Affinage

MGAT5

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

Length
741 aa
Mass
84.5 kDa
Annotated
2026-06-10
58 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MGAT5 encodes GnT-V, a Golgi glycosyltransferase that adds GlcNAc in β1,6 linkage to N-glycans, generating poly-N-acetyllactosamine branches that act as high-avidity galectin ligands and set surface signaling thresholds across immune, adhesion, and oncogenic programs (PMID:11217864, PMID:2956949, PMID:22715095). The resulting galectin-glycoprotein lattice restrains TCR clustering to raise the T-cell activation threshold and biases differentiation toward Th2, while also gating CTLA-4 endocytosis, such that Mgat5 loss produces T-cell hyperactivity (PMID:11217864, PMID:15585841, PMID:22389815). The same branched glycans on fibronectin receptors and integrins recruit galectin-3 to focal adhesions, activate FAK and PI3K-PKB(Akt) signaling, and amplify a positive feedback loop with N-glycan branching that drives membrane ruffling, cell motility, mechanosensitive invasion, and tumor progression; this circuit is reciprocally tuned by PTEN (PMID:10700233, PMID:16581792, PMID:17400585, PMID:33894774). In vivo, GnT-V is the exclusive source of N-linked β1,6 branches and cannot be substituted by its paralog GnT-Vb, and its catalytic specificity is governed by metal-independence, acidic pH optimum, donor-pocket hydrophobicity, and acceptor recognition by residues outside the catalytic site (PMID:22715095, PMID:19846580, PMID:35248671, PMID:37974463). GnT-V branches specific substrates to control their fate: it stabilizes the surface transporter hENT1 to set gemcitabine sensitivity, protects PSMA from autophagy-lysosomal degradation within a JAK2/STAT3 feedback loop, glycosylates TIMP-1 to activate VEGF signaling, and modifies apical kidney metalloproteases ANPEP and MEP1A (PMID:30143259, PMID:40112979, PMID:38499842, PMID:41323266). MGAT5 transcription is driven by Ets-1 and by RUNX2 binding the promoter, and its mRNA is stabilized by IGF2BP1 through m6A modification (PMID:10438459, PMID:37256183, PMID:34514861). The membrane enzyme is cleaved at His31 by γ-secretase to release a soluble form whose basic domain promotes angiogenesis by liberating FGF-2 from heparan sulfate proteoglycans independently of catalytic activity, and a SPPL3-cleaved active form is loaded into small extracellular vesicles that remodel recipient-cell glycans (PMID:17142794, PMID:11872751, PMID:36590176).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1987 Medium

    Establishing that GnT-V is a discrete enzymatic activity required directly measuring transfer of GlcNAc to a defined acceptor, providing the biochemical foundation for all downstream work.

    Evidence In vitro enzyme assay with UDP-[3H]-GlcNAc and synthetic trisaccharide acceptor in cell-line extracts, including an activity-null variant

    PMID:2956949

    Open questions at the time
    • Did not identify the gene/protein
    • No in vivo substrate identified
    • No structural basis for activity
  2. 2000 High

    It was unknown whether β1,6 branching contributed causally to malignancy; crossing Mgat5 knockout with an oncogene-driven tumor model showed branched glycans feed PI3K-PKB signaling and are required for tumor growth and metastasis.

    Evidence Mgat5 KO × polyomavirus middle T transgenic mice, in vivo tumor/metastasis assays, PI3K-PKB and membrane ruffling biochemistry

    PMID:10700233

    Open questions at the time
    • Specific glycoprotein substrates mediating the effect not defined
    • Mechanism linking branching to PI3K not resolved at this stage
  3. 2001 High

    How branched N-glycans regulate cell signaling was unclear; the discovery that galectin-3 forms an Mgat5-dependent lattice on the TCR established the galectin-glycoprotein lattice as the mechanistic principle setting activation thresholds.

    Evidence Mgat5 KO mice, galectin-3/TCR co-IP, lactose competition, TCR clustering and proliferation assays

    PMID:11217864

    Open questions at the time
    • Stoichiometry and structure of the lattice unresolved
    • Generality across other surface receptors not yet tested
  4. 2002 Medium

    A secreted GnT-V form was found to have a function independent of glycosyltransferase activity, revealing a moonlighting role in angiogenesis via FGF-2 release.

