Affinage

IMPDH2

Inosine-5'-monophosphate dehydrogenase 2 · UniProt P12268

Length
514 aa
Mass
55.8 kDa
Annotated
2026-04-28
71 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IMPDH2 is the rate-limiting enzyme of de novo guanine nucleotide biosynthesis, catalyzing the NAD+-dependent oxidation of IMP to XMP, and its activity is tuned by reversible polymerization into cytoophidium filaments that reduce sensitivity to allosteric GTP feedback inhibition (PMID:31999252, PMID:25601894). Post-translational regulation is multilayered: CDK1-mediated phosphorylation at Ser122 inhibits catalytic activity (reversed by FGFR-activated PP2A) (PMID:39739531), USP5 removes K48-linked ubiquitin chains to stabilize the protein (PMID:40164869), JOSD2 cleaves K63-linked ubiquitin at K134 to suppress activity and NF-κB signaling (PMID:40177575), and ANKRD9 directs ubiquitin-dependent degradation under basal conditions while co-assembling into stabilizing filaments during nutrient limitation (PMID:31337707). In the nucleus, IMPDH2 localizes to chromatin in a DNA-damage-dependent manner and modulates PARP1 activity through control of local NAD+ availability, linking guanine nucleotide metabolism to the DNA damage response (PMID:39532854). Gain-of-function mutations in IMPDH2 cause dystonia and neurodevelopmental disorders by disrupting GTP-mediated allosteric inhibition and destabilizing Bateman domain dimerization required for filament assembly (PMID:37414152, PMID:41343675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2009 Medium

    Establishing that IMPDH2 transcription is regulated by a cAMP response element answered how signaling pathways control enzyme abundance at the promoter level.

    Evidence Luciferase reporter assays with a promoter SNP (c.−95T>G) disrupting a CRE site in HEK293 and Jurkat cells

    PMID:19810816

    Open questions at the time
    • Endogenous transcription factor binding not confirmed by ChIP
    • In vivo relevance of this SNP not tested
  2. 2010 Medium

    Demonstrating that a naturally occurring IMPDH2 allozyme (Phe263) loses activity primarily through accelerated degradation revealed that protein stability, not just catalytic efficiency, governs IMPDH2 function.

    Evidence Enzymatic activity and protein stability assays on variant allozyme, interpreted against X-ray crystal structure

    PMID:20718729

    Open questions at the time
    • Degradation pathway (ubiquitin vs. autophagy) not identified
    • Clinical pharmacogenomic impact not quantified in vivo
  3. 2015 High

    Establishing IMPDH2 as the essential structural building block of cytoplasmic rod/ring (cytoophidium) structures, and showing that these filaments form in response to GTP biosynthesis inhibition, defined a novel metabolic ultrastructure and its assembly triggers.

    Evidence Microinjection of anti-IMPDH2 antibodies causing rapid RR disassembly; pharmacological induction by ribavirin/MPA with immunofluorescence in multiple cell types

    PMID:25601894 PMID:26165495

    Open questions at the time
    • Atomic-resolution filament architecture not yet determined at this time
    • Functional consequence of filament assembly on enzyme kinetics not resolved
  4. 2015 High

    Conditional deletion of Impdh2 in neural crest cells demonstrated that IMPDH2-dependent guanine nucleotide synthesis is essential for neural crest proliferation and organogenesis, establishing a non-redundant developmental role.

    Evidence Wnt1-Cre conditional knockout mouse with Rosa26 lineage tracing showing aganglionosis, craniofacial agenesis, and cardiac outflow tract defects

    PMID:26546974

    Open questions at the time
    • Whether IMPDH1 can partially compensate in other lineages not tested
    • Mechanism downstream of GTP depletion (proliferation vs. differentiation defect) not dissected
  5. 2017 High

    Identification of IMPDH2 as the isoform-selective target of the CyclophilinA–Sanglifehrin A complex revealed a non-catalytic regulatory interface on the CBS/Bateman domain that modulates cell growth.

    Evidence Affinity pulldown and Co-IP with enzymatic activity assays showing no catalytic inhibition; isoform selectivity over IMPDH1

    PMID:28076787

    Open questions at the time
    • Structural basis of PPIA–SFA–IMPDH2 ternary complex not resolved
    • Growth-modulating mechanism downstream of CBS domain engagement unknown
  6. 2019 High

    Discovery that ANKRD9 acts as a metabolic switch — promoting IMPDH2 ubiquitin-dependent degradation basally but co-assembling into stabilizing filaments under nutrient limitation — revealed how IMPDH2 protein levels are coupled to metabolic state.

