Affinage

OGA

Protein O-GlcNAcase · UniProt O60502

Length
916 aa
Mass
102.9 kDa
Annotated
2026-06-10
63 papers in source corpus 23 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/7 claims corpus-supported (71%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OGA (MGEA5/NCOAT) is a multi-domain glycoside hydrolase that removes O-GlcNAc from serine/threonine residues of nuclear and cytoplasmic proteins, opposing the glycosyltransferase OGT to set cellular O-GlcNAc homeostasis (PMID:20863279, PMID:16882729). Its N-terminal catalytic domain selects substrates not only through the GlcNAc moiety but through a conserved peptide-recognition groove that reads protein context beyond the sugar, as defined for substrates such as TAB1, FoxO1 and CREB (PMID:20863279, PMID:30693278). The C-terminal pseudo-HAT (pHAT) domain forms catalytically incompetent symmetric homodimers that allosterically tune the active-site environment and serve as a protein-interaction platform [PMID:bio_10.1101_2025.03.10.642372]; through this domain OGA is recruited to DNA-damage sites and deglycosylates the repair factors NONO and Ku70/80 to support non-homologous end joining (PMID:34135314). OGA and OGT engage in reciprocal inhibition: a flexible OGA segment occupies the OGT substrate groove and is itself O-GlcNAcylated, while OGT disrupts OGA dimerization and occludes its active site, coupling the two enzymes into a homeostatic unit (PMID:37907462, PMID:33333092). OGA abundance is further controlled post-translationally by ubiquitin-dependent proteasomal degradation through the E3 ligases UBR5 and the RBM14/TRIM33 axis, and transcriptionally via the RANBP2–CEBPα pathway, with loss of OGA elevating global O-GlcNAcylation in cancer contexts (PMID:38755129, PMID:38678556, PMID:34298689). Through site-specific deglycosylation of diverse substrates—including PDLIM7, ZEB1, KLF2 and NEK7—OGA influences p53 signaling, epithelial-mesenchymal transition, cellular senescence and NLRP3-dependent pyroptosis (PMID:38838015, PMID:40771411, PMID:40251583, PMID:41066511). Across organisms, OGA cycling links O-GlcNAc to nutrient and insulin-like signaling and is a principal driver of temperature-dependent changes in O-GlcNAc levels [PMID:16882729, PMID:bio_10.1101_2025.07.08.660373].

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 Medium

    Established that the MGEA5/OGA locus produces distinct protein isoforms with separate subcellular destinations, raising the question of compartment-specific function.

    Evidence Cell fractionation and genomic splice-variant mapping with antibody detection

    PMID:11341771

    Open questions at the time
    • Functional consequence of the 75 kDa nuclear isoform not defined
    • Catalytic activity of each isoform not directly compared
  2. 2005 High

    Characterized OGA as bifunctional, assigning a putative histone acetyltransferase activity to its C-terminal domain and a zinc-finger motif that binds the histone H4 tail.

    Evidence In vitro binding and acetyltransferase assays with zinc-finger mutagenesis

    PMID:16356930

    Open questions at the time
    • Physiological relevance of HAT activity in cells not established
    • Later structural work reclassifies this region as a catalytically incompetent pseudo-HAT
  3. 2006 High

    Placed O-GlcNAc cycling in the insulin-like signaling pathway by showing OGA loss reprograms nutrient storage and modifies dauer formation in C. elegans.

    Evidence oga-1 genetic knockout with daf-2 epistasis and metabolic biochemistry

    PMID:16882729

    Open questions at the time
    • Direct OGA substrates driving the metabolic phenotype not identified
    • Mammalian generality of the insulin-signaling link not addressed here
  4. 2010 High

    Resolved how OGA achieves substrate selectivity, identifying a peptide-recognition groove that reads protein context beyond the GlcNAc sugar.

