Affinage

Showing C1GALT1C1 — COSMC is a alias.

C1GALT1C1

C1GALT1-specific chaperone 1 · UniProt Q96EU7

Length
318 aa
Mass
36.4 kDa
Annotated
2026-06-09
61 papers in source corpus 28 papers cited in narrative 28 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

C1GALT1C1 (Cosmc) is an endoplasmic reticulum-resident molecular chaperone dedicated to folding and activating T-synthase (core 1 β3-galactosyltransferase/C1GALT1), the enzyme that builds the core 1 O-glycan (T antigen) precursor for all extended mucin-type O-glycans (PMID:12464682, PMID:18695044). Cosmc binds a cryptic hydrophobic recognition motif (CBRT) in the N-terminal stem of non-native T-synthase, prevents its aggregation and ubiquitin-proteasome-mediated degradation, and promotes ATP-independent refolding, with reactivation operating through a client-driven dissociation cycle (PMID:19923218, PMID:22416136, PMID:24616093); in the absence of Cosmc, T-synthase fails to reach the Golgi and is degraded (PMID:12464682, PMID:18061573). Its structured N-terminal domain mediates client binding while the C-terminal domain governs oligomerization and divalent-cation binding, and a transmembrane Cys-dependent disulfide dimer enforces ER retention (PMID:21262965, PMID:28665962). Loss of Cosmc function—via somatic mutation with loss of heterozygosity, promoter CpG hypermethylation, or transcriptional silencing—abolishes T-synthase activity and produces global Tn/sialyl-Tn antigen expression in cancers and other pathologies (PMID:18339842, PMID:23035125, PMID:26063800). Basal transcription is driven by SP1/SP3 sites within the core promoter and is suppressed by inflammatory cytokine-induced promoter methylation (PMID:26063800, PMID:27542280). In vivo, Cosmc is required embryonically and tissue-specifically: it controls intestinal mucus integrity and microbiota biogeography, B and T cell trafficking and BCR signaling/tolerance, and podocyte function, with several phenotypes arising cell non-autonomously (PMID:20439703, PMID:27930307, PMID:32778659, PMID:34613773, PMID:31904283). A germline transmembrane-domain variant (p.Ala20Asp) that reduces Cosmc protein expression causes multisystem disease with galactose-deficient IgA1, establishing a direct human disease link (PMID:37216524).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 High

    Established that core 1 O-glycosylation depends not only on a glycosyltransferase but on a dedicated partner, by showing T-synthase activity requires Cosmc and is otherwise lost to proteasomal degradation.

    Evidence Co-purification, cDNA rescue in Cosmc-mutant Jurkat cells, insect-cell co-expression, proteasome inhibitors

    PMID:12464682

    Open questions at the time
    • Mechanism of T-synthase recognition not yet defined
    • Subcellular site of action not resolved in this study
  2. 2007 High

    Resolved where the chaperone and client act, showing Cosmc is ER-localized while T-synthase functions in the Golgi and requires Cosmc for proper Golgi targeting.

    Evidence Immunocytochemistry, lactacystin proteasome inhibition, Cosmc overexpression rescue in colon cancer cells

    PMID:18061573

    Open questions at the time
    • Trafficking machinery handing off T-synthase from ER to Golgi unidentified
    • How Cosmc is retained in ER not yet defined
  3. 2008 High

    Defined the biochemical chaperone mechanism, demonstrating Cosmc directly binds T-synthase, prevents aggregation, and blocks its ubiquitin-mediated degradation, and clinically linked somatic Cosmc loss to tumor Tn/STn antigen expression.

    Evidence ATP-binding assays, ubiquitination assays, direct binding; plus Cosmc sequencing/LOH analysis in cancer cell lines and tumor specimens

    PMID:18339842 PMID:18695044

    Open questions at the time
    • Functional role of ATP binding not established
    • Whether Tn expression drives or merely marks malignancy unresolved
  4. 2009 High

    Reconstituted the chaperone reaction in vitro, proving Cosmc's lumenal domain binds denatured T-synthase and restores activity ATP-independently, and that a disease-associated mutant is functionally impaired.