    Evidence Co-IP, mutagenesis of ANKRD9 Cys109–Cys110, fluorescence microscopy of rod assembly, guanosine rescue experiments

    PMID:31337707

    Open questions at the time
    • E3 ligase that ubiquitinates IMPDH2 via ANKRD9 not identified
    • Stoichiometry of ANKRD9 within filaments unknown
  7. 2020 High

    Cryo-EM structures of IMPDH2 filaments in active and inactive conformations answered the long-standing question of how polymerization is functionally meaningful: filament assembly desensitizes the enzyme to GTP feedback inhibition, explaining filament formation under high guanine nucleotide demand.

    Evidence Cryo-EM of multiple conformational states with allosteric regulation functional assays

    PMID:31999252

    Open questions at the time
    • In vivo validation that filament-mediated desensitization drives proliferative advantage not yet shown
    • Dynamics of filament assembly/disassembly in real time not captured
  8. 2021 Medium

    Observation of IMPDH2 cytoophidium formation in mouse oocytes and granulosa cells in vivo, with pharmacological evidence linking filaments to mTOR-dependent meiosis resumption, extended the physiological relevance of IMPDH2 polymerization to reproductive biology.

    Evidence In vivo immunofluorescence in mouse ovary, MPA-induced filament formation with mTOR inhibitor and guanosine rescue

    PMID:34124077

    Open questions at the time
    • Direct genetic test (IMPDH2 polymerization-deficient mutant) in oocytes not performed
    • Whether filaments alter local GTP pools in granulosa cells not measured
  9. 2022 Medium

    Demonstrating that SARS-CoV-2 Nsp14 physically engages IMPDH2 to activate NF-κB signaling uncovered a viral hijacking mechanism that links purine metabolism to innate immune activation.

    Evidence Co-IP of Nsp14–IMPDH2, siRNA knockdown and pharmacological inhibition abolishing NF-κB reporter activation

    PMID:36177032

    Open questions at the time
    • Whether IMPDH2 enzymatic activity or a scaffolding role is required for Nsp14-mediated NF-κB not distinguished
    • Interaction validated in single lab only
  10. 2023 High

    Cryo-EM structures of disease-linked IMPDH2 mutants established the molecular basis of dystonia and neurodevelopmental disorders: mutations shift the conformational equilibrium toward an active, GTP-inhibition-resistant state.

    Evidence Cryo-EM of mutant IMPDH2, enzymatic assays measuring reduced GTP inhibition

    PMID:37414152

    Open questions at the time
    • Neuronal cell-type-specific consequences of gain-of-function not modeled
    • Whether pharmacological IMPDH2 inhibition can rescue disease phenotype untested
  11. 2024 High

    Discovery that CDK1 phosphorylates IMPDH2 at Ser122 to inhibit activity, and that FGFR signaling reverses this through PP2A-mediated dephosphorylation, established a cell-cycle-coupled regulatory circuit linking mitogenic signaling to guanine nucleotide supply during S-phase.

    Evidence In vitro CDK1 kinase assay, phosphosite mutagenesis, Co-IP of PP2A complex, cell cycle analysis

    PMID:39739531

    Open questions at the time
    • Whether Ser122 phosphorylation affects filament assembly not tested
    • In vivo validation in animal models lacking
  12. 2024 High

    Showing that nuclear IMPDH2 interacts with PARP1 on chromatin and controls local NAD+ availability revealed an unexpected non-canonical role: IMPDH2 couples purine metabolism to the DNA damage response by modulating PARP1 activity.

    Evidence Chromatin fractionation, Co-IP on chromatin, NAD+ measurements, nuclear-restricted IMPDH2 overexpression causing PARP1 cleavage and cell death

    PMID:39532854

    Open questions at the time
    • Mechanism of IMPDH2 nuclear import not identified
    • Whether IMPDH2 catalytic activity or scaffolding is required on chromatin not fully separated
  13. 2024 Medium

    Demonstrating that IMPDH2 filaments accumulate in neurodegeneration-resistant brain regions of AMPD2-deficient mice, and that blocking polymerization impairs neural progenitor GTP levels, established filament formation as a neuroprotective mechanism against purine imbalance.

    Evidence Mouse knockout model of AMPD2, immunofluorescence of IMPDH2 filaments, dominant-negative polymerization mutant in neural progenitors

    PMID:39075237

    Open questions at the time
    • Causal relationship between filament abundance and regional vulnerability not genetically proven
    • Whether therapeutic promotion of filament assembly is feasible not explored
  14. 2024 Medium

    Myeloid-specific Impdh2 deletion suppressed osteoclastogenesis and protected against ovariectomy-induced bone loss, revealing IMPDH2 as a metabolic gatekeeper of osteoclast differentiation through control of oxidative phosphorylation.

