Affinage

MGAT5

Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A · UniProt Q09328

Length
741 aa
Mass
84.5 kDa
Annotated
2026-04-28
58 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MGAT5 (GnT-V) is a Golgi-resident UDP-GlcNAc:α-mannoside β1,6-N-acetylglucosaminyltransferase that catalyzes the addition of β1,6-linked GlcNAc branches onto N-glycans, thereby generating high-avidity ligands for galectins and establishing a galectin–glycoprotein lattice that controls receptor clustering, surface residency, and signaling thresholds across immune, epithelial, and tumor cell contexts (PMID:2956949, PMID:11217864, PMID:16581792). In T cells, MGAT5-modified N-glycans on the TCR recruit galectin-3 to restrain TCR clustering and bias differentiation toward Th2 responses, while in tumor cells β1,6-branched glycans on integrins, hENT1, PSMA, TIMP-1, and kidney metalloproteases (ANPEP, MEP1A) promote FAK–PI3K/Akt signaling, membrane retention of transporters, protein stability, and motility (PMID:11217864, PMID:15585841, PMID:10700233, PMID:30143259, PMID:40112979, PMID:38499842, PMID:41323266). MGAT5 is released from the Golgi membrane by γ-secretase (presenilin complex) and SPPL3 cleavage to yield a secreted form that promotes FGF-2-dependent angiogenesis and can be delivered to recipient cells via small extracellular vesicles to remodel their glycan landscape (PMID:17142794, PMID:11872751, PMID:36590176). Loss of Mgat5 in vivo suppresses mammary and pancreatic tumor growth, restores sensitivity to immune checkpoint blockade, and shifts neural stem cell differentiation toward neurons at the expense of astrocytes (PMID:10700233, PMID:38912584, PMID:37172586).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1987 High

    The fundamental catalytic activity of MGAT5 was established: transfer of GlcNAc in β1,6 linkage from UDP-GlcNAc onto α-mannoside acceptors, defining it as the glycosyltransferase responsible for initiating the β1,6 branch on N-glycans.

    Evidence Cell-free enzymatic assay with synthetic trisaccharide acceptor and radiolabeled UDP-GlcNAc, product characterization by reverse-phase chromatography

    PMID:2956949

    Open questions at the time
    • No protein purification or cloning at this stage
    • Substrate specificity beyond synthetic acceptor not defined
    • In vivo relevance not yet demonstrated
  2. 1999 Medium

    Transcriptional regulation of MGAT5 by Ets-1 was identified, explaining how oncogenic signaling could upregulate β1,6 branching in cancer cells.

    Evidence Ets-1 mRNA correlation with GnT-V across 16 cancer lines (r=0.97), gain- and dominant-negative loss-of-function of Ets-1

    PMID:10438459

    Open questions at the time
    • Direct promoter binding by Ets-1 not shown
    • Other transcription factors not excluded
    • Regulation in non-cancer cell types not addressed
  3. 2000 High

    Genetic loss-of-function in mice demonstrated that MGAT5-derived β1,6 branching amplifies oncogenic PI3K/Akt signaling and is required for efficient mammary tumor growth and metastasis, establishing MGAT5 as a functional mediator—not merely a marker—of malignancy.

    Evidence Mgat5 knockout mice crossed with PyMT transgenic mice; PI3K/Akt activity, membrane ruffling, tumor growth and metastasis endpoints

    PMID:10700233

    Open questions at the time
    • Specific glycoprotein substrates mediating the PI3K feedback not identified
    • Mechanism of PI3K activation by β1,6 glycans not resolved
    • Immune contribution vs. cell-autonomous effects not distinguished
  4. 2001 High

    The galectin–glycoprotein lattice model was established: MGAT5-produced β1,6 N-glycans on the TCR recruit galectin-3 to restrict TCR clustering, setting T-cell activation thresholds and preventing autoimmunity.

    Evidence Mgat5 knockout mice showing enhanced TCR clustering and autoimmune disease, co-immunoprecipitation of galectin-3 with TCR, lactose competition phenocopy

    PMID:11217864

    Open questions at the time
    • Specific TCR subunit(s) carrying the critical glycosylation sites not mapped
    • Galectin-3 vs. other galectins not fully distinguished
    • Mechanism linking lattice to actin reorganization incomplete
  5. 2002 Medium

    A transferase-independent function was discovered: soluble (secreted) GnT-V promotes angiogenesis by liberating FGF-2 from heparan sulfate via a basic domain, revealing a non-catalytic role for the protein.

