Affinage

C1GALT1

Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 · UniProt Q9NS00

Length
363 aa
Mass
42.2 kDa
Annotated
2026-06-09
65 papers in source corpus 29 papers cited in narrative 29 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

C1GALT1 (T-synthase) is a Golgi-resident inverting glycosyltransferase that catalyzes the committed step of mucin-type O-glycan extension, transferring galactose from UDP-Gal onto GalNAc-Ser/Thr to form the core 1 structure (Galβ1-3GalNAcα-Ser/Thr) (PMID:35504880, PMID:18061573). Crystallographic and biophysical analysis shows it functions as an obligate GT-A fold dimer using an SN2 inverting mechanism, with substrate recognition driven primarily by the GalNAc moiety; the enzyme imposes a high-energy conformation on the α-GalNAc-Thr linkage to glycosylate both Ser and Thr acceptors, with peptide context (Gly at +1, Phe/Tyr at +3) tuning specificity (PMID:35504880, PMID:19073881). Maturation of vertebrate T-synthase requires the ER-specific chaperone Cosmc, which binds a hydrophobic stem-region motif (CBRT) only in non-native enzyme, restores activity in an ATP-independent client-driven cycle, and is required for productive Golgi trafficking and active localization (PMID:19923218, PMID:22416136, PMID:24616093, PMID:18061573). The enzyme is transcriptionally driven by SP1/SP3 acting on a CpG-island core promoter (PMID:26063800) and is post-translationally stabilized by O-GlcNAcylation at Thr229/Thr233, which also reinforces the Cosmc interaction and protects against proteasomal degradation (PMID:39126245). Core 1 O-glycans generated by C1GALT1 are essential in vivo: genetic loss causes embryonic-lethal angiogenic failure (PMID:17113876) and, in hematopoietic and renal cells, underglycosylation of substrates such as GPIbα and podocalyxin producing thrombocytopenia and kidney disease (PMID:17062753, PMID:23794065). In cancer the enzyme O-glycosylates numerous cell-surface receptors—MET, FGFR2, integrins β1 and α5, MUC1, MUC16, Smoothened and EGFR—to modulate their stability, dimerization, activation and downstream signaling (HGF/MET, bFGF/FGFR2, integrin/FAK, PI3K/AKT, Hedgehog, AKT/ERK), driving context-dependent tumor progression or, in pancreatic cancer, tumor suppression (PMID:23832667, PMID:24758762, PMID:30086262, PMID:34452648, PMID:39894896, PMID:39561885). Reduced C1GALT1 activity also underlies galactose-deficient IgA1 production relevant to IgA nephropathy (PMID:24398680, PMID:41905596).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    Establishing that core 1 O-glycans are physiologically essential, not merely structural decoration, anchored the enzyme's biological importance.

    Evidence Gene targeting and ENU hypomorphic mutation in mice with vascular and hematopoietic/renal phenotypes

    PMID:17062753 PMID:17113876

    Open questions at the time
    • Did not define the molecular catalytic mechanism
    • Substrate scope beyond GPIbα/podocalyxin not resolved in these studies
  2. 2007 High

    Defining the spatial logic—ER chaperone versus Golgi enzyme—showed that the enzyme's activity is gated by trafficking, not just expression.

    Evidence Immunocytochemistry, proteasome inhibition, and Cosmc overexpression rescue in mutant cells

    PMID:18061573

    Open questions at the time
    • Molecular basis of Cosmc recognition not yet identified
    • Did not address trafficking machinery beyond Cosmc
  3. 2009 High

    Direct in vitro reconstitution proved Cosmc is a bona fide folding chaperone specific for T-synthase, explaining Tn-syndrome at the protein-folding level.

    Evidence In vitro chaperone refolding assays with patient-derived Cosmc mutant and activity measurements

    PMID:19923218

    Open questions at the time
    • Recognition motif on T-synthase not yet mapped
    • Mechanism of client release undefined at this stage
  4. 2012 High

    Characterizing the binding/release cycle established that Cosmc operates ATP-independently in a client-driven manner, distinguishing it from canonical chaperones.

    Evidence In vitro binding and activity assays with recombinant immobilized Cosmc and free/non-native T-synthase

    PMID:22416136

    Open questions at the time
    • Structural basis of the complex not resolved
    • In-cell kinetics of the cycle not measured
  5. 2014 High

    Mapping the CBRT stem-region motif and validating it by domain swap defined the sequence determinant of chaperone specificity.

