Affinage

GFPT1

Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 · UniProt Q06210

Length
699 aa
Mass
78.8 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GFPT1 encodes glutamine:fructose-6-phosphate amidotransferase (GFAT1), the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), catalyzing the conversion of fructose-6-phosphate and glutamine to glucosamine-6-phosphate for UDP-GlcNAc production (PMID:11679416, PMID:32019926). GFAT1 activity is allosterically inhibited by its end-product UDP-GlcNAc, and this feedback is modulated by PKA phosphorylation at Ser205 (which lowers basal activity while abolishing UDP-GlcNAc inhibition) and by AMPK phosphorylation at Ser243 (which inhibits activity and reduces cellular O-GlcNAcylation), with mTORC2 controlling both GFPT1 expression and the dynamics of Ser243 phosphorylation under nutrient stress (PMID:33846315, PMID:28008135, PMID:27570073, PMID:30201609). In skeletal muscle, GFPT1 is essential for N-glycosylation of neuromuscular junction (NMJ) proteins including acetylcholine receptor subunits, and loss-of-function mutations cause limb-girdle congenital myasthenic syndrome with tubular aggregates, as demonstrated by patient myotubes and muscle-specific knockout mice (PMID:23569079, PMID:29905857). Under glucose starvation, GFAT1 engages in a non-canonical signaling role by forming a complex with TAB1 and TTLL5, in which its glutamate-producing activity enables TTLL5-mediated TAB1 glutamylation to activate p38 MAPK and promote autophagy (PMID:35945223).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Defining the transcriptional control of GFPT1 revealed a TATA-less, Sp1-driven promoter architecture with EGF-responsiveness, establishing how GFPT1 expression is basally maintained and growth-factor regulated.

    Evidence Promoter cloning, DNase I footprinting, EMSA, mutagenesis and reporter assays in mouse cells

    PMID:9060444

    Open questions at the time
    • Human promoter regulation not directly tested
    • Upstream signaling cascades linking EGF to Sp1 at the GFPT1 locus not delineated
  2. 2001 High

    Biochemical characterization of GFAT1 and its muscle-selective splice variant (GFAT1-L) established the kinetic basis for tissue-specific HBP regulation, showing that the 18-amino-acid insert alters substrate affinity and tightens UDP-GlcNAc feedback inhibition.

    Evidence Recombinant expression in COS-7 cells, enzymatic kinetics, RT-PCR and cDNA cloning across two independent labs

    PMID:11587069 PMID:11679416

    Open questions at the time
    • Physiological significance of the muscle-selective variant in vivo not demonstrated
    • Structural basis of kinetic differences was unknown until 2020
  3. 2001 Medium

    Identification of PKA-dependent regulation and UDP-GlcNAc feedback inhibition of the Drosophila GFAT1 ortholog indicated that cAMP/PKA signaling modulates HBP flux, though the precise phosphorylation site in the human enzyme was not yet mapped.

    Evidence Recombinant expression in yeast, enzyme activity assays with UDP-GlcNAc and PKA, site conservation analysis

    PMID:11716769

    Open questions at the time
    • Drosophila ortholog study; direct PKA phosphorylation site on human GFAT1 unresolved at this time
    • In vivo PKA regulation not demonstrated
  4. 2013 High

    Demonstrating that GFPT1 loss reduces steady-state levels of AChR subunits via defective N-glycosylation — not transcriptional changes — resolved how HBP deficiency leads to NMJ dysfunction in congenital myasthenic syndrome patients.

    Evidence Patient-derived myotube culture, surface AChR quantification, siRNA and pharmacological GFPT1 inhibition, Western blot

    PMID:23569079

    Open questions at the time
    • Whether all CMS-associated GFPT1 mutations act through the same glycosylation deficiency mechanism
    • Presynaptic contributions not addressed
  5. 2015 High

    Discovery that a 3′-UTR mutation creates a de novo miR-206* binding site that suppresses GFPT1 protein revealed a post-transcriptional pathomechanism for CMS, rescuable by anti-miR treatment.

    Evidence Luciferase reporter assay comparing WT vs mutant 3′-UTR, anti-miR-206* rescue in patient myoblasts

    PMID:25765662

    Open questions at the time
    • In vivo rescue not tested
    • Whether other CMS patients carry similar regulatory mutations
  6. 2016 High

    Placing GFPT1 expression under mTORC2 control — via Xbp1s nuclear accumulation and glutaminolysis-derived α-ketoglutarate — linked growth-factor/nutrient sensing to HBP transcriptional output.