    Evidence LysM-Cre conditional knockout, histomorphometry, transcriptomics, MPA pharmacological inhibition in OVX mouse model

    PMID:38009733

    Open questions at the time
    • Whether GTP depletion or secondary metabolic effects drive osteoclast block not dissected
    • Contribution of IMPDH1 in myeloid cells not assessed
  15. 2025 High

    Identification of USP5 as a K48-linkage-specific deubiquitinase stabilizing IMPDH2, and JOSD2 as a K63-linkage-specific deubiquitinase suppressing IMPDH2 activity at K134, revealed that distinct ubiquitin chain types exert opposing regulatory outcomes — stability versus activity modulation.

    Evidence USP5: domain mapping, K48-specific DUB assay, xenograft rescue; JOSD2: K63-specific DUB assay at K134, JOSD2 KO mice with macrophage phenotypes

    PMID:40164869 PMID:40177575

    Open questions at the time
    • E3 ligases conjugating K48 and K63 chains on IMPDH2 not identified
    • Whether ubiquitin editing occurs on filament-assembled versus free IMPDH2 unknown
  16. 2025 High

    Cryo-EM of the S160del disease mutant demonstrated that filament assembly and allosteric GTP regulation are mechanistically separable: S160del destabilizes Bateman domain dimerization (disrupting filaments) while independently retaining GTP insensitivity, refining the structure-function model of IMPDH2 regulation.

    Evidence Cryo-EM of S160del, Xenopus in vivo expression with metabolomics and somite phenotyping

    PMID:41343675

    Open questions at the time
    • Whether filament disruption alone is sufficient for disease pathogenesis not tested
    • Neuronal-specific consequences of Bateman domain destabilization not modeled in mammalian systems

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of E3 ubiquitin ligases that modify IMPDH2, the mechanism of IMPDH2 nuclear import, whether catalytic versus scaffolding functions are separable in the nuclear/chromatin compartment, and whether therapeutic modulation of filament assembly can rescue neurodevelopmental disease phenotypes.
  • E3 ligases for IMPDH2 K48 and K63 ubiquitination unidentified
  • Nuclear import signal and translocation mechanism unknown
  • No pharmacological strategy to selectively modulate filament assembly in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0016491 oxidoreductase activity 4
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 3 GO:0005634 nucleus 1 GO:0005694 chromosome 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 2 R-HSA-1640170 Cell Cycle 1 R-HSA-73894 DNA Repair 1
Partners
ANKRD9FANCIJOSD2MYCPARP1PPIASRPK1USP5
Complex memberships
ANKRD9–IMPDH2 rod complexIMPDH2 cytoophidium filament

