Affinage

IPMK

Inositol polyphosphate multikinase · UniProt Q8NFU5

Length
416 aa
Mass
47.2 kDa
Annotated
2026-06-10
34 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IPMK is a dual-specificity kinase that couples inositol phosphate and phosphoinositide metabolism to transcription, signal transduction, and metabolic homeostasis, acting both through its catalytic products and as a non-catalytic scaffold (PMID:22715467, PMID:30840891, PMID:38746349). Catalytically, it phosphorylates inositol phosphates to generate higher-order species (InsP4, InsP5) and can phosphorylate PIP2 to PIP3 on protein-bound substrates, exemplified by SF-1-bound PIP2 to drive nuclear receptor transcriptional output (PMID:22715467, PMID:40709844). These inositol phosphate products are functionally consequential: IPMK-generated Ins(1,4,5,6)P4/InsP6 is required for full HDAC3 deacetylase activity and thereby controls histone H4 acetylation and downstream gene transcription [PMID:38746349, PMID:bio_10.1101_2024.09.15.613154], while IPMK-dependent InsP5 stabilizes active mTORC1 signaling (PMID:41867875). Structurally, IPMK adopts a conserved ATP-grasp fold whose catalytic output is tuned by its disordered N-terminal regions, and its ATP pocket has been resolved at high resolution with inhibitors (PMID:30420721, PMID:41237254). Independent of catalysis, IPMK serves as a scaffold and chaperone: it forms an AMPK-ULK1 ternary complex to drive autophagy and lipophagy (PMID:30840891), stabilizes the PLCγ1-Sam68 complex to promote PLCγ1 Y783 phosphorylation and T-cell Ca2+/IL-2 signaling (PMID:39478550), protects TRAF6 from K48-linked degradation to sustain TLR4/NF-κB inflammatory and osteoclastogenic signaling (PMID:33956362, PMID:36830701), and binds the disordered region of SRF to extend its chromatin residence (PMID:39777465). IPMK additionally promotes hepatic insulin-Akt signaling (PMID:35822903) and integrates into Wnt and LKB1-AMPK pathways via regulated membrane and partner recruitment (PMID:22940627, PMID:24877601). IPMK protein levels are themselves controlled by K48/K11 ubiquitination through the E3 ligase MARCH7, linking its abundance to autophagy and fatty acid oxidation (PMID:40691175).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2012 High

    Established that IPMK acts directly on a protein-bound phosphoinositide to control transcription, defining a substrate-specific lipid kinase mode distinct from canonical PI3Ks.

    Evidence In vitro lipid kinase assay on SF-1-PIP2 complex with PIP2 displacement, PTEN dephosphorylation, and siRNA + reporter readout

    PMID:22715467

    Open questions at the time
    • Whether SF-1-PIP3 generation occurs at endogenous IPMK levels in vivo not established
    • Generality to other nuclear-receptor substrates unaddressed
  2. 2012 Medium

    Showed IPMK function in Wnt signaling depends on regulated membrane translocation, linking its subcellular targeting to pathway output.

    Evidence Live-cell imaging, Dvl3 Co-IP, deletion mutants, and CAAX-box rescue of canonical Wnt reporter

    PMID:22940627

    Open questions at the time
    • Catalytic vs scaffold requirement at the membrane not separated
    • Direct Dvl3-IPMK binding interface mapped only by deletion
  3. 2014 Medium

    Placed IPMK upstream of LKB1-AMPK activation through a direct protein-protein interaction, broadening its role into energy-sensing signaling.

    Evidence IPMK-/- MEF complementation, dominant-negative peptide disrupting IPMK-LKB1, AMPK phospho-western

    PMID:24877601

    Open questions at the time
    • Catalytic contribution unresolved
    • Direct vs indirect LKB1 binding not structurally defined
  4. 2016 Medium

    Connected IPMK to myogenic differentiation through a PLC-β1/β-catenin/MyoD axis, suggesting integration of inositol/phosphoinositide signaling with myogenic transcription.