    Evidence siRNA knockdown of mTORC2 components, metabolomics, nuclear fractionation, reporter assays

    PMID:27570073

    Open questions at the time
    • Whether mTORC2 regulation of GFPT1 is tissue-specific
    • Direct transcription factor binding to GFPT1 promoter not shown
  7. 2017 High

    Identification of AMPK-mediated Ser243 phosphorylation as an inhibitory modification of GFAT1 that reduces O-GlcNAcylation and promotes angiogenesis connected metabolic stress sensing to HBP flux control and vascular biology.

    Evidence Label-free phosphoproteomics, S243A mutagenesis, GFAT activity assays, O-GlcNAc blotting, endothelial sprouting assays

    PMID:28008135

    Open questions at the time
    • In vivo angiogenesis phenotype not tested
    • Whether Ser243 phosphorylation affects protein stability vs. catalysis differently in different tissues
  8. 2017 Medium

    Patient biopsy analysis showed that GFPT1-CMS causes glycosylation defects (reduced O-glycosylation and sialylation) extending beyond the NMJ to extra-junctional muscle membrane proteins, broadening the pathological scope beyond AChR.

    Evidence EM ultrastructure, lectin histochemistry, immunohistochemistry on biopsies from three unrelated patients

    PMID:28712002

    Open questions at the time
    • Specific glycoprotein substrates affected not individually identified
    • No reconstitution of glycosylation rescue
  9. 2018 High

    Muscle-specific Gfpt1 knockout in mice recapitulated CMS with NMJ structural disintegration and tubular aggregates, proving that muscle-intrinsic GFPT1 is necessary and sufficient for NMJ maintenance.

    Evidence Cre/LoxP conditional knockout, electrophysiology, EM, immunofluorescence, grip strength, proteomics

    PMID:29905857

    Open questions at the time
    • Whether presynaptic defects are secondary to postsynaptic glycosylation loss
    • Rescue by UDP-GlcNAc supplementation not attempted
  10. 2018 High

    mTORC2 was shown to modulate the amplitude and duration of GFPT1 Ser243 phosphorylation under nutrient stress, integrating growth-factor and energy-sensing pathways at GFPT1 to sustain UDP-GlcNAc production.

    Evidence pSer243-GFAT1 immunoblotting, 2-DG and glutamine deprivation, mTORC2-deficient cells, O-GlcNAcylation measurements

    PMID:30201609

    Open questions at the time
    • Whether mTORC2 acts directly on GFAT1 or indirectly through AMPK modulation
    • Structural basis for Ser243 effect on activity not resolved
  11. 2020 High

    The full-length crystal structure of human GFAT1 provided the first atomic-resolution model of UDP-GlcNAc feedback inhibition and revealed that the interdomain linker is the critical structural element mediating allosteric regulation, explaining how the longevity-associated G451E variant escapes feedback.

    Evidence X-ray crystallography with multiple ligand complexes, enzyme activity titrations, G451E mutagenesis, cellular UDP-GlcNAc measurements

    PMID:32019926

    Open questions at the time
    • Structure of the muscle-specific GFAT1-L splice variant not determined
    • Dynamics of the conformational change during catalytic cycle not captured
  12. 2021 High

    Mapping PKA phosphorylation to Ser205 of human GFAT1 and showing it simultaneously lowers basal activity and abolishes UDP-GlcNAc feedback inhibition resolved how cAMP signaling uncouples HBP flux from its metabolic feedback loop.

    Evidence Enzyme activity assays, site-directed mutagenesis (S205 and R203H), UDP-GlcNAc measurements in C. elegans and mammalian cells, structural analysis

    PMID:33846315

    Open questions at the time
    • In vivo physiological contexts where PKA-Ser205 regulation predominates not defined
    • Interplay between Ser205 and Ser243 phosphorylation not addressed
  13. 2022 High

    Discovery of a non-canonical signaling role for GFAT1 — forming a ternary complex with TAB1 and TTLL5 under glucose starvation to drive TAB1 glutamylation and p38 MAPK activation — established that GFAT1 functions beyond metabolic catalysis as a signaling scaffold.