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 Cryo-EM structures of human IMPDH2 in active and inactive conformations revealed that filament assembly tunes allosteric regulation by making the enzyme less sensitive to GTP-mediated feedback inhibition, explaining why self-assembly occurs under conditions of high guanine nucleotide demand. Cryo-EM structural determination of multiple IMPDH2 conformations (active and inactive) with functional validation of allosteric regulation eLife High 31999252
2017 IMPDH2 was identified as an intracellular target of the CyclophilinA (PPIA)–Sanglifehrin A (SFA) binary complex; the resulting ternary complex does not inhibit IMPDH2 enzymatic activity but instead interacts with the CBS (cystathionine-β-synthase) domain of IMPDH2 to modulate cell growth, demonstrating isoform selectivity for IMPDH2 over IMPDH1. Affinity pulldown, Co-IP, enzymatic activity assays, isoform selectivity assays Cell reports High 28076787
2019 ANKRD9 facilitates ubiquitin-mediated degradation of IMPDH2 under basal conditions; upon nutrient limitation ANKRD9 co-assembles with IMPDH2 into rod-like filaments in which IMPDH2 is stable. The conserved Cys109–Cys110 motif in ANKRD9 is required for the vesicle-to-rod transition and for binding/regulation of IMPDH2. Guanosine acts as a metabolic switch reversing ANKRD9/IMPDH2 rod assembly. Co-immunoprecipitation, site-directed mutagenesis of ANKRD9, fluorescence microscopy, IMPDH2 knockdown/overexpression, guanosine rescue experiments The Journal of biological chemistry High 31337707
2023 Disease-associated point mutations in IMPDH2 linked to dystonia and neurodevelopmental disorders disrupt GTP-mediated allosteric regulation; cryo-EM structures of one mutant show a shift in conformational equilibrium toward a more active (GTP-inhibition-resistant) state. Cryo-EM structural analysis of IMPDH2 mutants, enzymatic activity assays measuring GTP inhibition The Journal of biological chemistry High 37414152
2024 IMPDH2 serine 122 is phosphorylated by CDK1, which attenuates IMPDH2 catalytic activity for IMP oxidation and represses allosteric modulation by purine nucleotides. FGFR signaling triggers dephosphorylation of Ser122 via PP2A (assembled through FGFR3-mediated phosphorylation of PPP2R1A-Tyr261, enabling PPP2CA–PPP2R1A–IMPDH2 interactions), thereby activating IMPDH2 to support guanine nucleotide synthesis, S-phase completion, and cell proliferation. In vitro kinase assay (CDK1), site-directed mutagenesis, phosphoproteomics, Co-IP, enzymatic activity assays, cell cycle analysis Cell reports High 39739531
2024 Nuclear IMPDH2 interacts with PARP1 on chromatin and modulates PARP1 activity by controlling local NAD+ availability; IMPDH2 chromatin localization is DNA damage-dependent, and IMPDH2 repression leads to DNA damage accumulation. Restricting IMPDH2 exclusively to the nucleus depletes nuclear NAD+, triggering PARP1 cleavage and cell death. Chromatin fractionation, Co-IP on chromatin, NAD+ measurements, IMPDH2 knockdown with DNA damage readouts, nuclear-restricted IMPDH2 overexpression Nature communications High 39532854
2025 USP5 deubiquitinase binds IMPDH2 via its N-terminal cryptic ZnF-UBP and ZnF-UBP domains (interacting with IMPDH2 residues 251–514), removes Lys48-linked ubiquitin chains from IMPDH2, and thereby prevents its proteasomal degradation and stabilizes IMPDH2 protein levels to promote hepatocellular carcinoma proliferation and EMT. Co-IP domain mapping, deubiquitination assay (Lys48-linkage-specific), shRNA knockdown, xenograft models Oncogene High 40164869
2024 JOSD2 deubiquitinase binds the C-terminus of IMPDH2 and cleaves K63-linked polyubiquitin chains at IMPDH2-K134, suppressing IMPDH2 enzymatic activity and preventing downstream NF-κB activation and inflammation in macrophages. Co-IP, site-specific deubiquitination assay (K63-linkage), JOSD2 knockout mice, myeloid-specific deletion with bone marrow transplantation Acta pharmaceutica Sinica. B High 40177575
2015 Conditional deletion of Impdh2 in early neural crest cells (using Wnt1-Cre) in mice produces defects in multiple neural crest derivatives, including intestinal aganglionosis, craniofacial skeletal agenesis, and cardiac outflow tract malformations, demonstrating that IMPDH2-mediated guanine nucleotide synthesis is essential for neural crest cell proliferation and development. Conditional knockout mouse (Wnt1-Cre × Impdh2flox), Rosa26 reporter lineage tracing, histological analysis of neural crest derivatives Developmental biology High 26546974