    Evidence Overexpression in myoblasts, promoter reporters, β-catenin immunofluorescence, co-overexpression epistasis

    PMID:27563828

    Open questions at the time
    • Relies on overexpression, no loss-of-function
    • Molecular basis of β-catenin regulation unknown
  5. 2018 High

    Provided the structural and kinetic framework for IPMK, showing the disordered domains autoregulate catalysis and ATP binding.

    Evidence 2.5 Å crystal structure of ΔIPMK plus enzyme kinetics of WT vs truncation constructs

    PMID:30420721

    Open questions at the time
    • No structure with inositol/lipid substrate bound
    • Cellular relevance of disordered-domain autoinhibition untested
  6. 2019 High

    Defined a catalysis-independent scaffolding role for IPMK in autophagy via an AMPK-ULK1 ternary complex, separating its enzymatic and structural functions.

    Evidence Genetic deletion in cells/mice, reciprocal Co-IP of ternary complex, kinase-dead rescue, H4K16ac and lipophagy readouts

    PMID:30840891

    Open questions at the time
    • Structural basis of ternary complex assembly unknown
    • How IPMK selects between catalytic and scaffold roles unresolved
  7. 2020 Medium

    Demonstrated using a metazoan ortholog that IPMK IP3-kinase activity is required for IP3/Ca2+-dependent physiology.

    Evidence C. elegans ipmk-1 deletion, kinase-dead mutant, epistasis with ipp-5 loss and Ca2+ supplementation

    PMID:33316585

    Open questions at the time
    • Mammalian IP3/Ca2+ relevance not directly tested here
    • Tissue-specific contributions partly inferred
  8. 2021 Medium

    Identified IPMK as a stabilizer of TRAF6 against K48 ubiquitination, linking it to bone homeostasis and degradation control of an inflammatory adaptor.

    Evidence IPMK-TRAF6 Co-IP, linkage-specific ubiquitination assays, siRNA, RANKL osteoclast and OVX mouse models

    PMID:33956362

    Open questions at the time
    • Whether IPMK directly shields TRAF6 or recruits a DUB unknown
    • Catalytic requirement not tested
  9. 2023 Medium

    Showed IPMK is a positive regulator of TLR4/NF-κB signaling via TRAF6 K63-ubiquitination and is suppressed by LPS-induced miR-181c, revealing a feedback control of its abundance.

    Evidence miR-181c mimic, 3'UTR luciferase, CRISPR deletion of binding site in RAW 264.7, TRAF6 K63-ubiquitination, cytokine ELISA

    PMID:36830701

    Open questions at the time
    • Direct enzymatic mechanism linking IPMK to TRAF6 K63 chains unclear
    • In vivo relevance of miR-181c axis untested
  10. 2024 High

    Established a non-catalytic mechanism by which IPMK stabilizes the PLCγ1-Sam68 complex to drive T-cell receptor-proximal signaling.

    Evidence Yeast two-hybrid, Co-IP, CD4 T-cell-specific IPMK KO mice, dominant-negative peptide, PLCγ1 Y783 phospho, Ca2+/IL-2 readouts

    PMID:39478550

    Open questions at the time
    • Structural basis of IPMK-Sam68 binding unknown
    • Whether this generalizes beyond T cells untested
  11. 2024 High

    Mechanistically linked IPMK-generated inositol phosphates to chromatin regulation by showing IP4/InsP6 are required to activate HDAC3, with direct metabolite rescue.

    Evidence IPMK KO in U251 cells (and mice/intestine), HDAC3 enzyme assays on immunoprecipitates, kinase-dead rescue, exogenous IP4/InsP6 rescue, H4 acetylation MS, ChIP-seq

    PMID:38746349 PMID:bio_10.1101_2024.09.15.613154

    Open questions at the time
    • In vivo physiological selectivity of IP4 vs InsP6 partly from preprints
    • Genome-wide direct vs indirect transcriptional targets not fully resolved
  12. 2025 High

    Revealed a chaperone-like activity in which IPMK binds the SRF intrinsically disordered region to enhance DNA binding and extend chromatin residence.