    Evidence Purified soluble GnT-V protein in vitro and in vivo angiogenesis assays, domain analysis

    PMID:11872751

    Open questions at the time
    • Physiological source and regulation of soluble GnT-V secretion not defined at this point
    • FGF-2 release mechanism not structurally resolved
    • In vivo contribution vs. catalytic function not separated
  6. 2004 High

    MGAT5-dependent glycan branching was shown to skew T helper differentiation toward Th2 by suppressing IFN-γ and promoting IL-4, with pharmacological epistasis confirming pathway specificity.

    Evidence Mgat5 knockout mice, swainsonine treatment of human and mouse T cells, cytokine ELISAs, Th1/Th2 polarization assays

    PMID:15585841

    Open questions at the time
    • Downstream signaling intermediates between lattice and cytokine transcription not mapped
    • Contribution of individual galectin family members not resolved
  7. 2006 High

    Two advances converged: (1) the galectin-3/MGAT5 lattice was shown to control integrin-mediated focal adhesion signaling (FAK/PI3K) and fibronectin fibrillogenesis; (2) γ-secretase (presenilin complex) was identified as the protease that cleaves GnT-V at His31 to generate its secreted form.

    Evidence Mgat5-/- tumor cells with galectin-3 add-back and antibody blockade for integrin mechanism; N-terminal sequencing of soluble GnT-V, presenilin KO cells, γ-secretase inhibitor for cleavage mechanism

    PMID:16581792 PMID:17142794

    Open questions at the time
    • Whether γ-secretase cleavage is regulated by signaling cues unknown
    • Relative contributions of lattice-dependent vs. lattice-independent integrin regulation not fully resolved
  8. 2007 Medium

    Genetic epistasis between Mgat5 and Pten established a bidirectional feedback loop: PI3K/Akt signaling increases β1,6 branching, and β1,6 branching amplifies PI3K/Akt signaling.

    Evidence Pten/Mgat5 double-mutant MEFs, PI3K/Akt assays, L-PHA lectin staining

    PMID:17400585

    Open questions at the time
    • Molecular mechanism by which PI3K signaling upregulates β1,6 glycan output not identified
    • In vivo tumor relevance of the double-mutant interaction not tested
  9. 2009 High

    Rigorous enzyme kinetics distinguished MGAT5 from its paralog GnT-Vb (GnT-IX): MGAT5 is cation-independent and optimally active at Golgi pH, while GnT-Vb prefers O-mannosyl substrates, resolving potential functional redundancy.

    Evidence Purified enzyme kinetics with defined glycan acceptors, pH and cation-dependence profiles

    PMID:19846580

    Open questions at the time
    • No crystal structure available to explain selectivity differences
    • Tissue-specific substrate partitioning in vivo not addressed
  10. 2012 High

    In vivo substrate partitioning was confirmed: MGAT5 accounts for N-linked β1,6 branching and GnT-Vb for O-mannosyl β1,6 branching in brain, with double knockout eliminating all β1,6 products.

    Evidence Single and double knockout mice, glycan structural analysis, laminin binding assays

    PMID:22715095

    Open questions at the time
    • Functional consequences of brain-specific β1,6 N-glycan loss not deeply explored
    • Compensation mechanisms in peripheral tissues not examined
  11. 2018 Medium

    A specific transporter substrate was identified: MGAT5-catalyzed β1,6 branching on hENT1 stabilizes it at the plasma membrane, increasing gemcitabine uptake and chemosensitivity in bladder cancer.

    Evidence GnT-V shRNA knockdown, lectin blot for β1,6-GlcNAc on hENT1, membrane fractionation, drug uptake assays

    PMID:30143259

    Open questions at the time
    • Specific glycosylation sites on hENT1 not mapped
    • Galectin involvement in hENT1 retention not tested
    • Clinical validation absent
  12. 2021 Medium

    Two findings expanded MGAT5 biology: (1) MGAT5 mediates stiffness-dependent glioblastoma invasion via focal adhesion maturation and EMT; (2) IGF2BP1 stabilizes MGAT5 mRNA via m6A modification, linking epitranscriptomic regulation to cancer stemness.