    Evidence Deletion mutagenesis, synthetic peptide binding/inhibition, and β4GalT1 chimera transfer

    PMID:24616093

    Open questions at the time
    • Structure of the CBRT–Cosmc interface unresolved
    • How CBRT recognition discriminates native vs non-native states not detailed
  6. 2008 High

    Systematic acceptor-peptide profiling defined the sequence context that tunes T-synthase specificity beyond the GalNAc anchor.

    Evidence Oriented random glycopeptide library with PNA affinity isolation, Edman sequencing, and in vitro enzyme assay

    PMID:19073881

    Open questions at the time
    • Structural rationale for +1/+3 preferences provided only later
    • Does not address in-cell substrate selection
  7. 2022 High

    The crystal structure unified prior biochemistry by revealing an obligate GT-A dimer, SN2 inverting catalysis, and the conformational trick allowing dual Ser/Thr glycosylation.

    Evidence X-ray crystallography of enzyme–glycopeptide complex with biophysical and cellular validation

    PMID:35504880

    Open questions at the time
    • Does not capture the Cosmc-bound non-native state
    • In-cell conformational dynamics not addressed
  8. 2015 High

    Identifying SP1/SP3 at a CpG-island core promoter defined the basal transcriptional control distinct from Cosmc's epigenetic regulation.

    Evidence Luciferase reporter, site-directed mutagenesis, ChIP, mithramycin A treatment, methylome analysis

    PMID:26063800

    Open questions at the time
    • Upstream signals controlling SP1/SP3 at this promoter not defined here
    • Tissue-specific regulation not addressed
  9. 2024 Medium

    Discovery of O-GlcNAcylation at Thr229/Thr233 established a post-translational layer that stabilizes the enzyme and reinforces Cosmc binding.

    Evidence O-GlcNAc mapping, site-directed mutagenesis, Co-IP with Cosmc, proteasome inhibition

    PMID:39126245

    Open questions at the time
    • Enzymes adding/removing this modification not identified
    • Single-lab finding without structural confirmation
  10. 2023 Medium

    Linking the enzyme to the UDP-galactose transporter SLC35A2 connected nucleotide-sugar supply to enzyme stability and Golgi localization.

    Evidence Co-immunoprecipitation, immunofluorescence, and SLC35A2-KO cell analysis

    PMID:36933771

    Open questions at the time
    • Co-IP without reciprocal/structural validation of the interaction
    • Whether association is direct or complex-mediated unresolved
  11. 2013 High

    Identifying receptor substrates (MET, GPIbα) showed that core 1 glycosylation directly modulates receptor activation and protein stability, extending the enzyme into signaling and platelet biology.

    Evidence Lectin pull-down, RNAi/overexpression, phosphorylation and inhibitor epistasis, conditional KO, xenograft

    PMID:23794065 PMID:23832667

    Open questions at the time
    • Specific O-glycan sites on receptors not mapped
    • Generalizability across receptor classes not yet tested
  12. 2021 Medium

    A series of cancer studies established a recurring theme: C1GALT1 glycosylates surface receptors (FGFR2, integrins β1/α5, MUC1/MUC16) to tune adhesion and growth-factor signaling, with context-dependent pro- or anti-tumor outcomes.

    Evidence Lectin pull-down/MS substrate identification, pathway and inhibitor epistasis, CRISPR KO, in vivo models

    PMID:24758762 PMID:25089569 PMID:25762620 PMID:30086262 PMID:30087707 PMID:34452648

    Open questions at the time
    • Most substrate identifications rely on lectin-based assays from single labs
    • Determinants of pro- vs anti-tumor outcome not mechanistically resolved
  13. 2025 High

    An unbiased CRISPR screen placed C1GALT1 upstream of an oncogenic fusion by showing it glycosylates and stabilizes Smoothened to drive Hedgehog-dependent EWSR1::FLI1 expression, nominating it as a druggable dependency.

    Evidence Genome-scale CRISPR KO screen, SMO O-glycosylation assays, Hedgehog pathway epistasis, itraconazole, xenograft

    PMID:39894896

    Open questions at the time
    • SMO O-glycan sites not defined
    • Specificity of itraconazole for the C1GALT1 axis not fully isolated
  14. 2026 Medium

    B cell-specific knockout in a humanized IgA1 model refined the role in IgA nephropathy, showing galactose-deficient IgA1 alone is insufficient for glomerular deposition.