    Evidence In vitro refolding and solid-support binding assays with recombinant proteins, mutant comparison

    PMID:19923218

    Open questions at the time
    • Structural basis of binding not determined
    • Energetics of refolding without ATP unexplained
  5. 2010 High

    Demonstrated in vivo specificity and physiological essentiality, showing germline Cosmc ablation is embryonic lethal and selectively eliminates T-synthase among glycosylation enzymes.

    Evidence Germline/conditional mouse knockout, Tn immunostaining, enzyme activity and Western blots

    PMID:20439703

    Open questions at the time
    • Cause of embryonic lethality not pinpointed
    • Tissue-specific requirements not yet dissected
  6. 2011 Medium

    Defined the timing and structural determinant of ER retention, showing Cosmc acts co-translationally and uses a TMD Cys-dependent disulfide dimer for ER retention.

    Evidence Wheat-germ cell-free translation timing experiments; chimeric proteins with TfR and TMD Cys mutagenesis

    PMID:21262965 PMID:21496458

    Open questions at the time
    • Co-translational mechanism shown in single cell-free study
    • Whether dimerization is required for chaperone activity per se unclear
  7. 2012 High

    Established the chaperone cycle, showing Cosmc selectively binds non-native (not active dimeric) T-synthase and is released through client-driven competition with additional T-synthase molecules.

    Evidence In vitro binding/reactivation and competition assays with recombinant Cosmc lumenal domain

    PMID:22416136

    Open questions at the time
    • Stoichiometry of the in vivo cycle not measured
    • Co-factors regulating release not identified
  8. 2012 High

    Identified epigenetic silencing as a mechanism of functional loss, showing Cosmc promoter CpG hypermethylation abolishes transcripts and T-synthase activity, reversibly.

    Evidence Bisulfite sequencing, 5-aza-2'-deoxycytidine rescue, RT-PCR, activity and Tn assays in Tn4 B cells

    PMID:23035125

    Open questions at the time
    • Trigger initiating hypermethylation not defined here
    • Generality across cell types not established
  9. 2014 High

    Mapped the client recognition element, identifying CBRT in the T-synthase N-terminal stem as the Cosmc-binding motif sufficient to confer Cosmc dependence on a heterologous transferase.

    Evidence Deletion/point mutagenesis, synthetic peptide binding, refolding inhibition, β4GalT1 domain-swap chimera

    PMID:24616093

    Open questions at the time
    • Atomic-resolution structure of the Cosmc-CBRT interface lacking
    • Why CBRT is cryptic in native enzyme not explained
  10. 2015 High

    Defined transcriptional control of Cosmc, identifying SP1/SP3 sites in the core promoter driving basal expression and confirming selective promoter hypermethylation in silenced cells.

    Evidence Luciferase reporters, SP1/SP3 site mutagenesis, ChIP, mithramycin A, methylome analysis

    PMID:26063800

    Open questions at the time
    • Inducible/tissue-specific regulators beyond SP1/SP3 unknown
    • Link between methylation and TF occupancy not directly shown
  11. 2017 High

    Delineated Cosmc domain architecture, separating an N-terminal chaperone domain from a C-terminal oligomerization/metal-binding domain and revealing a disease mutant active in vitro yet defective in vivo.

    Evidence Limited proteolysis, crosslinking, blue native PAGE, thermal shift, truncation/point-mutant chaperone assays

    PMID:28665962

    Open questions at the time
    • Functional role of oligomerization and metal binding unresolved
    • Why E152K fails in vivo despite in vitro activity unexplained
  12. 2023 High

    Connected Cosmc to human Mendelian disease, showing a TMD variant (A20D) lowers Cosmc protein levels causing T-synthase loss, Tn antigen, galactose-deficient IgA1, and multisystem pathology.

    Evidence Patient genetics, Cosmc/T-synthase Western and activity assays, O-glycan profiling, transfection rescue

    PMID:37216524

    Open questions at the time
    • Mechanism by which TMD variant lowers protein expression not detailed
    • Tissue specificity of the defect incompletely explained
  13. 2023 Medium

    Implicated the UDP-galactose transporter in Cosmc/T-synthase stability, showing SLC35A2 associates with both and that its loss reduces their levels and Golgi localization.