    Evidence In vitro/in vivo angiogenesis assays with purified secreted GnT-V, basic-domain mapping

    PMID:11872751

    Open questions at the time
    • Protease generating the secreted form not identified here
    • Physiological relevance versus catalytic role unclear
  5. 2004 High

    Whether branching shapes T-cell fate was open; Mgat5 loss biased cytokine output toward Th1, defining branching as a negative regulator of TCR signaling controlling Th1/Th2 balance.

    Evidence Mgat5 KO mice and swainsonine (no additive effect), cytokine ELISA, polarization assays

    PMID:15585841

    Open questions at the time
    • Receptor substrates beyond the TCR not enumerated
    • Transcriptional consequences downstream not mapped
  6. 2006 High

    Linking the lattice to motility, galectin-3 binding to Mgat5 glycans on fibronectin receptors was shown to activate FAK/PI3K and recruit active integrin to adhesions.

    Evidence Mgat5-/- tumor cells, exogenous galectin-3 rescue, swainsonine/RGP inhibition, FAK/PI3K and integrin localization assays

    PMID:16581792

    Open questions at the time
    • Dose-dependence of galectin effects not fully resolved
    • Specific integrin glycosites not mapped
  7. 2006 High

    The origin of soluble GnT-V was unknown; γ-secretase was identified as the protease cleaving the enzyme at His31, mechanistically connecting presenilin activity to GnT-V shedding.

    Evidence N-terminal sequencing of soluble GnT-V, DFK-167 inhibitor, presenilin-1/2 double-KO cells, cleavage-site mutagenesis

    PMID:17142794

    Open questions at the time
    • Regulation of cleavage in physiological contexts unclear
    • Relationship to SPPL3-mediated cleavage not addressed
  8. 2007 Medium

    The directionality of the branching/PI3K relationship was tested using Mgat5/Pten epistasis, establishing positive feedback from PI3K signaling back to N-glycan branching.

    Evidence Mgat5/Pten double-mutant MEFs, PI3K/Akt and spreading assays, lectin flow cytometry, longevity analysis

    PMID:17400585

    Open questions at the time
    • Molecular mechanism coupling PI3K to MGAT5 expression/activity not defined
    • Single-lab epistasis
  9. 1999 Medium

    How MGAT5 is transcriptionally controlled was unknown; Ets-1 was identified as a regulator whose level correlates with and drives GnT-V expression.

    Evidence mRNA correlation across 16 cancer lines, Ets-1 and dominant-negative Ets-1 transfection

    PMID:10438459

    Open questions at the time
    • Direct promoter binding not shown here
    • Correlative across-line data
  10. 2009 High

    Distinguishing GnT-V from paralog GnT-Vb required kinetic characterization, defining GnT-V's metal-independence, pH optimum, and preference for N-glycan over O-mannose acceptors.

    Evidence In vitro kinetics with purified truncated enzymes, synthetic acceptors, HPLC product analysis

    PMID:19846580

    Open questions at the time
    • In vivo substrate preference not yet demonstrated
    • Structural basis of substrate discrimination unresolved
  11. 2011 Medium

    Branching was shown to control CTLA-4 endocytosis and contribute to autoimmunity, extending the lattice model to inhibitory receptor regulation and disease.

    Evidence Mgat5 KO mice, adoptive T-cell transfer, EAE model

    PMID:22389815

    Open questions at the time
    • Direct CTLA-4 glycosite mapping not shown
    • Non-T-cell contributions not dissected
  12. 2012 High

    Genetic dissection in brain established GnT-V as the sole in vivo source of N-linked β1,6 branches, non-redundant with GnT-Vb.

    Evidence GnT-V, GnT-Vb, and double-KO mice with glycan structural analysis

    PMID:22715095

    Open questions at the time
    • Tissue-specific substrate identities not addressed
    • Functional consequences in brain not characterized here
  13. 2013 Medium

    A direct transcriptional activator was confirmed when RUNX2 was shown to bind the MGAT5 promoter and drive expression in gastric cancer.

    Evidence ChIP-PCR, RUNX2 siRNA, qRT-PCR/Western, in vivo xenograft

    PMID:37256183

    Open questions at the time
    • Relationship to Ets-1 regulation not integrated
    • Single-lab cancer context
  14. 2018 Medium

    The first defined functional substrate emerged: GnT-V branching of hENT1 controls its surface accumulation and thereby gemcitabine uptake and chemosensitivity.