    Evidence B cell-specific conditional KO, passive transfer, Gd-IgA1 ELISA, kidney histology

    PMID:41905596

    Open questions at the time
    • Additional factors enabling mesangial deposition not identified
    • Mucosal-origin IgA1 properties driving deposition undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How upstream signaling (cytokine, NF-κB, miRNA) and post-translational regulation are integrated to set tissue-specific C1GALT1 activity, and whether the Cosmc-bound non-native state can be structurally resolved, remain open.
  • No structure of the Cosmc–T-synthase folding complex
  • Integration of transcriptional, miRNA, and PTM control not unified
  • Receptor O-glycan site maps largely missing

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:0005794 Golgi apparatus 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 2
Partners
COSMCSLC35A2

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 X-ray crystallography of C1GalT1 complexed to a glycopeptide revealed that C1GalT1 is an obligate GT-A fold dimer that follows an SN2 inverting mechanism. Substrate binding is primarily driven by the GalNAc moiety while the peptide sequence provides optimal kinetic and binding parameters. C1GalT1 recognizes a high-energy conformation of the α-GalNAc-Thr linkage (normally negligibly populated in solution), and by imposing this 3D arrangement—characteristic of α-GalNAc-Ser peptides—it ensures broad glycosylation of both Ser and Thr acceptor substrates. X-ray crystallography of enzyme–glycopeptide complex, biophysical assays, cellular studies, site-directed mechanistic analysis Nature Communications High 35504880
2009 The ER-localized molecular chaperone Cosmc directly interacts with partly denatured (non-native) T-synthase in vitro to cause partial restoration of T-synthase activity, in an ATP-independent fashion. A mutated Cosmc found in Tn-syndrome patients has reduced chaperone function. Cosmc is specific for T-synthase and does not act on another β-galactosyltransferase tested, representing the first ER chaperone identified for folding of a glycosyltransferase. In vitro chaperone refolding assay, mutagenesis of patient-derived Cosmc variant, activity assay The Journal of Biological Chemistry High 19923218
2012 Cosmc binds specifically to non-native (denatured) T-synthase but not to the active dimeric form. The Cosmc–T-synthase complex is relatively stable, forms in an ATP-independent manner not regulated by redox, calcium, pH, or intermolecular disulfide bonds, and leads to partial reactivation of T-synthase. Active T-synthase remains tightly noncovalently bound to Cosmc; dissociation is promoted in a client-driven process by further interactions with free native or non-native T-synthase. In vitro binding assays using recombinant proteins (free and solid-support-immobilized Cosmc), activity measurements, biochemical characterization The Journal of Biological Chemistry High 22416136
2014 A specific linear, relatively hydrophobic peptide motif (CBRT) in the N-terminal stem region of T-synthase is required for binding to Cosmc. A synthetic CBRT peptide directly binds Cosmc and inhibits Cosmc-assisted refolding of denatured T-synthase. Mutations within CBRT diminish Cosmc binding and result in formation of inactive T-synthase. Inserting the T-synthase stem region into the unrelated β4GalT1 confers Cosmc binding on that chimera, confirming CBRT as a sequence-specific chaperone recognition motif. Deletion mutagenesis, synthetic peptide binding assay, in vitro refolding assay, domain-swap chimera experiment The Journal of Biological Chemistry High 24616093
2007 Immunocytochemical analysis demonstrated that C1GalT (T-synthase) is localized in the Golgi apparatus, while its chaperone Cosmc resides in the endoplasmic reticulum. In cells with a Cosmc loss-of-function missense mutation (LSC cells), C1GalT protein is absent; proteasome inhibition restores C1GalT protein but it fails to reach the Golgi. Overexpression of Cosmc (but not C1GalT itself) restores correct Golgi localization of C1GalT and recovers core 1 synthase activity, demonstrating that Cosmc controls intracellular trafficking and active localization of C1GalT. Immunocytochemistry with specific monoclonal antibodies, proteasome inhibitor treatment, overexpression rescue, activity assay Biochemical and Biophysical Research Communications High 18061573