    Evidence Co-immunoprecipitation, Western blot in SLC35A2 KO cells, immunofluorescence

    PMID:36933771

    Open questions at the time
    • Co-IP without reciprocal validation of direct binding
    • Causal mechanism linking transporter loss to chaperone destabilization untested
  14. 2021 High

    Linked Cosmc-dependent O-glycosylation to immune homeostasis across tissues, showing it is required for B and T cell peripheral establishment/trafficking, BCR signaling restraint, intestinal mucus/microbiota, and podocyte function, often cell non-autonomously.

    Evidence Lineage-specific conditional knockouts (B cell, T cell, intestinal epithelium, podocyte) with adoptive transfer, intravital imaging, microbiome sequencing, mosaic-female analysis

    PMID:27930307 PMID:31317176 PMID:31904283 PMID:32778659 PMID:34613773

    Open questions at the time
    • Specific glycoprotein effectors in each tissue incompletely defined
    • Molecular basis of cell non-autonomous rescue not fully resolved
  15. 2024 Medium

    Began cataloguing tissue O-glycoprotein substrate landscapes and disease associations, identifying VEGFR2, CD44, nucleolin, podocalyxin/podoplanin, and LDLR as Cosmc-dependent glycoproteins with context-specific functional consequences.

    Evidence Conditional/CRISPR/shRNA Cosmc loss in endothelial, breast, pancreatic, podocyte, and hepatocyte systems with glycoprotein profiling and rescue

    PMID:23424651 PMID:26021314 PMID:31904283 PMID:32158257 PMID:39216105

    Open questions at the time
    • Direct mechanistic link from altered O-glycan to each phenotype not fully established
    • Several substrate findings from single labs without reciprocal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How somatic and cytokine-driven Cosmc loss mechanistically contributes to specific disease pathologies, and the atomic structure of the Cosmc–T-synthase complex, remain open.
  • No high-resolution structure of Cosmc or the chaperone-client complex
  • Causal chain from Tn antigen exposure to organ pathology incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3
Partners
C1GALT1SLC35A2