    Evidence Bacterial OGA crystal structure with human OGA mutagenesis and in vitro deglycosylation of TAB1/FoxO1/CREB

    PMID:20863279

    Open questions at the time
    • Structure of the full human enzyme groove not solved here
    • Sequence determinants of preferred substrates not enumerated
  5. 2019 Low

    Probed the molecular requirements of OGA recognition at the sugar moiety and at adjacent phosphorylation sites, defining crosstalk constraints on de-O-GlcNAcylation.

    Evidence Chemoenzymatic glycopeptide synthesis and peptide-microarray OGA activity assays

    PMID:30693278 PMID:30725225

    Open questions at the time
    • Single in vitro assays without in-cell validation
    • Effect sizes of phospho-crosstalk modest and substrate-limited
  6. 2021 High

    Connected OGA to genome maintenance, showing pHAT-dependent recruitment to lesions and deglycosylation of repair factors required for efficient NHEJ.

    Evidence Deletion mutants, affinity purification of NONO and Ku70/80, live-cell recruitment and NHEJ assays

    PMID:34135314

    Open questions at the time
    • Direct structural basis of pHAT-repair factor binding not resolved
    • Whether OGA acts in other repair pathways not tested
  7. 2021 Medium

    Identified transcriptional control of OGA via the RANBP2–CEBPα axis, linking OGA downregulation to elevated O-GlcNAc and hepatocellular carcinoma malignancy.

    Evidence Co-IP, OGA promoter assays, SUMOylation assays, in vivo HCC models

    PMID:34298689

    Open questions at the time
    • Direct CEBPα binding sites on the OGA promoter not mapped
    • Generality beyond HCC unknown
  8. 2020 Medium

    Showed OGA is itself an OGT substrate and mapped the OGT TPR residues governing this modification, embedding OGA in a reciprocal modification loop.

    Evidence GlcNAc electrophilic probe assay with a 30-mutant OGT TPR screen and OGA truncations

    PMID:33333092

    Open questions at the time
    • Functional consequence of OGA O-GlcNAcylation not established
    • Modified residues on OGA not pinpointed
  9. 2022 High

    Provided structural rationale for picomolar OGA inhibitors and used them chemoproteomically to detect endogenous OGA modifications including O-ubiquitination and N-formylation.

    Evidence X-ray structures of inhibitor-OGA complexes and chemoproteomic affinity purification

    PMID:34985906

    Open questions at the time
    • Functional roles of the detected endogenous PTMs not characterized
    • Inhibitor selectivity across the proteome not fully resolved
  10. 2022 Medium

    Defined an RNA-level control of OGA via NAT10-mediated ac4C mRNA stabilization, with functional importance during oocyte maturation.

    Evidence NAT10 knockdown transcriptomics, RNA stability assays, OGA knockdown in oocytes

    PMID:35937804

    Open questions at the time
    • Specific ac4C sites on OGA mRNA not pinpointed
    • Mechanistic link between OGA loss and maturation arrest unresolved
  11. 2023 High

    Resolved the structural basis of OGT-OGA mutual inhibition, establishing the enzyme pair as a self-limiting homeostatic unit.

    Evidence Cryo-EM of human OGT alone and the OGT-OGA complex

    PMID:37907462

    Open questions at the time
    • Dynamics and regulation of complex assembly in cells not defined
    • How upstream signals tip the balance not addressed
  12. 2024 Medium

    Demonstrated that ubiquitin-dependent degradation of OGA by UBR5 and by the RBM14/TRIM33 axis tunes cellular O-GlcNAc and drives cancer phenotypes.

    Evidence Co-IP, ubiquitination assays, E3 ligase knockdown, mutagenesis, and xenograft models

    PMID:38678556 PMID:38755129

    Open questions at the time
    • Direct ubiquitination sites on OGA not mapped
    • Relative contribution of each E3 pathway in normal tissue unknown
  13. 2024 High

    Showed a cancer-derived stalk-domain mutation reshapes OGA's interactome and substrate preference, with deglycosylated PDLIM7 suppressing p53 and enhancing motility.

