Affinage

GALNT2

Polypeptide N-acetylgalactosaminyltransferase 2 · UniProt Q10471

Length
571 aa
Mass
64.7 kDa
Annotated
2026-06-10
52 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GALNT2 encodes a Golgi polypeptide N-acetylgalactosaminyltransferase (GalNAc-T2) that initiates mucin-type O-glycosylation by transferring GalNAc from UDP-GalNAc onto serine/threonine residues of secreted and membrane substrates (PMID:22152306, PMID:22033505). Catalysis proceeds through a UDP-GalNAc-dependent induced-fit mechanism in which donor binding orders a flexible loop and drives the enzyme into its active state; a non-active-site F104S mutation abolishes peptide substrate binding by leaving this loop disordered (PMID:29601100). The catalytic domain selects initial glycosylation sites by sequence recognition while the lectin domain expands site exploration to increase clustered glycan density, as shown for the IgA1 hinge region (PMID:30759204). In hepatic and metabolic physiology, GalNAc-T2 O-glycosylates ApoC-III, ANGPTL3 and PLTP: glycosylation modulates ApoC-III-mediated inhibition of lipoprotein lipase, blocks proprotein-convertase cleavage of ANGPTL3, and sustains plasma PLTP activity, thereby controlling triglyceride clearance and HDL-C (PMID:22152306, PMID:27508872, PMID:32999434). GalNAc-T2 also glycosylates the insulin receptor and influences insulin signaling, in part through coordinated suppression of ENPP1, and promotes adipogenesis (PMID:23500900, PMID:35304331, PMID:31040393). Across multiple cancers it O-glycosylates receptor tyrosine kinases and adhesion receptors—EGFR, MET, AXL, IGF1R, ITGA5 and β1-integrin—tuning downstream PI3K/Akt, MAPK/ERK and FAK signaling with context-dependent suppressive or promoting effects on growth, migration and invasion (PMID:21990321, PMID:26848976, PMID:36058918, PMID:36409270, PMID:23117232). As an interferon-stimulated gene, GALNT2 O-glycosylates the SARS-CoV-2 spike at S810/813 to restrict viral glycoprotein processing and cell fusion, conferring antiviral activity (PMID:41387548). Loss of function causes a multisystem congenital disorder of glycosylation (GALNT2-CDG) with loss of ApoC-III O-glycosylation, low HDL-C, and neurodevelopmental phenotypes recapitulated in rodent models (PMID:32293671).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2011 High

    Established that GalNAc-T2 directly O-glycosylates a physiological substrate (ApoC-III) and that this modification is functionally consequential for lipid metabolism, linking the enzyme to triglyceride handling.

    Evidence In vitro peptide glycosylation, neuraminidase treatment, and plasma glycoproteomics in human loss-of-function carriers; recombinant enzyme activity on IgA1 hinge peptide

    PMID:22033505 PMID:22152306

    Open questions at the time
    • Did not resolve which other plasma glycoproteins drive the metabolic phenotype
    • Quantitative contribution of ApoC-III glycosylation to systemic triglyceride levels not isolated
  2. 2011 High

    Showed GalNAc-T2 glycosylation is not confined to secreted proteins but also modifies a membrane receptor (EGFR), establishing a route by which O-glycosylation tunes receptor tyrosine kinase signaling and tumor behavior.

    Evidence siRNA/overexpression in HCC cells, xenograft, and erlotinib epistasis with EGFR signaling readouts

    PMID:21990321

    Open questions at the time
    • Specific EGFR O-glycosites not mapped
    • Direct vs. indirect modification of EGFR not distinguished in this study
  3. 2012 Medium

    Extended the receptor-substrate model to adhesion machinery by showing β1-integrin O-glycosylation alters cell-matrix adhesion and FAK signaling, indicating GalNAc-T2 controls cell migration through integrin glycosylation.

    Evidence GALNT2 overexpression in trophoblast cells with VVA lectin pull-down, adhesion and migration assays, phospho-FAK Western blot

    PMID:23117232

    Open questions at the time
    • Lectin detection does not pinpoint the modified β1-integrin residues
    • Single overexpression system
  4. 2013 Medium

    Uncovered a glycosylation-independent branch in which GalNAc-T2 acts as a trans-acting factor on the ENPP1 3'-UTR to regulate insulin receptor signaling, broadening its role beyond enzymatic O-glycosylation.