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Cosmc (C1GALT1C1) is a specific molecular chaperone required for the activity of core 1 β3-galactosyltransferase (T-synthase/C1beta3Gal-T). Without Cosmc, T-synthase is targeted to proteasomes and degraded. A small portion of T-synthase co-purifies with Cosmc from cell extracts, demonstrating direct physical association. Expression of Cosmc cDNA in Jurkat cells (which carry a mutated Cosmc with a premature stop codon) restored T-synthase activity and T antigen expression. Co-purification from cell extracts, cDNA rescue in Cosmc-mutant Jurkat cells, co-expression in insect cells, proteasome inhibitor studies Proceedings of the National Academy of Sciences of the United States of America High 12464682
2002 C1Gal-T2 (an alias for C1GALT1C1 as used in this paper, but note: this paper describes a paralog C1Gal-T2 with 26% homology to C1Gal-T1 that also has core 1 synthase activity). LSC and Jurkat cells lacking core 1 synthase activity were found to have null alleles of C1Gal-T2, indicating C1Gal-T2 contributes to core 1 O-glycan synthesis. Stable transfection of LSC cells, microsome enzyme activity assay, flow cytometry, lectin blotting, allele sequencing The Journal of biological chemistry Medium 12361956
2008 Cosmc is an endoplasmic reticulum (ER)-localized, ATP-binding molecular chaperone that directly binds to human T-synthase, prevents its aggregation, and blocks ubiquitin-mediated degradation of T-synthase. Subcellular fractionation and immunolocalization, ATP-binding assays, ubiquitination assays, direct binding experiments The Journal of cell biology High 18695044
2008 Somatic loss-of-function mutations in Cosmc cause expression of tumor-associated Tn and sialyl-Tn (STn) antigens in diverse neoplastic cell lines (colon cancer, melanoma) and human cervical cancer specimens, accompanied by loss of heterozygosity at the X-linked Cosmc locus. Sequencing of Cosmc gene in cancer cell lines and tumor specimens, LOH analysis, correlation with antigen expression by immunostaining Cancer research High 18339842
2009 The lumenal domain of recombinant Cosmc directly interacts specifically with denatured (non-native) T-synthase in vitro, forming a stable complex and promoting partial refolding and restoration of T-synthase activity in an ATP-independent manner. A Tn-syndrome-associated mutant Cosmc has reduced chaperone function. The reactivated T-synthase remains noncovalently bound to Cosmc, and dissociation is promoted by client-driven competition with additional non-native T-synthase. In vitro refolding assay with recombinant proteins, solid-support binding assay, enzyme activity measurement, mutant Cosmc comparison The Journal of biological chemistry High 19923218
2010 Ablation of the X-linked Cosmc gene in mice causes embryonic lethality and widespread Tn antigen expression. Loss of Cosmc is specifically associated with loss of T-synthase protein but not other glycosylation enzymes, demonstrating that Cosmc is specifically required for T-synthase in vivo. Genetically mosaic mice with Cosmc deletion showed abnormalities correlated with Tn antigen expression. Conditional/germline gene knockout in mice, immunostaining for Tn antigen, enzyme activity assays, Western blot for glycosylation enzymes Proceedings of the National Academy of Sciences of the United States of America High 20439703
2011 The 18-amino acid transmembrane domain (TMD) of Cosmc is essential for ER localization and confers ER retention to chimeric proteins. A single Cys residue within the TMD is required for disulfide-bonded dimerization of Cosmc and ER retention; mutation of this Cys prevents dimer formation and eliminates ER retention. Chimeric protein construction with transferrin receptor, site-directed mutagenesis of Cys in TMD, immunofluorescence localization, biochemical analysis of dimer formation The Journal of biological chemistry High 21262965
2011 Cosmc mediates co-translational activation of C1GalT (T-synthase). Recombinant Cosmc must be present during translation of C1GalT to be effective; addition of Cosmc after translation does not restore activity, indicating Cosmc acts co-translationally to prevent unfavorable aggregation. Wheat germ cell-free translation system, simultaneous vs. post-translational addition of recombinant Cosmc, enzyme activity assay FEBS letters Medium 21496458