    Evidence Quantitative interactome/substrate proteomics, mutant expression, co-IP, and motility assays

    PMID:38838015

    Open questions at the time
    • Frequency and significance of the mutation in patient tumors not quantified
    • Structural basis for altered +2-proline preference not resolved
  14. 2025 Medium

    Identified additional site-specific OGA substrates (NEK7 T170/T172, ZEB1 S670, KLF2 S177) coupling deglycosylation to pyroptosis, EMT, and senescence in distinct disease models.

    Evidence Co-IP, site-directed mutagenesis, knockdown rescue, and in vivo/cellular functional assays

    PMID:40251583 PMID:40771411 PMID:41066511

    Open questions at the time
    • In vitro reconstitution of direct deglycosylation lacking for several substrates
    • KLF2 finding is Low-confidence and single-lab
  15. 2025 Medium

    Defined the multi-domain architecture, showing the pHAT domain forms symmetric homodimers that allosterically shape the active site via a conformational change.

    Evidence X-ray crystallography of the pHAT domain and cryo-EM of multi-domain OGA with SPR/SAXS (preprint)

    PMID:bio_10.1101_2025.03.10.642372

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Ligand or partner occupying the exposed pHAT peptide site not identified
  16. 2025 Medium

    Linked OGA activity to neuronal physiology and environmental sensing, implicating it in synaptic maturation, inhibitor-induced synaptotoxicity, and temperature-dependent O-GlcNAc dynamics.

    Evidence Hippocampal slice electrophysiology with structurally distinct inhibitors, spine morphology assays, and OGA null/inhibition across organisms

    PMID:40654706 PMID:41478829 PMID:bio_10.1101_2025.07.08.660373 PMID:bio_10.1101_2025.08.15.670533

    Open questions at the time
    • Substrates mediating synaptic and temperature effects not identified
    • Some findings are preprints or Low-confidence morphology-based readouts