    Evidence RNA pull-down/MS, knockdown/overexpression in HepG2 cells, insulin signaling and PEPCK readouts

    PMID:23500900

    Open questions at the time
    • Mechanism of ENPP1 3'-UTR binding by a Golgi glycosyltransferase not reconciled with its catalytic function
    • Single-lab RNA pull-down without reciprocal validation
  5. 2016 High

    Confirmed ANGPTL3 and PLTP as direct in vivo substrates and demonstrated rescue by hepatic reconstitution, cementing GalNAc-T2's causal role in HDL-C and lipid transfer physiology across mammals.

    Evidence O-glycoproteomics in human-deficient subject and rodents, hepatic Galnt2 reconstitution in mice, PLTP activity assay

    PMID:27508872

    Open questions at the time
    • Relative metabolic weight of PLTP vs. ANGPTL3 vs. ApoC-III not partitioned
  6. 2018 High

    Defined the catalytic logic of the enzyme by showing donor (UDP-GalNAc) binding orders a flexible loop to reach the active state, explaining how substrate recognition is gated by an induced-fit mechanism.

    Evidence Crystal structure of F104S mutant with UDP-GalNAc, STD-NMR, 19F NMR, MD simulations, active-site mutagenesis

    PMID:29601100

    Open questions at the time
    • Does not address how the lectin domain integrates with the catalytic cycle
    • Single-substrate structural context
  7. 2019 High

    Resolved how site-specific and clustered O-glycan density arise, attributing initial site selection to the catalytic domain and density amplification to lectin-domain-driven pathway exploration.

    Evidence In vitro IgA1 hinge glycosylation with LC-MS glycoform analysis and catalytic vs. lectin domain mutants

    PMID:30759204

    Open questions at the time
    • Whether the same domain division governs membrane-receptor substrates is untested
  8. 2019 Medium

    Showed receptor-substrate effects are context-dependent, with EGFR/MET glycosylation promoting malignancy in some tumors and suppressing it in others, indicating tissue-specific signaling outcomes of the same modification.

    Evidence Lectin pull-down and inhibitor epistasis across glioma, gastric, oral cancer models with PI3K/Akt/mTOR and FAK readouts; insulin-sensitizing adipogenesis in 3T3-L1

    PMID:24582885 PMID:26848976 PMID:30323967 PMID:31040393 PMID:31076460

    Open questions at the time
    • Molecular basis for opposite directionality across tissues unexplained
    • Glycosites on each receptor not mapped
  9. 2020 High

    Provided in vivo mechanism for the lipid phenotype by showing O-glycosylation near the ANGPTL3 cleavage site blocks proprotein-convertase processing, directly coupling GalNAc-T2 to ANGPTL3 activation.

    Evidence Galnt2 gain/loss in primary hepatocytes and mouse liver, ANGPTL3 cleavage Western blots, PC inhibitor epistasis

    PMID:32999434

    Open questions at the time
    • Stoichiometry of glycan occupancy needed to block cleavage not quantified
  10. 2020 High

    Established GALNT2 loss as the cause of a defined human congenital disorder of glycosylation with multisystem and neurodevelopmental phenotypes, validated in rodent models.

    Evidence Human patient biochemistry/glycoproteomics, mouse and rat knockouts with behavioral phenotyping

    PMID:32293671

    Open questions at the time
    • Which substrate losses drive the neurological phenotype not pinned down
  11. 2022 Medium

    Expanded the substrate repertoire to additional receptors (AXL, ITGA5, insulin receptor, IGF1R) and connected glycosylation to receptor stability, downstream pathway activation, and metabolic energy utilization.

    Evidence Lectin pull-down, CRISPR KO, proteasome inhibition, glycoproteomics in Galnt2-/- mice, metabolic phenotyping, inhibitor epistasis

    PMID:35304331 PMID:36058918 PMID:36409270 PMID:37597090

    Open questions at the time
    • Direct glycosite assignments on these receptors largely absent
    • Single-lab findings per receptor
  12. 2023 High

    Generated a comprehensive in vivo, tissue-specific map of GalNAc-T2-dependent O-glycosites, providing the substrate network underlying the enzyme's pleiotropic phenotypes.