2015 IMPDH2 is a major structural component (building block) of cytoplasmic rod/ring (RR) structures; microinjection of affinity-purified anti-IMPDH2 antibodies into live cells caused disassembly of RR structures within 10 minutes, demonstrating that IMPDH2 is essential for RR integrity and that mature RR are primarily stationary structures. Microinjection of anti-IMPDH2 antibodies into live cells, GFP-tagged IMPDH2 live imaging, fluorescence microscopy Cell & bioscience High 25601894
2015 Assembly of IMPDH2-based rod/ring (RR) structures in cells is induced by inhibition of GTP biosynthesis (by ribavirin or mycophenolic acid) and is cell-type dependent; CTPS and IMPDH2 can form mixed or separate RR structures depending on cell type and the inhibitor used, indicating that IMPDH2 and CTPS independently organize into cytoophidia. Drug treatment (DON, ribavirin, MPA), immunofluorescence, transfection of NHA-tagged CTPS1 in HeLa and COS-7 cells Journal of genetics and genomics Medium 26165495
2022 SARS-CoV-2 Nsp14 protein physically interacts with IMPDH2, and this interaction is required for Nsp14-mediated NF-κB activation and pro-inflammatory cytokine (IL-6, IL-8) induction; IMPDH2 knockdown or pharmacological inhibition (ribavirin, mycophenolic acid) abolishes Nsp14-driven NF-κB activation and restricts SARS-CoV-2 replication. Co-IP confirmation of Nsp14–IMPDH2 interaction, siRNA knockdown, pharmacological inhibition, NF-κB reporter assays Frontiers in immunology Medium 36177032
2020 FANCI directly binds IMPDH2 (shown by Co-IP), decreases IMPDH2 degradation, and promotes MEK/ERK/MMP signaling activation; overexpression of IMPDH2 reverses the growth inhibitory effects of FANCI knockdown in lung adenocarcinoma cells. Co-immunoprecipitation, immunofluorescence microscopy, Western blotting, FANCI knockdown with IMPDH2 rescue OncoTargets and therapy Medium 32021289
2021 CircPFKP directly interacts with IMPDH2 and promotes guanine nucleotide biosynthesis; replenishment of the intracellular guanine nucleotide pool reverses the proliferation-inhibitory effects of circPFKP knockdown, placing IMPDH2 downstream of circPFKP in prostate cancer cell proliferation. RNA-protein interaction assays, circRNA knockdown, guanosine rescue experiments, cell cycle analysis Cancer letters Medium 34673127
2024 IMPDH2 cytoophidium (filament) formation in neurodegeneration-resistant brain regions protects against GTP deprivation in AMPD2-deficient mice; IMPDH2 filaments are abundant in resistant regions but sparse in the vulnerable hippocampal dentate gyrus, and blocking IMPDH2 polymerization impairs GTP levels and growth of AMPD2-deficient neural progenitor cells. Mouse knockout models, immunofluorescence of IMPDH2 filaments, dominant-negative IMPDH2 variant to block polymerization, neural progenitor cell growth assays EMBO reports Medium 39075237
2024 IMPDH2 filaments resist allosteric inhibition by GTP in regenerating Xenopus tropicalis tadpole tail tissue; IMPDH2 inhibition impairs tail regeneration and reduces cell proliferation, demonstrating that IMPDH2 filament assembly is a physiologically relevant regulatory mechanism in vertebrate tissue regeneration. Chemical inhibition of IMPDH2, IMPDH2-fluorescent fusion live imaging in regenerating tadpole tail, cell proliferation assays bioRxivpreprint Medium 39131357
2025 An IMPDH2 neurodevelopmental disorder mutant (S160del) disrupts filament assembly by destabilizing dimerization of regulatory Bateman domains (shown by cryo-EM), alters purine pools in vivo in Xenopus tropicalis, and disrupts somite organization; GTP inhibition insensitivity of S160del is separable from Bateman domain dimerization, indicating that filament assembly and allosteric GTP regulation are mechanistically distinct. Cryo-EM structural analysis of S160del mutant, Xenopus tropicalis in vivo expression, metabolomics of purine pools, developmental phenotyping Proceedings of the National Academy of Sciences of the United States of America High 41343675
2009 A promoter SNP in IMPDH2 (c.-95T>G) disrupts a cyclic AMP response element (CRE) binding site and significantly decreases IMPDH2 transcriptional activity (~55–65% reduction) as measured by luciferase reporter assays in transfected HEK293 and Jurkat cells. Luciferase reporter gene assay, transient transfection in two cell lines Genetic testing and molecular biomarkers Medium 19810816