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OGA substrate selection, dimerization state, and OGT-coupling are dynamically integrated to direct deglycosylation toward specific targets in vivo remains unresolved.
  • No unified model linking pHAT dimerization, OGT inhibition, and substrate choice in cells
  • Physiological triggers that redistribute OGA among compartments and partners undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 5 GO:0016787 hydrolase activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0016740 transferase activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 1
Partners
KU70/80NEK7NONOOGTPDLIM7RBM14TRIM33UBR5
Complex memberships
OGA pseudo-HAT homodimerOGT-OGA mutual-inhibition complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MGEA5/OGA produces two protein isoforms (130 kDa and 75 kDa) arising from a splice variant lacking a putative acetyltransferase domain. Cell fractionation revealed the 130 kDa protein localizes to the cytoplasm/cytoskeleton while the 75 kDa protein localizes to the nucleus. Cell fractionation, polyclonal antibody detection, genomic organization analysis Biochemical and biophysical research communications Medium 11341771
2005 NCOAT/OGA is a bifunctional enzyme with both O-GlcNAcase (glycoside hydrolase) activity in its N-terminal domain and histone acetyltransferase (HAT) activity in its C-terminal domain. A zinc finger-like motif in the HAT domain directly binds histone H4 tail (both acetylated and unacetylated) in vitro, is required for efficient acetyltransferase activity, and catalyzes acetyl transfer to lysine 8 of histone H4. In vitro binding assay, mutagenesis of zinc finger-like motif, acetyltransferase activity assay The Journal of biological chemistry High 16356930
2006 C. elegans OGA ortholog oga-1 encodes an active O-GlcNAcase. Knockout of oga-1 accumulates O-GlcNAc on nuclear pores and other proteins, alters Ser/Thr phosphoprotein profiles, increases GSK-3β levels, elevates glycogen and trehalose stores, decreases lipid storage, and augments dauer formation induced by a temperature-sensitive insulin-like receptor mutant — placing O-GlcNAc cycling in the insulin-like signaling pathway controlling nutrient storage. Genetic knockout (oga-1(ok1207)), epistasis with daf-2 mutant, biochemical assays for glycogen/trehalose/lipid, western blot for O-GlcNAc and phosphoproteins Proceedings of the National Academy of Sciences of the United States of America High 16882729
2010 Human OGA possesses a conserved peptide-recognition groove beyond its GlcNAc-binding site. Structure of a bacterial OGA orthologue revealed this groove; conserved residues lining it in human OGA were mutated and tested for activity on three O-GlcNAcylated substrates (TAB1, FoxO1, CREB) in an in vitro deglycosylation assay, demonstrating a substrate-recognition mechanism involving interactions with protein context beyond the sugar moiety. Bacterial OGA crystal structure, site-directed mutagenesis of human OGA, in vitro deglycosylation assay with substrate proteins The Biochemical journal High 20863279
2021 OGA is recruited to DNA damage sites via O-GlcNAcylation-dependent mechanisms. The C-terminal pseudo-HAT domain of OGA is required for this recruitment and associates (via protein affinity purification) with DNA repair factors NONO and the Ku70/80 complex. Following DNA damage, NONO and Ku70/80 are O-GlcNAcylated by OGT; OGA subsequently deglycosylates them, and suppression of this deglycosylation prolongs NONO retention at lesions, delays its chromatin degradation, and impairs non-homologous end joining (NHEJ). Deletion mutant analysis, unbiased protein affinity purification, co-immunoprecipitation, live-cell recruitment assay, NHEJ functional assay Cell death & disease High 34135314
2020 OGT O-GlcNAcylates OGA protein. Using a GlcNAc electrophilic probe and 30 OGT TPR domain mutants, 15 'ladder-like' asparagine/aspartate residues spanning TPRs 3–7 and 10–13.5 were identified as affecting OGA O-GlcNAcylation. The OGA N-terminal region and pseudo-HAT domain are not required for its O-GlcNAcylation, indicating OGT interacts with OGA through its catalytic and/or stalk domains. GlcNAc electrophilic probe fluorescence assay, OGT TPR mutant screen, OGA truncation constructs International journal of biological macromolecules Medium 33333092