2006 Targeted disruption of the T-synthase gene (C1galt1) in mice causes embryonic lethality by E14 due to defective angiogenesis: T-synthase-null embryos express unsialylated Tn antigen instead of sialyl-T antigen in endothelial, hematopoietic, and epithelial cells and develop brain hemorrhage with chaotic microvascular networks, distorted capillary lumens, and defective pericyte–endothelial cell–ECM associations, revealing an essential requirement for core 1-derived O-glycans in angiogenesis. Gene targeting (knockout mice), immunostaining, vascular morphology analysis Methods in Enzymology High 17113876
2006 A hypomorphic loss-of-function point mutation in C1galt1 in plt1 mice causes recessive thrombocytopenia and kidney disease. GPIbα in platelets and podocalyxin in kidney were identified as major underglycosylated targets of C1GalT1, indicating that proper O-glycosylation of these substrates is essential for platelet production and kidney function. Thrombocytopenia was not rescued on a lymphocyte-deficient background, indicating an intrinsic (non-immune-mediated) defect in megakaryocytes. ENU mutagenesis screen, genetic mapping, biochemical identification of underglycosylated substrates (GPIbα, podocalyxin), rag1-null epistasis Proceedings of the National Academy of Sciences High 17062753
2013 Conditional ablation of C1galt1 in hematopoietic cells (Mx1-Cre) causes severe thrombocytopenia with giant platelets and prolonged bleeding times due to defective proplatelet formation during terminal megakaryocyte differentiation. GPIbα protein (but not mRNA) is significantly reduced in C1galt1-null megakaryocytes and platelets, suggesting increased proteolysis of under-O-glycosylated GPIbα. Circulating null platelets show increased microtubule coils despite normal tubulin levels. Conditional knockout (Mx1-Cre), bone marrow transplantation, flow cytometry, western blot, primary megakaryocyte culture Blood High 23794065
2013 C1GALT1 modifies O-glycans on the MET receptor tyrosine kinase in hepatocellular carcinoma cells (demonstrated by VVA and PNA lectin binding), enhancing HGF-induced MET dimerization and kinase activation. C1GALT1 overexpression enhanced HGF-induced MET phosphorylation and cell proliferation; C1GALT1 silencing suppressed MET phosphorylation and proliferation in vitro and in vivo. MET blockade abrogated C1GALT1-enhanced cell viability. RNAi knockdown and overexpression, lectin pull-down (VVA/PNA), phosphorylation assays, MET inhibitor epistasis, xenograft model Cancer Research High 23832667
2014 C1GALT1 modifies O-glycans on FGFR2 in colon cancer cells (first demonstration that FGFR2 carries O-glycans) and enhances bFGF-triggered FGFR2 phosphorylation and downstream malignant phenotypes. FGFR inhibitor BGJ398 blocked C1GALT1-enhanced effects, placing C1GALT1 upstream of FGFR2 activation. Lectin blotting, RNAi knockdown and overexpression, FGFR inhibitor epistasis, in vitro and xenograft assays Oncotarget Medium 24758762
2014 C1GALT1 modifies O-glycans on integrin β1 in hepatocellular carcinoma cells and regulates integrin β1 activity and downstream signaling, thereby promoting cell adhesion to ECM, migration, and invasion. Anti-integrin β1 blocking antibody significantly suppressed C1GALT1-enhanced phenotypes, placing C1GALT1 upstream of integrin β1 activity. Lectin pull-down, RNAi knockdown and overexpression, integrin β1 blocking antibody epistasis, xenograft model PLoS One Medium 25089569
2015 C1GALT1 modulates O-glycan structures on MUC1 in breast cancer cells and promotes MUC1-C/β-catenin signaling pathway activation, enhancing cell growth, migration, and invasion in vitro and tumor growth in vivo. Lectin blotting, RNAi knockdown and overexpression, pathway activation assays, xenograft model Oncotarget Medium 25762620
2018 C1GALT1 modifies O-glycan structures on integrin β1 (β1-integrin) in esophageal cancer cells and regulates downstream FAK signaling. C1GALT1 knockdown increased radiosensitivity; β1-integrin blocking antibody and FAK inhibitor enhanced radiation-induced apoptosis, placing C1GALT1–β1-integrin–FAK in a radioresistance pathway. Lectin blotting, RNAi knockdown, integrin blocking antibody and FAK inhibitor epistasis, irradiation assays Journal of Cancer Medium 30087707