    Evidence Reciprocal Co-IP, proximity ligation assay, TAB1-S438A mutagenesis, TTLL5 knockdown, mass spectrometry, autophagy and viability assays

    PMID:35945223

    Open questions at the time
    • Whether the GFAT1-TAB1-TTLL5 complex forms in non-cancer cell types
    • Structural basis of the ternary complex unknown
    • Relative contribution of catalytic vs. scaffolding functions under starvation not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for the GFAT1-L splice variant's altered kinetics, the interplay between Ser205 and Ser243 phosphorylation in vivo, whether the GFAT1-TAB1-TTLL5 signaling axis operates in muscle or other non-cancer tissues, and the potential for therapeutic UDP-GlcNAc supplementation to rescue CMS phenotypes.
  • No structure of the GFAT1-L muscle variant
  • Dual phosphorylation crosstalk unexplored
  • In vivo metabolic rescue of CMS not attempted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0016853 isomerase activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3
Partners
MAPK14PTENTAB1TTLL5
Complex memberships
GFAT1-TAB1-TTLL5 complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 GFPT1 encodes a rate-limiting enzyme (glutamine:fructose-6-phosphate amidotransferase) that catalyzes the first step of the hexosamine biosynthesis pathway, converting fructose-6-phosphate and glutamine to glucosamine-6-phosphate; a muscle-selective splice variant (GFAT1Alt/GFAT1-L) containing an 18-amino-acid insert at position 229 displays altered kinetics: ~2-fold higher apparent Km for fructose-6-phosphate and ~5-fold lower Ki for UDP-GlcNAc compared to ubiquitous GFAT1. Recombinant adenovirus expression in COS-7 cells, enzyme activity and kinetic assays, RT-PCR, cDNA cloning and sequencing Diabetes High 11587069 11679416
2001 GFAT1 activity in Drosophila (ortholog Dmel/GFAT1) is subject to feedback inhibition by UDP-N-acetylglucosamine (UDP-GlcNAc) and is phosphorylated and regulated by protein kinase A (PKA); one of the two putative PKA sites is conserved, and PKA-dependent regulation was demonstrated in a yeast total protein extract system. Recombinant expression in yeast, enzyme activity assays in cell extracts, site conservation analysis The Biochemical journal Medium 11716769
2016 mTORC2 promotes GFPT1 expression by sustaining sufficient levels of glutaminolysis catabolites (particularly α-ketoglutarate) and by enabling nuclear accumulation of the GFPT1 transcriptional regulator Xbp1s; loss of mTORC2 reduces GFPT1 expression and HBP flux. siRNA knockdown of mTORC2 components, metabolite measurements, nuclear fractionation, reporter assays, metabolomics Molecular cell High 27570073
2017 AMPK directly phosphorylates GFPT1 at serine 243 in response to VEGF stimulation or AICAR treatment; this phosphorylation inhibits GFAT1 enzymatic activity, reduces cellular O-GlcNAc levels, and promotes VEGF-induced endothelial sprouting/angiogenesis. A non-phosphorylatable S243A-GFAT1 mutant abolishes these effects. Label-free phosphoproteomics, siRNA knockdown, site-directed mutagenesis (S243A), GFAT activity assays, O-GlcNAc immunoblotting, in vitro angiogenesis (sprouting) assays The Biochemical journal High 28008135
2018 mTORC2 modulates both the amplitude and duration of GFPT1 Ser-243 phosphorylation during nutrient starvation; Ser-243 phosphorylation promotes GFPT1 protein expression and maintains UDP-GlcNAc production when nutrients are limiting, independently of AMPK in some conditions. Immunoblotting for pSer243-GFAT1, pharmacological inhibition of glycolysis (2-DG), glutamine deprivation, mTORC2-deficient cells, O-GlcNAcylation measurement The Journal of biological chemistry High 30201609
2020 Full-length crystal structure of human GFAT-1 was solved in complex with various ligands; UDP-GlcNAc directly binds GFAT-1 and inhibits its catalytic activity via feedback inhibition. The longevity-associated G451E variant (corresponding to C. elegans gain-of-function) shows drastically reduced sensitivity to UDP-GlcNAc inhibition; structural and biochemical data indicate the interdomain linker is critical for UDP-GlcNAc-mediated inhibition. X-ray crystallography (full-length human GFAT-1), enzyme activity assays with UDP-GlcNAc titration, site-directed mutagenesis (G451E), UDP-GlcNAc level measurement in mammalian cells Nature communications High 32019926