    Evidence PIFE and single-molecule FRET, live-cell SRF locus tracking, biochemical binding, IPMK depletion/overexpression

    PMID:39777465

    Open questions at the time
    • Whether catalysis contributes to the chaperone effect untested
    • Set of transcription factors subject to this activity unknown
  13. 2025 Medium

    Defined the cellular product spectrum of IPMK kinase activity, showing InsP5 as a direct inhibitor-sensitive product distinct from InsP6.

    Evidence Kinase inhibitors UNC7437/UNC9750 in metabolically labeled cells, tritiated inositol phosphate measurement

    PMID:40709844

    Open questions at the time
    • Downstream effectors of the InsP5 pool not all defined
    • Selectivity of inhibitors over related kinases requires controls
  14. 2025 High

    Provided high-resolution structural and chemical-probe characterization of the IPMK ATP pocket, enabling selective pharmacological targeting.

    Evidence 14 co-crystal structures at 1.7-2.0 Å with ATP-competitive inhibitors, IC50 and ITC

    PMID:41237254

    Open questions at the time
    • No co-structures with physiological inositol substrate
    • Cellular selectivity of probes characterized separately
  15. 2025 Medium

    Showed IPMK protein stability is set by K48/K11 ubiquitination and MARCH7, linking its turnover to autophagy and fatty acid oxidation.

    Evidence Linkage-specific ubiquitination assays, MARCH7 identification by Co-IP, stability assays, UFD1s-deficient mice

    PMID:40691175

    Open questions at the time
    • Signals triggering MARCH7-mediated turnover incompletely defined
    • Direct MARCH7-IPMK interaction interface not mapped
  16. 2026 Medium

    Connected IPMK lipid kinase output to tissue architecture by showing PIP3 generation governs integrin adhesion complex organization in muscle, distinct from its IP3/Ca2+ role.

    Evidence C. elegans ipmk-1 mutants, multiple double mutants, PIP3 immunofluorescence, GCaMP Ca2+, locomotion assays

    PMID:41697956

    Open questions at the time
    • Mammalian relevance to integrin adhesion untested
    • Effectors reading the PIP3/PIP2 ratio at boundaries unidentified
  17. 2026 Medium

    Implicated IPMK-dependent InsP5 in stabilizing active mTORC1 signaling in β-cells by slowing signal termination rather than initiation.

    Evidence IPMK inhibitor and ITPK1 knockdown, InsP5/InsP6/InsP7 metabolite measurement, mTORC1 substrate phospho, PI3K/Akt controls (preprint)

