode voltage-clamp in Xenopus oocytes. Computer simulation showed reduced Kir2.1 prolongs terminal action potential phase and, at low extracellular K+, induces Na+/Ca2+ exchanger-dependent delayed afterdepolarizations. Two-microelectrode voltage-clamp (Xenopus oocytes), ventricular myocyte computational modeling The Journal of clinical investigation High 12163457
2002 The R67W KCNJ2 mutation demonstrates loss of function and a dominant-negative effect on Kir2.1 current, establishing that Kir2.1 plays roles in both cardiac/skeletal muscle excitability and developmental signaling. Biophysical characterization by voltage-clamp in Xenopus oocytes American journal of human genetics Medium 12148092
2003 Different Andersen-Tawil syndrome KCNJ2 mutations cause channel dysfunction via distinct mechanisms: (1) some mutants co-assemble with wild-type at the membrane and exert dominant-negative effects; (2) V302M mutant loses co-assembly ability with wild-type and fails to traffic to the cell surface; (3) deletion mutants (Δ95-98, Δ314-315) fail to traffic to the membrane but retain co-assembly with wild-type, causing haplo-insufficiency. Heterologous expression in HEK293 cells, whole-cell patch-clamp, confocal fluorescence microscopy The Journal of biological chemistry High 14522976
2003 Filamin-A directly interacts with Kir2.1 via the Kir2.1 carboxyl terminus. This interaction increases the number of functional Kir2.1 channels at the plasma membrane without altering single-channel properties. Yeast two-hybrid screen, GST pulldown overlay assay, co-immunoprecipitation from arterial smooth muscle lysates, immunocytochemistry The Journal of biological chemistry High 12923176
2005 Crystal structures of the cytoplasmic domains of Kir2.1 and Kir3.1 show a G-loop that forms a diffusion barrier between cytoplasmic and transmembrane pores. G-loop mutations disrupted gating or inward rectification. A di-aspartate cluster at the distal cytoplasmic pore of Kir2.1 modulates inward rectification. X-ray crystallography, site-directed mutagenesis, electrophysiology Nature neuroscience High 15723059
2005 The KCNJ2 D172N mutation causes a gain-of-function in Kir2.1 (SQT3): larger outward IK1 at potentials between -75 mV and -45 mV with a shifted peak current, due to altered inward rectification. This gain-of-function accelerates final repolarization, shortens action potential duration, and predicts steeper restitution favoring re-entrant arrhythmias. Whole-cell patch-clamp (heterologous expression), computational modeling of human ventricular myocyte Circulation research High 15761194
2005 A Kir2.1 gain-of-function mutation (V93I) is associated with familial atrial fibrillation, demonstrating that increased Kir2.1 channel activity (opposed to ATS loss-of-function) can promote AF. Genetic screening, functional analysis by patch-clamp in heterologous expression system Biochemical and biophysical research communications Medium 15922306
2005 Kir2.1 preferentially exports from the Golgi to the plasma membrane via a tyrosine-dependent YXXPhi motif in its C-terminus (20-amino acid stretch). This dominant Golgi export signal controls the stoichiometry of Kir2.x heteromers at the cell surface. Chimeric channel construction, functional expression in oocytes and mammalian cells, subcellular trafficking analysis Journal of cell science High 15827083
2000 Kir2.1 gene expression in arterial smooth muscle is required for inward rectifier K+ currents and K+-induced vasodilation in cerebral arteries. Kir2.1 knockout mice lack these Kir currents and K+-induced dilatory response. Targeted gene disruption (Kir2.1-/- mice), patch-clamp of isolated cerebral artery myocytes, pressurized cerebral artery dilation assay Circulation research High 10904001
1994 Kir2.1 (IRK1) channel activity requires both PKA-mediated phosphorylation and ATP hydrolysis (via an ATPase-like mechanism). PKA increases current amplitude only when channels are also stimulated by Mg-ATP/Mg2+, while PKC activation down-regulates Kir2.1 currents, showing opposing regulation by these kinases. Giant inside-out patches from Xenopus oocytes, pharmacological manipulation of PKA, PKC, ATP analogs Neuron High 7993632
1994 Kir2.1 (IRK1) intrinsic gating depends on voltage, external K+ concentration, and intracellular Mg2+. Removal of intracellular Mg2+ permits brief outward currents at depolarization, demonstrating that Mg2+ is required for voltage-dependent gating/rectification. Stable expression in MEL cells, whole-cell and single-channel recording, Mg2+ manipulation The Journal of physiology High 8189383