2012 Cosmc binds specifically to denatured (non-native) T-synthase but not to the active dimeric form. Dissociation of T-synthase from the Cosmc complex is promoted by client-driven interaction with additional free non-native or native T-synthase molecules, defining a novel client-driven chaperone cycle. In vitro binding assays with recombinant lumenal domain of Cosmc on solid support, enzyme reactivation assays, competition experiments with free T-synthase forms The Journal of biological chemistry High 22416136
2012 Epigenetic silencing of Cosmc through hypermethylation of its promoter CpG islands leads to loss of Cosmc transcripts in Tn4 B cells, resulting in absence of T-synthase activity and Tn antigen expression. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restores Cosmc transcripts, T-synthase activity, and reduces Tn antigen expression. Bisulfite sequencing of Cosmc promoter, 5-aza-2'-deoxycytidine treatment, RT-PCR for Cosmc transcripts, T-synthase activity assay, flow cytometry for Tn antigen The Journal of biological chemistry High 23035125
2007 Immunocytochemical analysis established that C1GalT (T-synthase) localizes to the Golgi apparatus while Cosmc localizes to the endoplasmic reticulum in human colon cancer cells. In Cosmc-mutant LSC cells, C1GalT protein is absent; proteasome inhibition with lactacystin causes accumulation of C1GalT but not in the Golgi. Overexpression of Cosmc directs C1GalT to the Golgi and restores core 1 synthase activity, demonstrating Cosmc controls the intracellular dynamics and proper Golgi targeting of C1GalT. Monoclonal antibody-based immunocytochemistry, proteasome inhibitor (lactacystin) treatment, Cosmc overexpression, co-localization with organelle markers Biochemical and biophysical research communications High 18061573
2014 A cryptic linear, relatively hydrophobic peptide in the N-terminal stem region of T-synthase (termed CBRT, Cosmc binding region within T-synthase) is essential for binding to Cosmc. A synthetic CBRT peptide directly interacts with Cosmc and inhibits Cosmc-assisted in vitro refolding of T-synthase. Mutations within CBRT diminish T-synthase binding to Cosmc and result in formation of inactive T-synthase. Insertion of the T-synthase stem region into β4GalT1 confers Cosmc binding onto this chimera. Deletion mutagenesis, synthetic peptide binding assay, in vitro refolding inhibition assay, domain swap chimeric protein experiment, T-synthase activity assay The Journal of biological chemistry High 24616093
2015 The Cosmc core promoter, located within a CpG island (cCpG-II), contains two binding sites for Krüppel-like transcription factors (SP1/SP3), which drive basal ubiquitous transcription of Cosmc. Methylome analysis confirmed hypermethylation of the Cosmc core promoter in Tn4 B cells with silenced Cosmc, but not of the T-synthase promoter, demonstrating differential epigenetic regulation. Luciferase reporter assays, site-directed mutagenesis of SP1/SP3 binding sites, ChIP assays, mithramycin A treatment, methylome analysis/bisulfite sequencing The Journal of biological chemistry High 26063800
2017 Limited proteolysis reveals Cosmc has a structured N-terminal domain (CosmcΔ256) with wild-type chaperone activity. The C-terminal domain is required for oligomerization (Cosmc forms monomeric, dimeric, trimeric, and tetrameric species) and divalent cation binding. The N-terminal domain mediates T-synthase binding. The disease-associated CosmcE152K mutant shows wild-type-like activity in vitro despite loss of function in vivo. Limited proteolysis, chemical crosslinking, blue native PAGE electrophoresis, thermal shift assays for metal binding, in vitro chaperone activity assays with truncation and point mutants PloS one High 28665962