    Evidence Quantitative glycoproteomics across nine tissues in Galnt2-null vs. WT mice; STAT3 ChIP for transcriptional control of GALNT2 in glioblastoma stem cells

    PMID:37000153 PMID:37862385

    Open questions at the time
    • Functional consequences of most individual glycosites untested
    • Tissue-specific regulators of GALNT2 expression incompletely defined
  13. 2025 High

    Defined an antiviral function for GALNT2 as an interferon-stimulated gene that glycosylates viral spike protein to impair proteolytic priming and fusion, with human genetic support linking loss of function to COVID-19 severity.

    Evidence IFNAR-/- transcriptomics, scRNA-seq of patients, in vitro/in vivo infection, spike S810/813 mutagenesis, fusion assays, human variant association

    PMID:41387548

    Open questions at the time
    • Breadth of viral glycoprotein substrates beyond coronaviruses/influenza not fully delineated
  14. 2025 Medium

    Implicated Galnt2 in central glucose sensing, marking and braking VMH glucose-inhibited neurons within a hypothalamus-to-liver circuit controlling hepatic glucose production.

    Evidence Viral tracing, snRNA-seq, optogenetic/chemogenetic circuit dissection, metabolic phenotyping

    PMID:41092902

    Open questions at the time
    • Whether the neuronal role depends on enzymatic O-glycosylation or marker identity unresolved
    • Neuronal substrates not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the same O-glycosylation modification produces opposite signaling outcomes across tissues and how specific substrate glycosites mechanistically translate into the lipid, insulin, neurodevelopmental, and antiviral phenotypes.
  • Direct glycosite-to-phenotype causality largely uncharacterized
  • Reconciliation of catalytic vs. proposed RNA-binding/neuronal-marker roles missing
  • Substrate hierarchy driving each physiological output unknown

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 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1643685 Disease 1 R-HSA-168256 Immune System 1
Partners
ANGPTL3APOC3AXLEGFRIGF1RITGA5METPLTP