1996 PKA directly phosphorylates Kir2.1 (IRK1) at a C-terminal site (S425), mediating inhibition following serotonin 5-HT1A receptor activation via cAMP elevation. Mutant IRK1(S425N) lacking this PKA phosphorylation site is not inhibited by PKA. Whole-cell patch-clamp in COS-7 cells, pharmacological cAMP elevation, site-directed mutagenesis (S425N), receptor coexpression Proceedings of the National Academy of Sciences of the United States of America High 8650176
1996 m1 muscarinic receptor stimulation inhibits Kir2.1 (IRK1) current via PKC activation. m2 receptor stimulation does not affect Kir2.1. PKC activator phorbol ester mimics m1 inhibition, and PKC inhibitors (staurosporine, calphostin C) prevent it. cAMP and intracellular Ca2+ are not involved. Whole-cell patch-clamp in tsA cells, receptor coexpression, pharmacological PKC manipulation Molecular pharmacology High 8609894
1998 Tyrosine kinase phosphorylation directly suppresses Kir2.1 channel activity. The Y242 residue in the C-terminal domain is a direct TK substrate; Y242F mutant channels are insensitive to TK-mediated suppression. NGF, EGF, and insulin each suppress Kir2.1 activity via this mechanism. Patch-clamp in tsA-201 cells and Xenopus oocytes, site-directed mutagenesis (Y242F), receptor coexpression, pharmacological TK/PTP manipulation The Journal of biological chemistry High 9852063
2001 AKAP79 directly associates with the Kir2.1 channel via both N- and C-terminal intracellular domains (demonstrated by GST pulldown and co-immunoprecipitation), and enhances Kir2.1 response to elevated intracellular cAMP, suggesting AKAP79 anchors PKA near Kir2.1 phosphorylation sites. Co-immunoprecipitation, GST pulldown from cell lysates, whole-cell patch-clamp with cAMP stimulation The Journal of biological chemistry High 11287423
2001 Kir5.1 (KCNJ16) co-localizes with Kir2.1 in brain and kidney and forms electrically silent heteromeric channels with Kir2.1 when coexpressed in Xenopus oocytes, thereby negatively regulating Kir2.1 channel activity. Xenopus oocyte expression, two-electrode voltage-clamp, in situ hybridization, chromosomal mapping FEBS letters Medium 11240146
2002 Kir2.1 exhibits transverse tubular localization in ventricular cardiomyocytes (89% of cells) but less so in atrial cells (26%). Kir2.3 is strongly expressed at intercalated disks. These differential subcellular distributions contribute to the >10-fold larger IK1 in ventricle vs. atrium. Western blot, immunocytochemistry, patch-clamp electrophysiology in isolated canine cardiomyocytes American journal of physiology. Heart and circulatory physiology Medium 12181143
2002 Kir2.4 co-assembles with Kir2.1 to form functional heterotetrameric channels with properties distinct from either homomeric channel (greater Ba2+ sensitivity). Physical co-assembly confirmed by His-tag pulldown. Co-expression in Xenopus oocytes and COS-7 cells, dominant-negative suppression, His-tag pulldown/Western blot, tandem subunit expression The Journal of physiology High 12381809
2003 The G215D Kir2.1 mutant (Andersen syndrome) traffics normally to the plasma membrane, co-assembles with wild-type Kir2.1 into hetero-multimers (demonstrated by FRET), and exerts dominant-negative suppression of both inward and outward currents without trafficking defect. Whole-cell patch-clamp in COS7 cells, confocal microscopy with YFP/CFP-tagged channels, FRET analysis Journal of molecular and cellular cardiology Medium 12689820
2004 Cholesterol increase suppresses Kir2.1 whole-cell current in null cell lines by promoting transition of channels between active and silent states, without altering total protein levels, surface expression, unitary conductance, or open probability significantly. Kir2.x channels partition almost exclusively into cholesterol-rich lipid rafts (Triton-insoluble fractions). Whole-cell patch-clamp, cholesterol manipulation, single-channel recording, Western blot, cell surface biotinylation, lipid raft fractionation Biophysical journal High 15465867
2005 The KCNJ2 T192A mutation, located in the PIP2-binding site and Kir2.1 multimerization region, produces a non-functional channel and weak dominant-negative effect, implicating T192 as important for both PIP2 interaction and channel assembly. Xenopus oocyte expression system, voltage-clamp Circulation Medium 12045162
2006 The V302M mutation in the Kir2.1 G-loop specifically abolishes K+ conduction without altering subunit assembly or surface expression. The V302 side chain is critical for G-loop potassium conduction and PIP2 gating. Amino acid substitution analysis shows channel activity and PIP2 sensitivity are highly sensitive to the size, shape, and hydrophobicity at position 302. Site-directed mutagenesis, heterologous expression, patch-clamp, cell surface expression assay, crystal structure interpretation The Journal of biological chemistry High 17166852