2013 Forced expression of Cosmc in HCT116 colon cancer cells increases T antigen expression and enhances cell growth, migration, and invasion via increased phosphorylation of FAK, ERK, and Akt. These effects are suppressed by MEK or PI3K inhibitors. Knockdown of Cosmc in SW480 cells decreases malignant behaviors and these signaling pathways, effects reversed by constitutively active Akt or MEK. Forced overexpression and siRNA knockdown, Western blot for phospho-FAK/ERK/Akt, MEK/PI3K inhibitors, cell growth/migration/invasion assays, in vivo SCID mouse tumor model Molecular carcinogenesis Medium 23390052
2013 COSMC overexpression in HUVECs increases T antigen expression, enhances cell growth, and increases phosphorylation of AKT and ERK. VEGFR2 carries O-glycans modulated by COSMC; COSMC overexpression delays VEGFR2 degradation while COSMC knockdown facilitates it. COSMC regulates VEGF-triggered phosphorylation of VEGFR2. Overexpression and siRNA knockdown, Western blot for O-glycans on VEGFR2, VEGFR2 degradation assay, VEGF stimulation assay, cell growth assays PloS one Medium 23424651
2016 Deletion of Cosmc in mouse intestinal epithelial cells (IEC-Cosmc-KO) causes marked reduction of microbiota diversity progressing from proximal to distal gut mucosa (but not lumen), emergence of a proinflammatory pathobiont, and distal gut pathology. Cosmc regulates host genes, bacterial ligands, and nutrient availability to control microbiota biogeography. Loss of one Cosmc allele in males causes compromised mucus layer and spontaneous microbe-dependent inflammation; female mosaic heterozygotes are protected due to lateral migration of normal mucin glycocalyx from WT cells. Conditional intestinal epithelial cell-specific Cosmc knockout in mice, microbiome sequencing, histology, experimental colitis models, comparison of hemizygous males vs. heterozygous females Proceedings of the National Academy of Sciences of the United States of America High 27930307
2020 B cell-specific deletion of Cosmc causes developmental blocks in mouse B cells and failure to home to lymph nodes and non-lymphoid organs after transfer. Enzymatic desialylation of WT B cells also blocks migration into lymph nodes, indicating sialylated O-glycans are required for trafficking. Cosmc-deficient B cells show normal rolling and firm arrest on high endothelium venules (HEV) but impaired transendothelial migration and defective chemokine signaling responses. B cell-specific conditional Cosmc KO, adoptive transfer experiments, enzymatic desialylation of WT B cells, intravital imaging for rolling/arrest on HEV, chemokine signaling assays Nature communications High 32778659
2020 Podocyte-specific Cosmc knockout mice develop profound albuminuria, foot process effacement, glomerular sclerosis, progressive renal failure, and impaired survival. Podoplanin O-glycoprotein expression is lost, and Tn antigen is most abundantly found on podocalyxin in KO cells. Cosmc-deficient podocytes forming foot processes interdigitating with those of normal podocytes (but not other KO cells) maintain function, suggesting a cell non-autonomous mechanism for O-glycoproteins in podocyte function. Podocyte-specific conditional Cosmc knockout, albuminuria measurement, electron microscopy for foot processes, glomerular transcriptome analysis, immunostaining for O-glycoproteins, analysis of mosaic heterozygous females American journal of physiology. Renal physiology High 31904283
2019 T cell-specific Cosmc conditional knockout (TCKO) mice show near-complete elimination of Cosmc-null T cells from spleen and lymph nodes. Cosmc-null thymocytes complete thymic maturation but fail to populate secondary lymphoid organs both natively and upon adoptive transfer to WT recipients, demonstrating that extended O-glycosylation is required for establishment and maintenance of the peripheral T cell population. Conditional T cell-specific Cosmc KO, flow cytometry for T cell populations, adoptive transfer experiments, thymocyte maturation analysis Glycobiology High 31317176