2010 An IMPDH2 allozyme (Phe263) shows decreased enzymatic activity primarily due to accelerated protein degradation; these functional consequences are supported by the IMPDH2 X-ray crystal structure context. Enzyme activity assays, protein stability assays, resequencing of IMPDH2 in 288 individuals, X-ray crystal structure interpretation British journal of pharmacology Medium 20718729
2024 Impdh2 deletion in myeloid lineage cells (Impdh2LysM-/- mice) impairs osteoclastogenesis by suppressing osteoclast marker gene expression and mitochondrial oxidative phosphorylation, and alleviates ovariectomy-induced bone loss in vivo. IMPDH inhibitor (MPA) treatment induces IMPDH2 cytoophidium (filament) formation coincident with osteoclast differentiation block. Conditional myeloid-specific Impdh2 knockout mouse, histomorphometry, qPCR, genome-wide transcriptomics, MPA pharmacological inhibition, OVX mouse model Biochemical and biophysical research communications Medium 38959733
2023 EBV induces IMPDH2 expression through EBNA2-dependent and MYC-dependent mechanisms (established using EBNA2 and LMP1 knockout viruses), leading to nucleolar hypertrophy and efficient B-cell growth transformation; IMPDH2 inhibition with MPA blocks this transformation. EBV knockout virus infections (EBNA2 KO, LMP1 KO), RNA-seq, MPA pharmacological inhibition, xenograft mouse model Microbiology spectrum Medium 37409959
2024 IMPDH2 interacts with c-Myc to protect it from ubiquitination; the natural compound vitexicarpin binds IMPDH2, disrupts the IMPDH2–c-Myc interaction, and promotes c-Myc ubiquitination leading to EMT inhibition in colorectal cancer. Co-IP, ubiquitination assay, CETSA, label-free quantitative proteomics, Biacore binding assay, molecular docking, IMPDH2 overexpression/knockdown rescue Phytomedicine Medium 39008915
2025 IMPDH2 is directly phosphorylated at tyrosine 233 (Y233) within its Bateman domain by ALK and SRC oncogenic kinases; Y233 phosphorylation is essential for IMPDH2 enzymatic activity. Phosphoinositide-3-phosphate (PI3P) selectively binds and inhibits IMPDH2 but not IMPDH1, representing an isoform-specific lipid-mediated regulatory mechanism. Peptide-based mutagenesis, in vitro kinase assays (ALK, SRC), enzymatic assays, PI3P binding assays, isoform selectivity comparison bioRxivpreprint Medium bio_10.1101_2025.08.19.667179
2025 IMPDH2 interacts with SRPK1 in CD4+ T cells (confirmed by mass spectrometry, Co-IP, and confocal colocalization); IMPDH2 upregulates SRPK1 expression, which in turn activates the AKT/mTOR signaling pathway to promote CD4+ T cell proliferation and suppress apoptosis. Mass spectrometry interaction screen, Co-IP, confocal fluorescence colocalization, IMPDH2 knockdown/overexpression, Western blot of AKT/mTOR pathway Clinical immunology Medium 41213488
2026 tRF-1432 (a 5'-tRNA^Val-CAC-derived fragment generated by angiogenin cleavage) directly interacts with RNA-binding protein RBMS1, attenuating RBMS1-mediated destabilization of IMPDH2 mRNA and thereby increasing IMPDH2 protein levels and GTP-dependent chemoresistance in breast cancer. High-throughput sequencing, RNA-protein interaction assays, RBMS1 knockdown/rescue, IMPDH2 mRNA stability assays, syngeneic tumor models Cancer letters Medium 41791844
2023 IMPDH2 forms localized spots at branching sites and distal ends of astrocyte stem processes in adult mouse hippocampus, suggesting a role in site-specific GTP synthesis and local small GTPase regulation at specialized nodes in astrocyte branches. Immunofluorescence of endogenous IMPDH2 in adult mouse hippocampus and primary astrocyte cultures, quantitative distribution analysis Genes to cells Low 38009721
2021 IMPDH2 cytoophidium forms in vivo in growing mouse oocytes and in granulosa cells following LH surge; MPA-induced IMPDH2 cytoophidium formation in cumulus cells coincides with meiosis resumption in oocytes mediated through the mTOR pathway, and this effect is reversed by guanosine supplementation, linking IMPDH2 filament formation to oocyte meiotic competence. In vivo immunofluorescence in mouse ovary, MPA pharmacological inhibition, mTOR pathway inhibitor, guanosine rescue, confocal microscopy Frontiers in cell and developmental biology Medium 34124077