2023 Cryo-EM structure of the human OGT-OGA complex reveals that a long flexible OGA segment occupies the extended substrate-binding groove of OGT, positioning a serine for O-GlcNAcylation and preventing OGT from modifying other substrates; conversely, OGT disrupts OGA functional dimerization and occludes its active site, establishing mutual inhibition between the two enzymes as a mechanism for O-GlcNAc homeostasis. Cryo-electron microscopy structure determination of human OGT alone and OGT-OGA complex Nature communications High 37907462
2024 A cancer-derived point mutation on OGA's non-catalytic stalk domain aberrantly alters OGA's interactome and preferentially deglycosylates substrates with +2 proline relative to the O-GlcNAcylation site. The primary dysregulated substrate is PDLIM7; deglycosylated PDLIM7 suppresses p53 transcription and promotes MDM2-mediated p53 ubiquitination, while also upregulating actin-rich membrane protrusions and increasing cancer cell motility. Quantitative proteomics (interactome and substrate profiling), cancer-derived mutant OGA expression, co-immunoprecipitation, immunoblotting for p53/MDM2, cell motility assay Proceedings of the National Academy of Sciences of the United States of America High 38838015
2024 RBM14 promotes ubiquitin-dependent proteasomal degradation of OGA protein, thereby elevating cellular O-GlcNAcylation. RBM14 is itself O-GlcNAcylated at serine 521, which regulates its interaction with E3 ligase TRIM33 and consequently affects OGA protein stability. Mutation of S521 to alanine abrogates RBM14 oncogenic properties. Co-immunoprecipitation, proteasome inhibitor treatment, siRNA knockdown, site-directed mutagenesis (S521A), ubiquitination assay Cell reports Medium 38678556
2024 UBR5 acts as an E3 ubiquitin ligase that directly binds OGA, facilitating its ubiquitination and proteasomal degradation, thereby increasing O-GlcNAcylation-mediated EMT and gemcitabine resistance in pancreatic cancer cells. Co-immunoprecipitation, ubiquitination assay, UBR5 knockdown with OGA protein level measurement, in vivo xenograft model Cell death & disease Medium 38755129
2021 RANBP2 (SUMO E3 ligase) facilitates SUMOylation and degradation of CEBPα transcription factor; CEBPα directly augments OGA transcription. RANBP2-mediated CEBPα degradation thus downregulates OGA transcription, elevating global O-GlcNAcylation and promoting hepatocellular carcinoma malignancy. RANBP2-CEBPα co-immunoprecipitation, OGA promoter transcriptional assay, SUMOylation assay, in vitro and in vivo HCC models Cancers Medium 34298689
2022 NAT10-mediated ac4C modification on OGA mRNA suppresses its degradation, maintaining OGA mRNA stability and expression. Knockdown of OGA impairs oocyte maturation; as oocytes mature, OGA expression increases while O-GlcNAc levels decrease. NAT10 knockdown transcriptome analysis, OGA knockdown in oocytes, RNA stability assay, ac4C detection Frontiers in endocrinology Medium 35937804
2025 OGA is present in dendritic spines and promotes spine maturation, increases spine density, alters synapse size, and downregulates GluA2-containing AMPA receptors in developing and mature neurons. Immunohistochemistry, biochemical fractionation, functional spine morphology assays, AMPAR subunit analysis bioRxivpreprint Low bio_10.1101_2025.08.15.670533
2025 Multi-domain OGA structures (crystal structure of Trichoplax adhaerens pHAT domain, cryo-EM of multi-domain T. adhaerens and human OGAs) reveal that the pseudo-HAT (pHAT) domain forms catalytically incompetent symmetric homodimers exposing a putative peptide-binding site. In human OGA, pHAT domain positions allosterically determine the wider active site environment through a conformational change involving a tryptophan in a flexible arm region. X-ray crystallography (pHAT domain), cryo-EM (multi-domain OGA), surface plasmon resonance, small-angle X-ray scattering bioRxivpreprint Medium bio_10.1101_2025.03.10.642372