    Evidence CRISPR KO in glioblastoma stem cells on tunable nanofiber scaffolds; MeRIP-qPCR for IGF2BP1-MGAT5 mRNA binding and mRNA stability assays in liver cancer cells

    PMID:33894774 PMID:34514861

    Open questions at the time
    • Specific m6A sites on MGAT5 mRNA not mapped
    • How mechanotransduction feeds back to MGAT5 expression unknown
    • Single-lab findings for each
  13. 2022 Medium

    SPPL3 was identified as a second protease (alongside γ-secretase) that cleaves GnT-V to generate its secreted form, which is selectively loaded into non-exosomal small extracellular vesicles capable of intercellular glycan remodeling.

    Evidence SPPL3 knockdown/knockout, sEV fractionation, enzymatic activity assays, recipient cell glycan analysis

    PMID:36590176

    Open questions at the time
    • Relative contributions of γ-secretase vs. SPPL3 to GnT-V secretion not quantified
    • Physiological range and target cell specificity of sEV-mediated glycan transfer unknown
  14. 2023 Medium

    Structural insights into substrate recognition emerged: molecular dynamics simulations combined with mutagenesis revealed that GnT-V recognizes the N-glycan core via residues outside the catalytic pocket, and UDP binding induces a conformational change affecting acceptor orientation; separately, hydrophobic UDP-GlcNAc analogs were shown to selectively inhibit GnT-V over GnT-I–IV.

    Evidence MD simulations validated by site-directed mutagenesis and HPLC activity assays; purified enzyme panel assays with synthetic donor analogs

    PMID:35248671 PMID:37974463

    Open questions at the time
    • No experimental crystal or cryo-EM structure of GnT-V with bound acceptor
    • Selectivity of inhibitors not tested in cellular context
  15. 2024 Medium

    MGAT5 was shown to shield tumors from immune surveillance: Mgat5-deficient pancreatic tumors become sensitive to TNF superfamily-mediated killing by T cells and dendritic cells, and Mgat5 knockout restores responsiveness to immune checkpoint blockade in resistant PDAC.

    Evidence Mgat5 KO clonal PDAC lines, in vivo growth, immune cell depletion experiments, TNF family death pathway assays, anti-PD-1/CTLA-4 treatment

    PMID:38912584

    Open questions at the time
    • Specific glycoprotein substrates mediating immune evasion not identified
    • Mechanism linking β1,6 glycans to TNF pathway sensitivity unknown
    • Human tumor validation absent
  16. 2025 Medium

    Specific in vivo substrates of MGAT5 were mapped in kidney (ANPEP, MEP1A at accessible C-terminal glycosites) and in prostate cancer (PSMA at N121/N336), with β1,6 branching controlling PSMA stability via the autophagy-lysosome pathway and TIMP-1 glycosylation driving VEGF-mediated angiogenesis in diabetic retinopathy.

    Evidence Lectin-assisted proteomics in Mgat5-null kidney, site-specific glycosite mapping, PSMA glycosylation/degradation assays, GST pull-down of GnT-V/TIMP-1, in vivo diabetic retinopathy model

    PMID:38499842 PMID:40112979 PMID:41323266

    Open questions at the time
    • Full in vivo substrate repertoire beyond kidney and select cancer substrates remains unmapped
    • Structural basis for substrate selectivity at specific glycosites not determined
    • TIMP-1 and PSMA findings each from single laboratories