    Evidence GnT-V shRNA, hENT1 lectin blot, surface fractionation, gemcitabine uptake/viability assays

    PMID:30143259

    Open questions at the time
    • hENT1 glycosites not mapped
    • Single cancer-cell context
  15. 2021 Medium

    Post-transcriptional control of MGAT5 was established when IGF2BP1 was shown to stabilize MGAT5 mRNA via m6A, linking branching to liver cancer stemness.

    Evidence IGF2BP1 shRNA, MeRIP-qPCR, mRNA stability assay, stemness and in vivo tumorigenesis assays

    PMID:34514861

    Open questions at the time
    • m6A site on MGAT5 not pinpointed
    • Generality beyond liver cancer stem cells unknown
  16. 2021 Medium

    Branching was connected to mechanosensing when CRISPR deletion of MGAT5 abolished stiffness-dependent glioblastoma invasion via the galectin-3/integrin axis.

    Evidence CRISPR MGAT5 KO in GSCs, tunable-stiffness scaffolds, migration, focal adhesion/EMT readouts, galectin-3 binding

    PMID:33894774

    Open questions at the time
    • Specific mechanoreceptor substrates not identified
    • Single-lab GSC system
  17. 2022 Medium

    Selective inhibitor design and computational/biochemical analysis revealed GnT-V's unusual donor-pocket hydrophobicity tolerance and acceptor recognition by residues outside the catalytic site.

    Evidence In vitro inhibition with UDP-GlcNAc analogs across GnT-I–V, docking; MD simulations with mutagenesis

    PMID:35248671 PMID:37974463

    Open questions at the time
    • No experimental high-resolution structure
    • Inhibitor selectivity in cells not demonstrated
  18. 2022 Medium

    An intercellular dimension of GnT-V was revealed: SPPL3-cleaved active enzyme is loaded into small EVs that transfer to recipient cells and remodel their glycans.

    Evidence sEV fractionation, single-particle imaging, SPPL3 knockdown, sEV enzyme activity, recipient N-glycan profiling

    PMID:36590176

    Open questions at the time
    • Physiological relevance of glycan transfer in vivo unclear
    • Relationship of SPPL3 to γ-secretase cleavage not reconciled
  19. 2023 Medium

    A developmental role emerged: MGAT5 loss in neural stem/progenitor cells shifts differentiation toward neurons and depletes the niche, altering cortical layering.

    Evidence Mgat5 null mice, in vitro NSPC differentiation, in vivo cortical layering analysis

    PMID:37172586

    Open questions at the time
    • Substrate(s) governing NSPC fate not identified
    • Signaling pathway downstream not mapped
  20. 2024 Medium

    MGAT5 was implicated in immune evasion when its loss sensitized PDAC to TNF-superfamily death and enabled T/DC/NK-dependent tumor clearance with checkpoint blockade.

    Evidence Mgat5 KO PDAC lines, syngeneic in vivo models, immune-cell depletion, cell death pathway analysis, checkpoint blockade

    PMID:38912584

    Open questions at the time
    • Specific glycoprotein substrates controlling death sensitivity not defined
    • Single-lab models
  21. 2024 Medium

    Substrate-specific control of protein fate was extended to PSMA, whose GnT-V branching prevents autophagic degradation within a JAK2/STAT3/GnT-V/PSMA feedback loop, and to TIMP-1, whose glycosylation activates VEGF signaling.

    Evidence PSMA glycosite mapping, PSMA-JAK2 co-IP, autophagy inhibition, STAT3 assays; GnT-V/TIMP-1 GST pull-down, TIMP-1 mutant, angiogenesis and in vivo DR model

    PMID:38499842 PMID:40112979

    Open questions at the time
    • Mechanism of glycan-dependent degradation protection not fully resolved
    • Single-lab disease contexts
  22. 2025 Medium

    Unbiased in vivo substrate profiling identified ANPEP and MEP1A as major kidney GnT-V substrates and linked polarized trafficking to substrate-selective glycosylation.