2018 Disruption of C1galt1 in the KPC mouse pancreatic cancer model (KPCC mice) significantly accelerated PDAC development and metastasis. In human PDAC cells, C1GALT1 knockout via CRISPR/Cas9 caused aberrant glycosylation of MUC16 (identified by lectin pull-down and mass spectrometry) and upregulation of genes regulating tumorigenesis and metastasis. Conditional knockout in KPC mice (genetic epistasis), CRISPR/Cas9 KO, lectin pull-down, mass spectrometry, RNA sequencing, orthotopic model Gastroenterology High 30086262
2021 C1GALT1 modifies O-glycosylation on integrin α5 in gastric cancer cells (identified by lectin pull-down and mass spectrometry) and modulates activation of the PI3K/AKT pathway. Integrin α5 inhibition reversed C1GALT1-mediated tumor growth and metastasis in vitro and in vivo. Transcription factor SP1 was found to bind the C1GALT1 promoter and activate its expression, while miR-152 negatively regulates C1GALT1 by binding its 3′-UTR. Lectin pull-down, mass spectrometry, RNAi and overexpression, PI3K/AKT pathway assays, in vivo xenograft, ChIP/promoter binding, luciferase reporter Cell & Bioscience Medium 34452648
2025 C1GALT1 O-glycosylates the Hedgehog signaling component Smoothened (SMO), thereby stabilizing SMO and stimulating Hedgehog pathway activity, which directly activates EWSR1::FLI1 transcription in Ewing sarcoma cells. C1GALT1 was identified as required for EWSR1::FLI1 expression by genome-scale CRISPR/Cas9 knockout screening, and its pharmacological inhibition (itraconazole) reduced EWSR1::FLI1 levels and suppressed ES xenograft growth. Genome-scale CRISPR/Cas9 KO screen, O-glycosylation assays, Hedgehog pathway assays, xenograft model, itraconazole pharmacological inhibition Nature Communications High 39894896
2008 Systematic peptide substrate profiling using oriented random glycopeptides revealed that T-synthase prefers Gly at the +1 position and Phe/Tyr at the +3 position relative to the acceptor Thr-O-GalNAc. Basic residues (Lys, Arg, His) in any position are disfavored, suggesting electrostatic interactions modulate transferase specificity. Oriented random glycopeptide library, PNA lectin affinity isolation, Edman amino acid sequencing, in vitro enzyme assay Glycobiology High 19073881
2006 The C. elegans ortholog Ce-T-synthase (encoded by C38H2.2, 42.7% identity to human T-synthase) was cloned and shown to be a functional ortholog: it catalyzes addition of Gal to GalNAc-Ser/Thr to form core 1 O-glycans. Unlike vertebrate T-synthase, Ce-T-synthase does not require the Cosmc chaperone and instead requires invertebrate-specific factors for optimal activity. cDNA cloning, recombinant expression in mammalian and insect cells, enzyme activity assay, promoter-GFP analysis Glycobiology Medium 16762980
2015 The human C1GALT1 (T-synthase) promoter lacks a TATA box but contains a CpG island (tCpG) whose core promoter contains two binding sites for SP1/SP3 (Krüppel-like transcription factors). SP1/SP3 binding drives basal transcription of C1GALT1, as demonstrated by luciferase reporter assays, site-directed mutagenesis of binding sites, ChIP assays, and mithramycin A treatment. Unlike Cosmc, the T-synthase promoter CpG island is not hypermethylated in Tn-syndrome B cells, indicating differential epigenetic regulation. Luciferase reporter assay, site-directed mutagenesis, ChIP assay, mithramycin A treatment, methylome analysis The Journal of Biological Chemistry High 26063800
2014 IL-6 and IL-4 cytokines reduce IgA1 galactosylation directly by decreasing C1GalT1 expression and indirectly by increasing ST6GalNAc-II expression (which sialylates the GalNAc substrate, preventing C1GalT1-mediated galactosylation). These findings were confirmed by siRNA knockdown of C1GALT1 and ST6GalNAc-II genes and by in vitro enzyme reactions. siRNA knockdown, cytokine treatment of IgA1-secreting cells, in vitro enzyme reactions, O-glycan analysis The Journal of Biological Chemistry High 24398680
2012 Knockdown of C1galt1 (T-synthase) in corneal keratinocytes increased endocytic uptake of plasma membrane proteins via clathrin-mediated endocytosis (blocked by dynasore, nocodazole, chlorpromazine, and hyperosmotic sucrose), demonstrating that core 1 O-glycans contribute to apical barrier function by preventing clathrin-coated pit-mediated endocytosis. Tetracycline-inducible RNAi, cell surface biotinylation, subcellular fractionation, confocal microscopy, fluorescent nanosphere uptake, pharmacological inhibitors PLoS One Medium 22574202