2007 miR-1 post-transcriptionally represses KCNJ2 (Kir2.1) and GJA1 (connexin 43), causing membrane depolarization and slowed conduction. miR-1 overexpression in infarcted rat hearts exacerbates arrhythmogenesis, while antisense inhibitor of miR-1 relieves arrhythmogenesis. miRNA overexpression and antisense inhibition in rat hearts, electrophysiology, molecular target validation Nature medicine High 17401374
2008 Kir2.1 is degraded via the lysosomal pathway. Lysosomal inhibitors (NH4Cl, chloroquine, leupeptin) increase steady-state Kir2.1 protein levels and plasma membrane-originating inward rectifier current densities without altering current-voltage characteristics, establishing lysosomes as a major Kir2.1 degradation route. Lysosomal inhibitor treatment, Western blot, patch-clamp electrophysiology, confocal microscopy Biochemical and biophysical research communications Medium 18182162
2009 KCNJ2 V227F mutation causes a latent loss-of-function phenotype dependent on PKA-mediated phosphorylation at S425. Under basal conditions, V227F coexpressed with wild-type produces normal IK1, but PKA stimulation markedly reduces outward IK1. The S425N phosphorylation-null mutation eliminates PKA-induced reduction. Heterologous expression in COS-1 cells, whole-cell voltage-clamp, PKA-stimulating cocktail (forskolin/IBMX), site-directed mutagenesis (S425N) Circulation. Arrhythmia and electrophysiology High 19843922
2011 AMPK inhibits Kir2.1 by reducing channel protein abundance at the plasma membrane. This effect is partially mediated through AMPK phosphorylation of the ubiquitin ligase Nedd4-2; Nedd4-2(S795A) lacking the AMPK phosphorylation site is not augmented by AMPK, though wild-type Nedd4-2 alone also downregulates Kir2.1 currents. Xenopus oocyte co-expression, two-electrode voltage-clamp, confocal imaging of membrane protein abundance, mutagenesis of AMPK phosphorylation site on Nedd4-2 Biochemical and biophysical research communications Medium 21501591
2013 E299V KCNJ2 mutation causes gain-of-function with loss of inward rectification, generating a large abnormal outward IK1. Co-immunoprecipitation and kinetic analysis showed E299V and wild-type isoforms heteromerize, impairing function. Homomeric E299V results in gain-of-function. Whole-cell patch-clamp, co-immunoprecipitation, kinetic analysis, computational modeling Proceedings of the National Academy of Sciences of the United States of America High 23440193
2013 ESCRT (endosomal sorting complex required for transport) and ERAD (ER-associated degradation) both mediate Kir2.1 degradation in human cells, with ESCRT playing a more prominent role in controlling Kir2.1 surface expression. Yeast genetic screen (synthetic gene array), heterologous expression in human cells, loss-of-function of ESCRT/ERAD pathway components Molecular biology of the cell Medium 24227888
2014 A Kir2.1 gain-of-function mutation (M301K) causes loss of inward rectification in a charge-dependent manner. Homozygous M301K is non-functional, but heterozygous coexpression with wild-type yields larger outward currents above -30 mV. Neutral substitutions (M301A) show normal rectification, establishing that the positive charge at M301 specifically impairs rectification. Heterologous expression in mammalian cells, whole-cell patch-clamp, site-directed mutagenesis (M301K/R/A), neonatal rat ventricular myocyte overexpression Cardiovascular research High 22155372
2014 An SQT3-associated Kir2.1 mutation enhances channel surface expression and stability by reducing ubiquitylation and proteasomal degradation, alters protein partitioning in lipid rafts (shifting to cholesterol-poor domains), and reduces interaction with caveolin-2. Wild-type Kir2.1 binds both caveolin-1 and caveolin-2 and is degraded via the ubiquitin-proteasome pathway. Surface expression assay, ubiquitylation assay, lipid raft fractionation, co-immunoprecipitation, patch-clamp Human molecular genetics High 24794859
2018 Kir2.1 and Nav1.5 pre-assemble early in the forward trafficking pathway (at the trans-Golgi, via AP1 adaptor complex) and traffic together to common membrane microdomains. Trafficking-deficient Kir2.1 mutants reduce Nav1.5 surface expression; FRAP shows coexpression increases cytoplasmic mobility of both channels. AP1 co-localizes with and co-immunoprecipitates with both channels; Nav1.5 interacts with AP1 through Y1810. Patch-clamp, cell surface biotinylation, glycosylation analysis, FRAP, viral gene transfer in cardiomyocytes, co-immunoprecipitation, site-directed mutagenesis (Nav1.5Y1810), immunostaining, AP1 subunit silencing in hiPSC-CMs Circulation research High 29514831