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 ppGalNAc-T2 (GALNT2) directly O-glycosylates apolipoprotein C-III (apoC-III); a loss-of-function mutation impairs this glycosylation, leading to attenuated apoC-III inhibition of lipoprotein lipase (LPL) and improved postprandial triglyceride clearance. An apoC-III-based peptide was validated as a substrate for ppGalNAc-T2, and neuraminidase removal of sialic acids from apoC-III glycans decreased its ability to inhibit LPL. In vitro glycosylation assay with apoC-III-based peptide substrate; neuraminidase treatment; plasma glycoproteomics in human carriers of GALNT2 loss-of-function mutation Cell metabolism High 22152306
2016 GALNT2 deficiency reduces plasma PLTP (phospholipid transfer protein) activity and lowers HDL-C across mammals. O-glycoproteomics of a GALNT2-deficient human validated ANGPTL3 and ApoC-III as direct GalNAc-T2 substrates; additional rodent glycoproteomics identified PLTP as a substrate. Hepatic reconstitution of Galnt2 in mice rescued plasma PLTP activity. O-glycoproteomics in human GALNT2-deficient subject and rodents; hepatic Galnt2 reconstitution in mice; plasma PLTP activity assay Cell metabolism High 27508872
2011 GALNT2 modifies O-glycans on EGFR in hepatocellular carcinoma (HCC) cells, altering EGFR responses after EGF binding and suppressing EGF-induced cell growth, migration, and invasion. Inhibiting EGFR with erlotinib rescued the pro-malignant phenotypes caused by GALNT2 knockdown, establishing EGFR as a key downstream mediator. siRNA knockdown and overexpression of GALNT2 in HCC cells; in vitro growth/migration/invasion assays; in vivo xenograft; erlotinib epistasis experiment; Western blot for EGFR signaling Cancer research High 21990321
2013 GALNT2 downregulation increases ENPP1 expression and impairs insulin receptor (IR), IRS-1, and Akt phosphorylation, as well as insulin-mediated suppression of PEPCK in human HepG2 liver cells. Conversely, GALNT2 overexpression reduces ENPP1 levels and enhances insulin signaling. GALNT2 was identified as a trans-acting factor binding the ENPP1 3′-UTR by RNA pull-down and mass spectrometry. RNA pull-down with mass spectrometry; RT-PCR; Western blot for ENPP1, IR, IRS-1, Akt phosphorylation; ELISA for IR autophosphorylation; siRNA knockdown and overexpression in HepG2 cells Biochimica et biophysica acta Medium 23500900
2014 GALNT2 modifies O-glycans on EGFR in oral squamous cell carcinoma (OSCC) cells, enhancing EGF-induced EGFR and AKT phosphorylation and promoting cell migration and invasion. VVA lectin pull-down confirmed increased Tn antigen on EGFR upon GALNT2 overexpression. Overexpression and siRNA knockdown of GALNT2 in SAS cells; Vicia villosa agglutinin (VVA) pull-down assay; transwell migration/invasion assay; Western blot Oral oncology Medium 24582885
2016 GALNT2 suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying O-glycosylation of MET (hepatocyte growth factor receptor), reducing its phosphorylation. GALNT2 knockdown decreased Tn antigen expression on MET and enhanced MET phosphorylation; MET inhibitor PHA665752 reversed the pro-malignant effects of GALNT2 knockdown. siRNA knockdown of GALNT2 in GCA cells; Tn antigen detection by Western blot; in vitro growth/migration/invasion; in vivo metastasis; MET inhibitor epistasis Oncotarget Medium 26848976
2018 GALNT2 suppresses GCA malignancy through O-glycosylation of EGFR, reducing EGFR and Akt phosphorylation. GALNT2 knockdown decreased Tn antigen on EGFR; EGFR inhibitor gefitinib and Akt inhibitor MK2206 reversed pro-invasive effects of GALNT2 knockdown. siRNA knockdown in AGS/MKN28 cells; Western blot for pEGFR, pAkt, Tn antigen; migration/invasion assays; gefitinib/MK2206 epistasis American journal of cancer research Medium 30323967