    PMID:41867875

    Open questions at the time
    • Preprint, single lab
    • Molecular target of InsP5 in the mTORC1 module not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IPMK partitions between its catalytic (inositol phosphate/lipid kinase) and non-catalytic scaffold/chaperone functions in a given context, and the structural rules governing partner selection, remain unresolved.
  • No unified model linking substrate/partner choice to cellular state
  • Structures of IPMK-partner complexes (AMPK-ULK1, Sam68, SRF, HDAC3) lacking
  • In vivo product-versus-scaffold contributions rarely separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 2 GO:0044183 protein folding chaperone 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 4 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2 R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 2
Partners
AMPKHDAC3LKB1NR5A1SAM68SRFTRAF6ULK1
Complex memberships
AMPK-ULK1 ternary complexPLCγ1-Sam68 complexStar-PAP complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 IPMK physically interacts with nuclear receptor SF-1 and phosphorylates SF-1-bound PIP₂ to generate SF-1-PIP₃; this phosphorylation requires PIP₂ to be bound in the hydrophobic pocket of SF-1 and is specific to IPMK (not type 1 p110 PI3Ks). The resulting SF-1-PIP₃ is dephosphorylated by PTEN, and silencing IPMK reduces SF-1 transcriptional activity. In vitro lipid kinase assay with SF-1-PIP₂ complex, competitive displacement of PIP₂ from SF-1, comparison with p110 PI3Ks, PTEN dephosphorylation assay, IPMK siRNA knockdown + transcriptional reporter Science signaling High 22715467
2012 In response to Wnt3a stimulation, Dvl3 translocates IPMK to the cell membrane within 5 minutes; this translocation requires the PDZ domain and COOH-terminal proline-rich tail of Dvl3, and the NH2-terminal variable region of IPMK. IPMK membrane translocation is obligate for its function in canonical Wnt signaling. Re-targeting of IPMKΔN to the membrane with a CAAX box rescues Wnt3a downstream signaling. Live-cell imaging of IPMK translocation, co-immunoprecipitation, deletion mutants, CAAX-box rescue experiment, canonical Wnt reporter assay Cellular signalling Medium 22940627
2014 IPMK physically interacts with LKB1 and is required for metformin- and AICAR-induced LKB1-AMPK activation. A dominant-negative peptide that disrupts the IPMK-LKB1 protein-protein interaction attenuates metformin-mediated AMPK activation, establishing IPMK as an upstream regulator of LKB1-AMPK signaling. IPMK−/− MEF complementation, dominant-negative peptide disruption of IPMK-LKB1 interaction, AMPK phosphorylation western blot, overexpression rescue Molecular endocrinology Medium 24877601
2016 IPMK overexpression promotes myogenic differentiation, activates the cyclin D3 promoter via c-jun binding (same pathway as PLC-β1), and increases nuclear translocation/accumulation of β-catenin in differentiating myoblasts, leading to higher MyoD activation. PLC-β1, IPMK, and β-catenin act in the same signaling pathway. Overexpression in myoblasts, promoter-reporter assays, western blot for myogenic markers, immunofluorescence for β-catenin nuclear translocation, epistasis by co-overexpression Oncotarget Medium 27563828
2018 Crystal structure of human IPMK lacking disordered domains (ΔIPMK) at 2.5 Å confirms the conserved ATP-grasp fold. Kinetic analyses show that (i) the disordered domains suppress IPMK catalytic activity (1.8-fold increase in kcat for PIP₂ upon removal), and (ii) a putative 'ATP-clamp' sequence in the N-terminal disordered domain stabilizes ATP binding: its removal increases KM for ATP 4.9-fold. X-ray crystallography at 2.5 Å, enzyme kinetics (KM, kcat) for PIP₂ and ATP, comparison of wild-type vs. truncation constructs Scientific reports High 30420721
2019 IPMK is required for autophagy in cell lines and mouse liver; this regulation does not require IPMK catalytic activity. IPMK directly binds both AMPK and ULK1, forming a ternary complex that facilitates AMPK-dependent ULK1 phosphorylation. A second axis, IPMK-AMPK-Sirt1, mediates deacetylation of histone H4K16 to promote autophagy-related transcription. IPMK deletion virtually abolishes lipophagy and promotes liver damage. IPMK genetic deletion in cell lines and mice, co-immunoprecipitation of IPMK-AMPK-ULK1 ternary complex, kinase-dead IPMK rescue, ULK1 phosphorylation assay, H4K16ac measurement, lipophagy and liver pathology readouts Cell reports High 30840891