2017 In Kir2.1-Nav1.5 complexes, CaMKII inhibition decreases both INa and IK1 only when channels are coexpressed (not Kir2.1 alone), indicating the complex is a CaMKII substrate. 14-3-3 protein inhibition reduces currents from complexes but not individual channels. Dynamin-dependent endocytosis reduces Kir2.1 internalization but not Nav1.5 or the Kir2.1-Nav1.5 complex. The Kir2.1-Nav1.5 complex is degraded via Nedd4-2/proteasome pathway (like Nav1.5, not like Kir2.1 alone). Proximity ligation assay, patch-clamp, intracellular antibody dialysis, pharmacological inhibitors, co-immunoprecipitation Frontiers in physiology High 29184507
2018 Brugada syndrome-associated Nav1.5 trafficking-defective mutants decrease IK1 by failing to positively modulate Kir2.1/Kir2.2 channels. Golgi trafficking-defective Nav1.5 mutants additionally exert dominant-negative effects on Kir2.1/Kir2.2 and trap them, further reducing IK1. Conversely, ER trafficking-defective Nav1.5 can be partially rescued by Kir2.1/Kir2.2 via an unconventional GRASP-dependent secretory route. Mouse SCN5A haploinsufficiency models, heterologous expression, hiPSC-CM experiments, patch-clamp, immunostaining JCI insight High 30232268
2018 Kir2.1 promotes gastric cancer invasion and metastasis via a non-ion-conducting mechanism: it interacts with Stk38 kinase (confirmed by co-IP) to inhibit Smurf1-mediated ubiquitination and degradation of MEKK2, thereby activating the MEK1/2-ERK1/2-Snail pathway promoting EMT. Co-immunoprecipitation, siRNA knockdown, overexpression, invasion/metastasis assays, ubiquitination assay, signaling pathway inhibitors Cancer research Medium 29549164
2016 Kir2.1 function is required in cranial neural crest for craniofacial morphogenesis. In Xenopus, ATS-associated KCNJ2 mutations alter membrane voltage regionalization in ectoderm during neurulation and disrupt expression of craniofacial patterning genes. Optogenetic membrane potential manipulation in ectoderm during early neurulation is sufficient to cause craniofacial anomalies, identifying a bioelectric mechanism. Xenopus microinjection, optogenetics, voltage-sensitive dye imaging, in situ hybridization/immunostaining for patterning genes, Kcnj2KO mouse analysis The Journal of physiology High 26864374
2018 Kir2.1 is required in cranial neural crest for palatal shelf proliferation and closure. Loss of Kir2.1 reduces BMP signaling efficacy (decreased phospho-Smad 1/5/8 and BMP target expression Smad6, Satb2) without altering BMP ligand, receptor, or Smad levels. Cdo forms a complex with Kir2.1 to promote surface expression during myogenic differentiation. Kcnj2 KO mice, conditional neural crest-specific knockout, BMP signaling analysis (Western blot for phospho-Smad), proliferation assays Developmental biology Medium 29571612
2016 Cdo forms a protein complex with Kir2.1 during myogenic differentiation and promotes Kir2.1 surface expression via p38MAPK signaling. Cdo depletion reduces Kir2.1 surface expression and channel activity; constitutively active MKK6(EE) rescues Kir2.1 activity in Cdo-depleted cells. Co-immunoprecipitation, surface expression assay, patch-clamp, siRNA knockdown, MKK6(EE) rescue, Cdo-/- primary myoblasts PloS one Medium 27380411
2022 Kir2.1-mediated membrane hyperpolarization controls macrophage nutrient acquisition by supporting cell-surface retention of nutrient transporters (4F2hc, GLUT1) through modulation of plasma membrane phospholipid dynamics. Loss of Kir2.1 induces caloric restriction state, activates AMPK and GCN2, depletes epigenetic substrates for histone methylation, and suppresses transcription of metabolism-responsive inflammatory genes. Genetic knockdown/knockout, pharmacological channel blockade, nutrient uptake assays, Ca2+ imaging, lipid/phospholipid analysis, epigenetic analysis, in vivo sepsis model Nature communications High 35729093
2013 Lysosome-mediated and ESCRT-mediated degradation control Kir2.1 surface levels; select α-arrestins (Ldb19/Art1, Aly1/Art6, Aly2/Art3) promote Kir2.1 trafficking to the cell surface and increase its activity via Rsp5 ubiquitin ligase and calcineurin effectors. Yeast synthetic gene array screen, fluorogen-activating protein fusion for surface quantification, functional complementation assay The Journal of biological chemistry Medium 29784874
2012 SGK3 (serum/glucocorticoid-inducible kinase 3) upregulates Kir2.1-mediated currents and increases Kir2.1 protein abundance at the plasma membrane by promoting channel insertion (not reducing retrieval), as shown by similar brefeldin A-induced current decay with or without SGK3. Xenopus oocyte co-expression, two-electrode voltage-clamp, confocal imaging of membrane protein, brefeldin A trafficking assay The Journal of membrane biology Medium 23188060