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution experimental structure of MGAT5 with bound acceptor glycan exists, the full in vivo substrate repertoire is unmapped, and the molecular mechanism by which β1,6-branched glycans sensitize tumor cells to TNF-family-mediated immune killing remains unresolved.
  • Experimental 3D structure with acceptor glycan needed
  • Systematic in vivo substrate identification across tissues lacking
  • Mechanism linking glycan branching to TNF pathway death sensitivity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005794 Golgi apparatus 4 GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
ANPEPFOLH1IGF2BP1LGALS3MEP1APSEN1SPPL3TIMP1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MGAT5 (GlcNAc-TV) initiates β1,6 GlcNAc branching on N-glycans of the TCR complex, increasing N-acetyllactosamine ligands for galectins; galectin-3 associates with the TCR complex at the cell surface in an MGAT5-dependent manner, forming a galectin-glycoprotein lattice that restricts TCR clustering at the antigen presentation site, thereby raising T-cell activation thresholds. Mgat5-/- mice showed enhanced TCR clustering, actin microfilament reorganization, and autoimmune disease. Mgat5 knockout mice, lactose competition assay (phenocopy), co-immunoprecipitation of galectin-3 with TCR, TCR recruitment to agonist-coated beads, signaling and proliferation assays Nature High 11217864
2000 MGAT5-derived β1,6GlcNAc-branched N-glycans stimulate membrane ruffling and PI3K-PKB (Akt) activation, creating a positive feedback loop that amplifies oncogene signaling; Mgat5-deficient mice show markedly reduced mammary tumor growth and metastasis in a polyomavirus middle T oncogene model. Targeted gene knockout mice crossed with PyMT transgenic mice; PI3K/PKB activity assays; membrane ruffling assays; in vivo tumor growth and metastasis measurements Nature medicine High 10700233
2006 Galectin-3 binding to Mgat5-modified β1,6GlcNAc-branched N-glycans on fibronectin receptors regulates fibronectin fibrillogenesis and tumor cell motility by activating FAK and PI3K, recruiting conformationally active α5β1-integrin to fibrillar adhesions, and increasing F-actin turnover. Blocking Mgat5 or competing for galectin binding inhibits these processes. Mgat5-/- mammary epithelial tumor cells, swainsonine treatment, exogenous galectin-3 addition, RGD peptide inhibition, anti-galectin-3 antibodies, FAK/PI3K activity assays, fibronectin matrix remodeling assays Molecular and cellular biology High 16581792
1987 GnT-V (MGAT5) catalyzes transfer of GlcNAc in β1,6 linkage from UDP-GlcNAc onto α-mannoside acceptors (N-glycan precursors), as demonstrated by cell-free enzyme assays using a synthetic trisaccharide acceptor and UDP-[3H]-GlcNAc, producing a radiolabeled tetrasaccharide product. In vitro enzymatic assay with cell extracts, synthetic trisaccharide acceptor, UDP-[3H]-GlcNAc, reverse-phase chromatography product separation Biochemical and biophysical research communications High 2956949
2002 Secreted (soluble) GnT-V protein itself promotes tumor angiogenesis in vitro and in vivo at physiological concentrations independent of its glycosyltransferase activity, via its highly basic domain inducing release of FGF-2 from heparan sulfate proteoglycan on the cell surface/extracellular matrix. In vitro angiogenesis assays, in vivo angiogenesis models, addition of purified soluble GnT-V protein, domain analysis The Journal of biological chemistry Medium 11872751
2006 GnT-V is cleaved at its transmembrane/stem region boundary (at His31) by γ-secretase (presenilin-containing complex), generating the secreted ~100 kDa soluble form. Presenilin-1/2 double-deficient cells (no γ-secretase activity) completely lack soluble GnT-V secretion; FAD-linked presenilin-1 overexpression increases GnT-V secretion. N-terminal protein sequencing of purified soluble GnT-V, γ-secretase inhibitor (DFK-167) treatment, presenilin knockout cells, presenilin-1 overexpression, site-directed mutagenesis of cleavage site FASEB journal High 17142794
2004 MGAT5-mediated β1,6GlcNAc N-glycans on the TCR negatively regulate TCR signaling, promoting Th2 over Th1 differentiation; Mgat5-/- T cells produce more IFN-γ and less IL-4. Swainsonine (Golgi α-mannosidase II inhibitor blocking β1,6GlcNAc expression) phenocopies this increase in IFN-γ in human and mouse T cells, but has no additional effect in Mgat5-/- cells, confirming pathway specificity. Mgat5 knockout mice, cytokine ELISAs, swainsonine pharmacological inhibition, Th1/Th2 polarization assays, anti-CD3 stimulation of human T cells Journal of immunology High 15585841