2018 A GalNAc-T2 F104S mutant (not located at the active site) loses peptide substrate binding. Crystal structure of the mutant bound to UDP-GalNAc, combined with STD-NMR and MD simulations, revealed that the flexible loop is disordered in the mutant. 19F NMR demonstrated that wild-type GalNAc-T2 reaches the active state only in the presence of UDP-GalNAc, establishing a UDP-GalNAc-dependent induced-fit catalytic mechanism. Crystal structure of F104S mutant bound to UDP-GalNAc; saturation transfer difference (STD) NMR; 19F NMR spectroscopy; molecular dynamics simulations; active-site mutagenesis (F104S) Chemistry (Weinheim an der Bergstrasse, Germany) High 29601100
2019 GalNAc-T2 glycosylates IgA1 hinge-region in a semi-ordered process: the catalytic domain selects four initial sites based on amino-acid sequence recognition, and both the catalytic and lectin domains participate in subsequent site selections. The lectin domain enhances glycan density by increasing pathway exploration, linking site-specific glycan addition to overall clustered glycan density. In vitro glycosylation assay with IgA1 hinge-region peptide; LC-MS analysis of glycoforms; domain mutant analysis (catalytic vs. lectin domain) Glycobiology High 30759204
2019 GALNT2 facilitates glioma malignancy by O-glycosylating EGFR (detected by Tn antigen on EGFR via lectin pull-down), increasing EGFR phosphorylation and activating the PI3K/Akt/mTOR pathway, and regulating downstream effectors (p21, CDK4, cyclinD1, MMP2, MMP9). GALNT2 knockdown and overexpression in glioma cell lines; lectin pull-down; Western blot for pEGFR, PI3K/Akt/mTOR components; in vivo orthotopic xenograft with GALNT2 shRNA Clinical science (London, England : 1979) Medium 31076460
2012 GALNT2 O-glycosylates β1-integrin (increasing Tn antigen on β1-integrin detected by VVA binding) in extravillous trophoblast (EVT) cells, enhancing cell-collagen IV adhesion but suppressing FAK phosphorylation, cell migration, and invasion. Overexpression of GALNT2 in HTR8/SVneo cells; VVA lectin binding assay for Tn antigen on β1-integrin; collagen IV adhesion assay; transwell migration/invasion; Western blot for phospho-FAK Placenta Medium 23117232
2020 GALNT2-mediated O-glycosylation near the ANGPTL3 cleavage site inhibits proprotein convertase (PC)-mediated cleavage of ANGPTL3. In primary hepatocytes and in vivo in mice, suppression of Galnt2 dramatically increases Angptl3 cleavage, while Galnt2 overexpression blocks cleavage; cleavage is also blocked by PC inhibition. Galnt2 overexpression and siRNA knockdown in primary hepatocytes and in vivo mouse liver; Western blot for ANGPTL3 cleavage products; PC inhibitor comparison Scientific reports High 32999434
2020 GALNT2 loss of function causes a congenital disorder of glycosylation (GALNT2-CDG) characterized by loss of O-glycosylation of ApoC-III (a non-redundant GALNT2 substrate), low HDL-C, and multisystem developmental abnormalities. Rodent models of GALNT2-CDG recapitulate neurodevelopmental phenotypes including cerebellar motor deficits, decreased sociability, and impaired sensory processing. Human patient biochemical and glycoproteomics analysis; mouse and rat GALNT2 knockout models; behavioral phenotyping Brain : a journal of neurology High 32293671
2019 GALNT2 promotes adipogenesis and enhances insulin-induced IR, IRS1, and AKT activation in mouse 3T3-L1 preadipocytes, with the insulin-sensitizing effect abolished during late adipocyte maturation. GALNT2's effect is paralleled by coordinated changes in Enpp1 expression. Stable GALNT2 overexpression in 3T3-L1 cells; Oil Red-O staining; fluorimetric triglyceride assay; confocal microscopy of lipid droplets; Western blot for IR, IRS1, JNK, AKT phosphorylation; RT-PCR for adipogenesis genes International journal of obesity (2005) Medium 31040393
2022 GALNT2 modifies O-glycans on ITGA5 (integrin alpha 5) in non-small cell lung cancer cells, affecting activation of the PI3K/Akt and MAPK/ERK pathways. miR-30d was identified as a negative regulator of GALNT2 by high-throughput sequencing. Lectin pull-down for O-glycosylation of ITGA5; gain- and loss-of-function experiments; Western blot for PI3K/Akt, MAPK/ERK; in vivo tumor formation; miRNA high-throughput sequencing Cellular & molecular biology letters Medium 36058918