2022 Kir2.1 channel regulates macrophage M1 polarization via a Ca2+/CaMKII/ERK/NF-κB signaling pathway: Kir2.1-mediated membrane hyperpolarization drives Ca2+ influx, activating CaMKII/ERK/NF-κB; blocking Kir2.1 or high extracellular K+ suppresses M1 polarization and protects mice from LPS-induced peritonitis. siRNA knockdown, pharmacological blockade (ML133), Ca2+ imaging, Western blot for p-CaMKII/p-ERK/p-NF-κB, in vivo peritonitis model Journal of cell science Medium 35694964
1996 Polyamine-induced rectification of Kir2.1 (IRK1) depends strongly on external K+ concentration (not internal K+): increasing external K+ speeds activation kinetics and shifts rectification proportional to EK shift. This establishes that permeant K+ ions modulate polyamine block kinetics in a long, narrow pore with multiple binding sites. Patch-clamp of Kir2.1-expressing Xenopus oocytes, varied internal and external K+ concentrations, polyamine block kinetics analysis The Journal of general physiology High 8854340
2015 Kir2.1 in endothelial cells (ECs) of mesenteric arteries amplifies endothelium-dependent vasodilatation. EC-specific Kir2.1 knockdown mice show reduced K+-induced and agonist/IK/SK-induced vasodilatations. The Kir channel blocker Ba2+ does not affect TRPV4, IK, or SK channel currents, establishing Kir2.1 as a downstream booster of the vasodilatory signal. EC-specific Kir2.1 conditional KO mice, patch-clamp, pressurized artery myography, pharmacological channel blockers The Journal of physiology High 26840527
2007 Beta3-adrenoceptor activation increases Kir2.1 currents via PKC-dependent signaling (not PKA or CaMKII), while Kir2.2 is activated via PKA. This receptor-subtype-specific kinase pathway selectivity was established by kinase inhibitors and comparison of Kir2.2 mutants lacking PKC sites. Xenopus oocyte coexpression with human beta3-AR, two-electrode voltage-clamp, pharmacological kinase inhibitors, Kir2.2 PKC-site mutants Naunyn-Schmiedeberg's archives of pharmacology Medium 17534603
2013 Zacopride selectively activates Kir2.1 homomeric channels via a PKA-dependent pathway in HEK293 cells. It does not affect Kir2.2 or Kir2.3 homomeric channels or Kir2.x heteromers. The effect is abolished by PKA inhibition and by the S425L mutation at the PKA phosphorylation site. Whole-cell patch-clamp in HEK293 cells transfected with Kir2.x, PKA inhibition, S425L mutagenesis Science China. Life sciences Medium 23929001
2002 Activated Ras (Ras-L61) reduces Kir2.1 (IRK1) current density by delocalizing the channel from the plasma membrane to the cytoplasm via the MAPK pathway; MEK inhibitor PD98059 restores membrane localization and current. This establishes Ras-MAPK pathway as a regulator of Kir2.1 subcellular localization. Heterologous expression in HEK293 cells, patch-clamp, confocal microscopy of GFP-IRK1, Northern blot, MEK inhibitor treatment The Journal of biological chemistry Medium 11809752
2015 KCNJ2/Kir2.1 promotes multidrug resistance in small-cell lung cancer by interacting with MRP1/ABCC1 (confirmed by co-IP) and is regulated by the Ras/MAPK pathway and miR-7. Co-immunoprecipitation, shRNA knockdown, overexpression, cell growth/apoptosis/drug resistance assays Molecular cancer Medium 25880778
1997 Arg148 in the H5 pore domain of Kir2.1 (IRK1) serves as an external barrier for cationic blockers. Coexpression of R148H mutant with wild-type creates heteromeric channels with altered permeability ratios, increased Mg2+/Ca2+ sensitivity, and changed blocking kinetics. The R148 charge controls access of Mg2+ and Ca2+ to the electric field of the pore. Mutagenesis (R148H), Xenopus oocyte coexpression, single-channel recording, ion selectivity measurements, cation block analysis The Journal of general physiology High 9382895
2016 Kir2.1 inhibition in spinal microglia depolarizes their resting membrane potential, reduces proliferation after nerve injury, and attenuates neuropathic pain behaviors. Kir2.1 protein expression is increased at the plasma membrane of spinal microglia 2 days post-nerve injury, coinciding with peak proliferation. Patch-clamp, siRNA knockdown, ML133 pharmacological blockade, intrathecal injection in spared nerve injury model, immunofluorescence Glia Medium 32220118
2024 KCNJ2 inhibition potently mitigates neurodegenerative processes (neuronal death, tau phosphorylation, TDP-43 nuclear egress) after mechanical brain injury in iPSC-derived cortical organoids and in vivo, identified through genome-wide CRISPR interference screening. Genome-wide CRISPRi screen, iPSC-derived cortical organoids, ultrasound mechanical injury model, in vivo validation Cell stem cell Medium 38579683