2020 C. elegans IPMK-1 (ortholog of mammalian IPMK) requires its IP3-kinase activity for proper defecation rhythms and postembryonic development. These defects are rescued by loss of the IP3-phosphatase IPP-5 or supplemental Ca²⁺, placing IPMK-1 upstream of IP3/Ca²⁺ signaling. C. elegans deletion mutant (ipmk-1(tm2687)), tissue-specific rescue with GFP::IPMK-1, kinase-dead mutant, epistasis with ipp-5 loss-of-function, Ca²⁺ supplementation rescue Cell calcium Medium 33316585
2021 IPMK binds TRAF6 and reduces its K48-linked polyubiquitination (i.e., protects TRAF6 from proteasomal degradation) under RANKL stimulation. The antioxidant curcumenol (CUL) blocks the IPMK-TRAF6 interaction, promoting K48-linked ubiquitination and degradation of TRAF6, thereby suppressing osteoclastogenesis. Co-immunoprecipitation of IPMK-TRAF6, ubiquitination assays (K48- and K63-linkage), IPMK siRNA knockdown, RANKL-induced osteoclast differentiation assay, in vivo OVX mouse model Journal of bone and mineral research Medium 33956362
2022 IPMK-deficient hepatocytes exhibit decreased insulin-induced Akt-FoxO1 signaling and increased mRNA of gluconeogenic enzymes Pck1 and G6pc. Hepatocyte-specific IPMK deletion in mice exacerbates high-fat diet-induced hyperglycemia and reduces Akt phosphorylation in liver, establishing IPMK as a positive regulator of hepatic insulin signaling. Hepatocyte-specific IPMK knockout mice (high-fat diet), in vitro IPMK-KO hepatocytes, IPMK re-expression rescue, Akt phosphorylation western blot, pyruvate tolerance test Journal of cellular physiology Medium 35822903
2023 In macrophages, LPS stimulation triggers miR-181c-mediated downregulation of IPMK (via a conserved binding site in the IPMK 3'UTR). Preventing this downregulation (by genomic deletion of the miR-181c binding site) reduces TLR4-induced NF-κB signaling and proinflammatory cytokine production, and impairs K63-linked ubiquitination of TRAF6, establishing IPMK as a positive regulator of TRAF6-dependent TLR4 signaling. miR-181c mimic transfection, 3'UTR luciferase reporter, CRISPR deletion of miR-181c binding site in RAW 264.7 cells, TRAF6 K63-ubiquitination assay, cytokine ELISA, NF-κB signaling western blot Biomolecules Medium 36830701
2024 IPMK non-catalytically promotes PLCγ1 Y783 phosphorylation in T cells by stabilizing the PLCγ1-Sam68 complex. IPMK binds Sam68 (identified by yeast two-hybrid screening), and this interaction facilitates Sam68-PLCγ1 association and subsequent PLCγ1 phosphorylation. Disrupting IPMK-Sam68 binding with dominant-negative peptides impairs PLCγ1 phosphorylation, dampens Ca²⁺ signaling and IL-2 production. Yeast two-hybrid screening, co-immunoprecipitation, CD4-T cell-specific IPMK knockout mice (ConA hepatitis model), dominant-negative peptide, PLCγ1 Y783 phospho-western, Ca²⁺ measurement, IL-2 assay Cell communication and signaling High 39478550
2024 IPMK is required for full HDAC3 enzyme activity in human cells: IPMK knockout decreases cellular inositol phosphate levels (IP4/IP5/IP6), reduces HDAC3 deacetylase activity, and increases histone H4 acetylation. Wild-type but not kinase-dead IPMK rescues HDAC3 activity in knockout cells; exogenous Ins(1,4,5,6)P4 addition to immunoprecipitated HDAC3 from IKO cells fully rescues activity, while control inositol does not. IPMK knockout in U251 glioblastoma cells, HDAC deacetylase enzyme assay on immunoprecipitated complexes, mass spectrometry of histone H4 acetylation, ChIP-seq, kinase-dead IPMK rescue, exogenous IP4 rescue assay bioRxivpreprint High 38746349
2025 IPMK enhances the DNA-binding activity of transcription factor SRF by binding to SRF's intrinsically disordered region and inducing conformational changes detected by single-molecule FRET. In live cell nuclei, IPMK depletion reduces chromatin residence time of SRF, while elevated IPMK levels extend it. This IPMK-mediated chaperone-like activity promotes stable SRF-chromatin association. Protein-induced fluorescence enhancement (PIFE) single-molecule assay, single-molecule FRET, real-time tracking of SRF loci in live cells, biochemical binding assay, IPMK depletion/overexpression Nucleic acids research High 39777465