2022 GALNT2 modifies O-glycans on AXL receptor tyrosine kinase in colorectal cancer cells and regulates AXL protein levels via the proteasome-dependent pathway; GALNT2-promoted invasiveness was significantly reversed by AXL siRNA knockdown. GALNT2 overexpression and CRISPR/Cas9 knockout; siRNA knockdown; lectin pull-down for O-glycans on AXL; proteasome inhibitor experiments; migration/invasion and peritoneal metastasis assays Molecular oncology Medium 36409270
2022 The insulin receptor is a novel O-glycosylation substrate of GalNAc-T2. Galnt2-knockout mice display decreased adiposity, altered insulin signaling, and a shift in energy substrate utilization in the inactive phase. Galnt2-/- mouse model; glycoproteomics identifying insulin receptor as substrate; metabolic phenotyping including indirect calorimetry; GWAS correlation in UK Biobank Molecular metabolism Medium 35304331
2021 Computational flexible docking of peptide substrates into GalNAc-T2 identified enzyme residues R362, K363, Q364, H365, and W331 as regulators of pocket size and peptide binding at the -1 position, and K281 and K363 as gating residues at the +1 position, explaining the finely tuned peptide substrate specificity of GalNAc-T2. Rosetta Monte Carlo-minimization flexible docking of 361 peptides with experimental glycosylation efficiency data; computational scanning of enzyme-peptide interactions ACS catalysis Low 34322281
2023 In vivo O-glycoproteomics in Galnt2-null mice identified a network of glycoproteins lacking GalNAc-T2-specific O-glycans across nine mouse tissues, establishing tissue-specific regulation of O-glycosites. Known functions of these glycoproteins are consistent with the complex metabolic phenotypes of Galnt2-null animals. Quantitative glycoproteomics and proteomics across nine mouse tissues using HCD-triggered ETD/HCD MS; Galnt2-null mouse model comparison Proceedings of the National Academy of Sciences of the United States of America High 37862385
2023 GALNT2 modifies O-glycans on IGF1R in non-small cell lung cancer cells (detected by lectin pull-down), and IGF1R affects expression of apoptosis-related genes. GALNT2 knockdown-mediated radiosensitization was enhanced by IGF1R inhibition. miR-30a-5p was validated as an upstream negative regulator of GALNT2 by luciferase reporter assay. Lectin pull-down for O-glycans on IGF1R; GALNT2 knockdown; in vitro and in vivo radiosensitivity assays; IGF1R inhibitor epistasis; miRNA array; dual luciferase reporter assay Cell biology and toxicology Medium 37597090
2024 GALNT2 overexpression specifically in the pancreas (conditional transgenic mouse) causes loss of acinar mass and pancreatic steatosis (heterozygous) or complete pancreatic loss with lethal phenotype (homozygous). Adipocytes in the pancreas were shown to originate via transdifferentiation from pancreatic cells (reporter gene mouse). Additional O-glycosylation sites introduced by GalNT2 overexpression were identified by PNA lectin enrichment and mass spectrometric proteome analysis. Conditional transgenic mouse with pancreas-specific GalNT2 overexpression; reporter gene mouse for lineage tracing; PNA lectin enrichment and mass spectrometry Scientific reports Medium 39613794
2024 GALNT2 knockdown in renal cell carcinoma cells increased p-LATS2/LATS2 expression and subsequent YAP phosphorylation/degradation, suppressing cell proliferation. This was rescued by LATS2 knockdown, placing GALNT2 upstream of LATS2 in this pathway. miR-139-5p was validated as a direct negative regulator of GALNT2 via dual luciferase reporter assay targeting the GALNT2 3′-UTR. shRNA knockdown of GALNT2; LATS2 epistasis (double knockdown rescue); Western blot for p-LATS2, LATS2, p-YAP, YAP; dual luciferase reporter assay for miR-139-5p/GALNT2 3′-UTR interaction Discover oncology Medium 38478152