1998 The KCNJ2 promoter contains a minimal 172 bp TATA-less element driven by Sp1, Sp3, and NF-Y transcription factors at E box, Y box, and GC box elements. Upstream sequences restrict expression in a cell-type-dependent manner, identifying tissue-selective repressor elements. Promoter deletion analysis, transfection reporter assays, transcription factor co-transfection in cell lines The Journal of biological chemistry Medium 9712915

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nature medicine 906 17401374
2001 Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 726 11371347
2005 A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circulation research 446 15761194
2002 Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). The Journal of clinical investigation 393 12163457
2005 A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochemical and biophysical research communications 297 15922306
2000 Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation. Circulation research 284 10904001
2005 Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification. Nature neuroscience 240 15723059
2019 Functional dissection of the Sox9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture. Nature genetics 231 31358994
2005 Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation 208 15911703
2002 KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. American journal of human genetics 176 12148092
2004 Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophysical journal 155 15465867
1994 Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis. Neuron 135 7993632
2016 Differential Kv1.3, KCa3.1, and Kir2.1 expression in "classically" and "alternatively" activated microglia. Glia 134 27696527
2003 Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome. The Journal of biological chemistry 129 14522976
2016 Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium-dependent vasodilators. The Journal of physiology 111 26840527
2013 KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proceedings of the National Academy of Sciences of the United States of America 109 23440193
2016 Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2-associated Andersen-Tawil Syndrome. The Journal of physiology 106 26864374
2018 Cardiac Kir2.1 and NaV1.5 Channels Traffic Together to the Sarcolemma to Control Excitability. Circulation research 92 29514831
1994 The intrinsic gating of inward rectifier K+ channels expressed from the murine IRK1 gene depends on voltage, K+ and Mg2+. The Journal of physiology 89 8189383
2015 Upregulation of the inwardly rectifying potassium channel Kir2.1 (KCNJ2) modulates multidrug resistance of small-cell lung cancer under the regulation of miR-7 and the Ras/MAPK pathway. Molecular cancer 84 25880778
2002 Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle. American journal of physiology. Heart and circulatory physiology 82 12181143
2012 Phenotype variability in patients carrying KCNJ2 mutations. Circulation. Cardiovascular genetics 81 22589293
1996 [K+] dependence of polyamine-induced rectification in inward rectifier potassium channels (IRK1, Kir2.1). The Journal of general physiology 79 8854340
2002 Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia. Circulation 76 12045162
1998 Acute suppression of inwardly rectifying Kir2.1 channels by direct tyrosine kinase phosphorylation. The Journal of biological chemistry 75 9852063
1996 Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 74 8650176
2007 Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2. Journal of medical genetics 72 17551083
2003 Direct interaction between the actin-binding protein filamin-A and the inwardly rectifying potassium channel, Kir2.1. The Journal of biological chemistry 72 12923176
2013 Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 67 23867365
2005 Selective Golgi export of Kir2.1 controls the stoichiometry of functional Kir2.x channel heteromers. Journal of cell science 67 15827083
2014 Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype. Human molecular genetics 66 24794859
2011 A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents. Cardiovascular research 65 22155372
2007 Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome. Human mutation 62 17221872
2006 Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7). Heart rhythm 60 16500306
2018 Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling. Cancer research 56 29549164
2018 Kir2.1 is important for efficient BMP signaling in mammalian face development. Developmental biology 56 29571612
2001 Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1. The Journal of biological chemistry 56 11287423