2021 Protein kinase A (PKA) phosphorylates human GFAT-1 at Ser205 with two distinct effects: it lowers baseline GFAT-1 catalytic activity AND abolishes UDP-GlcNAc feedback inhibition, thereby uncoupling the metabolic feedback loop. The R203H variant interferes with both UDP-GlcNAc inhibition and PKA-mediated Ser205 phosphorylation. Enzyme activity assays, site-directed mutagenesis (R203H, phospho-site variants), UDP-GlcNAc measurements in C. elegans and mammalian cells, structural analysis Nature communications High 33846315
2013 Mutations in GFPT1 cause reduced cell-surface expression of acetylcholine receptor (AChR) at the neuromuscular junction; this is due to reduced steady-state levels of AChR α, δ, and ε subunits (but not β), not altered transcription, mediated through defective N-linked glycosylation (UDP-GlcNAc substrate reduction). siRNA silencing or pharmacological inhibition of GFPT1 enzymatic activity both recapitulate the reduction in surface AChR. Patient-derived myotube culture, cell-surface AChR quantification, siRNA knockdown, pharmacological GFPT1 inhibition, Western blot for AChR subunits, gene expression analysis Human molecular genetics High 23569079
2018 Muscle-specific knockout of Gfpt1 in mice (Gfpt1tm1d/tm1d) causes myasthenia and myopathy with postsynaptic NMJ morphological changes (loss of junctional folds) accompanied by presynaptic alterations and tubular aggregates in muscle, demonstrating that muscle-derived GFPT1 is sufficient and necessary for NMJ integrity and neurotransmission. Cre/LoxP muscle-specific conditional knockout mouse, electrophysiology, NMJ morphology (electron microscopy, immunofluorescence), grip strength testing, proteomics Human molecular genetics High 29905857
2022 Under glucose deprivation, GFAT1 interacts with TAB1 in a TAB1-S438 phosphorylation-dependent manner; GFAT1 binding to TAB1 facilitates TTLL5-GFAT1-TAB1 complex formation, and GFAT1's metabolic activity producing glutamate enables TTLL5-mediated TAB1 glutamylation, which recruits p38α MAPK and drives p38 activation to promote autophagy and tumor cell survival. Co-immunoprecipitation, proximity ligation assay, phospho-mutant constructs (TAB1-S438A), TTLL5 knockdown, autophagy and cell viability assays, mass spectrometry identification of glutamylation Cell discovery High 35945223
2021 GFAT1 inhibition reduces N-glycosylation of PD-L1, accelerating its proteasomal degradation; GFAT1 is required for glycosylation-dependent PD-L1 protein stability in lung cancer cells. Loss of GFAT1 activity after IFNγ stimulation enhances T cell activation and NK cell cancer-killing. Pharmacological GFAT1 inhibition, siRNA knockdown, PD-L1 glycosylation assessment (lectin blot/glycoprotein assay), proteasome inhibitor rescue, T cell and NK cell co-culture functional assays Carcinogenesis Medium 34270713
2016 In human keratinocytes, GFAT1 (not GFAT2) is the primary driver of UDP-GlcNAc pool maintenance and hyaluronan synthesis; GFAT1 siRNA silencing reduces UDP-GlcNAc and hyaluronan, while simultaneously inducing compensatory upregulation of glucosamine-6-phosphate deaminases (GNPDAs) and hyaluronan synthase 2 (HAS2), and inhibiting cell migration. siRNA silencing of GFAT1, GFAT2, GNPDA1, GNPDA2; UDP-GlcNAc quantification; hyaluronan ELISA; gene expression analysis; cell migration assay Glycobiology Medium 26887390
2015 A 3'-UTR c.*22C>A mutation in GFPT1 creates a de novo binding site for miR-206*, a muscle-abundant microRNA; this illegitimate miRNA binding reduces GFPT1 protein levels in patient myoblasts, and inhibition of miR-206* with a specific anti-miR rescues GFPT1 expression, establishing a post-transcriptional pathomechanism for CMS. Luciferase reporter assays (wild-type vs mutant 3'-UTR), anti-miR-206* inhibitor treatment, GFPT1 protein quantification in patient myoblasts, miRNA expression profiling Human molecular genetics High 25765662