2025 GALNT2 is an interferon-stimulated gene (ISG) that restricts replication of multiple coronaviruses and influenza A viruses in vitro and in vivo. Mechanistically, GALNT2-dependent O-linked glycosylation of the SARS-CoV-2 spike protein at serine 810/813 regulates viral glycoprotein proteolytic processing and impairs virus-cell fusion. Human GALNT2 loss-of-function variants are associated with elevated risk of COVID-19 hospitalization. Transcriptomic profiling of IFNAR-/- vs. wild-type mouse lungs; single-cell RNA-seq of COVID-19 patient samples; in vitro viral replication assays; in vivo infection models; site-directed mutagenesis of spike S810/813; mechanistic fusion assay Nature microbiology High 41387548
2025 Galnt2-expressing neurons in the ventromedial hypothalamus (VMH) form a VMH→PVH→LPGi→liver neurocircuit that detects neuroglycopenia and drives hepatic glucose production via intrahepatic sympathetic activation. Galnt2 functions as both a genetic marker and molecular brake of VMH glucose-inhibited neurons, modulating the glycemic threshold for hypoglycemia perception. Viral tracing; single-nucleus RNA sequencing; behavioral and metabolic phenotyping; optogenetic/chemogenetic circuit dissection Cell metabolism Medium 41092902
2024 Neuronal-specific conditional knockout of Galnt2 in mice causes behavioral deficits (locomotion, motor coordination, sociability, learning, memory) and spontaneous seizures, recapitulating GALNT2-CDG neurology. Glycoproteomics of cortical synaptosomes identified a non-redundant, isoform-specific Galnt2 contribution to the synaptosomal O-glycoproteome, identifying disrupted O-glycosites on candidate neuronal glycoproteins. Pan-neuronal conditional Galnt2 knockout mouse; behavioral battery (locomotion, rotarod, social interaction, Morris water maze, EEG for seizures); cortical synaptosomal glycoproteomics bioRxivpreprint Medium bio_10.1101_2024.09.30.615951
2011 Recombinant soluble GalNAc-T2 produced in insect (Sf9) cells was enzymatically active, catalyzing GalNAc transfer to synthetic IgA1 hinge-region peptide using UDP-GalNAc as donor. This confirmed the enzyme's activity toward IgA1 hinge-region peptide substrates. Baculovirus expression and purification of recombinant GalNAc-T2; in vitro enzymatic activity assay quantifying GalNAc attachment to synthetic IgA1 HR peptide; mass spectrometric confirmation of protein identity Protein expression and purification Medium 22033505
2023 GALNT2 promotes CD44 expression to sustain glioblastoma stem cells (GSCs), and STAT3 directly activates GALNT2 transcription by binding to the GALNT2 promoter. A GALNT2 inhibitor suppressed GSC self-maintenance in vitro and in vivo. GALNT2 knockdown in GSCs; CD44 expression analysis; ChIP assay for STAT3 binding to GALNT2 promoter; pharmacological GALNT2 inhibitor; in vivo xenograft Aging Medium 37000153
2024 GALNT2 was identified as a regulator of human commissural axon guidance by floor plate; CRISPR knockout of GALNT2 in human floor plate organoids impaired floor plate-mediated guidance of commissural axons in midline assembloids, implicating O-linked glycosylation in human-specific axon guidance. CRISPR knockout screen in human floor plate organoids (hFpO) assembled with spinal cord organoids (hSpO); secretome profiling; axon guidance assay in midline assembloids bioRxivpreprint Low bio_10.1101_2024.06.26.600229
2024 Isoferulic acid (IFA) directly interacts with GALNT2 protein (shown by Co-IP, molecular docking, and fluorescence spectroscopy) and inhibits alcohol-induced downregulation of GALNT2 activity in gastric epithelial cells, thereby promoting mucin synthesis. Co-immunoprecipitation; molecular docking; fluorescence spectroscopy; GALNT2 activity assay; in vivo rat gastric injury model; H&E staining; gastric hexosamine content Nutrients Low 38999895