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 IMPDH2 promotes colorectal cancer progression through activation of the PI3K/AKT/mTOR and PI3K/AKT/FOXO1 signaling pathways. Journal of experimental & clinical cancer research : CR 173 30518405
2020 Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation. eLife 80 31999252
2017 IMPDH2 Is an Intracellular Target of the Cyclophilin A and Sanglifehrin A Complex. Cell reports 47 28076787
2015 Assembly of IMPDH2-based, CTPS-based, and mixed rod/ring structures is dependent on cell type and conditions of induction. Journal of genetics and genomics = Yi chuan xue bao 45 26165495
2020 GTP metabolic reprogramming by IMPDH2: unlocking cancer cells' fuelling mechanism. Journal of biochemistry 38 32702086
2009 Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis. International journal of colorectal disease 38 19597826
2020 Shikonin is a novel and selective IMPDH2 inhibitor that target triple-negative breast cancer. Phytotherapy research : PTR 36 32779300
2005 Modulation of IMPDH2, survivin, topoisomerase I and vimentin increases sensitivity to methotrexate in HT29 human colon cancer cells. The FEBS journal 35 15670151
2015 Microinjection of specific anti-IMPDH2 antibodies induces disassembly of cytoplasmic rods/rings that are primarily stationary and stable structures. Cell & bioscience 32 25601894
2014 Enhanced expression of IMPDH2 promotes metastasis and advanced tumor progression in patients with prostate cancer. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 31 24659377
2006 ZNRD1 mediates resistance of gastric cancer cells to methotrexate by regulation of IMPDH2 and Bcl-2. Biochemistry and cell biology = Biochimie et biologie cellulaire 31 16609701
2010 Pharmacogenetics of the mycophenolic acid targets inosine monophosphate dehydrogenases IMPDH1 and IMPDH2: gene sequence variation and functional genomics. British journal of pharmacology 30 20718729
2008 Expression of IMPDH1 and IMPDH2 after transplantation and initiation of immunosuppression. Transplantation 30 18192912
2021 Circular RNA circPFKP promotes cell proliferation by activating IMPDH2 in prostate cancer. Cancer letters 27 34673127
2014 Elevated expression of IMPDH2 is associated with progression of kidney and bladder cancer. Medical oncology (Northwood, London, England) 26 25465060
2021 IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder. European journal of human genetics : EJHG 25 34305140
2022 SARS-CoV-2 Nsp14 protein associates with IMPDH2 and activates NF-κB signaling. Frontiers in immunology 24 36177032
1993 Chromosomal localization and structure of the human type II IMP dehydrogenase gene (IMPDH2). Genomics 24 8098009
2019 ANKRD9 is a metabolically-controlled regulator of IMPDH2 abundance and macro-assembly. The Journal of biological chemistry 22 31337707
2009 Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals. Drug metabolism and pharmacokinetics 20 20045992
2020 FANCI Cooperates with IMPDH2 to Promote Lung Adenocarcinoma Tumor Growth via a MEK/ERK/MMPs Pathway. OncoTargets and therapy 19 32021289
2015 Neural crest requires Impdh2 for development of the enteric nervous system, great vessels, and craniofacial skeleton. Developmental biology 19 26546974
2014 IMPDH2 mediate radioresistance and chemoresistance in osteosarcoma cells. European review for medical and pharmacological sciences 19 25392102
2024 Wnt/β-catenin signalling activates IMPDH2-mediated purine metabolism to facilitate oxaliplatin resistance by inhibiting caspase-dependent apoptosis in colorectal cancer. Journal of translational medicine 18 38310229
2007 Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells. Clinical chemistry 16 17463174
2022 Genistein promotes apoptosis of lung cancer cells through the IMPDH2/AKT1 pathway. American journal of translational research 15 36398246
2020 IMPDH2 promotes cell proliferation and epithelial-mesenchymal transition of non-small cell lung cancer by activating the Wnt/β-catenin signaling pathway. Oncology letters 15 32963625
2023 Berberrubine is a novel and selective IMPDH2 inhibitor that impairs the growth of colorectal cancer. Biochemical pharmacology 14 37871880
2023 Neurodevelopmental disorder mutations in the purine biosynthetic enzyme IMPDH2 disrupt its allosteric regulation. The Journal of biological chemistry 13 37414152
2011 Lymphocyte counts in kidney allograft recipients are associated with IMPDH2 3757T>C gene polymorphism. Transplantation proceedings 12 21996196
2025 Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer. Scientific reports 11 39774345
2024 Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity. Nature communications 11 39532854
2022 A recombinant scFv antibody-based fusion protein that targets EGFR associated with IMPDH2 downregulation and its drug conjugate show therapeutic efficacy against esophageal cancer. Drug delivery 11 35416106
2018 Polymorphisms in IMPDH2, UGT2B7, and CES2 genes influence the risk of graft rejection in kidney transplant recipients taking mycophenolate mofetil. Mutation research. Genetic toxicology and environmental mutagenesis 11 30442353
2009 IMPDH2 genetic polymorphism: a promoter single-nucleotide polymorphism disrupts a cyclic adenosine monophosphate responsive element. Genetic testing and molecular biomarkers 11 19810816