2022 Bicyclic picomolar thiazolidine inhibitors of human OGA were co-crystallized with OGA, revealing the structural basis for their exceptional potency (inhibitors extend out of the active site cleft). Chemoproteomic pull-down using these inhibitors identified endogenous OGA post-translational modifications including O-ubiquitination and N-formylation. X-ray crystal structures of inhibitor-OGA complexes, chemoproteomic affinity purification, targeted proteomics Journal of the American Chemical Society High 34985906
2019 OGA substrate specificity toward the sugar moiety was investigated using glycopeptides with chemoenzymatically modified GlcNAc residues prepared by OGT-catalyzed reactions; this in vitro assay revealed the structural requirements of the GlcNAc residue recognized by human OGA. Chemoenzymatic glycopeptide synthesis, in vitro OGA deglycosylation assay Frontiers in chemistry Low 30693278
2019 Nearby phosphorylation on a ZO-3-derived peptide affects de-O-GlcNAcylation by OGA (though to a lesser extent than phosphorylation affects O-GlcNAcylation by OGT), demonstrating crosstalk between phosphorylation and OGA activity at adjacent sites. Peptide microarray with OGA activity assay, phosphatase treatment Amino acids Low 30725225
2025 OGA deglycosylates NEK7 at T170 and T172; O-GlcNAcylated NEK7 has reduced interaction with NLRP3 (confirmed by co-IP). OGA knockdown increases NEK7 O-GlcNAcylation, weakens NEK7-NLRP3 interaction, inhibits pyroptosis, and reduces motor dysfunction/dopaminergic neurodegeneration in MPTP-treated mice. OGT deficiency abolished protective effects of OGA knockdown. Co-immunoprecipitation, site-directed mutagenesis (T170A, T172A), OGA knockdown, MPTP mouse model Journal of cellular and molecular medicine Medium 41066511
2025 OGA removes O-GlcNAcylation from ZEB1 at serine 670, decreasing ZEB1 protein stability. Artesunate directly binds OGA (confirmed by molecular docking and biolayer interferometry), induces OGA expression, and OGA knockdown reverses artesunate-mediated inhibition of HCC cell migration and invasion. Molecular docking, biolayer interferometry, immunoprecipitation, cycloheximide chase assay, OGA knockdown, cell migration/invasion assay Open life sciences Medium 40771411
2025 OGA suppresses O-GlcNAcylation of KLF2 at S177, reducing KLF2 protein stability; OGA knockdown promotes KLF2 O-GlcNAcylation and stability, inhibits senescence, and promotes mitophagy in dental pulp stem cells. KLF2 silencing reverses the effects of OGA knockdown. Immunoprecipitation, western blotting for O-GlcNAc on KLF2, OGA and KLF2 knockdown, senescence-associated β-galactosidase staining, mitophagy assay BMC oral health Low 40251583
2025 OGA inhibitors (ceperognastat, ASN90, MK8719) produce convergent acute synaptotoxic effects in mouse hippocampal slices: suppression of paired-pulse facilitation/depression and long-term potentiation, increased PSD-95, reduced Synaptophysin 1, and a biphasic shift in tau phosphorylation, suggesting a class-wide mechanism of synaptic impairment from OGA inhibition. Ex vivo hippocampal slice electrophysiology (LTP, paired-pulse), immunohistochemistry for synaptic proteins and tau phosphorylation bioRxiv / The journal of prevention of Alzheimer's disease Medium 40654706 41478829
2025 O-GlcNAc abundance depends on temperature across multiple organisms (Drosophila, zebrafish, mammalian cells). In cultured cells, the OGT/OGA protein ratio changes with temperature. Pharmacological OGA inhibition decoupled the temperature-dependent O-GlcNAc decrease in cultured cells, and an OGA null allele in Drosophila had the same effect, demonstrating that OGA activity is a key driver of temperature-dependent O-GlcNAc reduction. OGA inhibitor treatment, OGA null allele in Drosophila, temperature manipulation, O-GlcNAc western blotting, OGT/OGA protein quantification bioRxivpreprint Medium bio_10.1101_2025.07.08.660373