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents. Cell metabolism 114 27508872
2011 Mucin glycosylating enzyme GALNT2 regulates the malignant character of hepatocellular carcinoma by modifying the EGF receptor. Cancer research 99 21990321
2011 Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man. Cell metabolism 89 22152306
2014 GALNT2 enhances migration and invasion of oral squamous cell carcinoma by regulating EGFR glycosylation and activity. Oral oncology 85 24582885
2020 Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Brain : a journal of neurology 64 32293671
2014 A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease. PloS one 50 25084356
2015 Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated with High-Density Lipoprotein Cholesterol. American journal of human genetics 49 26637976
2019 Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis. Clinical science (London, England : 1979) 45 31076460
2016 Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation. Oncotarget 40 26848976
2022 The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer. Cellular & molecular biology letters 35 36058918
2013 GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia. PloS one 32 23894607
2021 GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma. Life sciences 28 33785338
2018 The O-glycosylating enzyme GALNT2 suppresses the malignancy of gastric adenocarcinoma by reducing EGFR activities. American journal of cancer research 28 30323967
2016 Association between the DOCK7, PCSK9 and GALNT2 Gene Polymorphisms and Serum Lipid levels. Scientific reports 28 26744084
2013 Role of GALNT2 in the modulation of ENPP1 expression, and insulin signaling and action: GALNT2: a novel modulator of insulin signaling. Biochimica et biophysica acta 27 23500900
2011 Association of the GALNT2 gene polymorphisms and several environmental factors with serum lipid levels in the Mulao and Han populations. Lipids in health and disease 25 21933382
2012 Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion. Placenta 24 23117232
2022 GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL. Molecular oncology 21 36409270
2020 GALNT2 regulates ANGPTL3 cleavage in cells and in vivo of mice. Scientific reports 20 32999434
2018 Paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice. European journal of pharmacology 19 30096295
2015 Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia. Journal of cellular and molecular medicine 19 26493351
2019 GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling. International journal of obesity (2005) 18 31040393
2016 Looking beyond GWAS: allele-specific transcription factor binding drives the association of GALNT2 to HDL-C plasma levels. Lipids in health and disease 17 26817450
2023 Quantitative mapping of the in vivo O-GalNAc glycoproteome in mouse tissues identifies GalNAc-T2 O-glycosites in metabolic disorder. Proceedings of the National Academy of Sciences of the United States of America 16 37862385
2022 Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis. International journal of molecular sciences 16 35055114
2018 Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic Mechanism for GalNAc-Ts. Chemistry (Weinheim an der Bergstrasse, Germany) 16 29601100
2016 GALNT2 effect on HDL-cholesterol and triglycerides levels in humans: Evidence of pleiotropy? Nutrition, metabolism, and cardiovascular diseases : NMCD 14 28153384
2015 Functional variants of lipid level modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 genes in healthy Roma and Hungarian populations. Pathology oncology research : POR 14 25573592
2020 Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 33152927
2019 IgA1 hinge-region clustered glycan fidelity is established early during semi-ordered glycosylation by GalNAc-T2. Glycobiology 12 30759204
2022 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. Molecular metabolism 11 35304331
2015 Gene environment interaction of GALNT2 and APOE gene with hypertension in the Chinese Han Population. Bio-medical materials and engineering 11 26405973
2021 Structural basis for peptide substrate specificities of glycosyltransferase GalNAc-T2. ACS catalysis 10 34322281
2011 Production of N-acetylgalactosaminyl-transferase 2 (GalNAc-T2) fused with secretory signal Igκ in insect cells. Protein expression and purification 10 22033505
2023 Apolipoprotein-CIII O-Glycosylation, a Link between GALNT2 and Plasma Lipids. International journal of molecular sciences 8 37834292
2020 GALNT2 Gene Variant rs4846914 Is Associated with Insulin and Insulin Resistance Depending on BMI in PCOS Patients: a Case-Control Study. Reproductive sciences (Thousand Oaks, Calif.) 8 33171515
2023 GALNT2, an O-glycosylating enzyme, is a critical regulator of radioresistance of non-small cell lung cancer: evidence from an integrated multi-omics analysis. Cell biology and toxicology 7 37597090
2021 Maternal GALNT2 Variations Affect Blood Pressure, Atherogenic Index, and Fetal Growth, Depending on BMI in Gestational Diabetes Mellitus. Frontiers in endocrinology 7 34267728
2023 GALNT2 sustains glioma stem cells by promoting CD44 expression. Aging 6 37000153
2010 A polymorphism in the GALNT2 gene and ovarian cancer risk in four population based case-control studies. International journal of molecular epidemiology and genetics 5 21532840
2025 Exploring the combined roles of GALNT1 and GALNT2 in hepatocellular carcinoma malignancy and EGFR modulation. Discover oncology 4 40095226
2024 GalNT2-mediated O-glycosylation affects pancreas development and function in mice. Scientific reports 4 39613794
2021 Morphological and molecular characterization of GALNT2-mediated adipogenesis. International journal of obesity (2005) 3 33658684
2025 Galnt2 neurons in the ventromedial hypothalamus counterregulate hypoglycemia via a brain-liver neurocircuit. Cell metabolism 2 41092902
2024 GALNT2 targeted by miR-139-5p promotes proliferation of clear cell renal cell carcinoma via inhibition of LATS2 activation. Discover oncology 2 38478152
2024 Gastroprotective Effect of Isoferulic Acid Derived from Foxtail Millet Bran against Ethanol-Induced Gastric Mucosal Injury by Enhancing GALNT2 Enzyme Activity. Nutrients 2 38999895
2023 Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia. Advanced biology 2 36861373
2025 Interferon-stimulated gene GALNT2 restricts respiratory virus infections. Nature microbiology 1 41387548
2023 Role of a novel mouse mutant of the Galnt2 gene in otitis media. Frontiers in neurology 1 36874359
2024 GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes. Acta diabetologica 0 38627282
2023 Corrigendum: Role of a novel mouse mutant of the Galnt2 gene in otitis media. Frontiers in neurology 0 37885477
2022 Effects of RNA Modification "Writers" of GALNT2 on the Tumor Microenvironment in Cervical Squamous Cell Carcinoma. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 0 36374960

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