2023 Growth Transformation of B Cells by Epstein-Barr Virus Requires IMPDH2 Induction and Nucleolar Hypertrophy. Microbiology spectrum 10 37409959
2021 Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells. Frontiers in cell and developmental biology 9 34124077
2023 Single-cell RNA sequencing in double-hit lymphoma: IMPDH2 induces the progression of lymphoma by activating the PI3K/AKT/mTOR signaling pathway. International immunopharmacology 8 37907047
2008 Interpopulation variation frequency of human inosine 5'-monophosphate dehydrogenase type II (IMPDH2) genetic polymorphisms. Genetic testing 7 18976158
2021 Actein antagonizes colorectal cancer through blocking PI3K/Akt pathways by downregulating IMPDH2. Anti-cancer drugs 6 33929996
2019 Design, synthesis and biological evaluation of Helicobacter pylori inosine 5'-monophosphate dehydrogenase (HpIMPDH) inhibitors. Further optimization of selectivity towards HpIMPDH over human IMPDH2. Bioorganic chemistry 6 30974298
2023 Rare variants in IMPDH2 cause autosomal dominant dystonia in Chinese population. Journal of neurology 5 36648520
2010 Inter-ethnic variability of three functional polymorphisms affecting the IMPDH2 gene. Molecular biology reports 5 21181270
2025 USP5 deubiquitinates and stabilizes IMPDH2, to promote hepatocellular carcinoma progression. Oncogene 4 40164869
2024 IMPDH2 dephosphorylation under FGFR signaling promotes S-phase progression and tumor growth. Cell reports 4 39739531
2024 Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages. Acta pharmaceutica Sinica. B 4 40177575
2024 IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway. Current molecular pharmacology 3 38676510
2024 Lower ratio of IMPDH1 to IMPDH2 sensitizes gliomas to chemotherapy. Cancer gene therapy 3 38871858
2024 Vitexicarpin suppresses malignant progression of colorectal cancer through affecting c-Myc ubiquitination by targeting IMPDH2. Phytomedicine : international journal of phytotherapy and phytopharmacology 3 39008915
2024 IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency. EMBO reports 3 39075237
2024 IMPDH2 suppression impedes cell proliferation by instigating cell cycle arrest and stimulates apoptosis in pediatric hepatoblastoma. Journal of cancer research and clinical oncology 3 39085725
2023 Point mutations in IMPDH2 which cause early-onset neurodevelopmental disorders disrupt enzyme regulation and filament structure. bioRxiv : the preprint server for biology 3 36993700
2023 B7-H3 Associates with IMPDH2 and Regulates Cancer Cell Survival. Cancers 3 37444640
2025 IMPDH2's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target. Cell proliferation 2 40251939
2024 Deletion of Impdh2 in adipocyte precursors limits the expansion of white adipose tissue and enhances metabolic health with overnutrition. Biochemical and biophysical research communications 2 38692012
2024 Impdh2 deficiency suppresses osteoclastogenesis through mitochondrial oxidative phosphorylation and alleviates ovariectomy-induced osteoporosis. Biochemical and biophysical research communications 2 38959733
2024 Appendage regeneration requires IMPDH2 and creates a sensitized environment for enzyme filament formation. bioRxiv : the preprint server for biology 2 39131357
2023 IMPDH2 forms spots at branching sites and distal ends of astrocyte stem processes. Genes to cells : devoted to molecular & cellular mechanisms 2 38009721
2026 Glucose Induces DNMT1/IMPDH2-Dependent Metabolic Memory in Endothelial Cells Upon Reprograming Nucleotide Metabolism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41445454
2026 Integrated screens reveal that guanine nucleotide depletion, which is irreversible via targeting IMPDH2, inhibits pancreatic cancer and potentiates KRAS inhibition. Gut 1 41494804
2024 Corrigendum to: IMPDH2 Positively Impacts the Proliferation Potential of Hepatoblastoma Cells by Activating JunB Signaling Pathway. Current molecular pharmacology 1 40492554
2023 Genetic analysis of IMPDH2 gene in Taiwanese patients with isolated or combined dystonia. Parkinsonism & related disorders 1 36657279
2026 ANKRD9 negatively regulates chicken myogenesis through ubiquitin-mediated regulation of IMPDH2. Poultry science 0 41691811
2026 tRF-1432 orchestrates RBMS1-IMPDH2 regulatory control to drive purine-dependent chemoresistance in breast cancer. Cancer letters 0 41791644
2025 Domain-specific AI segmentation of IMPDH2 rod/ring structures in mouse embryonic stem cells. BMC biology 0 40350411
2025 An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somitogenesis. bioRxiv : the preprint server for biology 0 40654686
2025 IMPDH2 facilitates CD4+ T cell activation through AKT/mTOR pathway by upregulating SRPK1 in myasthenia gravis. Clinical immunology (Orlando, Fla.) 0 41213488
2025 An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somite organization. Proceedings of the National Academy of Sciences of the United States of America 0 41343675
2025 DHL-11, a novel prieurianin-type limonoid isolated from Munronia henryi, targeting IMPDH2 to inhibit triple-negative breast cancer. Acta pharmaceutica Sinica. B 0 41584327
2024 IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency. bioRxiv : the preprint server for biology 0 38328116
2024 Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression. The pharmacogenomics journal 0 38769303