2021 GFPT1 is the primary GFAT isoform in cardiomyocytes (not GFAT2); GFPT1 but not GFPT2 knockdown reduces stress-induced protein O-GlcNAcylation in neonatal cardiac preparations. GFAT2 expression is restricted to cardiac fibroblasts, while GFAT1 is expressed in both myocytes and fibroblasts. Targeted siRNA knockdown of GFPT1 and GFPT2 separately, O-GlcNAcylation Western blot, immunostaining of rodent cardiac preparations, single-cell RNA-seq data analysis, Western blot in human iPSC-derived cardiomyocytes Biochemical and biophysical research communications Medium 34735873
2007 In zebrafish, a nonsense mutation in gfpt1 (eartha mutant) specifically disrupts late-stage melanocyte differentiation (melanin production) during regeneration but not development; genetic analysis shows gfpt1 acts cell-autonomously within melanocytes to promote ontogenetic melanocyte darkening, placing gfpt1 in a regeneration-specific differentiation pathway. Forward genetic screen, positional cloning, melanocyte ablation (MoTP), mosaic analysis (cell autonomy), in situ hybridization PLoS genetics Medium 17542649
2000 Overexpression of GFAT in primary mesangial cells activates the PAI-1 promoter 2-3 fold in a manner dependent on GFAT enzymatic activity (abrogated by GFAT inhibitors azaserine and DON); downstream glucosamine also activates the PAI-1 promoter, and GFAT overexpression increases TGF-β1 and TGF-β receptor mRNAs, establishing GFAT activity as a regulator of fibrogenic gene expression via hexosamine flux. GFAT overexpression in primary mesangial cells, luciferase reporter assay, pharmacological enzyme inhibition, glucosamine supplementation, RT-PCR for TGF-β mRNAs American journal of physiology. Renal physiology Medium 10997922
1997 The mouse GFAT promoter lacks a canonical TATA box and is controlled by three Sp1-binding elements in a proximal GC-rich region (~-120 bp upstream of TSS); Sp1 binding was confirmed by DNase I footprinting, EMSA, and site-directed mutagenesis. This proximal region also confers EGF-responsiveness. Promoter cloning, primer extension, luciferase reporter assays, DNase I footprinting, EMSA, site-directed mutagenesis Nucleic acids research High 9060444
2017 Mutations in GFPT1-related LG-CMS are associated with loss of postsynaptic junctional folds, denervation-reinnervation at NMJs, reduced O-glycosylation, and reduced sialylation of transmembrane proteins in extra-junctional areas of patient muscle biopsies, demonstrating that GFPT1 deficiency causes glycosylation defects that structurally compromise all three NMJ components. Neuromuscular biopsy analysis (EM ultrastructure), immunohistochemistry, glycan analysis (lectin histochemistry), NMJ morphometry from three unrelated patients Journal of neurology Medium 28712002
2022 GFAT1 interacts with PTEN in cervical cancer cells (co-localization by immunofluorescence, confirmed by co-immunoprecipitation) and promotes PTEN ubiquitination and proteasomal degradation; GFPT1 knockdown stabilizes PTEN and inhibits proliferation, which is rescued by PTEN silencing. Co-immunoprecipitation, immunofluorescence co-localization, GFPT1 overexpression and knockdown, ubiquitination assay, colony formation/Edu/MTT proliferation assays, in vivo xenograft Carcinogenesis Medium 36040914
2018 2-Deoxy-D-glucose treatment causes AMPK-mediated phosphorylation of GFAT1, leading to reduction of total N-glycoproteins and ER stress-associated apoptosis in pancreatic cancer cells; metformin (AMPK activator) synergistically enhances this effect, linking GFAT1 phosphorylation to disruption of protein N-glycosylation. Proteomics (2DG-treated cells), GFAT1 phosphorylation immunoblotting, lectin-based N-glycoprotein detection, ER stress marker quantification, AMPK inhibitor/activator co-treatment, cell growth assay Biochemical and biophysical research communications Medium 29753740