2018 CRISPR/Cas9 knockout of T-synthase (C1GALT1) in colorectal cancer HCT116 cells induced Tn antigen expression and enhanced proliferation, adhesion, migration, and invasion. T-synthase deficiency directly induced epithelial-to-mesenchymal transition (EMT) with decreased E-cadherin and increased snail and fibronectin expression. CRISPR/Cas9 KO, flow cytometry, western blot, invasion/migration assays, EMT marker analysis BioMed Research International Medium 30035127
2023 The UDP-galactose transporter SLC35A2 (UGT) physically associates with C1GalT1 (T-synthase) in HEK293T cells. SLC35A2 also associates with Cosmc. In SLC35A2-deficient cells, C1GalT1 and Cosmc protein levels are decreased, their Golgi localization is less pronounced, and O-glycosylation is reduced. Endogenous Cosmc was found to localize in both the ER and Golgi apparatus of wild-type cells. Co-immunoprecipitation, western blot, immunofluorescence microscopy, SLC35A2 KO cells, subcellular fractionation Biochimica et Biophysica Acta – Molecular Cell Research Medium 36933771
2020 miR-124-3p directly targets T-synthase (C1GALT1) mRNA, reducing T-synthase protein expression in aged colon, disrupting O-glycosylation of mucins, compromising the colonic mucus barrier, and increasing susceptibility to colitis. Young mice overexpressing miR-124-3p phenocopied aged-colon glycosylation defects and developed more severe colitis. miRNA target validation, miR-124-3p overexpression in vivo, western blot, O-glycan analysis, colitis scoring Aging Cell Medium 33040455
2024 C1GalT1 undergoes O-GlcNAc modification at Thr229 and Thr233. This O-GlcNAcylation stabilizes C1GalT1 protein and strengthens its interaction with Cosmc. Mutation at these residues attenuates C1GalT1 stability and promotes its degradation via the proteasome pathway. O-GlcNAc modification identification, site-directed mutagenesis (Thr229/Thr233), Co-IP with Cosmc, proteasome inhibitor treatment, western blot Acta Biochimica et Biophysica Sinica Medium 39126245
2024 C1GALT1 knockdown decreased terminal galactose O-glycosylation and phosphorylation of EGFR in glioblastoma cells, attenuated downstream AKT/ERK phosphorylation, and reduced expression of cyclin D1 and MMP9. Transcription factor SP1 was found to bind the C1GALT1 promoter and regulate its expression in glioma. siRNA knockdown, O-glycan analysis, EGFR and AKT/ERK phosphorylation assays, xenograft model, SP1 promoter binding analysis Cellular Signalling Medium 39561885
2012 T-synthase knockdown via shRNA induced galectin-1 secretion both in vitro and in vivo, enhanced Th2 cytokine (IL-10 and IL-4) production, and promoted CD8+ T-cell apoptosis through galectin-1, prolonging skin allograft survival in mice. This places C1GALT1 upstream of galectin-1-mediated immune suppression. shRNA knockdown in CT26 cells and in vivo (intramuscular electroporation), ELISA for cytokines/galectin-1, apoptosis assays, skin allograft survival model Journal of Clinical Immunology Medium 22392045
2026 In vivo experiment using B cell-specific C1galt1 knockout in a human IGHA1 knock-in mouse demonstrated that loss of C1galt1 in B cells markedly elevated circulating Gd-IgA1 under physiological and inflammatory conditions but did not substantially enhance glomerular IgA deposition, indicating that galactose-deficient IgA1 per se is not sufficient to drive glomerular deposition. In a passive transfer model, mucosal-origin IgA1 induced stronger mesangial deposition than serum or myeloma IgA1 despite similar or lower Gd-IgA1 content. B cell-specific conditional knockout, passive transfer model, ELISA for Gd-IgA1, kidney histology, flow cytometry Kidney International Medium 41905596
2026 Inhibition of NF-κB/p65 by a selective IKKβ inhibitor (TPCA-1) in EBV-immortalized IgA1-producing B cells reduced C1GALT1 gene expression and increased Gd-IgA1 production. Co-localization of NF-κB/p65 with transcription factor SP1 was altered in nuclei, suggesting the NF-κB pathway regulates IgA1 O-glycosylation via SP1-mediated transcriptional control of C1GALT1. IKKβ inhibitor treatment, flow cytometry, imaging, gene expression analysis, nuclear translocation assay bioRxivpreprint Low 42146603