    Evidence Lectin-assisted proteomics, glycosite mapping, single-cell transcriptomics, epithelial polarization assay

    PMID:41323266

    Open questions at the time
    • Functional consequences of ANPEP/MEP1A branching not established
    • Trafficking machinery directing apical accumulation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure and unified mechanistic account of how subcellular trafficking and substrate accessibility dictate which proteins GnT-V branches in a given tissue remain unresolved.
  • No experimental enzyme structure in the corpus
  • Rules governing tissue/substrate selectivity incomplete
  • Reconciliation of multiple cleaved/secreted/EV forms not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005576 extracellular region 2 GO:0005794 Golgi apparatus 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 3
Partners
ISLRJAK2LGALS3PSEN1PSMATIMP-1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MGAT5 initiates GlcNAc β1,6 branching on N-glycans, increasing N-acetyllactosamine that serves as ligand for galectins; galectin-3 was shown to associate with the TCR complex at the cell surface in an MGAT5-dependent manner, forming a galectin-glycoprotein lattice that restricts TCR recruitment to the site of antigen presentation and raises the T-cell activation threshold. Lactose competition for galectin binding phenocopied Mgat5-/- TCR clustering. Mgat5-deficient mice showed enhanced TCR clustering, actin microfilament re-organization, and downstream signaling. Mgat5 knockout mice, lactose competition assay, co-immunoprecipitation of galectin-3 with TCR complex, TCR clustering assay with agonist-coated beads, proliferation assays Nature High 11217864
2000 MGAT5-produced β1,6GlcNAc-branched N-glycans stimulate membrane ruffling and PI3K-PKB (Akt) activation, fueling a positive feedback loop that amplifies oncogene signaling. Loss of Mgat5 in mice markedly reduced mammary tumor growth and metastasis driven by the polyomavirus middle T oncogene, demonstrating that tumor progression depends on Mgat5 glycan-mediated focal adhesion signaling. Mgat5 knockout mice crossed with polyomavirus middle T oncogene transgenics; in vivo tumor growth and metastasis assays; PI3K-PKB signaling assays; membrane ruffling assays Nature medicine High 10700233
2006 Galectin-3 binding to Mgat5-modified β1,6GlcNAc N-glycans on fibronectin receptors regulates fibronectin fibrillogenesis and tumor cell motility. At optimal doses, exogenous galectin-3 activates FAK and PI3K, recruits conformationally active α5β1-integrin to fibrillar adhesions, and increases F-actin turnover. These effects are dependent on galectin-glycan binding and are absent in Mgat5-/- cells. Mgat5-/- mammary tumor cells, exogenous galectin-3 rescue, swainsonine inhibition, RGD peptide inhibition, anti-galectin-3 domain antibodies, FAK/PI3K biochemical assays, α5β1-integrin localization Molecular and cellular biology High 16581792
2004 β1,6GlcNAc N-glycans produced by Mgat5 on the TCR negatively regulate TCR signaling to promote Th2 over Th1 differentiation. Mgat5-/- T cells and swainsonine-treated T cells produce more IFN-γ and less IL-4; swainsonine had no additional effect in Mgat5-/- cells, confirming specificity. Mgat5 deficiency caused ~10-fold increase in IFN-γ production by polarized Th2 cells. Mgat5 knockout mice, swainsonine (Golgi α-mannosidase II inhibitor), cytokine ELISA, T-cell polarization assays Journal of immunology High 15585841
2002 A secreted form of GnT-V promotes angiogenesis in vitro and in vivo independently of its glycosyltransferase activity. The highly basic domain of secreted GnT-V induces release of FGF-2 from heparan sulfate proteoglycans on the cell surface/extracellular matrix. In vitro angiogenesis assays, in vivo angiogenesis assays, addition of purified secreted GnT-V protein, domain analysis with basic domain The Journal of biological chemistry Medium 11872751
2006 Golgi-resident GnT-V is cleaved at its transmembrane region by γ-secretase (containing presenilin-1) to generate a soluble secreted form (~100 kDa) starting at His31. The cleavage was specifically inhibited by γ-secretase inhibitor DFK-167 and was completely abolished in presenilin-1/2 double-deficient cells. Overexpression of FAD-linked presenilin-1 increased GnT-V secretion rate. N-terminal protein sequencing of purified soluble GnT-V, γ-secretase inhibitor DFK-167, presenilin-1/2 double-knockout cells, presenilin-1 overexpression, site-directed mutagenesis of cleavage site FASEB journal High 17142794
1999 Transcription factor Ets-1 regulates expression of the GnT-V (MGAT5) gene. GnT-V mRNA levels correlated with Ets-1 expression across 16 cancer cell lines (r=0.97). Transfection of Ets-1 cDNA enhanced GnT-V expression in low-Ets-1 cells; dominant-negative Ets-1 reduced GnT-V expression in high-Ets-1 cells. mRNA correlation across cell lines, Ets-1 cDNA transfection, dominant-negative Ets-1 transfection The Journal of biological chemistry Medium 10438459