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1976 The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies. The Journal of comparative neurology 560 1107363
1983 Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides. Differentiation; research in biological diversity 527 6198232
1981 The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination. Journal of neuroscience research 262 7334533
1978 Immunohistochemical demonstration of S-100 protein and GFA protein in interstitial cells of rat pineal gland. Brain research 176 342071
1985 Glial fibrillary acidic (GFA) protein in vertebrates: immunofluorescence and immunoblotting study with monoclonal and polyclonal antibodies. The Journal of comparative neurology 154 3900154
1979 Development, reactivity and GFA immunofluorescence of astroglia-containing monolayer cultures from rat cerebrum. Journal of neurocytology 148 233314
1986 Short- and long-term consequences of intracranial injections of the excitotoxin, quinolinic acid, as evidenced by GFA immunohistochemistry of astrocytes. Brain research 134 2938667
1979 GFA and S 100 protein levels as an index for malignancy in human gliomas and neurinomas. Journal of the National Cancer Institute 131 216839
2016 mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1. Molecular cell 112 27570073
1983 Amino acid sequence data on glial fibrillary acidic protein (GFA); implications for the subdivision of intermediate filaments into epithelial and non-epithelial members. The EMBO journal 112 6685624
1982 Glial fibrillary acidic (GFA) protein in Schwann cells: fact or artifact? The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 110 6182187
1985 Image analysis of GFA-positive astrocytes from adolescence to senescence. Experimental brain research 98 3987847
2017 GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis. The Biochemical journal 93 28008135
1986 Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil. Cell and tissue research 92 2874885
2018 IL-8-induced O-GlcNAc modification via GLUT3 and GFAT regulates cancer stem cell-like properties in colon and lung cancer cells. Oncogene 78 30305725
2011 Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations. Journal of neurology 75 21975507
1984 Masking of epitopes in tissue sections. A study of glial fibrillary acidic (GFA) protein with antisera and monoclonal antibodies. Histochemistry 71 6084655
1984 Glial fibrillary acidic (GFA) protein in Müller glia. Immunofluorescence study of the goldfish retina. Brain research 62 6375808
1988 Effects of oxygen rearing on the electroretinogram and GFA-protein in the rat. Investigative ophthalmology & visual science 61 3182197
2001 A glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus denitrificans detected and purified via two-dimensional proton exchange NMR spectroscopy. The Journal of biological chemistry 58 11741920
2016 Hexosamine biosynthesis in keratinocytes: roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis. Glycobiology 53 26887390
1989 Long term neurotoxicity of styrene. A quantitative study of glial fibrillary acidic protein (GFA) and S-100. British journal of industrial medicine 51 2751929
2020 Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis. Nature communications 50 32019926
2013 GFPT1-myasthenia: clinical, structural, and electrophysiologic heterogeneity. Neurology 49 23794683
2013 Mutations in GFPT1 that underlie limb-girdle congenital myasthenic syndrome result in reduced cell-surface expression of muscle AChR. Human molecular genetics 48 23569079
1983 Glial fibrillary acidic (GFA) protein-containing cells in the human pineal gland. Journal of neuropathology and experimental neurology 48 6864234
2004 Blocking angiogenesis and tumorigenesis with GFA-116, a synthetic molecule that inhibits binding of vascular endothelial growth factor to its receptor. Cancer research 47 15150116
1985 Simultaneous expression of glial fibrillary acidic (GFA) protein and neuron-specific enolase (NSE) by the same reactive or neoplastic astrocytes. Neuropathology and applied neurobiology 47 3001557
2020 LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p. Biological chemistry 44 32229685
2001 A novel variant of glutamine: fructose-6-phosphate amidotransferase-1 (GFAT1) mRNA is selectively expressed in striated muscle. Diabetes 44 11679416
2000 Overexpression of GFAT activates PAI-1 promoter in mesangial cells. American journal of physiology. Renal physiology 41 10997922
1986 Microinjection of monoclonal antibodies to vimentin, desmin, and GFA in cells which contain more than one IF type. Experimental cell research 41 3080318
1997 Effects of overexpression of glutamine:fructose-6-phosphate amidotransferase (GFAT) and glucosamine treatment on translocation of GLUT4 in rat adipose cells. Molecular and cellular endocrinology 40 9453242
1977 Antigens in human glioblastomas and meningiomas: Search for tumour and onco-foetal antigens. Estimation of S-100 and GFA protein. British journal of cancer 39 65176
2017 Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy. Journal of neurology 38 28712002