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Cytokines alter IgA1 O-glycosylation by dysregulating C1GalT1 and ST6GalNAc-II enzymes. The Journal of biological chemistry 142 24398680
2017 Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1. Journal of the American Society of Nephrology : JASN 113 28209808
2018 Disruption of C1galt1 Gene Promotes Development and Metastasis of Pancreatic Adenocarcinomas in Mice. Gastroenterology 79 30086262
2007 Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA nephropathy. Kidney international 76 17228361
2013 C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization. Cancer research 74 23832667
2006 Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene. Proceedings of the National Academy of Sciences of the United States of America 64 17062753
2014 C1GALT1 overexpression promotes the invasive behavior of colon cancer cells through modifying O-glycosylation of FGFR2. Oncotarget 62 24758762
2009 The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. The Journal of biological chemistry 61 19923218
2015 Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway. Oncotarget 58 25762620
2018 Differential expression of Cosmc, T-synthase and mucins in Tn-positive colorectal cancers. BMC cancer 52 30115016
2014 C1GALT1 promotes invasive phenotypes of hepatocellular carcinoma cells by modulating integrin β1 glycosylation and activity. PloS one 44 25089569
2021 C1GALT1 in health and disease. Oncology letters 39 34149900
2010 A novel fluorescent assay for T-synthase activity. Glycobiology 38 20959392
2016 Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency. Gut microbes 36 27874308
2021 Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy. Journal of the American Society of Nephrology : JASN 34 33593824
2006 Identification of core 1 O-glycan T-synthase from Caenorhabditis elegans. Glycobiology 33 16762980
2013 C1galt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes. Blood 32 23794065
2009 Genetic variant of C1GalT1 contributes to the susceptibility to IgA nephropathy. Journal of nephrology 32 19229831
2018 T-Synthase Deficiency Enhances Oncogenic Features in Human Colorectal Cancer Cells via Activation of Epithelial-Mesenchymal Transition. BioMed research international 31 30035127
2006 Targeted disruption of the gene encoding core 1 beta1-3-galactosyltransferase (T-synthase) causes embryonic lethality and defective angiogenesis in mice. Methods in enzymology 30 17113876
2012 Tight complex formation between Cosmc chaperone and its specific client non-native T-synthase leads to enzyme activity and client-driven dissociation. The Journal of biological chemistry 29 22416136
2020 Elevated miR-124-3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T-synthase. Aging cell 27 33040455
2018 Knockdown of C1GalT1 inhibits radioresistance of human esophageal cancer cells through modifying β1-integrin glycosylation. Journal of Cancer 26 30087707
2021 A novel mechanism for C1GALT1 in the regulation of gastric cancer progression. Cell & bioscience 25 34452648
2015 Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation. The Journal of biological chemistry 24 26063800
2008 Systematic determination of the peptide acceptor preferences for the human UDP-Gal:glycoprotein-alpha-GalNAc beta 3 galactosyltransferase (T-synthase). Glycobiology 24 19073881
2022 Structural basis for the synthesis of the core 1 structure by C1GalT1. Nature communications 23 35504880
2022 Dysregulation and prometastatic function of glycosyltransferase C1GALT1 modulated by cHP1BP3/ miR-1-3p axis in bladder cancer. Journal of experimental & clinical cancer research : CR 23 35864552
2023 In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression. Cellular oncology (Dordrecht, Netherlands) 21 36745330
2012 Targeted disruption of core 1 β1,3-galactosyltransferase (C1galt1) induces apical endocytic trafficking in human corneal keratinocytes. PloS one 20 22574202
2017 C1GALT1 Seems to Promote In Vitro Disease Progression in Ovarian Cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 19 28498248
2014 Identification of a novel protein binding motif within the T-synthase for the molecular chaperone Cosmc. The Journal of biological chemistry 19 24616093
2021 C1GALT1, Negatively Regulated by miR-181d-5p, Promotes Tumor Progression via Upregulating RAC1 in Lung Adenocarcinoma. Frontiers in cell and developmental biology 18 34307388
2021 Expression and Impact of C1GalT1 in Cancer Development and Progression. Cancers 18 34944925
2012 Interaction of C1GALT1-IL5RA on the susceptibility to IgA nephropathy in Southern Han Chinese. Journal of human genetics 18 23190752
2018 Clinic implication of MUC1 O-glycosylation and C1GALT1 in esophagus squamous cell carcinoma. Science China. Life sciences 15 30076562
2023 C1GalT1 expression reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression. Cell death & disease 14 37612278