2021 B cell-specific deletion of Cosmc causes spontaneous autoimmunity with elevated self-reactive IgM and IgG autoantibodies, enhanced basal B cell activation, increased spontaneous germinal center B cells, and multiple pathological phenotypes. Mechanistically, loss of Cosmc-dependent core 1 O-glycans confers enhanced B cell receptor (BCR) signaling through diminished BCR internalization. B cell-conditional Cosmc KO mice, autoantibody profiling, BCR signaling assays, BCR internalization assays, germinal center analysis by flow cytometry Science advances High 34613773
2023 A germline hemizygous variant in C1GALT1C1 (c.59C>A, p.Ala20Asp) within the transmembrane domain of Cosmc results in dramatically reduced Cosmc protein expression (though the A20D-Cosmc protein retains function when expressed). This causes large reduction of T-synthase protein and activity in a cell/tissue-specific manner, leading to Tn-antigen expression on multiple glycoproteins, elevated galactose-deficient IgA1, and multisystem disease. Transient transfection of patient cells with WT C1GALT1C1 partially rescued T-synthase and glycosylation defect. Patient genetic analysis, Cosmc and T-synthase protein expression by Western blot, T-synthase activity assay, O-glycan profiling, transient transfection rescue experiment Proceedings of the National Academy of Sciences of the United States of America High 37216524
2023 SLC35A2 (UDP-galactose transporter) associates with Cosmc as well as with C1GalT1 (T-synthase). In SLC35A2-deficient cells, protein levels of both C1GalT1 and Cosmc are decreased and their Golgi localization is less pronounced, suggesting NSTs contribute to stabilization and targeting of Cosmc and its client. Co-immunoprecipitation, Western blot in SLC35A2 KO cells, immunofluorescence localization Biochimica et biophysica acta. Molecular cell research Medium 36933771
2015 COSMC knockdown in pancreatic cancer cell lines via lentiviral shRNA reduces proliferation, increases migration, and decreases apoptosis. Nucleolin is identified as a novel O-GalNAc-modified protein in COSMC-deficient PDAC cell lines. Lentiviral shRNA knockdown, cell viability/migration/apoptosis assays, lectin-based glycoprotein enrichment with mass spectrometry, Western/Far-Western blot Molecular cancer Medium 26021314
2020 Cosmc disruption via CRISPR/Cas9 in breast cancer cells (MCF7, T47D) suppresses cell growth in vitro and in vivo. Mechanistically, Cosmc deficiency impairs protein expression of CD44 and the associated MAPK signaling pathway; reconstitution of CD44 substantially reverses these alterations, demonstrating that CD44 requires normal O-glycosylation for proper expression and signaling. CRISPR/Cas9 Cosmc deletion, RTCA proliferation assay, colony formation, in vivo xenograft, Western blot for CD44 and MAPK pathway, CD44 reconstitution rescue Cancer management and research Medium 32158257
2016 TNF-α downregulates COSMC mRNA and protein expression and induces hypermethylation of CpG islands in the COSMC gene promoter, leading to elevated Tn antigen levels. This defines a cytokine-Cosmc-Tn signaling axis. Cytokine treatment of gingival fibroblasts, RT-PCR and Western blot for COSMC, methylation-specific PCR/bisulfite sequencing of COSMC promoter, Tn antigen immunostaining Oncotarget Medium 27542280
2024 Hepatocyte-specific deletion of Cosmc in mice abolishes extended O-glycans on liver glycoproteins and causes expression of Tn antigen on hepatocyte-derived membrane glycoproteins and serum glycoproteins. The LDL receptor (LDLR), an O-glycosylated hepatocyte glycoprotein, is reduced from ~145 kDa to ~120 kDa in the absence of Cosmc-dependent glycosylation, but LDLR expression, HMG-CoA reductase expression, and cholesterol metabolism are unaffected, indicating that core 1 O-glycans on LDLR are not required for its stability or function. Hepatocyte-specific conditional Cosmc KO mouse, Western blot for LDLR and HMG-CoA reductase, O-glycan profiling, Tn antigen detection in serum Glycobiology Medium 39216105
2020 COSMC coding mutations in advanced Alzheimer's disease brain tissue result in significantly reduced T-synthase activity (3-fold lower than advanced AD without mutations), demonstrating that somatic COSMC mutations can impair T-synthase function in brain tissue. Sequencing of COSMC in brain tissue, Q-RT-PCR, Western blotting, T-synthase activity assay Alzheimer's & dementia (New York, N. Y.) Medium 32607408