1999 The transcription factor Ets-1 regulates GnT-V (MGAT5) gene expression in cancer cells; Ets-1 mRNA levels correlate tightly with GnT-V mRNA across 16 cancer cell lines (r=0.97), and overexpression of Ets-1 enhances GnT-V expression while dominant-negative Ets-1 reduces it. Correlation analysis across cancer cell lines, Ets-1 cDNA transfection, dominant-negative Ets-1 transfection, RT-PCR The Journal of biological chemistry Medium 10438459
2007 Mgat5 and PTEN interact functionally to regulate PI3K/Akt signaling, cell spreading, and proliferation: Pten heterozygosity enhances adhesion-dependent PI3K/Akt signaling and cell spreading, while Mgat5 deficiency normalizes these responses in Pten+/- cells. Pten heterozygosity is also associated with increased surface β1,6GlcNAc-branched N-glycans, suggesting positive feedback from PI3K signaling to N-glycan branching. Pten/Mgat5 double-mutant mouse embryonic fibroblasts, PI3K/Akt activity assays, cell spreading assays, L-PHA lectin staining, in vivo longevity analysis Glycobiology Medium 17400585
2009 GnT-V (MGAT5) and its paralog GnT-Vb (GnT-IX) have distinct catalytic properties: GnT-V is fully active without exogenous cations (pH optimum 6.5–7.0), while GnT-Vb is stimulated by Mn²⁺ (pH optimum 8.0) and has ~2.5-fold higher Km for biantennary N-glycan acceptors but much greater efficiency on O-mannosyl glycopeptide substrates. Both transfer GlcNAc in β1,6 linkage to the Man of GlcNAcβ1,2Man moiety. In vitro enzymatic assays with purified enzymes, synthetic and natural glycan acceptors, kinetic measurements (Km, Vmax), EDTA/cation dependence, pH profiles, product characterization Glycobiology High 19846580
2012 In vivo, GnT-V (MGAT5) and GnT-Vb (GnT-IX) have complementary substrate specificities: GnT-V null brains lack N-linked β1,6-glycans but have normal O-Man β1,6-branched structures; GnT-Vb null brains have normal N-linked β1,6-glycans but reduced O-Man β1,6-branched glycans. Only deletion of both enzymes eliminates all β1,6-branched glycans. GnT-V and GnT-Vb single and double knockout mice, glycan structural analysis, antibody binding assays (IIH6C4), laminin binding assays The Journal of biological chemistry High 22715095
2022 GnT-V (MGAT5) in small extracellular vesicles (sEVs) is a cleaved (secreted) form generated by SPPL3 protease cleavage; GnT-V is selectively enriched in non-exosomal sEVs among various glycosyltransferases. Enzymatically active GnT-V in sEVs is transferred to recipient cells and remodels their N-glycan structures to express GnT-V-produced β1,6-branched glycans. Glycosyltransferase activity measurements in sEV fractions, SPPL3 knockdown/knockout, single-particle imaging, fractionation experiments, recipient cell glycan structural analysis iScience Medium 36590176
2018 GnT-V enhances gemcitabine chemosensitivity in bladder cancer cells by adding β1,6-GlcNAc branches to the nucleoside transporter hENT1, which increases hENT1 accumulation at the plasma membrane and thus gemcitabine uptake. GnT-V silencing reduces β1,6-GlcNAc on hENT1 and decreases membrane hENT1 levels and drug uptake. GnT-V shRNA knockdown, lectin blot for β1,6-GlcNAc on hENT1, membrane fractionation, drug uptake assays, cell viability assays Biochemical and biophysical research communications Medium 30143259
2021 MGAT5-catalyzed β1,6-branched N-glycan production is required for stiffness-dependent invasion of glioblastoma stem-like cells (GSCs). CRISPR-Cas9 deletion of MGAT5 suppressed stiffness dependence of migration on 166 kPa nanofiber scaffolds and abolished associated focal adhesion (FA) maturation and EMT protein expression, demonstrating MGAT5 as a critical mediator of mechanotransduction. CRISPR-Cas9 MGAT5 deletion in GSCs, 3D nanofiber scaffolds with tunable stiffness, cell migration assays, galectin-3 binding, FA and EMT protein expression analysis Journal of experimental & clinical cancer research Medium 33894774
2023 Loss of MGAT5 in neural stem/progenitor cells (NSPCs) shifts differentiation toward neurons and away from astrocytes in vitro and in vivo, leading to accelerated neuronal differentiation, depletion of the NSPC niche, and a shift in cortical neuron layers in Mgat5-null mice. Mgat5 homozygous null mice, NSPC culture differentiation assays, in vivo cortical neuron layer analysis, cell fate marker immunostaining Stem cell reports Medium 37172586