2018 mTORC2 modulates the amplitude and duration of GFAT1 Ser-243 phosphorylation to maintain flux through the hexosamine pathway during starvation. The Journal of biological chemistry 37 30201609
2000 GFAT as a target molecule of methylmercury toxicity in Saccharomyces cerevisiae. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 10783151
2005 Exploring QSAR of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists using FA and GFA techniques. Bioorganic & medicinal chemistry 36 15670924
2001 Functional regulation of glutamine:fructose-6-phosphate aminotransferase 1 (GFAT1) of Drosophila melanogaster in a UDP-N-acetylglucosamine and cAMP-dependent manner. The Biochemical journal 36 11716769
2020 GFAT1/HBP/O-GlcNAcylation Axis Regulates β-Catenin Activity to Promote Pancreatic Cancer Aggressiveness. BioMed research international 35 32149084
2017 Nephroprotective Effects of Anthocyanin from the Fruits of Panax ginseng (GFA) on Cisplatin-Induced Acute Kidney Injury in Mice. Phytotherapy research : PTR 35 28731262
2007 Mutations in gfpt1 and skiv2l2 cause distinct stage-specific defects in larval melanocyte regeneration in zebrafish. PLoS genetics 35 17542649
1997 Cloning and partial characterization of the mouse glutamine:fructose-6-phosphate amidotransferase (GFAT) gene promoter. Nucleic acids research 35 9060444
2019 Mammalian Target of Rapamycin 2 (MTOR2) and C-MYC Modulate Glucosamine-6-Phosphate Synthesis in Glioblastoma (GBM) Cells Through Glutamine: Fructose-6-Phosphate Aminotransferase 1 (GFAT1). Cellular and molecular neurobiology 34 30771196
2007 Exploring QSTR and toxicophore of hERG K+ channel blockers using GFA and HypoGen techniques. Journal of molecular graphics & modelling 34 17928249
1984 Astrocytes in smears of CNS tissues as visualized by GFA and vimentin immunofluorescence. Medical biology 34 6379328
1982 Glial cells identified by anti-alpha-albumin (anti-GFA) in human pineal gland. Journal of neurochemistry 33 7035619
1979 The immunocytochemical localization of GFA protein in experimental murine CNS tumors. Acta neuropathologica 33 760368
2022 GFAT1-linked TAB1 glutamylation sustains p38 MAPK activation and promotes lung cancer cell survival under glucose starvation. Cell discovery 32 35945223
2001 Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle. Journal of human genetics 32 11587069
2015 A 3'-UTR mutation creates a microRNA target site in the GFPT1 gene of patients with congenital myasthenic syndrome. Human molecular genetics 30 25765662
1986 Irreversible effects of dichloromethane on the brain after long term exposure: a quantitative study of DNA and the glial cell marker proteins S-100 and GFA. British journal of industrial medicine 30 3707866
2001 Angiotensin II activates the GFAT promoter in mesangial cells. American journal of physiology. Renal physiology 29 11399656
1988 An immunohistochemical study of glial fibrillary acidic (GFA) protein and S-100 protein in the colon affected by Hirschsprung's disease. Acta neuropathologica 29 3407393
2021 Protein kinase A controls the hexosamine pathway by tuning the feedback inhibition of GFAT-1. Nature communications 28 33846315
2019 Elevation of O-GlcNAc and GFAT expression by nicotine exposure promotes epithelial-mesenchymal transition and invasion in breast cancer cells. Cell death & disease 28 31019204
2018 2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells. Biochemical and biophysical research communications 28 29753740
2012 Limb-girdle myasthenia with tubular aggregates associated with novel GFPT1 mutations. Muscle & nerve 28 22987706
1987 GFA protein reactivity in nerve sheath tumors: a polyvalent and monoclonal antibody study. Journal of neuropathology and experimental neurology 28 3309191
1985 Immuno gold staining (IGS) for electron microscopical demonstration of glial fibrillary acidic (GFA) protein in LR white embedded tissue. Histochemistry 28 3910622
1980 Accumulation of GFA, the monomeric precursor of the gliofilaments, during development in normal mice and dysmyelinating mutants. Journal of neuroscience research 28 7192321
1980 In vitro polymerization of glial fibrillary acidic (GFA) protein extracted from multiple sclerosis (MS) brain. Neurochemical research 27 6769059
2018 GFPT1 deficiency in muscle leads to myasthenia and myopathy in mice. Human molecular genetics 25 29905857
2021 Inhibition of GFAT1 in lung cancer cells destabilizes PD-L1 protein. Carcinogenesis 22 34270713
1985 Identification of a human granulocyte functional antigen (GFA-2) involved in antibody-dependent cell-mediated cytotoxicity and phagocytosis. Journal of immunology (Baltimore, Md. : 1950) 22 3989303
2021 GFAT and PFK genes show contrasting regulation of chitin metabolism in Nilaparvata lugens. Scientific reports 20 33664411
1984 Morphometry of GFA and vimentin positive astrocytes in grafted and lesioned cortex cerebri. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 20 24873962