2025 IPMK is ubiquitinated at K48 and K11 linkages (targeting it for proteasomal degradation) and this ubiquitination is regulated by UFD1s-dependent competition for the E3 ligase MARCH7. Under stress, UFD1s reduces K48/K11 ubiquitination of IPMK, thereby modulating IPMK stability and its downstream effects on autophagy and fatty acid oxidation. Ubiquitination linkage assays (K48, K11, K63), E3 ligase identification (MARCH7), co-immunoprecipitation, IPMK protein stability assays, autophagy and fatty acid oxidation readouts in UFD1s-deficient mice Nature communications Medium 40691175
2025 14 co-crystal structures (1.7–2.0 Å resolution) of human IPMK kinase domain with ATP-competitive inhibitors reveal an unoccupied pocket in the ATP-binding site and two ordered water molecules in hydrogen-bonding networks; engagement of this pocket by inhibitors is associated with highest potency. X-ray crystallography (14 co-crystal structures), radiolabeled kinase assay (IC50), isothermal titration calorimetry (KD) Journal of medicinal chemistry High 41237254
2025 IPMK kinase activity is required for synthesis of higher-order inositol phosphates (InsP4, InsP5) in human cells; pharmacological IPMK inhibition selectively reduces cellular InsP5 without altering InsP6, revealing InsP5 as a direct cellular product whose accumulation depends on IPMK kinase activity. IPMK kinase inhibitors (UNC7437, UNC9750) in metabolically labeled U251-MG cells, tritiated inositol phosphate level measurement, transcriptome analysis Journal of medicinal chemistry Medium 40709844
2026 In C. elegans muscle, ipmk-1 loss causes abnormal clumping of integrin adhesion complex (IAC) proteins at muscle cell boundaries and decreased locomotion; ipmk-1; pix-1 doubles display large gaps between muscle cells. Genetic analysis with daf-18 (PTEN) partial suppression of the clumping phenotype, and PIP3 localization studies, indicate that the PIP3/PIP2 ratio at the muscle cell boundary is important for proper IAC organization, and that the MCB defect is due to decreased PIP3 rather than decreased IP3/Ca²⁺ signaling. C. elegans ipmk-1 loss-of-function mutants, double mutants (ipmk-1; pix-1; ipmk-1; pak-1; ipmk-1; rrc-1; ipmk-1; ipp-5; ipmk-1; daf-18), PIP3 localization (immunofluorescence), GCaMP Ca²⁺ measurements, locomotion assays Genetics Medium 41697956
2026 Suppression or acute pharmacological inhibition of IPMK in pancreatic β-cells selectively reduces cellular IP5 levels without altering IP6, and impairs basal and insulin-stimulated mTORC1 signaling (particularly under low growth factor conditions) by accelerating termination of the mTORC1 signal rather than preventing its initiation. IP5 depletion does not impair PI3K/Akt activation, implicating IP5 as a metabolite that stabilizes active mTORC1. IPMK inhibitor treatment, ITPK1 knockdown, combined inhibition, IP5/IP6/IP7 metabolite measurements, mTORC1 substrate phosphorylation western blots, PI3K/Akt activation assay in pancreatic β-cells bioRxivpreprint Medium 41867875
2024 IPMK binds to HDAC3 and drives InsP6 synthesis; InsP6 selectively activates HDAC3 at 10 nM by recruiting the DAD domain of its corepressor. IPMK deletion diminishes HDAC3 activation, causes histone hyperacetylation and MMP gene transcription, and compromises intestinal barrier integrity; InsP6 treatment rescues these effects. Co-immunoprecipitation (IPMK-HDAC3), HDAC3 enzyme activity assay, IPMK knockout cells/mice, InsP6 rescue, intestinal permeability assays, inflammatory bowel disease model bioRxivpreprint Medium bio_10.1101_2024.09.15.613154
2024 IPMK is recruited to the Star-PAP nuclear RNA polymerase complex, where it modifies Star-PAP-linked phosphoinositides (converting PIP2 to PIP3). Knockdown of IPMK reduces expression of Star-PAP target genes, placing IPMK in a nuclear phosphoinositide signalosome that regulates poly(A) polymerase activity in response to stress. Co-immunoprecipitation of IPMK with Star-PAP complex, phosphoinositide coupling assays, IPMK knockdown + Star-PAP target gene expression bioRxivpreprint Low bio_10.1101_2024.07.01.601467