2020 C1GALT1 expression is associated with galactosylation of IgA1 in peripheral B lymphocyte in immunoglobulin a nephropathy. BMC nephrology 14 31941451
2012 C1GALT1 polymorphisms are associated with Henoch-Schönlein purpura nephritis. Pediatric nephrology (Berlin, Germany) 14 22544166
2007 Immunocytochemical analysis for intracellular dynamics of C1GalT associated with molecular chaperone, Cosmc. Biochemical and biophysical research communications 14 18061573
2024 Unraveling the role of C1GALT1 in abnormal glycosylation and colorectal cancer progression. Frontiers in oncology 13 38699634
2022 Update on the role of C1GALT1 in cancer. Oncology letters 13 35154428
2020 COSMC mutations reduce T-synthase activity in advanced Alzheimer's disease. Alzheimer's & dementia (New York, N. Y.) 9 32607408
2024 Hydroxychloroquine ameliorates immune functionality and intestinal flora disorders of IgA nephropathy by inhibition of C1GALT1/Cosmc pathway. Immunopharmacology and immunotoxicology 8 38151955
2023 SLC35A2 deficiency reduces protein levels of core 1 β-1,3-galactosyltransferase 1 (C1GalT1) and its chaperone Cosmc and affects their subcellular localization. Biochimica et biophysica acta. Molecular cell research 8 36933771
2013 A study on the association between C1GALT1 polymorphisms and the risk of Henoch-Schönlein purpura in a Chinese population. Rheumatology international 8 23624553
2012 Knockdown of core 1 beta 1, 3-galactosyltransferase prolongs skin allograft survival with induction of galectin-1 secretion and suppression of CD8+ T cells: T synthase knockdown effects on galectin-1 and CD8+ T cells. Journal of clinical immunology 8 22392045
2024 C1GALT1 high expression enhances the progression of glioblastoma through the EGFR-AKT/ERK cascade. Cellular signalling 7 39561885
2022 Down-Regulation of C1GALT1 Enhances the Progression of Cholangiocarcinoma through Activation of AKT/ERK Signaling Pathways. Life (Basel, Switzerland) 7 35207462
2013 A fluorescence-based assay for Core 1 β3galactosyltransferase (T-synthase) activity. Methods in molecular biology (Clifton, N.J.) 7 23765650
2025 EGFR TKIs suppress MUC1 glycosylation through the PI3K/AKT/SP1/C1GALT1 pathway to enhance TnMUC1 CAR-T efficacy in EGFR-mutant NSCLC. Cell reports. Medicine 6 40562040
2024 O-GlcNAcylation determines the function of the key O-GalNAc glycosyltransferase C1GalT1 in bladder cancer. Acta biochimica et biophysica Sinica 6 39126245
2023 Expression and Characterisation of the First Snail-Derived UDP-Gal: Glycoprotein-N-acetylgalactosamine β-1,3-Galactosyltransferase (T-Synthase) from Biomphalaria glabrata. Molecules (Basel, Switzerland) 5 36677618
2024 Inhibition of the galactosyltransferase C1GALT1 reduces osteosarcoma cell proliferation by interfering with ERK signaling and cell cycle progression. Cancer gene therapy 4 38622340
2023 microRNA-1-3p and T-synthase mRNA have high diagnostic efficacy on intestinal mucosal barrier dysfunction in patients with severe acute pancreatitis. The Kaohsiung journal of medical sciences 4 37306210
2024 Universal Glycosyltransferase Continuous Assay for Uniform Kinetics and Inhibition Database Development and Mechanistic Studies Illustrated on ST3GAL1, C1GALT1, and FUT1. ACS omega 3 38645360
2025 The O-glycosyltransferase C1GALT1 promotes EWSR1::FLI1 expression and is a therapeutic target for Ewing sarcoma. Nature communications 2 39894896
2024 C1GALT1 induces the carcinogenesis of thyroid cancer through regulation by miR-141-3p and GLUT1. Heliyon 2 38845937
2024 C1GALT1-mediated O-glycan T antigen increase enhances the migration and invasion ability of gastric cancer cells. Biochemical and biophysical research communications 2 39243676
2015 Association between C1GALT1 variants and genetic susceptibility to IgA nephropathy in Uygur. Genetics and molecular research : GMR 2 26125729
2023 The biological role of core 1β1-3galactosyltransferase (T-synthase) in mucin-type O-glycosylation in Silkworm, Bombyx mori. Insect biochemistry and molecular biology 1 36990248
2026 Absence of glomerular IgA1 deposition despite overexpression of galactose-deficient IgA1 in the B cell c1galt1 knockout mouse. Kidney international 0 41905596
2026 Inhibition of p65 NF-κB enhances production of galactose-deficient IgA1 through suppression of C1GALT1 and SP1 in plasmablast-like cell subpopulations. bioRxiv : the preprint server for biology 0 42146603
2017 The Association of rs1047763 and rs1008898 of C1GALT1 with IgA Nephropathy Risk: A Global Meta-Analysis. Monoclonal antibodies in immunodiagnosis and immunotherapy 0 28636500
2015 Relationship between rs1047763 polymorphism of the C1GALT1 gene and susceptibility to immunoglobulin A nephropathy in Xinjiang Uyghur people. Genetics and molecular research : GMR 0 26782518

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