1978 Distribution of myosin and the glial fibrillary acidic protein (GFA protein) in rat spinal cord and in the human frontal cortex as revealed by immunofluorescence microscopy. Cell and tissue research 20 567531
1984 Glial fibrillary acidic (GFA) protein in rat spinal cord. An immunoperoxidase study in semithin sections. Brain research 19 6386101
2013 Exome sequencing detection of two untranslated GFPT1 mutations in a family with limb-girdle myasthenia. Clinical genetics 18 23488891
2013 Glutamine: fructose-6-phosphate amidotransferase (GFAT): homology modelling and designing of new inhibitors using pharmacophore and docking based hierarchical virtual screening protocol. SAR and QSAR in environmental research 18 23767808
2021 FOXA2 inhibits doxorubicin-induced apoptosis via transcriptionally activating HBP rate-limiting enzyme GFPT1 in HCC cells. Journal of physiology and biochemistry 17 34291417
2019 Leukoencephalopathy due to variants in GFPT1-associated congenital myasthenic syndrome. Neurology 17 30635494
2017 The sweet side of AMPK signaling: regulation of GFAT1. The Biochemical journal 17 28336748
2015 Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1). Biomolecules 17 26501342
1991 Demonstration of glial fibrillary acidic (GFA) protein by electron immunocytochemistry in the granular cells of a choristoma of the neurohypophysis. Histochemistry 17 1917581
1981 A glial fibrillary acidic protein (GFA)-containing cell clone derived from mouse cerebella transformed 'in vitro' by SV-40. Brain research 17 6265035
2004 Molecular screening of the human glutamine-fructose-6-phosphate amidotransferase 1 (GFPT1) gene and association studies with diabetes and diabetic nephropathy. Molecular genetics and metabolism 16 15308130
1986 Irreversible effects of xylene on the brain after long term exposure: a quantitative study of DNA and the glial cell marker proteins S-100 and GFA. Neurotoxicology 16 3822254
2022 GFPT1 promotes the proliferation of cervical cancer via regulating the ubiquitination and degradation of PTEN. Carcinogenesis 14 36040914
2021 Cardiomyocyte protein O-GlcNAcylation is regulated by GFAT1 not GFAT2. Biochemical and biophysical research communications 14 34735873
1976 Quantitative studies of the brain specific antigens GFA, 14-3-2, synaptin C1, D1, D2, D3 and D5 in jimpy mouse. Neuroscience letters 14 19604866
2023 Improved antitumor activity against prostate cancer via synergistic targeting of Myc and GFAT-1. Theranostics 13 36632215
2022 Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation. Brain and behavior 13 34978387
1985 Delayed development of GFA immunoreactivity in the parietal cortex during thyroid hormone deficiency. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 13 24874596
1978 [Disappearance of the gliofibrillar protein (GFA) during the cultivation of glioblastoma cells]. Comptes rendus hebdomadaires des seances de l'Academie des sciences. Serie D: Sciences naturelles 13 99269
2010 Expression of GFAT1 and OGT in podocytes: transport of glucosamine and the implications for glucose uptake into these cells. Journal of cellular physiology 12 20506529
2021 High GFPT1 expression predicts unfavorable outcomes in patients with resectable pancreatic ductal adenocarcinoma. World journal of surgical oncology 11 33517899
2009 Molecular characterization, chromosomal location, alternative splicing and polymorphism of porcine GFAT1 gene. Molecular biology reports 11 19757168
2023 Protective Effect and Mechanism of Xbp1s Regulating HBP/O-GlcNAcylation through GFAT1 on Brain Injury after SAH. Biomedicines 10 37238930
2022 miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 10 34986481
2022 GFAT1 is highly expressed in cancer stem cells of pancreatic cancer. Annals of translational medicine 10 35722419
2021 Novel compound heterozygous variants in the GFPT1 gene leading to rare limb-girdle congenital myasthenic syndrome with rimmed vacuoles. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 10 33438142
2020 Congenital myasthenic syndrome caused by a frameshift insertion mutation in GFPT1. Neurology. Genetics 10 32754643
2004 Scrutiny of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) locus reveals conserved haplotype block structure not associated with diabetic nephropathy. Diabetes 10 14988277
1991 Combined lead acetate and disulfiram treatment-induced alterations of glial fibrillary acidic protein (GFA) immunoreactive astrocytes in brain smears. Toxicology 10 1992564
2019 Novel compound heterozygous GFPT1 mutations in a family with limb-girdle myasthenia with tubular aggregates. Neuromuscular disorders : NMD 9 31255525
1984 Cell-specific domains of glial- and muscle-type intermediate filament proteins. Immunoaffinity chromatography and immunoblotting study of GFA protein and desmin. Experimental cell research 9 6479239
1980 Immunoperoxidase staining of glial fibrillary acidic (GFA) protein polymerized in vitro: an ultramicroscopic study. Neurochemical research 9 7007903
2022 Knockdown of GFAT disrupts chitin synthesis in Hyphantria cunea larvae. Pesticide biochemistry and physiology 8 36464356