2024 Mgat5 is required for in vivo tumor growth of pancreatic ductal adenocarcinoma (PDAC) but not for in vitro growth; Mgat5-deficient tumor cells show increased sensitivity to TNF superfamily-mediated cell death and are cleared by T cells and dendritic cells, with NK cells playing an early role. Mgat5 knockout in an immunotherapy-resistant PDAC line restored sensitivity to immune checkpoint blockade. Mgat5 knockout clonal cell lines, in vivo vs. in vitro growth comparison, T cell/NK cell/dendritic cell depletion experiments, TNF family cell death pathway assays, immune checkpoint blockade treatment JCI insight Medium 38912584
2023 GnT-V (MGAT5) recognizes the N-glycan core via residues outside its catalytic pocket, and UDP binding affects acceptor orientation through a conformational change at the Manα1,6-Man linkage, as determined by molecular dynamics simulations validated by biochemical experiments with site-specifically mutated residues. Molecular dynamics simulations, biochemical mutagenesis experiments, HPLC-based enzyme activity assays FEBS letters Medium 37974463
2022 UDP-GlcNAc analogs with increased hydrophobicity (phosphate groups replaced by hydrophobic groups) selectively inhibit GnT-V enzymatic activity compared to other GnT family members (GnT-I–IV), indicating GnT-V is uniquely tolerant of hydrophobicity in the donor substrate and that its catalytic pocket is structurally distinct. Purified truncated enzyme HPLC-based activity assays for GnT-I–V, synthesis of 10 UDP-GlcNAc analogs, docking models Biochimica et biophysica acta. General subjects Medium 35248671
2021 IGF2BP1 binds directly to MGAT5 mRNA and stabilizes it through m6A RNA methylation modification, promoting MGAT5 expression and consequently the liver cancer stem cell phenotype (self-renewal, chemoresistance, tumorigenesis). MeRIP-qPCR for IGF2BP1-MGAT5 mRNA binding, MGAT5 mRNA stability assays, IGF2BP1 shRNA knockdown, stemness and tumorigenesis assays Stem cells and development Medium 34514861
2001 GnT-V overexpression in hepatocellular carcinoma (7721) cells enhances cell migration and increases surface integrin α5 subunit ~2.9-fold without altering β1 subunit levels, and also elevates E-cadherin and β-catenin expression, linking MGAT5-mediated N-glycan branching to adhesion molecule regulation and migration. GnT-V cDNA transfection, agarose drop migration assay, flow cytometry for integrin subunits, immunocytochemistry for E-cadherin, Western blot for β-catenin Shi yan sheng wu xue bao Low 12549224
2025 GnT-V (MGAT5) selectively modifies the major kidney tubule apical surface metalloproteases ANPEP and MEP1A at highly accessible, C-terminal domain glycosylation sites. Upon epithelial cell polarization, GnT-V products accumulate to the apical side, suggesting polarized subcellular trafficking contributes to selective substrate modification in vivo. Lectin-assisted proteomics in Mgat5-null mouse kidney, single-cell transcriptomics, glycosite mapping, epithelial cell polarization experiments with apical/basolateral fractionation iScience Medium 41323266
2025 GnT-V (MGAT5) catalyzes β1,6-GlcNAc branching at N121 and N336 of PSMA, which is critical for PSMA protein stability (non-N-glycosylated PSMA is degraded via the autophagy-lysosome pathway). PSMA directly interacts with JAK2 (confirmed by co-immunoprecipitation), which activates STAT3 transcriptional activation, driving PSMA overexpression and aberrant N-glycosylation in a positive feedback loop. Site-specific N-glycosylation mapping of PSMA, GnT-V inhibition/knockdown, autophagy-lysosome pathway inhibitors, co-immunoprecipitation of PSMA and JAK2, STAT3 activity assays International journal of biological macromolecules Medium 40112979
2024 GnT-V (MGAT5) binds to TIMP-1 (confirmed by GST pull-down) and promotes N-glycosylation of TIMP-1; this aberrant GnT-V-mediated N-glycosylation of TIMP-1 activates the VEGF signaling pathway and promotes retinal microvascular endothelial cell angiogenesis in diabetic retinopathy. Kifunensine treatment, GnT-V knockdown, or TIMP-1 mutation reverses these effects. GST pull-down assay for GnT-V/TIMP-1 interaction, lectin blot for TIMP-1 glycosylation, GnT-V knockdown, TIMP-1 glycosylation-site mutants, angiogenesis assays, VEGF ELISA, in vivo DR model Molecular biology reports Medium 38499842