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Direct modification and activation of a nuclear receptor-PIP₂ complex by the inositol lipid kinase IPMK. Science signaling 106 22715467
2019 IPMK Mediates Activation of ULK Signaling and Transcriptional Regulation of Autophagy Linked to Liver Inflammation and Regeneration. Cell reports 42 30840891
2014 Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action. Molecular endocrinology (Baltimore, Md.) 40 24877601
2017 MicroRNA-18a inhibits ovarian cancer growth via directly targeting TRIAP1 and IPMK. Oncology letters 34 28588697
2021 An Antioxidant Sesquiterpene Inhibits Osteoclastogenesis Via Blocking IPMK/TRAF6 and Counteracts OVX-Induced Osteoporosis in Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 28 33956362
2016 Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism. Biochemical Society transactions 25 26862216
2023 Ebastine exerts antitumor activity and induces autophagy by activating AMPK/ULK1 signaling in an IPMK-dependent manner in osteosarcoma. International journal of biological sciences 20 36632464
2022 IPMK modulates hepatic glucose production and insulin signaling. Journal of cellular physiology 19 35822903
2018 Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity. Scientific reports 19 30420721
2020 Inositol polyphosphate multikinase IPMK-1 regulates development through IP3/calcium signaling in Caenorhabditis elegans. Cell calcium 15 33316585
2021 IP6K3 and IPMK variations in LOAD and longevity: Evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival. Mechanisms of ageing and development 13 33497757
2022 The novel biomarker circ_0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis. International urology and nephrology 11 35986866
2021 Myeloid IPMK promotes the resolution of serum transfer-induced arthritis in mice. Animal cells and systems 10 34408810
2016 IPMK and β-catenin mediate PLC-β1-dependent signaling in myogenic differentiation. Oncotarget 10 27563828
2012 Dvl3 translocates IPMK to the cell membrane in response to Wnt. Cellular signalling 10 22940627
2024 A non-catalytic role of IPMK is required for PLCγ1 activation in T cell receptor signaling by stabilizing the PLCγ1-Sam68 complex. Cell communication and signaling : CCS 8 39478550
2023 miRNA-Induced Downregulation of IPMK in Macrophages Mediates Lipopolysaccharide-Triggered TLR4 Signaling. Biomolecules 8 36830701
2024 IPMK regulates HDAC3 activity and histone H4 acetylation in human cells. bioRxiv : the preprint server for biology 7 38746349
2025 Design, Synthesis, and Cellular Characterization of a New Class of IPMK Kinase Inhibitors. Journal of medicinal chemistry 6 40709844
2019 Inositol Polyphosphate Multikinase (IPMK), a Gene Coding for a Potential Moonlighting Protein, Contributes to Human Female Longevity. Genes 6 30744060
2025 A UFD1 variant encoding a microprotein modulates UFD1f and IPMK ubiquitination to play pivotal roles in anti-stress responses. Nature communications 5 40691175
2025 Single-molecule analysis reveals that IPMK enhances the DNA-binding activity of the transcription factor SRF. Nucleic acids research 4 39777465
2025 IPMK depletion influences genome-wide DNA methylation. Biochemical and biophysical research communications 2 40300331
2023 IPMK modulates FFA-induced insulin resistance in primary mouse hepatocytes. bioRxiv : the preprint server for biology 2 37162825
2020 Out of Phase: How IPMK Inhibits TFEB. Developmental cell 2 33290690
2025 Structural Rationalization of IPMK Inhibitor Potency. Journal of medicinal chemistry 1 41237254
2024 X-ray crystallographic analyses of 14 IPMK inhibitor complexes. bioRxiv : the preprint server for biology 1 38766172
2024 Design, synthesis and cellular characterization of a new class of IPMK kinase inhibitors. bioRxiv : the preprint server for biology 1 38798512
2026 IPMK at the crossroads of cellular signaling in health and disease. FEBS letters 0 41495964
2026 IPMK-1 (inositol phosphate multikinase) is required for integrin adhesion complex organization and muscle cell adhesion in Caenorhabditis elegans. Genetics 0 41697956
2026 IPMK-1 governs C. elegans physiology through ceTOR but lifespan via a distinct IP3-dependent pathway. Mechanisms of ageing and development 0 41865774
2026 Suppression of ITPK1 and IPMK activities impairs mTORC1 signaling in pancreatic β-cells and implicates IP5 in stabilizing activated mTORC1. bioRxiv : the preprint server for biology 0 41867875
2025 From Obscurity to Prominence: IPMK's Expanding Role in Cellular Signaling, Physiology, and Disease. Biomolecules 0 41008573
2025 Structural rationalization of IPMK inhibitor potency. bioRxiv : the preprint server for biology 0 41279675

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