2003 Gastric parietal cell secretory membrane contains PKA- and acid-activated Kir2.1 K+ channels. American journal of physiology. Cell physiology 52 14602583
2003 Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome. Journal of molecular and cellular cardiology 51 12689820
2001 Genetic and functional linkage of Kir5.1 and Kir2.1 channel subunits. FEBS letters 51 11240146
2009 Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in catecholaminergic polymorphic ventricular tachycardia. Circulation. Arrhythmia and electrophysiology 49 19843922
2002 Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility. The Journal of clinical investigation 47 11827999
2022 Kir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters. Nature communications 45 35729093
2006 An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway. The Journal of biological chemistry 45 17166852
2002 Kir2.4 and Kir2.1 K(+) channel subunits co-assemble: a potential new contributor to inward rectifier current heterogeneity. The Journal of physiology 45 12381809
2018 Brugada syndrome trafficking-defective Nav1.5 channels can trap cardiac Kir2.1/2.2 channels. JCI insight 43 30232268
2017 Sucrose withdrawal induces depression and anxiety-like behavior by Kir2.1 upregulation in the nucleus accumbens. Neuropharmacology 43 29191750
2001 Channelopathies: Kir2.1 mutations jeopardize many cell functions. Current biology : CB 43 11566119
2008 Lysosome mediated Kir2.1 breakdown directly influences inward rectifier current density. Biochemical and biophysical research communications 42 18182162
2006 Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome. Human mutation 42 16541386
2005 Differential regulation of Kir4.1 and Kir2.1 expression in the ischemic rat retina. Neuroscience letters 42 16330144
2015 Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function. American journal of physiology. Regulatory, integrative and comparative physiology 41 26224687
2006 KCNJ2 mutations in arrhythmia patients referred for LQT testing: a mutation T305A with novel effect on rectification properties. Heart rhythm 41 17341397
2012 Proarrhythmia in KCNJ2-linked short QT syndrome: insights from modelling. Cardiovascular research 37 22308236
2004 Polymorphic ventricular tachycardia and KCNJ2 mutations. Heart rhythm 37 15851159
2017 Kir2.1-Nav1.5 Channel Complexes Are Differently Regulated than Kir2.1 and Nav1.5 Channels Alone. Frontiers in physiology 36 29184507
2011 Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochemical and biophysical research communications 36 21501591
2008 Inward rectifier K(+) currents and Kir2.1 expression in renal afferent and efferent arterioles. Journal of the American Society of Nephrology : JASN 35 18178799
2024 KCNJ2 inhibition mitigates mechanical injury in a human brain organoid model of traumatic brain injury. Cell stem cell 34 38579683
2022 Inwardly Rectifying Potassium Channel Kir2.1 and its "Kir-ious" Regulation by Protein Trafficking and Roles in Development and Disease. Frontiers in cell and developmental biology 33 35223865
2006 Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome. Journal of medical genetics 31 16571646
1999 Direct block of native and cloned (Kir2.1) inward rectifier K+ channels by chloroethylclonidine. British journal of pharmacology 31 10516659
1997 A conserved arginine residue in the pore region of an inward rectifier K channel (IRK1) as an external barrier for cationic blockers. The Journal of general physiology 31 9382895
2020 Long noncoding RNA TCONS-00106987 promotes atrial electrical remodelling during atrial fibrillation by sponging miR-26 to regulate KCNJ2. Journal of cellular and molecular medicine 30 32954646
2007 Cloning and expression of cardiac Kir2.1 and Kir2.2 channels in thermally acclimated rainbow trout. American journal of physiology. Regulatory, integrative and comparative physiology 30 17289820
2013 ESCRT regulates surface expression of the Kir2.1 potassium channel. Molecular biology of the cell 29 24227888
2010 Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry. Circulation. Cardiovascular genetics 29 21148745
2007 Activation of inwardly rectifying Kir2.x potassium channels by beta 3-adrenoceptors is mediated via different signaling pathways with a predominant role of PKC for Kir2.1 and of PKA for Kir2.2. Naunyn-Schmiedeberg's archives of pharmacology 29 17534603
2020 Syncytium cell growth increases Kir2.1 contribution in human iPSC-cardiomyocytes. American journal of physiology. Heart and circulatory physiology 28 32986966
2014 KCNJ2 mutation causes an adrenergic-dependent rectification abnormality with calcium sensitivity and ventricular arrhythmia. Heart rhythm 28 24561538