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a beta-N-acetylglucosaminidase. Biochemical and biophysical research communications 139 11341771
2005 A single nucleotide polymorphism in MGEA5 encoding O-GlcNAc-selective N-acetyl-beta-D glucosaminidase is associated with type 2 diabetes in Mexican Americans. Diabetes 135 15793264
2014 Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice. Molecular neurodegeneration 130 25344697
2006 Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer. Proceedings of the National Academy of Sciences of the United States of America 126 16882729
2011 Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes, chromosomes & cancer 100 21717526
2014 TGFBR3 and MGEA5 rearrangements in pleomorphic hyalinizing angiectatic tumors and the spectrum of related neoplasms. The American journal of surgical pathology 61 24705316
2010 Human OGA binds substrates in a conserved peptide recognition groove. The Biochemical journal 59 20863279
2012 Prediction of bladder cancer based on urinary content of MGEA5 and OGT mRNA level. Clinical laboratory 51 22783592
2016 An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells. ACS chemical biology 49 27622469
2016 Plant immunity induced by COS-OGA elicitor is a cumulative process that involves salicylic acid. Plant science : an international journal of experimental plant biology 41 27095400
2019 Systemic defense activation by COS-OGA in rice against root-knot nematodes depends on stimulation of the phenylpropanoid pathway. Plant physiology and biochemistry : PPB 38 31302409
2015 Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors. International journal of molecular sciences 38 26343633
2022 NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. Frontiers in endocrinology 35 35937804
2015 A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain-Permeable OGA Inhibitors. Angewandte Chemie (International ed. in English) 35 26545827
2022 OGA activated glycopeptide-based nano-activator to activate PKM2 tetramerization for switching catabolic pathways and sensitizing chemotherapy resistance. Biomaterials 32 35462306
2023 Cryo-EM structure of human O-GlcNAcylation enzyme pair OGT-OGA complex. Nature communications 31 37907462
2002 Analysis of MGEA5 on 10q24.1-q24.3 encoding the beta-O-linked N-acetylglucosaminidase as a candidate gene for type 2 diabetes mellitus in Pima Indians. Molecular genetics and metabolism 31 12359146
2024 OGT and OGA: Sweet guardians of the genome. The Journal of biological chemistry 28 38447797
2021 OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair. Cell death & disease 28 34135314
2014 OGA heterozygosity suppresses intestinal tumorigenesis in Apc(min/+) mice. Oncogenesis 26 25000257
2020 The Dysregulation of OGT/OGA Cycle Mediates Tau and APP Neuropathology in Down Syndrome. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 24 33258073
2005 The histone acetyltransferase NCOAT contains a zinc finger-like motif involved in substrate recognition. The Journal of biological chemistry 23 16356930
2024 Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease. Alzheimer's & dementia (New York, N. Y.) 22 39748851
2022 Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications. Journal of the American Chemical Society 21 34985906
2023 Adipocyte-derived exosomes promote the progression of triple-negative breast cancer through circCRIM1-dependent OGA activation. Environmental research 20 37775001
2021 RANBP2 Activates O-GlcNAcylation through Inducing CEBPα-Dependent OGA Downregulation to Promote Hepatocellular Carcinoma Malignant Phenotypes. Cancers 19 34298689
2020 Cardiomyocyte Oga haploinsufficiency increases O-GlcNAcylation but hastens ventricular dysfunction following myocardial infarction. PloS one 19 33253217
2018 The t(1;10)(p22;q24) TGFBR3/MGEA5 Translocation in Pleomorphic Hyalinizing Angiectatic Tumor, Myxoinflammatory Fibroblastic Sarcoma, and Hemosiderotic Fibrolipomatous Tumor. Archives of pathology & laboratory medicine 19 29979612
2012 Computational analysis of human OGA structure in complex with PUGNAc and NAG-thiazoline derivatives. Journal of chemical information and modeling 17 22937904
2013 OGT and OGA expression in postmenopausal skeletal muscle associates with hormone replacement therapy and muscle cross-sectional area. Experimental gerontology 16 24365779
2021 Cisplatin enhances protein O‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells. International journal of oncology 15 33846785
2020 Elucidating the protein substrate recognition of O-GlcNAc transferase (OGT) toward O-GlcNAcase (OGA) using a GlcNAc electrophilic probe. International journal of biological macromolecules 15 33333092