2007 Mgat5 and Pten interact functionally in opposing directions to regulate PI3K/Akt signaling, cell spreading, and proliferation. Pten heterozygosity enhances cell adhesion-dependent PI3K/Akt signaling and is associated with increased surface β1,6GlcNAc-branched N-glycans; Mgat5/Pten double-mutant cells normalize these effects, indicating positive feedback from PI3K signaling to N-glycan branching. Mgat5/Pten double-mutant mouse embryonic fibroblasts, PI3K/Akt signaling assays, cell spreading and proliferation assays, flow cytometric lectin binding for N-glycan quantification, in vivo longevity analysis Glycobiology Medium 17400585
2009 GnT-V (MGAT5) and its paralog GnT-Vb have distinct catalytic properties: GnT-V is active without exogenous cations and inhibited by EDTA, has a pH optimum of 6.5–7.0, and shows poor activity toward O-mannose-linked glycopeptides. Both enzymes transfer GlcNAcβ1,6 to Man residues of N-glycan substrates, but GnT-Vb shows ~2.5-fold higher Km for the biantennary N-glycan acceptor and much higher activity toward O-mannose glycopeptides. In vitro enzyme kinetics assays with purified truncated enzymes, synthetic trisaccharide and glycopeptide acceptors, HPLC product analysis Glycobiology High 19846580
2012 In vivo, GnT-V (MGAT5) is responsible for synthesizing N-linked β1,6-branched glycans; GnT-V null brains lacked N-linked β1,6-glycans but had normal O-mannose β1,6-branched structures, showing GnT-Vb cannot compensate for GnT-V loss for N-glycan branching. Double knockout of GnT-V and GnT-Vb eliminated both N-linked and O-mannose β1,6-branched glycans in brain. GnT-V knockout mice, GnT-Vb knockout mice, GnT-V/GnT-Vb double knockout mice, glycan structural analysis The Journal of biological chemistry High 22715095
2011 Mgat5 N-glycan branching regulates CTLA-4 endocytosis; deficiency promotes T-cell hyperactivity. Adoptive transfer of myelin-reactive Mgat5-/- T cells into Mgat5+/+ versus Mgat5-/- recipients caused more severe EAE in Mgat5-/- recipients, indicating that Mgat5 branching deficiency in recipient naive T cells and/or non-T cells also contributes to autoimmune disease pathogenesis. Mgat5 knockout mice, adoptive T-cell transfer, EAE model of autoimmune encephalomyelitis ISRN neurology Medium 22389815
2013 RUNX2 transcription factor directly binds to the MGAT5 promoter and activates MGAT5 transcription in gastric cancer cells, as confirmed by ChIP-PCR. RUNX2 silencing reduced MGAT5 expression and suppressed tumor proliferation, invasion, migration, and metastasis in vivo. ChIP-PCR, JASPAR promoter binding prediction, RUNX2 siRNA knockdown, qRT-PCR, Western blot, in vivo xenograft Frontiers in oncology Medium 37256183
2018 GnT-V modifies human equilibrative nucleoside transporter 1 (hENT1) with β1,6-GlcNAc branched N-glycans; silencing GnT-V dramatically decreased β1,6-GlcNAc structure on hENT1, reduced hENT1 accumulation at the plasma membrane, and decreased gemcitabine uptake and chemosensitivity in bladder cancer cells. GnT-V shRNA knockdown, lectin blot for β1,6-GlcNAc on hENT1, cell surface fractionation, gemcitabine uptake assay, cell viability assay Biochemical and biophysical research communications Medium 30143259
2021 IGF2BP1 binds to MGAT5 mRNA through m6A modification and stabilizes it, promoting MGAT5 expression and liver cancer stem cell phenotypes (self-renewal, chemoresistance). MeRIP-qPCR confirmed direct IGF2BP1 binding to MGAT5 mRNA via m6A. IGF2BP1 shRNA knockdown, MeRIP-qPCR, mRNA stability assay (qRT-PCR), cancer stem cell phenotype assays, in vivo tumorigenesis Stem cells and development Medium 34514861
2022 GnT-V (MGAT5) is selectively enriched in small extracellular vesicles (sEVs) among glycosyltransferases. GnT-V in sEVs exists as a cleaved form, and cleavage by SPPL3 protease is required for its loading into sEVs. Enzymatically active GnT-V in sEVs transfers to recipient cells and remodels their N-glycan structures to express GnT-V-produced glycans. Fractionation of sEV subtypes, single-particle imaging, SPPL3 protease involvement (knockdown), enzyme activity assays in sEVs, N-glycan profiling of recipient cells iScience Medium 36590176
2022 Structure-based design identified UDP-GlcNAc analogs with increased hydrophobicity (phosphate group replacement) as selective inhibitors of GnT-V activity. GnT-V is relatively tolerant of donor substrate hydrophobicity compared with other GlcNAc transferases (GnT-I–IV), suggesting unique catalytic pocket properties. In vitro HPLC-based enzyme assay with purified truncated GnT-V and other GlcNAc transferases, synthetic UDP-GlcNAc analog compounds, docking models Biochimica et biophysica acta. General subjects Medium 35248671
2023 Molecular dynamics simulations and biochemical experiments revealed that residues outside the catalytic pocket of GnT-V are involved in recognition of the core part of the N-glycan acceptor. UDP binding was found to affect the orientation of the acceptor substrate via conformational change at the Manα1,6-Man linkage. Molecular dynamics simulation, biochemical mutagenesis and enzyme activity assays FEBS letters Medium 37974463