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 A unique molecular chaperone Cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proceedings of the National Academy of Sciences of the United States of America 402 12464682
2008 Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc. Cancer research 241 18339842
2010 Cosmc is an essential chaperone for correct protein O-glycosylation. Proceedings of the National Academy of Sciences of the United States of America 171 20439703
2014 The Cosmc connection to the Tn antigen in cancer. Cancer biomarkers : section A of Disease markers 127 24643043
2008 Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone Cosmc. The Journal of cell biology 109 18695044
2015 COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer. Molecular cancer 101 26021314
2015 The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL. PloS one 82 25951175
2010 Down-regulation of core 1 beta1,3-galactosyltransferase and Cosmc by Th2 cytokine alters O-glycosylation of IgA1. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 79 20551088
2008 External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 76 18202089
2016 Cosmc is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk. Proceedings of the National Academy of Sciences of the United States of America 73 27930307
2002 Molecular cloning and characterization of a novel UDP-Gal:GalNAc(alpha) peptide beta 1,3-galactosyltransferase (C1Gal-T2), an enzyme synthesizing a core 1 structure of O-glycan. The Journal of biological chemistry 63 12361956
2009 The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. The Journal of biological chemistry 61 19923218
2012 Epigenetic silencing of the chaperone Cosmc in human leukocytes expressing tn antigen. The Journal of biological chemistry 57 23035125
2018 Differential expression of Cosmc, T-synthase and mucins in Tn-positive colorectal cancers. BMC cancer 52 30115016
2008 New mutations in C1GALT1C1 in individuals with Tn positive phenotype. British journal of haematology 36 18537974
2015 DNA methylation in Cosmc promoter region and aberrantly glycosylated IgA1 associated with pediatric IgA nephropathy. PloS one 31 25647400
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
2013 The molecular chaperone Cosmc enhances malignant behaviors of colon cancer cells via activation of Akt and ERK. Molecular carcinogenesis 27 23390052
2020 Cosmc controls B cell homing. Nature communications 24 32778659
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 No evidence for a role of cosmc-chaperone mutations in European IgA nephropathy patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 23 18840896
2020 Cosmc-dependent mucin-type O-linked glycosylation is essential for podocyte function. American journal of physiology. Renal physiology 22 31904283
2015 Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29. International journal of clinical and experimental pathology 19 26045765
2014 Identification of a novel protein binding motif within the T-synthase for the molecular chaperone Cosmc. The Journal of biological chemistry 19 24616093
2014 Astragalus membranaceus up-regulate Cosmc expression and reverse IgA dys-glycosylation in IgA nephropathy. BMC complementary and alternative medicine 18 24942185
2011 The transmembrane domain of the molecular chaperone Cosmc directs its localization to the endoplasmic reticulum. The Journal of biological chemistry 18 21262965
2019 Cosmc overexpression enhances malignancies in human colon cancer. Journal of cellular and molecular medicine 17 31633299
2013 COSMC is overexpressed in proliferating infantile hemangioma and enhances endothelial cell growth via VEGFR2. PloS one 17 23424651
2012 Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy. International urology and nephrology 17 23136028
2023 Germline C1GALT1C1 mutation causes a multisystem chaperonopathy. Proceedings of the National Academy of Sciences of the United States of America 16 37216524
2020 Cosmc Disruption-Mediated Aberrant O-glycosylation Suppresses Breast Cancer Cell Growth via Impairment of CD44. Cancer management and research 15 32158257
2017 Biochemical characterization of functional domains of the chaperone Cosmc. PloS one 15 28665962
2010 The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy. Clinical and investigative medicine. Medecine clinique et experimentale 15 20144270
2007 Immunocytochemical analysis for intracellular dynamics of C1GalT associated with molecular chaperone, Cosmc. Biochemical and biophysical research communications 14 18061573
2016 TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc. Molecular medicine reports 13 28035353
2022 Emerging Roles of the Unique Molecular Chaperone Cosmc in the Regulation of Health and Disease. Biomolecules 10 36551160
2011 Co-translational function of Cosmc, core 1 synthase specific molecular chaperone, revealed by a cell-free translation system. FEBS letters 10 21496458
2020 COSMC mutations reduce T-synthase activity in advanced Alzheimer's disease. Alzheimer's & dementia (New York, N. Y.) 9 32607408
2019 Cosmc is required for T cell persistence in the periphery. Glycobiology 9 31317176
2009 Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy? BMC medical genetics 9 19778426
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
2021 Cosmc deficiency causes spontaneous autoimmunity by breaking B cell tolerance. Science advances 8 34613773
2020 Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens. Cancer management and research 8 32104083
2023 X-linked C1GALT1C1 mutation causes atypical hemolytic uremic syndrome. European journal of human genetics : EJHG 7 36599939
2017 CD3/CD28 dynabeads induce expression of tn antigen in human t cells accompanied by hypermethylation of the cosmc promoter. Molecular immunology 7 28708980
2011 [Effect of methylation modification on the expression of Cosmc gene in peripheral B lymphocyte of IgA nephropathy patients]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 7 22332537
2020 Overexpression of Cosmc suppresses cell migration and invasion in different subtypes of breast cancer cells via Tn and T glycans. Bioscience reports 6 32452513
2010 Functional assays for the molecular chaperone cosmc. Methods in enzymology 6 20816162
2016 The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn. Oncotarget 5 27542280
2021 Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure. Aging 4 34644263
2020 MicroRNA‑196b targets COSMC in pediatric IgA nephropathy. Molecular medicine reports 4 32186752
2019 Serum level of advanced oxidation protein products (AOPPs) in patients with Henoch-Schonlein purpura and its relationship with aberrant glycosylation of IgA1 and Cosmc mRNA expression. International journal of dermatology 4 31250447
2024 Cosmc regulates O-glycan extension in murine hepatocytes. Glycobiology 3 39216105
2020 The Cosmc-mediated effects of neutrophil elastase on T antigen expression in BEAS-2B cells. Respiratory physiology & neurobiology 3 32683071
2022 COSMC expression as a predictor of remission in IgA nephropathy. International urology and nephrology 2 36306048
2020 Effects of non-caloric ultrashort wave on the expression of CoQ10 and C1GALT1C1 in rats with cerebral ischemia reperfusion injury. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2 32132294
2025 C1GALT1C1-Associated Mosaic Disorder of Glycosylation in a Female. Journal of inherited metabolic disease 1 39949072
2026 Deletion of Core 1 β3GalT-specific molecular chaperone (Cosmc) in murine intestinal epithelia leads to major alterations in glycocalyx and tumorigenesis. The Journal of biological chemistry 0 41759737
2026 LncSLED1 inhibits monosodium urate-induced macrophage inflammation by promoting Cosmc methylation to upregulate CA72-4. Central-European journal of immunology 0 42245127
2016 [Association of Cosmc gene mutation with susceptibility to Henoch-Schönlein purpura in children]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 27412546

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