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 726 11217864
2000 Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nature medicine 474 10700233
2006 Galectin binding to Mgat5-modified N-glycans regulates fibronectin matrix remodeling in tumor cells. Molecular and cellular biology 161 16581792
2004 N-acetylglucosaminyltransferase V (Mgat5)-mediated N-glycosylation negatively regulates Th1 cytokine production by T cells. Journal of immunology (Baltimore, Md. : 1950) 133 15585841
1999 Regulation of the GnT-V promoter by transcription factor Ets-1 in various cancer cell lines. The Journal of biological chemistry 92 10438459
2002 UDP-N-acetylglucosamine:alpha-6-D-mannoside beta1,6 N-acetylglucosaminyltransferase V (Mgat5) deficient mice. Biochimica et biophysica acta 81 12417426
2002 A secreted type of beta 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation: a novel function of GnT-V distinct from the original glycosyltransferase activity. The Journal of biological chemistry 78 11872751
2011 Polymorphisms in B3GAT1, SLC9A9 and MGAT5 are associated with variation within the human plasma N-glycome of 3533 European adults. Human molecular genetics 74 21908519
2010 MGAT5 alters the severity of multiple sclerosis. Journal of neuroimmunology 63 20117844
2019 Decreased miR-124-3p promoted breast cancer proliferation and metastasis by targeting MGAT5. American journal of cancer research 54 30949412
2008 Knockdown of Mgat5 inhibits breast cancer cell growth with activation of CD4+ T cells and macrophages. Journal of immunology (Baltimore, Md. : 1950) 51 18292539
2021 Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing. Journal of experimental & clinical cancer research : CR 49 33894774
2021 IGF2BP1 Promotes the Liver Cancer Stem Cell Phenotype by Regulating MGAT5 mRNA Stability by m6A RNA Methylation. Stem cells and development 46 34514861
1987 Activity of UDP-GlcNAc:alpha-mannoside beta(1,6)N-acetylglucosaminyltransferase (GnT V) in cultured cells using a synthetic trisaccharide acceptor. Biochemical and biophysical research communications 43 2956949
2023 Aberrant N-glycosylation in cancer: MGAT5 and β1,6-GlcNAc branched N-glycans as critical regulators of tumor development and progression. Cellular oncology (Dordrecht, Netherlands) 38 36689079
2012 Developmental expression of the neuron-specific N-acetylglucosaminyltransferase Vb (GnT-Vb/IX) and identification of its in vivo glycan products in comparison with those of its paralog, GnT-V. The Journal of biological chemistry 36 22715095
2007 Mgat5 and Pten interact to regulate cell growth and polarity. Glycobiology 32 17400585
2007 Beta N-acetylglucosaminyltransferase V (Mgat5) deficiency reduces the depression-like phenotype in mice. Genes, brain, and behavior 32 17883406
2017 Phostine PST3.1a Targets MGAT5 and Inhibits Glioblastoma-Initiating Cell Invasiveness and Proliferation. Molecular cancer research : MCR 30 28634226
2003 GnT-V, macrophage and cancer metastasis: a common link. Clinical & experimental metastasis 30 12856724
2013 Hypomorphic MGAT5 polymorphisms promote multiple sclerosis cooperatively with MGAT1 and interleukin-2 and 7 receptor variants. Journal of neuroimmunology 29 23351704
2011 Mgat5 deficiency in T cells and experimental autoimmune encephalomyelitis. ISRN neurology 28 22389815
2009 Comparison of the substrate specificities and catalytic properties of the sister N-acetylglucosaminyltransferases, GnT-V and GnT-Vb (IX). Glycobiology 28 19846580
2020 Genetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative Colitis. Clinical and translational gastroenterology 26 32352685
2006 A secreted type of beta1,6 N-acetylglucosaminyltransferase V (GnT-V), a novel angiogenesis inducer, is regulated by gamma-secretase. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 17142794
2013 Downregulation of the GnT-V gene inhibits metastasis and invasion of BGC823 gastric cancer cells. Oncology reports 22 23563846
2023 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. Stem cell reports 20 37172586
2018 Hydrogen Sulfide Demonstrates Promising Antitumor Efficacy in Gastric Carcinoma by Targeting MGAT5. Translational oncology 19 29800930
2012 Physiological roles of N-acetylglucosaminyltransferase V(GnT-V) in mice. BMB reports 19 23101508