2021 MGAT5-catalyzed N-glycan branching is a critical regulator of stiffness-dependent invasion in glioblastoma stem-like cells (GSCs). CRISPR-Cas9 deletion of MGAT5 in GSCs suppressed β1,6-branched N-glycan expression, abolished stiffness-dependent migration at 166 kPa, and reduced focal adhesion and EMT protein expression, linking MGAT5 N-glycosylation to mechanosensing via the galectin-3/integrin axis. CRISPR-Cas9 MGAT5 knockout, 3D nanofiber scaffold with adjustable stiffness, cell migration assay, focal adhesion protein expression, galectin-3 lectin binding Journal of experimental & clinical cancer research Medium 33894774
2024 Mgat5-deficient pancreatic ductal adenocarcinoma cells show increased sensitivity to TNF superfamily-mediated cell death pathways, and Mgat5 loss leads to tumor clearance that is dependent on T cells and dendritic cells (with early NK cell involvement) in vivo. Mgat5 knockout in an immunotherapy-resistant PDAC line significantly decreased tumor growth and increased survival upon immune checkpoint blockade. Mgat5 knockout clonal PDAC cell lines, in vivo syngeneic tumor models, T-cell/NK-cell depletion experiments, TNF superfamily cell death pathway analysis, immune checkpoint blockade treatment JCI insight Medium 38912584
2023 Loss of MGAT5 in neural stem/progenitor cells (NSPCs) shifts differentiation toward neurons and away from astrocytes in vitro, and causes accelerated neuronal differentiation and depletion of the NSPC niche in vivo, resulting in a shift in cortical neuron layers in Mgat5 null mice. Mgat5 null mice, in vitro NSPC differentiation assays, in vivo cortical layering analysis Stem cell reports Medium 37172586
2024 GnT-V catalyzes β1,6-GlcNAc branching at N121 and N336 of PSMA; non-N-glycosylated PSMA is degraded via the autophagy-lysosome pathway. PSMA directly interacts with JAK2 (confirmed by co-immunoprecipitation), facilitating STAT3 activation, which in turn drives overexpression of both PSMA and GnT-V, forming a JAK2/STAT3/GnT-V/PSMA positive feedback loop. Site-specific N-glycosylation mapping, PSMA mutants, co-immunoprecipitation of PSMA-JAK2, autophagy-lysosome pathway inhibition, STAT3 transcription factor assays International journal of biological macromolecules Medium 40112979
2025 In mouse kidney, GnT-V selectively modifies two metalloproteases on the apical surface of tubules — ANPEP (alanyl aminopeptidase) and MEP1A (meprin α) — as its major in vivo substrates, at highly accessible glycosites clustered in C-terminal domains. Upon epithelial cell polarization, GnT-V products accumulate at the apical side, implicating polarized subcellular trafficking in substrate-selective glycosylation. Lectin-assisted proteomics (identification of GnT-V substrates), glycosite mapping, single-cell transcriptomics, epithelial cell polarization assay iScience Medium 41323266
2024 GnT-V binds to TIMP-1 (confirmed by GST pull-down) and promotes N-glycosylation of TIMP-1. GnT-V-mediated TIMP-1 N-glycosylation activates the VEGF signaling pathway, promoting retinal microvascular endothelial cell angiogenesis and ARPE-19 cell injury in diabetic retinopathy. GST pull-down, Western blot/Lectin blot, TIMP-1 mutation, GnT-V overexpression/knockdown, angiogenesis assay, in vivo DR model Molecular biology reports Medium 38499842
2023 ISLR interacts directly with MGAT5 in gastric cancer cells, confirmed by co-immunoprecipitation. MGAT5 overexpression partially rescues the inhibitory effects of ISLR knockdown on cancer cell viability, proliferation, migration, invasion, and EMT. Co-immunoprecipitation, ISLR knockdown, MGAT5 overexpression rescue, proliferation/migration/invasion assays Iranian journal of basic medical sciences Low 37427332
1987 GnT-V (MGAT5) enzymatic activity was directly measured in cell-line extracts using UDP-[3H]-GlcNAc and a synthetic trisaccharide acceptor, demonstrating the enzyme transfers GlcNAc to form the β1,6 branch product. The PHAR 2.1 variant of BW5147 cells expressed no detectable activity. In vitro enzyme activity assay with synthetic trisaccharide acceptor, reverse-phase chromatography product separation Biochemical and biophysical research communications Medium 2956949
2016 Loss of mgat5a in zebrafish enhances hair cell regeneration and regeneration of lateral line axons and caudal fins. Pharmacological inhibition of N-glycosylation with swainsonine phenocopied the mgat5a mutant. Overexpression analysis showed that N-glycosylation alters the responsiveness of TGF-β signaling, positioning MGAT5 as a negative regulator of tissue regeneration through modulation of TGF-β signaling. mgat5a insertional and CRISPR/Cas9 mutant zebrafish, hair cell regeneration assay, swainsonine pharmacological inhibition, mRNA overexpression, TGF-β signaling assay Cell regeneration Medium 27795824