2002 Modulation of the inward rectifier potassium channel IRK1 by the Ras signaling pathway. The Journal of biological chemistry 28 11809752
2009 Specific and slow inhibition of the kir2.1 K+ channel by gambogic acid. The Journal of biological chemistry 27 19366693
2007 Low-affinity spermine block mediating outward currents through Kir2.1 and Kir2.2 inward rectifier potassium channels. The Journal of physiology 27 17640933
2012 Up-regulation of the inwardly rectifying K⁺ channel Kir2.1 (KCNJ2) by protein kinase B (PKB/Akt) and PIKfyve. The Journal of membrane biology 26 23188060
2001 Unitary conductance variation in Kir2.1 and in cardiac inward rectifier potassium channels. Biophysical journal 26 11566776
1999 Expression of Ras-GRF in the SK-N-BE neuroblastoma accelerates retinoic-acid-induced neuronal differentiation and increases the functional expression of the IRK1 potassium channel. The European journal of neuroscience 26 10103089
2022 Kir2.1 channel regulates macrophage polarization via the Ca2+/CaMK II/ERK/NF-κB signaling pathway. Journal of cell science 25 35694964
2017 Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria. PLoS computational biology 25 28609477
2007 Lentiviral vector-mediated expression of GFP or Kir2.1 alters the electrophysiology of neonatal rat ventricular myocytes without inducing cytotoxicity. American journal of physiology. Heart and circulatory physiology 25 17675572
1998 Long-term exposure to retinoic acid induces the expression of IRK1 channels in HERG channel-endowed neuroblastoma cells. Biochemical and biophysical research communications 25 9535729
1998 Multiple promoter elements interact to control the transcription of the potassium channel gene, KCNJ2. The Journal of biological chemistry 25 9712915
1996 Modulation of the inwardly rectifying potassium channel IRK1 by the m1 muscarinic receptor. Molecular pharmacology 24 8609894
2013 Non dominant-negative KCNJ2 gene mutations leading to Andersen-Tawil syndrome with an isolated cardiac phenotype. Basic research in cardiology 22 23644778
2020 The inhibition of Kir2.1 potassium channels depolarizes spinal microglial cells, reduces their proliferation, and attenuates neuropathic pain. Glia 21 32220118
2018 A Novel KCNJ2 Mutation Identified in an Autistic Proband Affects the Single Channel Properties of Kir2.1. Frontiers in cellular neuroscience 21 29615871
2013 Cholesterol sensitivity of KIR2.1 depends on functional inter-links between the N and C termini. Channels (Austin, Tex.) 21 23807091
2013 Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes. Science China. Life sciences 21 23929001
2023 Amyloid beta accumulation in TgF344-AD rats is associated with reduced cerebral capillary endothelial Kir2.1 expression and neurovascular uncoupling. GeroScience 20 37326915
2021 Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration. International journal of molecular sciences 19 33669857
2016 Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells. Biochemical and biophysical research communications 19 27235552
2006 Kir2.3 isoform confers pH sensitivity to heteromeric Kir2.1/Kir2.3 channels in HEK293 cells. Heart rhythm 19 17399639
2018 Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model. The Journal of biological chemistry 18 29784874
2020 Magnesium Deficiency Causes Transcriptional Downregulation of Kir2.1 and Kv4.2 Channels in Cardiomyocytes Resulting in QT Interval Prolongation. Circulation journal : official journal of the Japanese Circulation Society 17 32554946
2016 Cdo Regulates Surface Expression of Kir2.1 K+ Channel in Myoblast Differentiation. PloS one 17 27380411
2014 Up-regulation of Kir2.1 (KCNJ2) by the serum & glucocorticoid inducible SGK3. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 24556932
2008 Expression of Kir2.1 channels in astrocytes under pathophysiological conditions. Molecules and cells 17 18319624
2003 Expression of the inwardly rectifying K+ channel Kir2.1 in native bovine corneal endothelial cells. Investigative ophthalmology & visual science 17 12882801
2017 Characterization of a Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for the Study of Variant Pathogenicity: Validation of a KCNJ2 Mutation. Circulation. Cardiovascular genetics 16 29021306
2015 Inwardly rectifying Kir2.1 currents in human β-cells control electrical activity: characterisation and mathematical modelling. Biochemical and biophysical research communications 16 25727015
2011 Characterization of a novel, dominant negative KCNJ2 mutation associated with Andersen-Tawil syndrome. Channels (Austin, Tex.) 16 22186697

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