2006 GnT-V expression and metastatic phenotypes in macrophage-melanoma fusion hybrids is down-regulated by 5-Aza-dC: evidence for methylation sensitive, extragenic regulation of GnT-V transcription. Gene 18 16556489
2011 Knockdown of Mgat5 inhibits CD133+ human pulmonary adenocarcinoma cell growth in vitro and in vivo. Clinical and investigative medicine. Medecine clinique et experimentale 15 21631992
2012 Down-regulation of GnT-V enhances nasopharyngeal carcinoma cell CNE-2 radiosensitivity in vitro and in vivo. Biochemical and biophysical research communications 14 22780953
2022 Structure-based design of UDP-GlcNAc analogs as candidate GnT-V inhibitors. Biochimica et biophysica acta. General subjects 12 35248671
2016 Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice. Behavioural brain research 12 27329152
2023 RUNX2 promotes gastric cancer progression through the transcriptional activation of MGAT5 and MMP13. Frontiers in oncology 11 37256183
2020 miR-124-3p Regulates FGF2-EGFR Pathway to Overcome Pemetrexed Resistance in Lung Adenocarcinoma Cells by Targeting MGAT5. Cancer management and research 11 33223850
2015 Effect of GnT-V knockdown on the proliferation, migration and invasion of the SMMC7721/R human hepatocellular carcinoma drug-resistant cell line. Molecular medicine reports 11 26531171
2015 Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration β1, 6-GlcNAc branched N-glycans. International journal of clinical and experimental pathology 11 26617699
2024 N-glycosylation by Mgat5 imposes a targetable constraint on immune-mediated tumor clearance. JCI insight 10 38912584
2022 N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells. iScience 10 36590176
2016 The Role of MGAT5 in Human Umbilical Vein Endothelial Cells. Reproductive sciences (Thousand Oaks, Calif.) 10 27334383
2011 Down-regulation of GnT-V inhibits nasopharyngeal carcinoma cell CNE-2 malignancy in vitro and in vivo. Cancer letters 10 21676538
2023 Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. Journal of integrative medicine 9 37980180
2018 GnT-V promotes chemosensitivity to gemcitabine in bladder cancer cells through β1,6 GlcNAc branch modification of human equilibrative nucleoside transporter 1. Biochemical and biophysical research communications 9 30143259
2016 Loss of Mgat5a-mediated N-glycosylation stimulates regeneration in zebrafish. Cell regeneration (London, England) 8 27795824
2023 The cancer-associated glycosyltransferase GnT-V (MGAT5) recognizes the N-glycan core via residues outside its catalytic pocket. FEBS letters 7 37974463
2021 The polymorphisms of FGFR2 and MGAT5 affect the susceptibility to COPD in the Chinese people. BMC pulmonary medicine 7 33879098
2014 Predominant expression of N-acetylglucosaminyltransferase V (GnT-V) in neural stem/progenitor cells. Stem cell research 6 25524127
2008 Positive expressions of N-acetylglucosaminyltransferase-V (GnT-V) and beta1-6 branching N-linked oligosaccharides in human testicular germ cells diminish during malignant transformation and progression. International journal of oncology 6 18097551
2025 Increased N-glycosylation of PSMA by GnT-V enhances tumor malignancy through interacting with JAK2 and the subsequent STAT3-mediated transcriptional activation in prostate cancer. International journal of biological macromolecules 4 40112979
2024 Structure and function of N-acetylglucosaminyltransferase V (GnT-V). Biochimica et biophysica acta. General subjects 4 39233219
2024 GnT-V-mediated aberrant N-glycosylation of TIMP-1 promotes diabetic retinopathy progression. Molecular biology reports 2 38499842
2002 Sequences of the mouse N-acetylglucosaminyltransferase V (Mgat5) mRNA and an mRNA expressed by an Mgat5-deficient cell line. Glycobiology 2 12122020
2025 Selective modification of glycoprotein substrates by GnT-V in mouse kidney. iScience 1 41323266
2023 ISLR interacts with MGAT5 to promote the malignant progression of human gastric cancer AGS cells. Iranian journal of basic medical sciences 1 37427332
2001 [GnT-V overexpression in human hepatocarcinoma cells affects its migration and expression of cell adhesion molecules]. Shi yan sheng wu xue bao 1 12549224
2025 MGAT3 and MGAT5 overexpression alters the protein cargo of extracellular vesicles released by metastatic melanoma cells. Biochemical and biophysical research communications 0 40199132
2008 Evidence for tyrosinase as a beta1,6 branch containing glycoprotein: substrate of GnT-V. Life sciences 0 18655794