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 728 11217864
2000 Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nature medicine 475 10700233
2006 Galectin binding to Mgat5-modified N-glycans regulates fibronectin matrix remodeling in tumor cells. Molecular and cellular biology 163 16581792
2004 N-acetylglucosaminyltransferase V (Mgat5)-mediated N-glycosylation negatively regulates Th1 cytokine production by T cells. Journal of immunology (Baltimore, Md. : 1950) 134 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 75 21908519
2010 MGAT5 alters the severity of multiple sclerosis. Journal of neuroimmunology 64 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 50 33894774
2021 IGF2BP1 Promotes the Liver Cancer Stem Cell Phenotype by Regulating MGAT5 mRNA Stability by m6A RNA Methylation. Stem cells and development 47 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) 39 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 29 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 27 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
2022 N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells. iScience 11 36590176
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
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) 9 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
2024 Structure and function of N-acetylglucosaminyltransferase V (GnT-V). Biochimica et biophysica acta. General subjects 5 39233219
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 GnT-V-mediated aberrant N-glycosylation of TIMP-1 promotes diabetic retinopathy progression. Molecular biology reports 2 38499842
2023 ISLR interacts with MGAT5 to promote the malignant progression of human gastric cancer AGS cells. Iranian journal of basic medical sciences 2 37427332
2002 Sequences of the mouse N-acetylglucosaminyltransferase V (Mgat5) mRNA and an mRNA expressed by an Mgat5-deficient cell line. Glycobiology 2 12122020
2001 [GnT-V overexpression in human hepatocarcinoma cells affects its migration and expression of cell adhesion molecules]. Shi yan sheng wu xue bao 2 12549224
2025 Selective modification of glycoprotein substrates by GnT-V in mouse kidney. iScience 1 41323266
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

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