2022 Acute inhibition of OGA sex-dependently alters the networks associated with bioenergetics, autophagy, and neurodegeneration. Molecular brain 14 35248135
2020 Diazaspirononane Nonsaccharide Inhibitors of O-GlcNAcase (OGA) for the Treatment of Neurodegenerative Disorders. Journal of medicinal chemistry 14 33197187
2024 O-GlcNAcylation of RBM14 contributes to elevated cellular O-GlcNAc through regulation of OGA protein stability. Cell reports 13 38678556
2024 E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA. Cell death & disease 12 38755129
2022 Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT/OGA Expression via hsa-miR-542-5p. Frontiers in oncology 12 35795059
2024 OGA mutant aberrantly hydrolyzes O-GlcNAc modification from PDLIM7 to modulate p53 and cytoskeleton in promoting cancer cell malignancy. Proceedings of the National Academy of Sciences of the United States of America 10 38838015
2023 Development of a PET Tracer for OGA with Improved Kinetics in the Living Brain. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 10 37934021
2022 Carbohydrate-derived bicyclic selenazolines as new dual inhibitors (cholinesterases/OGA) against Alzheimer's disease. Bioorganic chemistry 10 35779403
2023 Restoration of coronary microvascular function by OGA overexpression in a high-fat diet with low-dose streptozotocin-induced type 2 diabetic mice. Diabetes & vascular disease research 9 37186669
2021 Nanomolar inhibition of human OGA by 2-acetamido-2-deoxy-d-glucono-1,5-lactone semicarbazone derivatives. European journal of medicinal chemistry 9 34186233
2019 Production of Glycopeptide Derivatives for Exploring Substrate Specificity of Human OGA Toward Sugar Moiety. Frontiers in chemistry 9 30693278
2018 Increased OGA Expression and Activity in Leukocytes from Patients with Diabetes: Correlation with Inflammation Markers. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 9 29890544
2019 Targeted RNA-sequencing identifies FBXW4 instead of MGEA5 as fusion partner of TGFBR3 in pleomorphic hyalinizing angiectatic tumor. Virchows Archiv : an international journal of pathology 8 30911815
2018 Novel glucopyranoside C2-derived 1,2,3-triazoles displaying selective inhibition of O-GlcNAcase (OGA). Carbohydrate research 8 30412832
2017 Measuring O-GlcNAc cleavage by OGA and cell lysates on a peptide microarray. Analytical biochemistry 8 28571750
2007 MGEA5-14 polymorphism and type 2 diabetes in Mexico City. American journal of human biology : the official journal of the Human Biology Council 8 17546623
2021 O-GlcNAcylation Quantification of Certain Protein by the Proximity Ligation Assay and Clostridium perfringen OGAD298N(CpOGAD298N). ACS chemical biology 7 34105348
2020 OGA Inhibition Alters Energetics and Nutrient Sensing in Alzheimer's Disease Cytoplasmic Hybrids. Journal of Alzheimer's disease : JAD 6 33285636
2019 Study of cross talk between phosphatases and OGA on a ZO-3-derived peptide. Amino acids 6 30725225
2022 Facile Labeling of Sieve Element Phloem-Protein Bodies Using the Reciprocal Oligosaccharide Probe OGA . Frontiers in plant science 5 35222474
2023 Cancer-derived mutation in the OGA stalk domain promotes cell malignancy through dysregulating PDLIM7 and p53. Research square 4 36993758
2022 2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes. International journal of molecular sciences 3 35162960
2019 Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation. Bioorganic & medicinal chemistry letters 3 30713024
2024 OGT and OGA gene-edited human induced pluripotent stem cells for dissecting the functional roles of O-GlcNAcylation in hematopoiesis. Frontiers in cell and developmental biology 2 38752196
2025 OGA promotes human dental pulp stem cell senescence and inhibits mitophagy by inhibition of O-GlcNAcylation of KLF2. BMC oral health 1 40251583
2025 Synaptic Toxicity of OGA Inhibitors and the Failure of Ceperognastat. bioRxiv : the preprint server for biology 1 40654706
2025 Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1. Open life sciences 1 40771411
2025 O-GlcNAcylation Mediated by OGA Activates NEK7/NLRP3 Pathway to Promote Pyroptosis in Parkinson's Disease. Journal of cellular and molecular medicine 1 41066511
2015 Use of a mutant OGA for detecting O-GlcNAc modified proteins. The Biochemical journal 1 26567273
2026 Synaptic toxicity of OGA inhibitors and the failure of ceperognastat. The journal of prevention of Alzheimer's disease 0 41478829
2026 Protein-encapsulated fluorogenic probes for the selective detection of endogenous O-GlcNAcase (OGA). Chemical science 0 41710206

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